Enrique Cornejo Cisneros and Susana M. Lazarte
RESPIRATORY TRACT INFECTIONS
Acute Rhinosinusitis
GENERAL PRINCIPLES
· Defined as inflammation of the mucosa of the nasal passage and paranasal sinuses lasting up to 4 weeks.
· The most common etiology is a viral upper respiratory infection. Bacteria can secondarily infect an inflamed sinus cavity, but this only accounts for 0.5% to 2% of cases.1
· Since management of an acute viral rhinosinusitis (AVRS) is supportive, the main focus for the clinician should be in identifying those cases with acute bacterial rhinosinusitis (ABRS).
· The most common bacteria associated with ABRS are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.
· Complications of ABRS are very uncommon and include orbital cellulitis, cavernous sinus thrombosis, osteomyelitis, meningitis, and brain abscess. These complications represent medical emergencies that require hospitalization.
DIAGNOSIS
Clinical Presentation
· The diagnosis is clinical. Acute rhinosinusitis of any etiology presents with three major symptoms: nasal congestion or blockage, purulent rhinorrhea, and facial pain or pressure.2,3
· AVRS symptoms typically peak within 2 to 3 days of onset, decline gradually thereafter, and disappear within 10 to 14 days. Any pattern that deviates from the “classical” viral disease progression could suggest bacterial infection.
· Three criteria help distinguish ABRS from AVRS4:
o Persistent signs and symptoms lasting for ≥10 days.
o Severe symptoms for 3 to 4 consecutive days at the beginning of illness: high fever (≥39°C) and purulent rhinorrhea or facial pain.
o “Double sickening”: new onset of fever or increased nasal discharge following a typical viral upper respiratory tract infection (URI) that lasted 5 to 6 days and was initially improving.
Diagnostic Testing
· Imaging studies such as plain radiographs and CT scans are of little diagnostic value in uncomplicated acute rhinosinusitis. An abnormal radiographic finding cannot distinguish a viral from bacterial etiology.5
· Cultures obtained by sinus aspiration are not indicated for uncomplicated ABRS. They could be performed if the patient has failed to respond to initial empiric antimicrobial therapy.
TREATMENT
· Intranasal saline irrigation with either physiologic or hypertonic saline can be beneficial in symptomatic control, although the evidence supporting it is still very weak.4
· Topical or systemic decongestants, antihistamines, and mucolytics are frequently used for symptom control. However, there are no significant data to support their use. Topical decongestants should not be used for more than 3 consecutive days to avoid rebound congestion.
· Intranasal corticosteroids have been shown to provide a modest relief in symptoms when compared to placebo and should be strongly considered in patients with allergic rhinitis.6
· Management of AVRS is supportive.
· If ABRS is diagnosed, antibiotic therapy may be started. It is important, however, to note that many patients will improve without antibiotic therapy. The recommended initial duration of empiric therapy is 5 to 7 days.4
· First-line antimicrobial agents:
o Amoxicillin-clavulanate 500 mg/125 mg PO tid or 875 mg/125 mg PO bid
o Doxycycline 100 mg PO bid or 200 mg PO once a day
· If symptoms worsen after 48 to 72 hours of initial empiric antimicrobial therapy or if they fail to improve after 3 to 5 days, second-line agents may be considered.4
· Second-line antimicrobial agents:
o Amoxicillin-clavulanate 2,000 mg/125 mg PO bid
o Levofloxacin 500 mg PO once a day
o Moxifloxacin 400 mg PO once a day
· If second-line agents are used, duration of therapy can be extended to 7 to 10 days.
Pharyngitis
GENERAL PRINCIPLES
· Acute pharyngitis is one of the most common conditions encountered in primary care. Most cases are of viral etiology, benign, and self-limited.
· The major treatable causative agent is group A streptococcus (GAS). Approximately 10% to 20% of sore throats yield positive cultures for GAS.7
· Other less common causes of acute bacterial pharyngitis include Corynebacterium diphtheriae, Neisseria gonorrhoeae, Chlamydophila pneumoniae, and Mycoplasma pneumoniae, among others.
· When evaluating patients with sore throat, it is also important to consider the possibility of infectious mononucleosis (Epstein-Barr Virus) or acute retroviral syndrome (HIV).
DIAGNOSIS
Clinical Presentation
Symptoms include sore throat, odynophagia, fever, and malaise. When caused by a virus, typical symptoms of a URI can also be present (nasal congestion, rhinorrhea, hoarseness, cough). Exam may reveal pharyngeal erythema, tonsillar exudates, or anterior cervical adenopathy.
Diagnostic Criteria
The Centor clinical scoring system can help to identify those patients who have a higher likelihood of GAS pharyngitis (Table 26-1).7,8 However, clinical features alone do not reliably discriminate between GAS and viral pharyngitis. These criteria should be used in conjunction with other diagnostic tests for GAS.
TABLE 26-1 Modified Centor Criteria to Diagnose Group A Streptococcal Pharyngitis
Data from McIsaac WJ, White D, Tannenbaum D, et al. A clinical score to reduce unnecessary antibiotic use in patients with sore throat. CMAJ 1998;158:75–83.
Diagnostic Testing
· Throat cultures are 90% to 95% sensitive but can take 18 to 24 hours or more to yield results.9,10
· Rapid antigen detection tests (RADTs) can be done at the office and are highly specific (approximately 95%). However, the sensitivity is variable (70% to 95%).9,10
· RADT should be performed in patients with a Centor score of 2 to 3. There is no need for further testing for a Centor score <2.7,9
· Routine use of throat culture for the diagnosis of GAS after a negative RADT is not recommended in adults.9,10
· Antistreptococcal antibody titers are not recommended for routine diagnosis of acute pharyngitis, as they reflect past but not current events.10
TREATMENT
· Treatment of acute viral pharyngitis is supportive.
· The goals of therapy for GAS pharyngitis are to reduce duration and severity of symptoms, to reduce the risk of complications such as rheumatic fever or peritonsillar abscess, and to reduce transmission to close contacts.
· Recommended duration of therapy is 10 days.
· Preferred treatment options include the following:
o Benzathine penicillin G 1.2 million units IM for one dose
o Penicillin V 500 mg PO bid or 250 mg PO four times daily
o Amoxicillin 500 mg PO tid
· For patients with penicillin allergy, treatment options include cefadroxil or cephalexin (only if allergic reaction is not anaphylaxis), clarithromycin or azithromycin (for 5 days), or clindamycin.
Acute Bronchitis
GENERAL PRINCIPLES
· Acute bronchitis is a self-limited inflammation of the large airways of the lung that is characterized by cough without pneumonia.11
· Viruses account for the majority of cases (>90%) and include influenza, parainfluenza, respiratory syncytial virus, coronavirus, adenovirus, rhinovirus, and human metapneumovirus.
· The role of bacteria in acute bronchitis is unclear, but implicated species include Bordetella pertussis, Mycoplasma pneumoniae, and Chlamydophila pneumoniae. As a group, these agents account for 5% to 10% of uncomplicated acute bronchitis in adults.12
· Of all the etiologic agents that cause acute bronchitis, influenza virus and Bordetella pertussis require special attention because of their morbidity and treatment options.
· For pertussis (whooping cough), universal childhood vaccination is recommended. It has been proven that immunization during childhood wears off over time. Therefore, adults aged 19 to 64 years should receive a single booster administration with Tdap (acellular pertussis vaccine combined with tetanus toxoid and reduced diphtheria toxoid). In addition, adults aged 65 years and older who have not previously received Tdap should receive a single booster administration with Tdap.
DIAGNOSIS
Clinical Presentation
· Patients present with cough lasting more than 5 days, which may be associated with sputum production. Cough may last up to 3 weeks for an episode of acute bronchitis.
· Purulent sputum is common and results from sloughing off of the bronchial epithelium. It is not necessarily an indication of a bacterial rather than a viral infection.
· While evaluating a patient with acute cough, the clinician should be careful in ruling out more serious conditions, such as pneumonia. The presence of abnormal vital signs and abnormal findings on chest examination (e.g., rales, egophony, fremitus) raises concern for pneumonia.
· Pertussis (whooping cough) should be suspected after ≥2 weeks of cough that then becomes paroxysmal (succession of coughs without inspiration), is associated with an inspiratory “whoop” between paroxysms, and may be associated with posttussive emesis. The disease can be mild, and the characteristic “whoop” may be absent in previously immunized patients.
Diagnostic Testing
· Routine sputum cultures are not recommended since bacterial pathogens only play a minor role in acute bronchitis.
· Influenza testing should be considered based on seasonal patterns of influenza and patient presentation.
· Testing for pertussis includes nasopharyngeal culture and polymerase chain reaction (PCR).
· Chest radiography (CXR) is not indicated in the absence of abnormal vital signs or concerning physical exam findings. The exception is cough in the elderly patient, in which pneumonia could have a more subtle presentation.
TREATMENT
· Treatment is largely supportive in patients with acute bronchitis.
· Antivirals for influenza should be considered if influenza infection is confirmed within 24 to 48 hours of onset of symptoms.
· Routine antibiotic treatment of uncomplicated acute bronchitis is not recommended, regardless of duration of cough. Multiple randomized trials have failed to support a significant role for antibiotic therapy in acute bronchitis.11–13
· The one circumstance for which evidence supports antibiotic treatment of uncomplicated acute bronchitis is when there is suspicion of pertussis.12
· Treatment of pertussis can decrease the duration and severity of cough if started within 2 weeks of symptom onset. Treatment is also important to reduce the spread of the infection.
· Treatment regimens for pertussis in adults14:
o Erythromycin 500 mg PO four times daily for 14 days
o Clarithromycin 500 mg PO bid for 7 days
o Azithromycin 500 mg PO once on day 1, followed by 250 mg PO once a day on days 2 to 5
· In case of allergy or intolerance to macrolides, trimethoprim-sulfamethoxazole (TMP-SMX) 160 to 800 mg PO bid for 14 days may be used.14
· Postexposure prophylaxis for pertussis is indicated for close contacts within 3 weeks of the onset of cough in the index case. The regimens are the same as for the treatment of pertussis.
Influenza
GENERAL PRINCIPLES
Definition
· Influenza is caused by infection with one of three subtypes of circulating RNA viruses: influenza A, B, or C.
· Influenza C virus causes a mild respiratory illness, and its diagnosis, treatment, and prevention are generally not pursued.
· Two important concepts in influenza pathogenesis are antigenic drift and antigenic shift:
o Antigenic drift:
§ Results from point mutations in the envelope glycoproteins (hemagglutinin or neuraminidase) within a strain, which occur season to season
§ Can lead to outbreaks of variable extent and severity
§ Vaccine changed annually to account for antigenic drift
o Antigenic shift:
§ Results from complete changes in the hemagglutinin or neuraminidase, creating a new strain (e.g., from H2N2 to H3N2)
§ Can lead to epidemics and pandemics
· Complications from influenza include primary influenza viral pneumonia, exacerbation of underlying medical conditions (e.g., pulmonary or cardiac disease), secondary bacterial pneumonia (S. pneumoniae, S. aureus, H. influenzae), sinusitis, and otitis media.
Epidemiology
· Influenza is predominantly seasonal with the Northern Hemisphere affected from November to April and the Southern Hemisphere affected May to September.
· Spread from person to person occurs primarily through large-particle respiratory droplet transmission, which requires close contact. Contact with respiratory droplet–contaminated surfaces is another possible source of transmission.
· Certain groups are at increased risk of severe disease or death secondary to influenza virus infection. These groups include elderly persons (age >65), persons with chronic medical conditions, immunocompromised persons, and pregnant women.
Prevention
· The current recommendation for influenza vaccination in the US is for annual administration to patients at least 6 months of age in the absence of contraindications to influenza vaccine.
· Contraindications include previous severe reaction to an influenza vaccination, severe allergy to chicken eggs, history of Guillain-Barré syndrome (GBS) within 6 weeks following receipt of influenza vaccine, and being moderately or severely ill (with or without fever).
· Following recommendations for influenza vaccination is especially important for high-risk individuals, their close contacts, and health care workers.
· The U.S. Centers for Disease Control and Prevention (CDC) offers annual guidelines for influenza vaccination (http://www.cdc.gov/flu, last accessed December 29, 2014).
DIAGNOSIS
Clinical Presentation
Most patients with influenza exhibit an acute, uncomplicated, self-limiting course, and some may even be asymptomatic. Symptoms may include abrupt onset of fever, headache, myalgia, and malaise, associated with manifestations of an URI.
Diagnostic Testing
· Respiratory specimens for diagnosis should be obtained preferably within 5 days of illness onset, as viral shedding in immunocompetent patients will be substantially decreased after that time.15
· Several diagnostic options are available:
o Viral culture is the gold standard. Results take days to come back. Used for public health surveillance.
o Immunofluorescence: slightly lower sensitivity and specificity than culture, but results available within hours. Performance depends on laboratory expertise.
o RT-PCR: more sensitive than culture. Results available within 4 to 6 hours. Differentiates between types and subtypes.
o Rapid antigen testing: convenient and fast, with results in 10 to 30 minutes. Significantly lower sensitivity than RT-PCR and culture.
TREATMENT
· Clinical trials have shown that early antiviral treatment can shorten the duration of symptoms, can shorten the duration of hospitalization, and may reduce the risk of complications from influenza.15,16
· Clinical benefit is stronger if therapy is started within 48 hours of illness onset.15,16
· However, treatment of any person with confirmed or suspected influenza who requires hospitalization is recommended, even if the patient presents >48 hours after illness onset.16
· Adamantanes: amantadine and rimantadine. These are only effective against influenza A. Due to high levels of resistance in the US, CDC no longer recommends its use.16
· Neuraminidase inhibitors: zanamivir and oseltamivir.
o Effective against both influenza A and B
o Oseltamivir: 75 mg PO bid for 5 days
o Zanamivir: two 5-mg inhalations (10 mg total) bid for 5 days
· Postexposure chemoprophylaxis may be considered in close contacts of a confirmed or suspected case of influenza during that person’s infectious period if those contacts are at high risk for complications of influenza. It should only be used when antivirals can be started within 48 hours of the most recent exposure. Options include
o Oseltamivir: 75 mg PO once a day for 10 days
o Zanamivir: two 5-mg inhalations (10 mg total) once a day for 10 days
· Influenza viruses and their susceptibility to antiviral medications evolve rapidly. Physicians should keep abreast of patterns of influenza circulation and susceptibility in their communities. Updated information in the US can be found on the CDC website: http://www.cdc.gov/flu (last accessed December 29, 2014).
Community-Acquired Pneumonia
GENERAL PRINCIPLES
Etiology
· Community-acquired pneumonia (CAP) is an infection of the lung parenchyma acquired outside of hospitals or extended-care facilities.
· Bacteria are the most common cause of CAP. The most common pathogens involved are Streptococcus pneumoniae, Mycoplasma pneumoniae, Haemophilus influenza, and Chlamydophila pneumoniae.
· Less common causes include Legionella spp., Staphylococcus aureus, Enterobacteriaceae, and Pseudomonas aeruginosa.
· The most common cause of viral CAP in adults is influenza.
Prevention
· Two types of pneumococcal vaccines are approved for use in the US for prevention of noninvasive and invasive pneumococcal infections: pneumococcal polysaccharide vaccine (PPSV23) and pneumococcal protein-conjugate vaccine (PCV13).
· PPSV23 is recommended for all adults ≥65 years of age and in persons 19 to 64 years of age who have a condition that increases the risk of pneumococcal disease (including cigarette smoking, chronic lung disease, chronic heart disease, diabetes, among others).
· PCV13 is recommended (in addition to PPSV23) for use in individuals aged 19 or older with functional or anatomic asplenia, immunocompromising conditions, cerebrospinal fluid leaks, cochlear implants, or advanced kidney disease. In late 2014 the Advisory Committee on Immunization Practices (ACIP) recommended PCV13 for all adults ≥65 years.
DIAGNOSIS
Clinical Presentation
· Common symptoms include fever, cough, sputum production, dyspnea, and pleuritic chest pain. Malaise, anorexia, chills, and abdominal complaints are also frequent.
· Clinical features of pneumonia may be lacking or altered in elderly patients. Confusion or delirium could be the initial presentation in the elderly.
· On exam, audible rales may be present. If a consolidation develops, bronchial breath sounds, dullness, egophony, and whispered pectoriloquy are associated findings.
· Tachypnea and hypotension are ominous findings and warrant more rapid evaluation.
Diagnostic Testing
· A CBC often reveals a leukocytosis with a leftward shift.
· A CXR should be obtained in all patients suspected of having pneumonia. The presence of an infiltrate on CXR is diagnostic of pneumonia when clinical features are supportive.
· The radiographic appearance of CAP may include lobar consolidation, interstitial infiltrates, or cavitation.
· Routine testing for microbiologic diagnosis is usually not indicated in the outpatient setting, since most patients do well with empiric antibiotic therapy.
· Exceptions may apply if clinical or epidemiologic clues raise suspicion for specific pathogens that would alter empiric therapy.
· Consider the following tests in selected patients in the appropriate clinical scenario: rapid antigen test for influenza, urinary antigen test for Legionella, urinary antigen test for pneumococcus, and sputum for acid-fast staining.
· Pretreatment sputum Gram stain and culture are useful only when quality specimens can be obtained.
TREATMENT
· The decision as to whether the patient can be safely treated as an outpatient or needs admission to the hospital can be assisted by the use of severity-of-illness scores such as the Pneumonia Severity Index (PSI)17 (Table 26-2) or the CURB-65 score18 (Table 26-3).
· Most patients will have a good response to empiric antibiotic therapy; however, treatment should always be tailored to provide narrow coverage if the etiologic agent is known.
· The following are risk factors associated with drug-resistant Streptococcus pneumoniae (DRSP): age > 65 years; β-lactam, macrolide, or fluoroquinolone therapy within the last 3 months; alcoholism; medical comorbidities; immunosuppressive therapy or illness; and exposure to a child in a daycare center.
· Comorbidities including chronic heart, lung, liver, or renal disease, diabetes mellitus, malignancy, and asplenia should be taken into account when choosing empiric antibiotic therapy.
· Empiric regimen for previously healthy patients, with no use of antimicrobials within the previous 3 months and with no risk factors for DRSP: macrolide or doxycycline.19
· Empiric regimen for patients with comorbidities, use of antimicrobials within the previous 3 months, or risk factors for DRSP infection19:
o A respiratory fluoroquinolone
o A β-lactam plus a macrolide
o A β-lactam plus doxycycline (less evidence than macrolide combination)
· The following are the suggested oral doses for the abovementioned antimicrobial agents:
o Macrolides: azithromycin, 500 mg on day one followed by 4 days of 250 mg a day; clarithromycin, 500 mg bid; and erythromycin: 250 mg every 6 hours
o Doxycycline: 100 mg bid
o Respiratory fluoroquinolones: levofloxacin, 750 mg daily; moxifloxacin, 400 mg daily; gemifloxacin, 320 mg daily
o β-Lactams: amoxicillin, 1,000 mg tid; amoxicillin-clavulanate, 2,000 mg/125 mg PO bid; cefpodoxime, 200 mg bid; cefuroxime, 500 mg bid
· The minimum duration of therapy is 5 days. Patients should be afebrile for 48 to 72 hours and clinically stable before stopping antibiotic therapy.
· Patients with CAP should be appropriately vaccinated for influenza and pneumococcal infection.
· Smoking cessation should be a goal for all patients with CAP who smoke.
TABLE 26-2 Pneumonia Severity Index
Data from Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 1997;336:243–50.
TABLE 26-3 CURB-65 Score
Data from Lim WS, van der Eerden MM, Laing R, et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax 2003;58:377–82.
COMPLICATIONS
Complications from CAP include bacteremia with extrapulmonary infection, parapneumonic effusion, empyema, necrotizing pneumonia, and lung abscess.
Tuberculosis
GENERAL PRINCIPLES
· Tuberculosis (TB) is a systemic disease caused by Mycobacterium tuberculosis. It is one of the most common infectious causes of death worldwide.
· TB most commonly affects the lungs; however, any organ or tissue can be involved. Extrapulmonary TB accounts for 14% to 25% of reported cases globally.20
· TB is transmitted by aerosolized droplets that deposit in the alveoli after inhalation. The bacilli proliferate in the alveolar macrophages and spread to lymph nodes. Subsequent hematogenous dissemination leads to seeding in extrapulmonary locations.
· TB infection can be immediately cleared, lead to primary disease, evolve to latent infection, or reappear as reactivation disease (most common presentation).
· Risk factors associated with TB include malnutrition, immunosuppression (HIV, transplant, tumor necrosis factor [TNF]-α inhibitors), systemic disease (diabetes, renal disease, malignancy), substance abuse, close household contact of a patient with TB, birth in a TB-endemic area, and exposure to crowded settings with poor ventilation.
DIAGNOSIS
Clinical Presentation
· Pulmonary TB most commonly presents with productive cough, which may be accompanied by other respiratory symptoms (shortness of breath, chest pain, hemoptysis) and/or constitutional symptoms(e.g., loss of appetite, weight loss, fever, night sweats, and fatigue).
· Tuberculosis suspect: patient with symptoms or signs suggestive of TB, most commonly an otherwise unexplained productive cough for more than 2 to 3 weeks.
· Definite tuberculosis: patient with Mycobacterium tuberculosis identified from a clinical specimen, either by culture or by a nucleic acid amplification test.
Diagnostic Testing
· Patients meeting clinical and/or epidemiologic criteria for TB should have a CXR. Reactivation TB typically involves focal infiltration of the apical-posterior segments of the upper lobes or the superior segment of the lower lobes.
· All patients with CXR findings suggestive of TB should have sputum specimens (coughed and induced or from bronchoscopy) submitted for microbiologic examination.
· All patients suspected of having pulmonary TB should have at least two, and preferably three, sputum specimens obtained for microscopic examination. When possible, at least one early-morning specimen should be obtained (sputum collected at this time has the highest yield).21
· Acid-fast bacteria observed on stained sputum specimens may represent M. tuberculosis or nontuberculous mycobacteria. Thus, acid-fast staining should be confirmed by culture or molecular testing.
· For all patients suspected of having extrapulmonary TB, appropriate specimens from the suspected sites of involvement should be obtained for microscopy, culture, and histopathologic examination.
· All patients with suspected or confirmed TB should have testing for HIV.
TREATMENT
· Treatment guidelines are available through the World Health Organization (www.who.int) and the Infectious Diseases Society of America (IDSA) (www.idsociety.org, last accessed December 29, 2014).
· The goals of therapy are eradication of M. tuberculosis infection, preventing TB relapse, preventing development of drug resistance, and preventing TB transmission.
· Treatment should be undertaken with the guidance of an expert and may include hospitalization to initiate therapy, patient education, and respiratory isolation.
· Directly observed therapy (DOT) is considered the standard of care. This allows confirmation of completion of therapy and prevents emergence of drug resistance.
· The local public health authorities should be notified of all cases of TB so that contacts can be identified and arrangements for DOT can be made.
· Initial therapy for tuberculosis should include four drugs: isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E).
· All TB treatment regimens include an initial intensive phase and a continuation phase. Recommended doses for first-line drugs can be found in Table 26-4.20
· The WHO recommends a standard regimen for new TB patients (presumed, or known, to have drug-susceptible TB) that includes a 2-month initial phase with all four drugs followed by a 4-month continuation phase with isoniazid and rifampicin: 2HRZE/4HR.20
· The optimal dosing frequency for new TB patients is daily throughout the course of therapy. The WHO offers two alternatives to this regimen20:
o Daily intensive phase followed by three times weekly continuation phase [2HRZE/4(HR)3], provided that each dose is directly observed
o Three times weekly dosing throughout therapy [2(HRZE)3/4(HR)3], provided that every dose is directly observed and the patient is not living with HIV or living in an HIV-prevalent setting
· To minimize neurotoxicity, supplemental pyridoxine should be provided (25 to 50 mg daily) in patients taking isoniazid.
· HIV-positive patients should be treated with the same regimens. Some experts recommend prolonged therapy (8 months or more) in certain circumstances. Treatment requires the supervision of an HIV specialist.
· Extrapulmonary TB should be treated with the same regimens as pulmonary TB. However, experts recommend 9 months of therapy for TB of bone and joints and 9 to 12 months of therapy for TB meningitis. In TB meningitis, ethambutol could be replaced by streptomycin.
· Unless drug resistance is suspected, adjuvant corticosteroid treatment is recommended for TB meningitis and pericarditis.
TABLE 26-4 Recommended Doses of First-Line Antituberculosis Drugs for Adults
Data from WHO. Treatment of Tuberculosis: Guidelines, 4th ed. Geneva, Switzerland: World Health Organization; 2010.
SPECIAL CONSIDERATIONS
· Multidrug-resistant tuberculosis (MDR-TB): resistance to at least isoniazid and rifampin.
· Extensively drug-resistant tuberculosis (XDR-TB): resistance to isoniazid, rifampin, and fluoroquinolones, as well as aminoglycosides (amikacin, kanamycin) or capreomycin, or both.
· An assessment of the likelihood of drug resistance should be performed for all patients. The most critical risk factor for MDR-TB is prior TB treatment. Other risk factors include contact with a proven MDR case, patients who remain sputum smear positive at month 2 or 3 of therapy, and HIV infection.
· Treatment of MDR-TB and XDR-TB requires a TB expert.
MONITORING/FOLLOW-UP
· For smear-positive pulmonary TB patients treated with first-line drugs, sputum smear microscopy should be performed at completion of the intensive phase of treatment.
o If the specimen obtained at the end of the intensive phase (month 2) is smear positive, sputum smear microscopy should be repeated at the end of month 3.
o If the specimen obtained at the end of month 3 is smear positive, sputum culture and drug susceptibility testing (DST) should be performed.21
· All new pulmonary TB patients who were smear positive at the start of treatment should have sputum specimens for smear microscopy at the end of months 5 and 6.
· Cure: A patient whose sputum smear or culture was positive at the beginning of the treatment but who was smear or culture negative in the last month of treatment and on at least one other occasion.20
· Treatment failure: A patient whose sputum smear or culture is positive at 5 months or later during treatment, or a patient found to harbor a MDR strain at any point during treatment, whether they are smear negative or positive.20 Patients who fail treatment should be managed by a TB expert.
· Follow-up radiographic examinations are usually unnecessary and might be misleading.
Latent Tuberculosis
GENERAL PRINCIPLES
Mycobacterium tuberculosis infection can be contained by host defenses and remain latent. Latent TB infection (LTBI) has the potential to progress to active disease at any time. The lifetime risk of progression is 10%.
DIAGNOSIS
· Latent TB patients are asymptomatic.
· The goal of screening for LTBI is to identify patients at increased risk for developing active TB and who would, therefore, benefit from treatment. These include the following:
o Close contacts of patients with pulmonary TB
o Health care workers and other occupations with exposure to patients with active TB
o Recent immigrants (within 5 years) from high-prevalence countries
o Patients with abnormal CXR with signs of healed TB
o Patients with silicosis, intravenous drug use, diabetes mellitus, HIV, end-stage renal disease, lymphoma, leukemia, and head and neck malignancy
o Patients with transplant, chemotherapy, or other major immunosuppressive conditions
o Treatment with TNF-α inhibitors or systemic glucocorticoids
o Conditions associated with rapid weight loss or chronic malnutrition
· Screening for LTBI is done by tuberculin skin testing (TST) or by interferon-gamma release assays (IGRAs). A positive screening test without active disease is indicative of LTBI.
· The tuberculin material used for skin testing is purified protein derivative (PPD), injected using the Mantoux technique. The test is interpreted by reading (at 48 to 72 hours) the transverse diameter of the area of induration (not erythema) at the site of injection.
· Interpretation of TST can be found in Table 26-5.22
· Close contacts of patients with active TB with a nonreactive TST should have a repeat test after 10 weeks.
· Bacillus Calmette-Guérin (BCG) vaccination in the 1st year of life has been reported to be a source of false-positive results on TST. Of note, BCG vaccination causes no significant effect on TST after 10 years or more. In contrast to TST, IGRAs are not affected by BCG vaccination status.
TABLE 26-5 Tuberculin Skin Test Interpretation
CXR, chest radiograph; IVDU, intravenous drug users; DM, diabetes mellitus; ESRD, end-stage renal disease; TB, tuberculosis.
TREATMENT
· Two regimens are now jointly recommended for the treatment of LTBI by the CDC:22,23:
o Isoniazid 5 mg/kg/day (maximum 300 mg) for 9 months
o Isoniazid 15 mg/kg (maximum 900 mg) plus rifapentine, both given once a week by DOT for 12 weeks
· The isoniazid-rifapentine regimen is only recommended for patients with LTBI aged ≥12 years and who have factors that are predictive of TB developing (e.g., recent exposure to contagious TB, conversion from negative to positive on TST or IGRA, and radiographic findings of healed pulmonary TB). The regimen is not recommended for HIV-positive patients who are receiving antiretroviral therapy.
· The weekly dose of rifapentine according to body weight is 300 mg (10 to 14 kg), 450 mg (14.1 to 25 kg), 600 (25.1 to 32 kg), 750 (32.1 to 49.9 kg), and 900 (≥50 kg).
· Patients taking isoniazid should receive supplemental pyridoxine (25 to 50 mg daily) to minimize neurotoxicity.
· Treatment of LTBI after MDR-TB and XDR-TB exposure is a complex issue and should be undertaken with the guidance of a TB expert.
URINARY TRACT INFECTIONS
Uncomplicated Urinary Tract Infections in Women
GENERAL PRINCIPLES
· Uncomplicated urinary tract infection (UTI) refers to cystitis and pyelonephritis in premenopausal, nonpregnant women with no known urologic abnormalities or comorbidities.
· UTI is the most common bacterial infection encountered in the ambulatory care setting in the US, accounting for 8.6 million visits (84% by women) in 2007. The self-reported annual incidence of UTI in women is 12%.24
· The vast majority of episodes of uncomplicated UTI are caused by Escherichia coli (75% to 95%). Other pathogens include Klebsiella pneumoniae, Staphylococcus saprophyticus, and Proteus mirabilis. Isolation of Enterococcus faecalis, and Streptococcus agalactiae could represent contamination of the urine specimen.
· The pathogenesis involves bacteria from the bowel or the vagina colonizing the periurethral mucosa and ascending through the urethra to the bladder. Pyelonephritis occurs when pathogens ascend to the kidneys through the ureters or, less commonly, when pathogens are seeded by hematogenous spread (e.g., Staphylococcus aureus or M. tuberculosis).
· Risk factors include previous history of UTI, sexual intercourse, use of spermicides, and a history of UTI in a first-degree female relative.
DIAGNOSIS
· Cystitis: symptoms include dysuria, frequency, urgency, suprapubic pain, or hematuria.
· Pyelonephritis: symptoms include fever (>38°C), chills, flank pain, costovertebral angle tenderness, nausea, or vomiting. Symptoms of cystitis may or may not be present.
· A urine dipstick test can detect leukocyte esterase (enzyme released by leukocytes) or nitrite (converted from urinary nitrate by Enterobacteriaceae). The presence of either of these predicts UTI with a sensitivity of 75% and a specificity of 82%.24
· Microscopic examination can be done in a voided midstream urine specimen to detect the presence of pyuria, defined as ≥10 leukocytes/mm3 in uncentrifuged urine or >5 leukocytes/high-power field (HPF) in a centrifuged sediment. Pyuria is present in almost all women with acute cystitis or pyelonephritis.
· Urine cultures can be performed to confirm the presence of bacteriuria and to evaluate the antimicrobial susceptibility of the pathogen involved.
· A urine culture is not necessary for the diagnosis of uncomplicated cystitis, given the reliability of patient symptoms in establishing the diagnosis. The combination of dysuria and frequency without vaginal discharge or irritation raises the probability of cystitis in a woman to more than 90%.25
· A urine culture must be obtained in all patients suspected of having pyelonephritis, and treatment should be adjusted based on antimicrobial susceptibility results. A urine culture is also warranted if symptoms are atypical, if there is failure to respond to initial therapy, or if there is recurrence of symptoms within a month of prior treatment.
· The traditional definition of a positive urine culture is ≥105 colony-forming units (CFUs)/mL together with pyuria, obtained from voided midstream urine. It has been suggested that this criterion is appropriate for pyelonephritis but may lack sensitivity to diagnose cystitis. If culture is indicated for the diagnosis of cystitis, a lower threshold of ≥102 CFU/mL may increase the sensitivity for detection in symptomatic women, with a positive predictive value of 88%.26
TREATMENT
· Treatment guidelines from the IDSA emphasize the importance of considering the ecologic adverse effects of antimicrobial agents when selecting a treatment regimen. These effects include the selection and subsequent colonization or infection with multidrug-resistant organisms.
· Local antimicrobial susceptibility patterns of E. coli should be considered in empiric antimicrobial selection.
· For uncomplicated cystitis, studies suggest a 20% TMP-SMX resistance prevalence as the threshold at which this agent is no longer recommended for empiric treatment.27
· For pyelonephritis, a 10% fluoroquinolone resistance prevalence is the threshold for using an alternative agent in conjunction with or in place of a fluoroquinolone, based on expert opinion.27
· Empiric therapy of uncomplicated cystitis can be found in Table 26-6.27
· Acute uncomplicated pyelonephritis can be treated in the outpatient setting. However, admission is warranted in severe disease with high fever, pain, marked debility, hemodynamic instability, and poor PO tolerance or if there is concern about compliance with therapy.
· Empiric therapy of uncomplicated pyelonephritis in the outpatient setting can be found in Table 26-7.27
· Empiric therapy of pyelonephritis requiring inpatient admission should include intravenous antibiotics such as a fluoroquinolone, an aminoglycoside (with or without ampicillin), an extended-spectrum cephalosporin or extended-spectrum penicillin (with or without an aminoglycoside), or a carbapenem. The choice between these agents should be based on local resistance data, and the regimen should be adjusted based on susceptibility results.27
· Follow-up urine cultures are not needed in patients with acute cystitis or pyelonephritis whose symptoms resolve on antibiotics.
· Symptomatic therapy of severe dysuria with phenazopyridine (100 to 200 mg tid) can be considered. Symptoms usually respond to antibiotics within 48 hours.
TABLE 26-6 Empiric Therapy of Uncomplicated Cystitis in Women
TMP-SMX, trimethoprim-sulfamethoxazole.
TABLE 26-7 Outpatient Empiric Therapy of Uncomplicated Pyelonephritis in Women
TMP-SMX, trimethoprim-sulfamethoxazole.
SPECIAL CONSIDERATIONS
· Antimicrobial prophylaxis has been shown to reduce the risk of UTI recurrence by approximately 95% in women who have had three or more UTIs in the past 12 months or two or more UTIs in the past 6 months.24
· Postcoital antimicrobial prophylaxis includes a single dose of nitrofurantoin 50 to 100 mg, TMP-SMX 40/200 mg, or cephalexin 250 mg.
· Continuous antimicrobial prophylaxis includes a daily bedtime dose of nitrofurantoin 50 to 100 mg, TMP-SMX 40/200 mg, or cephalexin 125 to 250 mg. Fosfomycin 3-g sachet every 10 days is also an option.
Uncomplicated Urinary Tract Infections in Men
GENERAL PRINCIPLES
· Uncomplicated UTI refers to cystitis and pyelonephritis in men with no known urologic abnormalities or comorbidities.
· Uncomplicated UTI are much less common in men than in women. This is thought to be due to the greater length and drier surrounding environment of the male urethra, as well as the antibacterial properties of prostatic fluid.28
· The etiologic agents causing uncomplicated UTI in men are similar to those in women. Escherichia coli is the most common causative organism.
· Risk factors include insertive anal intercourse, intercourse with a female partner colonized with uropathogens, and lack of circumcision.28
· In a patient without an obvious risk factor, further evaluation for predisposing conditions (e.g., anatomic abnormalities) should be considered.
· Prostatitis should be suspected in men with recurrent cystitis.
DIAGNOSIS
· Symptoms of uncomplicated cystitis or pyelonephritis in men are similar to those in women.
· The differential diagnosis includes urethritis in sexually active men with genital lesions or urethral discharge, as well as prostatitis in patients with fever, chills, pelvic pain, or obstructive urinary symptoms.
· A urine dipstick test can detect the presence of leukocyte esterase or nitrite. Microscopic examination can be done to detect the presence of pyuria.
· A urine culture must be obtained in all male patients suspected of having an uncomplicated UTI. A positive urine culture is defined as ≥104 CFU/mL, obtained from voided midstream urine.28 A posttreatment urine culture to document urinary tract sterility is recommended in men.
TREATMENT
· Duration of therapy for uncomplicated cystitis should be for a minimum of 7 days.28 Treatment options include TMP-SMX, 1 double-strength tablet (160/800 mg) bid; ciprofloxacin, 500 mg bid; and levofloxacin, 500 mg PO daily.
· Duration of therapy for uncomplicated pyelonephritis should be 10 to 14 days.28 Recommended antimicrobial agents and their doses are the same as the ones described for women. See Table 26-7.
Complicated Urinary Tract Infections
GENERAL PRINCIPLES
· A complicated UTI is the one associated with an underlying condition that increases the risk of infection or of failing therapy.
· Conditions that suggest a potential complicated UTI29:
o Presence of an indwelling urethral catheter, stent, or nephrostomy tube
o Intermittent bladder catheterization
o An obstructive uropathy of any etiology
o Vesicoureteric reflux or other functional abnormalities
o Urinary tract modifications, such as an ileal loop or pouch
o Renal insufficiency and transplantation, diabetes mellitus, and immunodeficiency
o Peri- and postoperative UTI
o Chemical or radiation injuries of the uroepithelium
· Escherichia coli is the most common causative organism. Other pathogens include Proteus mirabilis, Klebsiella pneumoniae, Pseudomonas spp., Serratia spp., Enterococcus, and staphylococci.
DIAGNOSIS
Pyuria and bacteriuria may be absent if the infection does not communicate with the collecting system (i.e., if there is an obstruction). Urine cultures and susceptibility testing should always be obtained prior to therapy.
TREATMENT
· Therapy involves selecting an appropriate antimicrobial regimen and managing the underlying urologic abnormality (when possible).
· Empiric therapy should be based on culture and susceptibility results.
· Complicated cystitis can be managed as an outpatient. However, hospitalization could be required depending on illness severity. Treatment is recommended for 7 to 14 days.
· Patients with complicated pyelonephritis should be initially managed as inpatients. Treatment is recommended for 14 days.
· Recommended initial empiric regimens29:
o Fluoroquinolones: ciprofloxacin or levofloxacin
o Aminopenicillin (amoxicillin or ampicillin) plus β-lactamase inhibitor
o Cephalosporins: cefuroxime, ceftriaxone, and cefotaxime
o Aminoglycoside: gentamicin and tobramycin
· Recommended empiric regimens for severe infection or in case of initial treatment failure (within 1 to 3 days) should include coverage for Pseudomonas spp.29:
o Fluoroquinolones: ciprofloxacin or levofloxacin
o Piperacillin plus β-lactamase inhibitor
o Cephalosporins: ceftazidime, cefepime
o Carbapenem: imipenem, meropenem
o Aminoglycoside plus fluoroquinolone
Asymptomatic Bacteriuria
· Asymptomatic bacteriuria is defined as isolation of a specified quantitative count of bacteria in an appropriately collected urine specimen obtained from a patient without symptoms or signs of UTI.30
· In asymptomatic women:
o Two consecutive voided urine specimens with isolation of the same bacterial strain in quantitative counts ≥105 CFU/mL
or
o A single catheterized urine specimen with one bacterial species isolated in a quantitative count ≥102 CFU/mL
· In asymptomatic men:
o A single, clean-catch voided urine specimen with one bacterial species isolated in a quantitative count ≥105 CFU/mL
or
o A single catheterized urine specimen with one bacterial species isolated in a quantitative count ≥102 CFU/mL
· Screening for and treatment of asymptomatic bacteriuria is only recommended in the following situations30: pregnant women, before transurethral resection of the prostate, and before other urologic procedures for which mucosal bleeding is anticipated.
· Screening for or treatment of asymptomatic bacteriuria is not recommended for the following persons: premenopausal nonpregnant women, diabetic women, older persons living in the community, elderly institutionalized subjects, persons with spinal cord injury, and catheterized patients while the catheter remains in situ.
· Antimicrobial treatment of asymptomatic women with catheter-acquired bacteriuria that persists 48 hour after indwelling catheter removal may be considered.
SKIN AND SOFT TISSUE INFECTIONS
Cellulitis and Erysipelas
GENERAL PRINCIPLES
· Cellulitis and erysipelas are skin infections that are not secondary to an underlying suppurative focus, such as abscesses, septic arthritis, or osteomyelitis. However, cellulitis can be associated with purulent drainage or exudates in the absence of a drainable abscess.
· Erysipelas involves the upper dermis and superficial lymphatics, while cellulitis involves the deeper dermis and subcutaneous fat.
· Erysipelas is usually caused by β-hemolytic streptococci, more commonly group A (i.e., S. pyogenes). Groups C and G have also been implicated. Group B streptococci and S. aureus are less frequent.
· Cellulitis without purulent drainage or exudate is more commonly caused by β-hemolytic streptococci. Less frequently, S. aureus (both methicillin-sensitive and methicillin-resistant strains) is the causative agent.
· Cellulitis presenting with purulent drainage or exudate is more commonly caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), representing up to 59% of cases presenting to emergency departments in the US.31
· These infections arise when there is disruption of the skin barrier. However, breaches in the skin are not always clinically apparent and may be unnoticed.
· Predisposing conditions include previous cutaneous damage, edema from venous insufficiency or lymphatic obstruction, obesity, or previous cutaneous infection (e.g., impetigo, tinea).32 Diabetes, arterial insufficiency, eczema, and intravenous drug use also predispose to infection.
· Risk factors associated with CA-MRSA can be found on Table 26-8.31,33
TABLE 26-8 Risk Factors Associated with Community-Acquired Methicillin-Resistant Staphylococcus aureus (CA-MRSA) Skin and Soft Tissue Infections
DIAGNOSIS
· Both erysipelas and cellulitis present as rapidly spreading areas of erythema, warmth, and edema, sometimes associated with lymphangitis and inflammation of the regional lymph nodes.
· Vesicles, bullae, petechiae, and ecchymoses can be found occasionally.
· The most common site of infection is the lower extremities.
· Erysipelas has the distinctive feature of being a raised lesion with sharply demarcated borders. Cellulitis generally lacks sharp demarcated borders. It can present with or without purulent drainage or exudates, in the absence of a drainable abscess.
· The differential includes contact dermatitis, stasis dermatitis, deep venous thrombosis, acute gout, drug reactions, insect bites, early herpes zoster, and erythema migrans. Physicians must also maintain a high index of suspicion for severe processes such as necrotizing fasciitis, as the initial presentation can be quite benign (see section on necrotizing fasciitis).
· Blood cultures are positive in ≤5% of cases.34 Cultures from needle aspiration of intact skin or from punch biopsies have variable results and are generally not helpful. In the case of cellulitis associated with purulent drainage or exudates, cultures should be obtained to guide therapy.
TREATMENT
· A large proportion of patients can be treated with oral medications. Parenteral therapy is indicated for severely ill patients or for those unable to tolerate oral medications.
· For uncomplicated cellulitis, 5 to 10 days of antibiotic therapy is recommended in the outpatient setting.35 For severe disease, a longer course of antibiotics may be warranted.
· Efforts should be made to treat any underlying predisposing condition.
· Elevation of the affected extremity aids in healing by promoting gravity drainage of the edema and inflammatory substances.
· Erysipelas:
o Therapy should cover β-hemolytic streptococci. Penicillin remains the treatment of choice. Therapeutic options for erysipelas are summarized in Table 26-9.
o If there is high suspicion for methicillin-sensitive Staphylococcus aureus (MSSA) infection, a penicillinase-resistant semisynthetic penicillin or a first-generation cephalosporin should be used.
· Nonpurulent cellulitis:
o Empiric therapy should cover β-hemolytic streptococci and MSSA.
o Empiric coverage for CA-MRSA is recommended in patients who do not respond to β-lactam therapy, in those with systemic toxicity, or in those with risk factors for CA-MRSA (see Table 26-8).
o Therapeutic options for nonpurulent cellulitis are summarized in Table 26-10.
· Purulent cellulitis:
o Empiric therapy should cover CA-MRSA, pending culture results.
o Empiric therapy to cover β-hemolytic streptococci is likely unnecessary.
o If parenteral therapy is needed, vancomycin is the treatment of choice.
o Therapeutic options for purulent cellulitis are summarized in Table 26-11.
TABLE 26-9 Empiric Antimicrobial Therapy for Erysipelas
TABLE 26-10 Empiric Antimicrobial Therapy for Nonpurulent Cellulitis
TABLE 26-11 Empiric Antimicrobial Therapy for Purulent Cellulitis
Abscesses, Furuncles, and Carbuncles
GENERAL PRINCIPLES
· Cutaneous abscesses are collections of pus within the dermis and deeper cutaneous tissues.
· Furuncles (boils) are collections of pus that form at the site of hair follicles, in which suppuration extends through the dermis into the subcutaneous tissue. Carbuncles are coalesced furuncles.
· Cutaneous abscesses are typically polymicrobial, containing bacteria that constitute the normal regional skin flora, often combined with organisms from adjacent mucous membranes.34
· Staphylococcus aureus is the predominant agent isolated from cutaneous abscesses, with CA-MRSA representing up to 61% of isolates in patients presenting to emergency departments in the US.31
· Furuncles and carbuncles are usually caused by MSSA or MRSA.34 Furuncles and carbuncles can also be caused by other organisms, including Pseudomonas aeruginosa (hot tub or whirlpool exposure), atypical mycobacteria (nail salon footbaths), or Candida spp. (immunosuppressed, broad-spectrum antibiotic exposure).
DIAGNOSIS
· Cutaneous abscesses usually present as painful, tender, and fluctuant red nodules. These lesions can have an overlying pustule and are often associated with surrounding erythema and swelling.
· Furuncles have a similar appearance, with a hair emerging through the pustule. Carbuncles present as a coalescent inflammatory mass with pus draining from multiple follicular orifices.
· Fever, chills, and systemic toxicity are unusual with cutaneous abscesses. These manifestations are more common with carbuncles.
· Gram stain and culture are useful to tailor antibiotic therapy when indicated.
TREATMENT
· For cutaneous abscesses, the primary treatment involves incision and drainage of the pus, as well as probing the cavity to break up any loculation. Antibiotic therapy is usually not necessary for simple abscesses.
· For small furuncles, moist heat to promote drainage is usually sufficient. Larger furuncles and all carbuncles require incision and drainage.
· Antibiotics are recommended for cutaneous abscesses, carbuncles, and furuncles in the following circumstances35:
o Severe or extensive disease involving multiple sites
o Rapid progression with associated cellulitis
o Signs and symptoms of systemic disease
o Associated comorbidities or immunosuppression
o Extremes of age
o Abscess in areas difficult to drain completely (face, hand, genitalia)
o Associated septic phlebitis
o Lack of response to incision and drainage alone
· Empiric antibiotic therapy for cutaneous abscesses, carbuncles, and furuncles should include coverage for CA-MRSA. If antibiotics are started, therapy should be tailored according to culture and susceptibility results. Recommended duration of therapy is 5 to 10 days. Empiric therapeutic options can be found in Table 26-11.
Impetigo
GENERAL PRINCIPLES
· Impetigo is a contagious epidermal skin infection caused by β-hemolytic streptococci and/or S. aureus. It can be classified into bullous and nonbullous forms.
· It most commonly occurs among children aged 2 to 5 years, although older children and adults may also be affected.
· The infection spreads easily among individuals in close contact and is usually facilitated by warm and humid conditions.
· Staphylococcus aureus (both MSSA and MRSA) is the most common cause of both forms of impetigo. β-Hemolytic streptococci (mainly S. pyogenes) can cause nonbullous impetigo, either alone or in combination with S. aureus.34
· Poststreptococcal glomerulonephritis may be a complication of impetigo caused by certain strains of S. pyogenes. However, it is unclear if treatment of impetigo prevents this sequela. Rheumatic fever has not been reported after streptococcal impetigo.
DIAGNOSIS
· Impetigo usually occurs on exposed areas of the body, most frequently the face and extremities. There are usually multiple well-localized, painful lesions.
· Bullous impetigo: superficial vesicles that enlarge to form flaccid bullae filled with clear yellow fluid that leaves a thin brown crust when ruptured.
· Nonbullous impetigo: the most common form. Papules that evolve into vesicles surrounded by erythema. The lesions later become pustules that break down to form the characteristic thick golden crusts. The process usually takes 4 to 6 days.
· Ecthyma: ulcerative form of impetigo with lesions extending into the dermis.
TREATMENT
· Antibiotic therapy should cover for both β-hemolytic streptococci and MSSA. If there is significant concern for CA-MRSA (see Table 26-8), empiric coverage should be modified accordingly. Duration of therapy is 7 to 10 days.
· Topical therapy is as effective as oral systemic antibiotics and may be used when lesions are limited in number. Topical agents include mupirocin 2%, tid for 7 days, and retapamulin 1%, bid for 5 days.34,36
· Empiric systemic therapy for both β-hemolytic streptococci and MSSA includes any one of the following:
o Dicloxacillin 500 mg PO every 6 hour
o Cephalexin 500 mg PO every 6 hour
o Amoxicillin-clavulanate 875/125 mg PO bid
o Clindamycin 300 to 450 mg PO every 8 hour (use in case of β-lactam allergy)
· Options for empiric systemic therapy of CA-MRSA can be found in Table 26-11.
Necrotizing Fasciitis
GENERAL PRINCIPLES
· Necrotizing fasciitis (NF) is a subcutaneous infection that tracks along superficial and deep fascial planes and is characterized by rapid progression and high mortality.
o Type I: polymicrobial infection (average five organisms per lesion) caused by aerobic and anaerobic bacteria.
o Type II: usually caused by GAS, either alone or in combination with other bacteria, most commonly S. aureus.
· The infection usually develops from an initial break in the skin related to trauma, surgery, or other predisposing lesions. The initial lesion is seen in 80% of cases, and many times, it is trivial. There is no visible skin lesion in up to 20% of patients.34
· Risk factors:
o Type I: usually associated with surgical procedures involving the bowel or penetrating abdominal trauma, decubitus ulcers or perianal abscesses, IV drug use, and spread from a Bartholin abscess or a minor vulvovaginal infection.
o Type II: often associated with a history of skin trauma. An underlying predisposing condition such as diabetes, arteriosclerotic vascular disease, or venous insufficiency with edema is frequently present.
DIAGNOSIS
· NF is a surgical emergency, and early diagnosis is crucial. The physician should keep a high index of suspicion in the proper clinical setting as the overlying superficial tissue can initially appear unaffected.
· In the initial phases, the affected area may be erythematous, swollen, and exquisitely tender.
· The following clinical features should suggest the presence of necrotizing fascitis34:
o Severe, constant pain, out of proportion from physical findings
o Gas in the soft tissues, detected by palpation or imaging
o Edema that extends beyond the margin of erythema
o Cutaneous anesthesia
o Skin necrosis
o Systemic toxicity (fever, leukocytosis, delirium, renal failure)
o Rapid spread of skin changes while on antibiotics
· Ultimately, the diagnosis of NF is established surgically, with direct examination of the involved tissues.
· Imaging studies have variable degrees of sensitivity and specificity and should not delay surgery.
TREATMENT
Any patient with clinical findings suspicious for an early necrotizing soft tissue infection should be admitted to the hospital. Surgical evaluation should be obtained immediately for drainage and debridement.
Animal and Human Bite Wounds
GENERAL PRINCIPLES
· Dog bites are the most common animal bites, accounting for 80% to 90% of cases.
· Human bite wounds often result from aggressive behavior and are frequently more serious than animal bites.
· These wounds are polymicrobial. The predominant pathogens are the oral flora of the biting animal, along with human skin flora.
· Pasteurella species are isolated from 50% of dog bite wounds and 75% of cat bite wounds. Staphylococci, streptococci, and anaerobic bacteria are also isolated after bites from both animals. Capnocytophaga canimorsus can cause bacteremia and fatal sepsis after animal bites, especially in patients with asplenia or underlying hepatic disease.34
· Human bite wounds reflect the normal oral flora of the biter, with streptococci (especially viridans streptococci) present in 80% of wounds. Other causative agents include staphylococci, Haemophilusspecies, Eikenella corrodens, and anaerobes. Human bites also have the potential to transmit various viral diseases, such as herpes, hepatitis B and C, and HIV infection.
· Infectious complications of bite wounds include septic arthritis, osteomyelitis, subcutaneous abscess formation, tendonitis, and, rarely, bacteremia.
DIAGNOSIS
· Dog bites can cause a wide variety of lesions, from minor abrasions to tissue avulsions and crush injuries.
· Cat bites often cause deep puncture wounds, frequently evolving into anaerobic abscesses. When these types of wounds occur in the hand, there is high risk for septic arthritis or osteomyelitis.
· Human bite wounds can be classified into occlusive bite wounds, occurring when teeth are closed forcibly and break the skin, or clenched fist injuries, which occur when the fist of one person strikes the teeth of another.
· Occlusive bite wounds can be seen as a semicircular or oval area of erythema or bruising. Clenched fist injuries usually imply wounds overlying the metacarpophalangeal joints.
TREATMENT
· Initial wound management with irrigation (sterile normal saline) and debridement is essential.
· Primary closure is generally contraindicated. Scarring and disfigurement related to facial wounds may, however, necessitate primary closure.
· Antibiotic therapy should be given empirically for 7 to 10 days. Therapeutic options include any one of the following:
o Amoxicillin-clavulanate 875/125 mg PO bid
o Doxycycline 100 mg PO bid
o Penicillin V 500 mg PO q 6 h plus clindamycin 300 mg PO tid
o Cefuroxime 500 mg PO bid plus clindamycin 300 mg PO tid
o TMP-SMX 160/800 mg PO bid plus clindamycin 300 mg PO tid
· A tetanus (Td) booster should be given if indicated (i.e., more than 10 years since last booster).
· Rabies prophylaxis should be considered for all feral and wild animal bites and in geographic areas where there is a high prevalence of rabies. It is not routinely indicated for domestic dog and cat bites. The local department of health should be consulted about the risks and benefits of rabies prophylaxis.34
Spider Bites
GENERAL PRINCIPLES
· Very few species of spiders are medically important. The most important clinical syndromes resulting from spider bite are
o Latrodectism: caused by widow spiders (Latrodectus spp.)
o Loxoscelism: caused by recluse spiders (Loxosceles spp.)
· Widow spiders:
o Have a worldwide distribution. In the US, the species more commonly implicated in latrodectism are L. mactans and L. hesperus.37
o They are generally shiny black and could be identified by red or orange markings (hourglass or dot shaped) on their ventral abdomen.
· Recluse spiders:
o Most commonly located in North America and South America. The majority of cases of loxoscelism in North America are attributed to L. reclusa and L. deserta. In South America, most cases are attributed to L. laeta, L. intermedia, and L. gaucho.37
o They are usually brown and could be identified by violin-shaped markings on their dorsal surface.
DIAGNOSIS
· The diagnosis of spider bite is usually clinical, based on a clear history of a spider biting the patient and then being identified. Spider bites are usually single lesions.
· Latrodectism:
o The bite lesion can present as blanched circular patch with surrounding erythema. A central punctum can be visualized.
o Causes local, regional, or generalized pain associated with nonspecific symptoms and autonomic effects. Diaphoresis can be observed at the bite site or in an asymmetric regional distribution.
o Severe envenomation can manifest as nausea, vomiting, headache, tachycardia, hypertension, muscle fasciculation or spasm, and patchy localized paralysis. Abdominal wall rigidity can be present. Rare complications include priapism, cardiomyopathy, shock, or pulmonary edema.
· Loxoscelism:
o Cutaneous form: initial local pain and erythema. The lesion can develop central pallor. Severe forms have gradual increase in pain and can progress into a necrotic ulcer after 72 hours.
o Systemic form: less common. Can present with fever, headache, nausea, vomiting, and myalgia. It is characterized by intravascular hemolysis and renal failure. Thrombocytopenia and rhabdomyolysis can also develop.
TREATMENT
· Most cases will only require local wound care.
· A tetanus (Td) booster should be given if indicated.
· Pain control with nonopioid and opioid analgesics is recommended.
· If bacterial superimposed infection is suspected, appropriate antibiotic coverage for cellulitis should be initiated.
· Latrodectism:
o Benzodiazepines could be used for muscle spasms.
o The use of antivenom is controversial and is usually reserved for severe cases. If use of antivenom is considered, consultation with a medical toxicologist is recommended.
· Loxoscelism:
o Dapsone has been suggested to prevent the development of necrosis according to evidence from animal models. However, prospective trials in humans are lacking. Dapsone is contraindicated if the patient has glucose-6-phosphate dehydrogenase (G6PD) deficiency.
o Antivenoms are only available in Brazil, Argentina, Peru, and Mexico. However, the benefit from antivenom use has not been well established through randomized clinical trials. If use of antivenom is considered, consultation with a medical toxicologist is recommended.
Herpes Zoster
GENERAL PRINCIPLES
· Varicella-zoster virus (VZV) causes two distinct syndromes: primary infection presents as varicella (chickenpox), and subsequent reactivation of latent VZV presents as herpes zoster (shingles).
· VZV is transmitted from person to person by direct contact or by aerosolization of virus from skin lesions.
· Primary varicella is a contagious and usually benign illness that occurs in epidemics mainly among susceptible children. After its resolution, latent infection develops within the sensory dorsal root ganglia.
· Reactivation of the virus leads to herpes zoster, which involves a localized cutaneous eruption with dermatomal distribution.
· The lifetime risk of herpes zoster is estimated to be 10% to 20%.38
· The main risk factors include increasing age (risk doubles after age 50), altered cell-mediated immunity, and HIV infection.
· Complications of herpes zoster in immunocompetent patients include postherpetic neuralgia, bacterial skin infection, encephalitis, myelitis, and cranial and peripheral nerve palsies. In immunosuppressed patients, complications include disseminated herpes zoster (more than two dermatomes) and zoster encephalitis. These cases should be treated with intravenous acyclovir and hospitalization.
DIAGNOSIS
· Abnormal skin sensations precede the rash by 1 to 5 days, ranging from tingling or itching to severe pain. Pain of variable severity occurs in virtually all patients with acute herpes zoster.38
· The rash is unilateral (does not cross the midline), has a dermatomal distribution, and is characterized by erythematous papules that evolve into vesicles and pustules. The lesions later crust after a period of 7 to 10 days.
· The thoracic and lumbar dermatomes are the most commonly involved sites. Lesions overlap adjacent dermatomes in 20% of cases.
· Herpes zoster ophthalmicus: VZV reactivation within the trigeminal ganglion. Potential sight-threatening condition.
· Ramsay Hunt syndrome (herpes zoster oticus): VZV reactivation within the geniculate ganglion. Triad of ipsilateral facial paralysis, ear pain, and vesicles in the auditory canal.
· Diagnosis is essentially clinical. If diagnostic uncertainty exists, culture, direct immunofluorescence assay, or PCR of vesicular fluid can assist in the diagnosis.
TREATMENT
· Goals of antiviral therapy include accelerating healing, limiting the severity and duration of pain, and reducing complications.
· Antiviral agents include acyclovir, 800 mg PO q4h (five times daily); famciclovir, 500 mg PO q8h (three times daily); and valacyclovir, 1,000 mg PO q8h (three times daily). These agents have demonstrated clinical benefit when started within 72 hours of the onset of rash. Recommended duration of therapy is 7 days.
· Herpes zoster ophthalmicus requires evaluation by an ophthalmologist and usually involves initial parenteral therapy.
TRAVEL MEDICINE
Pretravel Consultation
· Primary care physicians should be able to provide advice for low-risk travel destinations, but referral to an infectious disease specialist or travel clinic is preferred.39
· If these are not available, then the primary care provider should be able to identify high-risk travel by assessing:
o Country or area of destination
o Purpose of travel and activities planned, for example, extreme sports (risk of falls, weather, insect exposure) and medical/missionary work (risks of needle sticks, exposure to transmissible diseases)
o Travel and lodging accommodations: access to running water, food safety, and exposure to insect bites (e.g., mosquito nets in malaria areas)
o Patient’s medical problems and medications that may contribute to increased risk for acquiring infections or other travel-related complications (e.g., immunosuppressed status, age, risk for dehydration/heat stroke in hot weather, photosensitivity due to medications and interactions with potential prophylactic drugs to be taken)
· Pretravel consultation does not only pertain to infections that the patient is at risk of acquiring but also includes advice regarding personal safety, prevention of sunburns or other extreme weather effect, and safe sex measures.
· Specific topics to discuss include management of traveler’s diarrhea, malaria prophylaxis and insect avoidance, and personal safety among other more specific concerns depending on the patient’s destination.
· For more specific and detailed information, follow CDC recommendations for US travelers, which can be found at www.cdc.gov/travel (last accessed April 14, 2014), and select the country of destination. This includes latest vaccination recommendations and information on any recent travel advisory or outbreak.
· Additional advisories related to travel destinations can be obtained through the U.S. Department of State’s website (www.travel.state.gov, last accessed December 29, 2014).
· For a brief overview of recommendations regarding prevention and counseling of the most common infections to consider, depending on the travel destination, see Table 26-12.
· Pretravel vaccination:
o Depends on the destination (including specific region within a country), the season, and activity the patient will be doing.
o A detailed immunization history should be obtained, since not all recommended vaccines may be required.
o Some patients may require polio vaccination or booster immunization.
o Tetanus-diphtheria-acellular pertussis (Tdap) booster should also be administered.
· For the most common immunizations, see Table 26-12.
· Rabies vaccine may be considered only in patients who will be in close contact with at risk mammals in specific areas of the world.
TABLE 26-12 Summary of Most Common Travel Associated Diseases
The Returning Traveler
· In the case of the ill returning traveler, the provider must recognize that the infection may have been acquired during travel. If so, the provider can start the initial diagnostic workup and treatment while referring the patient to a travel medicine clinic as appropriate.
· Common diseases should be excluded, such as influenza, CAP, S. aureus, or S. pyogenes skin infections. HIV should always be explored as a possibility in a returning traveler with fever, lymphadenopathy, sore throat, and/or rash.
· Specific infectious diseases should be considered according to returning destination, for example, malaria or dengue in tropical countries, tick-borne diseases from Eastern Europe, and encephalitis in Southeast Asia.
· Therefore, visiting the CDC website (www.cdc.gov/travel, last accessed December 29, 2014) may be helpful for assessment of the returning traveler who presents with a suspicious disease.
Traveler’s Diarrhea
GENERAL PRINCIPLES
· Traveler’s diarrhea (TD) is usually a benign, self-limited illness of 3 to 5 days duration, but its sudden onset during travel can be quite disruptive. It is by far the most common illness of travelers.
· The primary care provider should discuss prevention and treatment.
· The most common pathogen is enterotoxigenic E. coli, which causes watery diarrhea that can lead to dehydration. Other common pathogens include Salmonella spp. (nontyphi), Campylobacter sp., and Shigella spp.
· Norovirus has to be considered in cruise trips, since it been associated with several travel-related outbreaks especially in this type of travel, due to the nature of sanitation and confinement.
· Other pathogens include parasites, of which Giardia lamblia is the most common.
· Prevention centers on avoiding contaminated food and water. Encouraging common sense practices such as eating thoroughly cooked or peeled foods and drinking only bottled or filtered water will minimize the incidence of disease.
o Antibiotic prophylaxis with systemic antibiotics such as ciprofloxacin is not routinely recommended in the prevention of traveler’s diarrhea, mainly due to systemic adverse effects and emergence of antimicrobial resistance.
o Rifaximin is minimally absorbed systemically and has been associated with effective reduction of traveler’s diarrhea in trips <3 weeks’ duration.40
o Antibiotic prophylaxis is recommended mainly in those at very high risk of developing TD or those patients whose underlying conditions put them at risk of severe complications and dehydration.
DIAGNOSIS
True disease is defined as three or more loose stools in 24 hours along with fever, nausea, vomiting, or abdominal cramping. Etiologic workup is usually not warranted during travel, unless the symptoms are severe in which case the patient should seek local medical care.
TREATMENT
· Every traveler should be educated regarding the prevention, recognition, and treatment of diarrhea that occurs during his or her trip.
· Hydration is the mainstay of treatment. Patients should be advised that if they are unable to drink fluids, they should seek prompt local medical attention. Likewise, if fever or blood in the stool is present, local medical care should be sought.
· Patients without fever or blood in their stool can manage their diarrhea symptomatically with loperamide. Bismuth subsalicylate can be used as a second-line agent, and patients should be advised to bring it with them.
· Antimicrobial agents can shorten the duration of disease by up to a day and may be provided to patients to bring with them.
o First-line therapy is typically a fluoroquinolone (ciprofloxacin 500 mg PO bid for 1 to 3 days).
o Azithromycin 1,000 mg for one dose is a second-line agent, especially in areas such as Asia and parts of Latin America where fluoroquinolone resistance is increasing among Campylobacter spp.41
Malaria
· Malaria is commonly caused by Plasmodium falciparum and P. vivax, with P. falciparum causing more severe disease and P. vivax causing relapsing disease.
· Prophylactic regimens vary from region to region according to the susceptibility of Plasmodium sp. to different antimicrobials. Therefore, the consulting provider should go to the CDC website to become acquainted with the most updated data prior to suggesting a regimen. When deciding on a regimen, it should be individualized to the traveler’s comorbidities, preferences, and contraindications, if any.
· Malaria presents as a nonspecific illness with severe fevers, chills, headache, nausea, vomiting, and myalgia. Malaria by P. falciparum is an emergency given the risk for severe disease with central nervous system involvement; thus, prompt diagnosis and management are key.
· If suspected, a thick and thin blood smear should be ordered.
· A detailed history of adherence to malaria prophylaxis should be obtained.
· A summary of CDC recommendations for prophylactic regimens in the traveler from the US is presented in Table 26-13.
TABLE 26-13 Summary of CDC Recommendations for Malaria Prophylaxis for Travelers from the US
DIARRHEAL ILLNESS
GENERAL PRINCIPLES
· Infectious diarrhea remains among the top five causes of morbidity and mortality in the world.
· In the US, it remains an important concern for public health, as evidenced by repeated nationwide recalls of contaminated foods determined to be the source of outbreaks. It can be caused by virus, bacteria, and parasites (protozoa).
· Diarrhea is defined as the passage of three or more stools in a day, which are of decreased consistency than usual for the individual.42 In general, infectious diarrhea can be classified as follows:
o Acute watery diarrhea: <14 days (e.g., Norovirus, Rotavirus, Vibrio spp.).
o Acute bloody diarrhea, also known as dysentery (i.e., Shiga toxin–producing E. coli, Campylobacter spp., Shigella spp.).
o Persistent diarrhea: between 14 and 30 days duration. Parasites should be ruled out in the appropriate context.
o Chronic diarrhea: more than 30 days duration, less likely of infectious origin.
· Viral etiologies remain the most common cause of acute infectious diarrhea and are usually self-limited but pose a high risk for dehydration and spread.
· Salmonella spp., enterohemorrhagic E. coli (Shiga toxin producing), and Clostridium perfringens are among the most common bacterial pathogens associated with foodborne outbreaks.43
· Clostridium difficile–associated diarrhea has been increasing and is no longer considered exclusively a nosocomial infection. The wide use of broad-spectrum antibiotics in the community along with the presence of a more virulent strain have contributed to its emergence as a cause of acute infectious diarrhea in the ambulatory practice and in groups previously not considered at risk.44
· The most common causes of infectious diarrhea are presented in Table 26-14.
TABLE 26-14 Summary of the Most Common Diarrheal Illnesses Worldwide
HUS, hemolytic-uremic syndrome; FQ, fluoroquinolones; TMP-SMX, trimethoprim-sulfamethoxazole.
DIAGNOSIS
· As for many infectious diseases, the clinical presentation and exposure/epidemiologic history will guide the diagnostic workup. Travel history, food exposures, occupational exposures, and immune status should be reviewed.
· Stool culture should only be ordered if42
o Severe disease: fever, mucous, >1-day duration
o Bloody diarrhea
o Immunosuppressed: >65 years, HIV, transplant patient, steroids, TNF inhibitors
o Hospitalized <3 days
o Positive lactoferrin test
· Currently, several pathogens can be detected by immunoassays in stool, such as rotavirus, Giardia lamblia, and Cryptosporidium.
· Stool examination for ova and parasites should be ordered if the patient is from a developing country or a returning traveler with consistent clinical picture, appropriate exposure, and persistent or chronic diarrhea and in patients with HIV/AIDS.
TREATMENT
Rehydration
· The initial assessment should include an evaluation of the patient’s hydration status.
· Rehydration should be prompt. For the majority of adult patients with mild-to-moderate dehydration, soups and juices are generally sufficient.
· For more moderate-to-severe dehydration, patients should be encouraged to consume oral rehydration solutions with glucose-based electrolyte solutions.
o The World Health Organization and United Nations Children’s Fund oral rehydration solution consists of the following: 2.6 g NaCl, 13.5 g glucose, 1.5 g KCl, and 2.9 g trisodium citrate all in 1 L of water (total osmolality 245 mOsm/kg).
o Similar commercial oral rehydration products are available (e.g., Pedialyte). These products contain sodium, potassium, and carbohydrate and have an appropriate osmolality (approximately 200 to 300 mOsm/kg).
o Intravenous therapy should be administered to those who are obtunded or unable to tolerate oral therapy.
Empiric Treatment
· The majority of disease lasts <1 day and is of viral etiology, making antimicrobial therapy of no benefit.42
· Unnecessary harm can occur from misuse of antimicrobials, including prolonged carriage of Salmonella spp., worsening hemolytic-uremic syndrome from induction of Shiga toxin production, or development of C. difficilecolitis.
· Loperamide is an antimotility agent that is not systemically absorbed. It can often limit the symptoms of acute diarrhea, but it should not be used during disease caused by known or suspected invasive organisms (as evidenced by bloody diarrhea). Complications of loperamide therapy include worsening of HUS and toxic megacolon.
· Nonpharmacologic therapies are of varying benefit.
o Strict handwashing for exposed and infected persons is imperative in limiting the spread of disease.
o The BRAT (bananas, rice, applesauce, toast) diet is of no proven benefit.
o Dairy avoidance is important given the potential for transient lactase deficiency.
· Specific therapy is presented in Table 26-14.
Clostridium difficile Infection
General Principles
· Clostridium difficile infection (CDI) is caused by cytotoxin production, resulting in the formation of colonic pseudomembranes and inflammatory colitis.
· Disease is usually associated with prior antibiotic use, and more recently, a more virulent strain of C. difficile is increasing in frequency in the community.44
· Main risk factors include hospitalization, history of recent hospitalization, recent antibiotic use, and immunosuppression.
· Most patients have a history of antibiotic use in the prior 3 to 5 days, but it could be as remote as 90 days prior to symptoms.
· Disease is usually recognized by the onset of diarrhea in the appropriate clinical setting.
· Prevention of CDI is important.
o Proper hand hygiene, contact precautions, and isolation of the patient with active diarrhea are the most effective ways to prevent spread to others.
o Of note, commercially available alcohol-based hand sanitizers do not eliminate the spores and thus are not recommended as an adequate hand hygiene method for the prevention of C. difficiletransmission.45,46
o Patients should be instructed to disinfect surfaces at home with a 10% bleach solution, even if they are not visibly soiled, to kill the spores and prevent reinfection.46,47
o Patients who require prolonged or repeated systemic antibiotic therapy for other reasons may require concomitant treatment with either metronidazole or oral vancomycin to prevent relapse.45
o Ultimately, the best way to prevent emergence of C. difficile is to avoid the indiscriminate use of broad-spectrum antibiotics in the community.
· Recurrent CDI from either relapse or reinfection has been reported in up to 25% of the cases.45
DIAGNOSIS
· Common symptoms include liquid stools with abdominal pain, fever, mucus, and/or blood, almost always preceded by antimicrobial use or recent hospital discharge.
· Diarrhea can be severe and lead to volume depletion quickly, especially in the elderly and immunosuppressed.
· It may present solely as constipation, which can be an ominous sign since the patient may be developing toxic megacolon, which constitutes an emergency as perforation may be imminent.
· Leukocytosis is usually present, and hypoalbuminemia can be a sign of severe disease.47
· Diagnosis is made most often by detection of toxin A and/or B in the stool, for which several techniques are available, with variable sensitivity and specificity.45 These include PCR for both toxins, enzyme immunoassay of toxins A/B, cell culture toxicity, and detection of hypervirulent 027 strain. For the treating provider, it is important to remember that the assay should test for both toxins, since disease can be present with either isolated toxin.
· Toxin assays should only be ordered on loose stools.
· There is no benefit in ordering the test more than once in a patient in whom CDI is suspected.45
· In severely ill patients who require hospitalization, endoscopic diagnosis may be required to prove the presence of pseudomembranes, which also confirms the diagnosis.
TREATMENT
· The first step in the management of CDI is to stop the antimicrobials the patient may be on during the onset of diarrhea.
· In the outpatient setting, either oral metronidazole or oral vancomycin can be used, since its equivalence has been shown in nonsevere disease.44,45 Metronidazole is usually preferred over oral vancomycin due to cost reasons.
· Metronidazole 500 mg orally every 8 hours and vancomycin 125 mg orally every 6 hours are the recommended doses.
· Vancomycin should be the agent of choice in severe cases.45,47
· Note that higher doses of oral vancomycin have not proven to be more effective, and thus, 125 mg is preferred.
· The duration of treatment in mild-to-moderate disease is 10 to 14 days.
· Newer antibiotics approved for the management of CDI (rifaximin, fidaxomicin) are not recommended as first-line therapy for the first episode or first recurrence.
· Studies on the use of probiotics have had mixed results regarding their role in prevention of CDI.45
· The first recurrence should be treated the same way as the initial episode, unless a more severe presentation warrants hospitalization or changing from metronidazole to vancomycin.45 For further recurrences, oral vancomycin is the drug of choice, and a prolonged taper is recommended. A consultation with an infectious diseases specialist is advised in these cases.
SUPERFICIAL FUNGAL INFECTIONS
Tinea Versicolor
· The most common skin fungal infection not caused by dermatophytes is tinea versicolor, which is caused by Malassezia spp.
· It typically presents as hypopigmented or erythematous macules in trunk, which in most cases are nonpruritic or tender. In darker-skinned patients, macules may be hyperpigmented.
· See Chapter 41 for information on diagnosis and treatment.
INFECTIONS BY DERMATOPHYTES
· Dermatophytes (Trichophyton spp.) are the most common fungi causing infection of the skin, hair, and nails. In isolation, they rarely cause severe disease, but they can play a role in the development of more severe bacterial infections.
· Tinea infections are named by their location and include tinea pedis (athlete’s foot), tinea cruris (jock itch), tinea capitis (scalp ringworm), tinea corporis (ringworm), tinea faciei, tinea barbae, and tinea unguium (i.e., onychomycosis).
o Usually present as areas of mild inflammation with pain and itching.
o The margin of the infection is usually the area of most intense inflammation, and central clearing is frequently seen.
o Tinea pedis usually starts in the interdigital spaces and may spread to the dorsum or lateral aspect of the foot. The skin may crack and become macerated.
o Onychomycosis is a common dermatophyte infection of the nails. The nails become thickened and discolored (white, yellow, or brown).
· Visualization of fungi on microscopic examination of skin scrapings can generally provide the diagnosis. Ultraviolet light can help identify infected hairs for further evaluation. Fungal culture can also be useful.
· Treatment of tinea and onychomycosis is discussed in detail in Chapter 41.
SPOROTRICHOSIS
· Sporotrichosis is a subcutaneous infection caused by Sporothrix schenckii and presents as a nodular, pustular skin lesion.
· It is found in decaying plant matter, and infections are frequently linked to gardening.
· Ulcers may or may not be painful. It usually spreads via the lymphatic vessels, which accounts for streaking, regional lymph node swelling, and secondary ulcerations.
· Pulmonary disease is a rare manifestation.
· Diagnosis is made by visualization on skin biopsy and culture.
· Although the lesions are rarely life threatening, treatment is usually indicated.
· Oral itraconazole (200 mg solution daily for 3 to 6 months) has largely replaced potassium iodide (1 to 2 drops three times daily for 3 to 6 months) as the treatment of choice in the developed world.
· Pulmonary disease should be treated more aggressively because of its progressive nature.
CANDIDAL INFECTIONS
· Candida spp. are normally present in the gastrointestinal tract. They are frequently recovered from bladder catheters, sputum, skin, and the female genital tract.
· Isolation of these organisms does not necessarily represent true infection.
· Pathologic infections caused by Candida spp. can range from cutaneous to severe systemic disease.
· This discussion will focus only on frequently encountered outpatient infections.
Candiduria
· Candiduria is frequently observed but rarely clinically significant.
· Prior antibiotic use and genitourinary (GU) tract manipulation are risk factors for candiduria.
· Treatment is not necessary in every patient with candiduria.
· Without treatment, healthy patients generally clear the yeast in their urine.
· Only symptomatic patients (e.g., dysuria), neutropenic or posttransplant patients, and those undergoing GU tract manipulations should be treated.
· Fluconazole 200 mg daily for 7 to 14 days will reduce the duration of candiduria.
Oral Candidiasis
· Thrush is frequently seen in immunosuppressed patients, patients with diabetes, patients treated with antibiotics and inhaled corticosteroids, and children.
· Presents as curd-like patches on the tongue and buccal mucosa. Lesions can be scraped off leaving an erythematous lesion that may bleed.
· Esophageal disease may occur independently of oral disease and presents as severe odynophagia.
· Clinical exam is generally sufficient for diagnosis.
· Treatment with topical therapy such as clotrimazole troches (10 mg five times daily) and nystatin (4 to 6 mL of 100,000 units/mL qid) is generally effective.
· Oral fluconazole (100 mg daily for 7 to 14 days) may be needed for recurrent disease and is usually indicated at higher doses (200 to 400 mg daily) for esophageal disease.
Candidal Vaginitis
· Candidal vaginitis is a common infection occurring in patients with diabetes , with recent antibiotic use, and in pregnancy. This injection is discussed in more detail in Chapter 3.
· Oral contraceptives may also increase the risk of colonization, and cessation of oral contraceptives may be needed to cure recurrent cases.
· Patients present with dysuria, vaginal discharge, and erythema of the external genitalia.
· Visualization of yeast on a wet preparation of vaginal fluid aids in diagnosis, though empiric treatment is often recommended.
· Topical therapy (e.g., nystatin, miconazole, clotrimazole, terconazole) is sufficient for uncomplicated disease.
· Fluconazole 150 mg for one dose is also an approved therapy but can be more expensive. Many patients will find it to be much more convenient.
DEEP FUNGAL INFECTIONS
Histoplasmosis
GENERAL PRINCIPLES
· Histoplasmosis, caused by Histoplasma capsulatum, occurs worldwide.
· In the US, infection is mostly seen in the Ohio and Mississippi River valleys.48
· Risk factors include visits to caves with bat droppings and exposure to construction zones, bird droppings, or contaminated soil in endemic areas.
· Transmission is airborne, and depending on the patient’s immune status, the patient may develop disease or present with lower respiratory symptoms, which usually resolve within 1 month.
· In this case, the only sequelae may be calcified nodules seen in the lungs on radiography or asymptomatic mediastinal lymphadenopathy.
· Acute infection can disseminate, and complications may arise such as fibrosing mediastinitis, arthritis and arthralgias, hepatic involvement, and erythema nodosum.
· Clinical resolution appears to depend on cell-mediated immunity.
DIAGNOSIS
· Diagnosis can be made by histopathologic visualization, growth in culture, or high titers on complement fixation assays (serologic testing).48
· Detection of Histoplasma antigen in the urine is useful primarily in disseminated disease and in patients with HIV/AIDS.
TREATMENT
· Treatment is usually not needed for mild-to-moderate disease.48
· Persistent symptoms may require treatment, which can be accomplished with itraconazole 200 mg solution tid for 3 days and then once daily for 6 to 12 weeks.48
· Severe disease requires hospitalization and initial treatment with IV amphotericin B.
· Chronic cavitary disease requires prolonged treatment with itraconazole and monitoring of drug levels.
Blastomycosis
GENERAL PRINCIPLES
· Blastomycosis is caused by the dimorphic fungus Blastomyces dermatitidis.
· It is commonly found in the southeast and south central US as well as the Great Lakes region and territories around the St. Lawrence River.
· Patients acquire infection via inhalation of conidia.
· Acute infection can mimic influenza or pneumonia.
· It can also present in an indolent fashion, being confused with TB or malignancy due to its ability to form mass-like lesions.
· Extrapulmonary sites of infection include bone, skin, and the GU tract.
· Cutaneous involvement may be the only sign of infection, which consists of violaceous verrucous raised lesions on the upper extremities or face.
DIAGNOSIS
· Diagnosis is based on isolation of the fungus in culture from a biopsy specimen.49
· The diagnosis should be sought in patients with history of weight loss, night sweats, and lower respiratory symptoms, with or without skin lesions in the appropriate epidemiologic area.
· A presumptive diagnosis can be made on histopathologic findings, revealing the classic broad-based budding yeast.
· Serologic testing is unreliable and plays only a supportive role.49
TREATMENT
· Treatment has reduced the mortality associated with blastomycosis from >90% to <10%.
· Mild-to-moderate disease can be treated with itraconazole (200 to 400 mg PO daily for a minimum of 2 months). Most patients require at least 6 months of therapy.49
· Severe disease requires hospitalization and prolonged treatment with amphotericin B, which can be changed to itraconazole after the patient has improved.
· Given difficulties with absorption of itraconazole, one should consider monitoring drug levels.
· The oral solution has better absorption than tablets, which need to be taken with food or after drinking an acidic beverage.
Coccidioidomycosis
GENERAL PRINCIPLES
· Coccidioidomycosis, otherwise known as valley fever, is caused by Coccidioides immitis or C. posadasii.
· In the US, infection is endemic to the southwestern region.
· Patients present 1 to 3 weeks after exposure with an acute illness indistinguishable from bacterial pneumonia that resolves spontaneously; however, some patients may experience prolonged fatigue.
· Patients with acute self-limited disease may have symptoms similar to an upper respiratory infection.
· Complications include dissemination to the central nervous system (CNS), skin, and bone. In a minority of patients, chronic disease or lung nodules may develop. Patients may also have a rash similar to erythema multiforme or erythema nodosum.
· Latent infections and reactivation can occur in immunosuppressed patients.
· Transmission is airborne, and even a short stay in an endemic area may be sufficient to cause infection and disease.
DIAGNOSIS
· Detailed residence and travel history should be obtained in any patient presenting outside of an endemic area.
· CXRs can reveal multiple nodules with hilar adenopathy.
· Serologic testing (complement fixation antigen) is more reliable than in other endemic mycoses.50
· Definitive diagnosis is made by culture of the organism from a pulmonary sample.50
· The microbiology laboratory should be notified if one is attempting to recover coccidioidomycosis through culture as this pathogen is a select agent per the CDC.
TREATMENT
· Acute infection in otherwise healthy individuals does not necessarily require treatment.
· Patients with immunosuppression, diabetes, or underlying cardiopulmonary disease should receive treatment.
· Itraconazole or fluconazole at doses of 200 to 400 mg daily for three to six is recommended.50
· For severe disease or disease in pregnancy, amphotericin B is the treatment of choice.
Cryptococcosis
GENERAL PRINCIPLES
· Cryptococcosis is caused by Cryptococcus neoformans, a yeast distributed throughout the world in soil. Various other species exist but rarely cause disease in humans.
· Infection begins with inhalation of spores; exposure to bird droppings is a common risk factor.
· Pulmonary infection presents as cough, fever, dyspnea, and multiple nodular lung densities.
· Disease is more common in immunosuppressed patients, such as HIV-infected patients, those on chronic steroids, chronic TNF-α inhibitors, and pregnant women.
· Meningitis commonly occurs, and all patients with pulmonary disease should have a lumbar puncture performed to evaluate for CNS disease.
· Patients with CNS disease can present with various symptoms, but generally all patients complain of severe headache.
DIAGNOSIS
· Diagnosis is made by culture or positive cryptococcal antigen titer on the serum or cerebrospinal fluid.51
· When none of these tests are available, then India ink preparations should be used to identify encapsulated yeast on direct microscopic examination.
· Patients who undergo lumbar puncture should have an opening pressure documented.
TREATMENT
· Treatment for pulmonary disease is fluconazole 200 to 400 mg daily for 6 to 12 months. Itraconazole is a second-line agent.51
· Treatment of disseminated cryptococcal disease should be conducted with the aid of a specialist and usually requires hospitalization.
TICK-BORNE DISEASE
· Common tick-borne diseases in the US include ehrlichiosis, anaplasmosis, Lyme disease, Rocky Mountain spotted fever (RMSF), and babesiosis. Each is endemic in various geographical regions based on tick distribution.
· Other diseases transmitted by ticks within the US include the following:
o Tularemia: acquisition of Francisella tularensis via ticks is thought to be the most common way Americans contract the disease.
o Colorado tick fever: a Coltivirus infection transmitted by the wood tick Dermacentor andersoni, in the Western coast states and Colorado area.
o Tick-borne relapsing fever: Borrelia spp. infection transmitted by Ornithodoros spp. ticks.
o Tick paralysis: caused by tick salivary neurotoxins rather than by transmission of a microbial infection. Many tick species have been implicated.
o Southern tick-associated rash illness (STARI) is an entity that can strongly resemble Lyme disease but typically occurs in areas where Lyme disease is uncommon. In spite of the name, it also occurs in the Mid-Atlantic states and the Midwest. There is currently no diagnostic test.
· Tick-borne diseases peak in the spring through fall but can occur any time during the year.
· Knowledge of disease distribution and patient travel history to endemic areas is important to diagnosis.
· In the primary care setting, the role of the provider should be to identify a probable tick or arthropod-borne disease in order to consult an infectious diseases specialist and/or admit if needed.
· In this section, only the most common tick-borne diseases in the US will be discussed, since they may present with frequency in the primary care setting.
Lyme Disease
GENERAL PRINCIPLES
· Lyme disease is the most common tick-borne disease in North America and Europe.
· In the US, Lyme disease is caused by Borrelia burgdorferi; other Borrelia species are the pathogens in the rest of the world.
· Lyme disease occurs with more frequency throughout the northeastern US as well as north central states.
· It is transmitted by the tick Ixodes scapularis (deer tick), which is also the vector for babesiosis and anaplasmosis.
· The most common acute presentation is a single cutaneous lesion (erythema migrans) with systemic symptoms such as fever, myalgia, and arthralgia.
· If untreated, complicated Lyme can include neurologic disease (neuroborreliosis) and/or cardiac disease, most typically presenting with second- or third-degree heart block.
· Post–Lyme disease syndrome (PTLDS) consists of chronic/recurrent subjective constitutional or neurologic symptoms (e.g., fatigue, malaise, headache, arthritis, myalgia, and poor concentration, third nerve palsy) after appropriately treated Lyme disease.52 It is not felt to be a manifestation of persistent infection.
· The best way to prevent Lyme disease is by avoiding tick bites, wearing appropriate clothing and using tick repellent when tick exposure is possible, and performing daily tick checks.
· Widespread chemoprophylaxis with antibiotics is not recommended, given the low incidence of Lyme disease among the population of patients with known tick bites.
· Per the guidelines of the IDSA, a single dose of doxycycline 200 mg should be given to patients in whom an Ixodes sp. tick is removed after 36 hours (by witnessed time or degree of tick engorgement) in areas where the prevalence of B. burgdorferi infection of ticks is at least 20%.52
· These recommendations require that health care providers in endemic areas are able to identify Ixodes ticks and their different stages.
DIAGNOSIS
· In the setting of a tick bite or appropriate epidemiologic background, the diagnosis is clinical but can be confirmed with serologic testing.52
· Many patients do not recall a specific tick bite; therefore, known tick bites are not necessary for making the diagnosis.
Clinical Presentation
· Acutely, the patient presents with a rash (erythema migrans, EM) occurring 7 to 10 days after tick exposure. Classically, this lesion is at least 5 cm in biggest diameter, which starts as a red papule and clears in the center as it enlarges. The lesion is unique, though other secondary similar lesions may appear.
· In addition to the EM rash, patients may develop fevers, constitutional symptoms, and adenopathy.
· Chronic forms (i.e., not previously treated) of disease may present as second- or third-degree heart block, chronic oligoarthritis, subacute encephalopathy, or axonal polyneuropathy.
· PTLDS should not be considered in patients who do not have a convincing history of previously treated Lyme disease.52
Diagnostic Testing
· The CDC recommends a two-tier process. Initially, an enzyme immunodiffusion analysis (EIA, ELISA) or immunofluorescence (IFA) is done, and if positive or equivocal, it is confirmed by Western blot.
· Positive ELISA must be confirmed by Western blot analysis.52
· Serology alone should not be the sole means of diagnosis and should not be used as a screening test in unselected populations.
TREATMENT
· First-line treatment of acute disease is doxycycline (100 mg PO bid) for 14 days to decrease duration and prevent development of late manifestations of disease.
· Doxycycline has the added advantage of effectively treating Anaplasma phagocytophilum, which is transmitted by the same deer tick.
· Alternative agents include cefuroxime or ceftriaxone.
· Those with meningitis and/or carditis require more aggressive, often inpatient, treatment.
· Cardiac disease due to Lyme disease is treated with 28 days of IV ceftriaxone.
Rocky Mountain Spotted Fever
GENERAL PRINCIPLES
· RMSF fever is caused by Rickettsia rickettsii transmitted by the dog tick Dermacentor variabilis.
· It was originally isolated from the northern regions of the Rocky Mountains in the US; however, the disease is most prevalent in the Atlantic coastal states and south central US.
· Disease begins 5 to 7 days after tick exposure.
· It can be a lethal disease; the diagnosis should be recognized early so that treatment can be initiated promptly.
DIAGNOSIS
· Diagnosis rests largely on the clinical syndrome:
o Patients initially present with marked constitutional symptoms (e.g., fever, malaise, fatigue, arthralgia, myalgia, headache, anorexia, nausea, and emesis).
o Rash begins on the 3rd to 5th day of symptoms.
o Typically, it starts as a maculopapular eruption (later becoming petechial) on the extremities, specifically the wrists and ankles and often involving the palms and soles, and progresses toward the trunk.53
o A minority of patients never develop the characteristic rash (i.e., “spotless”).
· A history of tick exposure in a patient with these symptoms in the right epidemiologic area is sufficient to initiate treatment.
· Failure to initiate prompt treatment can lead to severe disease with meningeal involvement, respiratory failure, renal dysfunction, and death.
· Acute and convalescent serologies can confirm the diagnosis.53
· Direct immunofluorescence of skin lesions can aid in diagnosis.
· Additional laboratory abnormalities may include elevated transaminases, leukopenia, and thrombocytopenia. All may be seen in ehrlichiosis and anaplasmosis, adding further difficulty in differentiation. PCR techniques are under development.
TREATMENT
· Early treatment (often before the rash develops) reduces overall mortality.53
· Doxycycline (100 mg bid) should be initiated promptly when disease is suspected.
· Patients severely ill with RMSF require hospital admission.
Ehrlichiosis and Anaplasmosis
GENERAL PRINCIPLES
· Human granulocytic anaplasmosis (HGA) is caused by A. phagocytophilum and is transmitted by Ixodes spp. It is commonly found in the northeastern parts of the US. It is more common than ehrlichiosis.
· Human monocytic ehrlichiosis (HME) is caused by Ehrlichia chaffeensis and is transmitted by the Lone Star tick, Amblyomma americanum. In the US, it mainly occurs in the South Central, Southeastern, and Mid-Atlantic states.
· More severe infection appears to occur in the immunocompromised patients.
· Since they have the same vector, coinfection with anaplasmosis and Lyme disease can occur in the appropriate geographic area.
DIAGNOSIS
· As in other tick-borne diseases, clinical suspicion is the most important step in the diagnosis.
· Patients may present with a nonspecific febrile illness (e.g., malaise, fatigue, myalgias, and headache) after tick exposure, though they may not remember exposure or contact to a tick. Neurologic symptoms and signs are also possible.
· Rash is much less common than with RMSF, particularly so with HGA.52
· Common laboratory findings include thrombocytopenia, leukopenia, and elevated transaminases.
· Any of these findings in a febrile patient in the summer months in endemic areas should raise suspicion of these entities and prompt empiric treatment.
· Severe complications include seizure, coma, renal failure, cardiopulmonary failure, and clinical picture similar to the systemic inflammatory response syndrome.
· Diagnosis can be made by acute and convalescent serologies.52
· PCR testing is available with good sensitivity and specificity when obtained prior to administration of antimicrobial therapy.52 When available, this should be the test of choice.
· As these organisms are typically found within macrophages, a peripheral smear showing intracellular morulae may be seen, aiding in the diagnosis.
TREATMENT
· The mainstay of treatment is doxycycline 100 mg bid for 10 days, which is also effective for the frequent alternative diagnosis of RMSF and possible coexistent Lyme disease.52
· Patients should rapidly respond to therapy.
· Rifampin therapy (300 mg PO bid) can be used as an alternative in less severe anaplasmosis.
Babesiosis
GENERAL PRINCIPLES
· Babesiosis, a malaria-like illness, is caused by the intraerythrocytic parasite, Babesia microti, and is found mainly in the northeastern US. It is transmitted by I. scapularis.
· Blood transfusion is also a possible means of infection.
· Asplenia is a major risk factor for severe disease.
· The majority of infections in immunocompetent hosts are probably asymptomatic.
· Possible coinfection with Lyme disease and ehrlichiosis should be considered.
DIAGNOSIS
· In symptomatic patients, fever, malaise, and headache usually begin 1 week after tick exposure.
· Severe hemolytic anemia, renal failure, and hypotension can develop in some patients.
· Hepatosplenomegaly may occur.
· Laboratory findings include those compatible with hemolysis (e.g., anemia, abnormal red cell morphology, elevated lactic dehydrogenase, and decreased haptoglobin), thrombocytopenia, elevated transaminases, and hyperbilirubinemia.
· Diagnosis can be made by identification of ring forms on blood smear.
· Serologic assays can be of benefit.
TREATMENT
· First-line therapy is with atovaquone (750 mg PO every 12 hours) plus azithromycin (500 to 1,000 mg on day 1 and then 250 mg PO daily) or clindamycin (300 to 600 mg every 8 hours) for 4 to 10 days.52
· Severe disease should be treated with quinine plus clindamycin.
FEVER OF UNKNOWN ORIGIN
· Temperature must be >38.3°C on several occasions over a period >3 weeks with a diagnosis remaining uncertain after 1 week of hospitalization.
· Given the changes in delivery of medical care, the requirement for hospitalization in the developed world has become less stringent.
· Finding the correct diagnosis in these situations can be challenging, and it is of utmost importance to avoid excessive and unnecessary testing as well as empiric antimicrobial therapy. Both of these errors can be misleading and cause increased morbidity for the patient.
· So long as the patient is not acutely ill, there is no need to rush to empiric therapy. Reassurance should be provided.
· Case series suggest >200 potential causes. A systematic approach to evaluate for more common causes of FUO is important and an algorithm has been proposed by Mourad et al.54
· Commonly, disease has been classified into three categories: malignancy, connective tissue disease/vasculitis, and infectious.
· Malignancy:
o Of the many potential malignant causes of fever, lymphoma is probably the most common.
o Clinical clues include night sweats, weight loss, and lymphadenopathy.
o CT scanning of the chest, abdomen, and pelvis may be of benefit.
o In addition, bone marrow biopsy can be considered.
· Connective tissue diseases/vasculitis:
o Multiple autoimmune diseases have been implicated in causing FUO.
o Rheumatoid arthritis and systemic lupus erythematosus are common causes as well as granulomatosis with polyangiitis (Wegener) so laboratory testing for antinuclear antibody (ANA), rheumatoid factor (RF), or antinuclear cytoplasmic antibody (ANCA) should be done in these cases.
o Results of CT scanning may provide clues to accessible lesions for biopsy as well.
· Infectious:
o The most common infections to consider include tuberculosis and subacute endocarditis in the developed world.
o Workup for infectious causes includes CXR, CBC, blood cultures, sedimentation rate, C-reactive protein, and blood cultures.
o Echocardiogram can be useful in evaluating for cardiac vegetations. A panorex radiograph should also be considered since dental abscess can be a cause of fever.
· Other causes:
o Frequently, a medication that the patient is already taking may be the cause of fever. Any nonessential medications should be discontinued.
o Blood clots are another frequent cause of fever, and Doppler ultrasounds of the lower extremities may be helpful.
IMMUNOSUPPRESSION
· The topic of infections in a non–HIV-infected patient who is immunocompromised is quite complex and cannot be covered in its entirety in the scope of this chapter. See Chapter 27.
· This section aims to give a very brief overview of common infections in this population as well as when to suspect immunodeficiencies in adult patients.
· Many patients who have undergone transplantation (solid organ or bone marrow) remain under close supervision of the transplant team. This is especially true in the highly vulnerable and complex posttransplantation period, which can last up to 1 year after transplant.
· Much disease is managed by or with the help of specialists. Severe disease can develop quickly, and care frequently requires an inpatient setting.
Antitumor Necrosis Factor Agents
· Immune-modulating therapy has become commonplace in the management of various autoimmune processes.
· TNF is a major cytokine in the control of disease, but its misdirection is thought to be involved in the pathophysiology of inflammatory disorders.
· TNF seems to exert its effect by activating natural killer cells and CD8+ lymphocytes.
· The most concerning infection in patients receiving anti-TNF agents is reactivated TB.
o Patients should have PPD testing performed before initiating therapy with anti-TNF agents.
o Should they have a PPD ≥5 mm, therapy for latent infection (after active infection has been ruled out) should be initiated before starting anti-TNF therapy.
o There is no need to delay anti-TNF therapy until treatment of latent infection has been completed.
Primary Immunodeficiencies
One of the more challenging diagnoses for clinicians is that of primary immunodeficiencies. These relatively common processes tend to have obscure presentations and are frequently overlooked as potential underlying disease states. In addition, their complexity and various forms are difficult to fully comprehend. Often times, simple treatments such as monthly intravenous immune globulin can reduce the number of infections that patients endure.
DEFICIENCIES IN B-CELL FUNCTION AND ANTIBODY PRODUCTION
· These relatively common conditions typically present as recurrent sinopulmonary disease, but could present with bronchiectasia or urinary problems.
· Recurrent infections with encapsulated organisms (e.g., streptococci) are another clue.
· Primary B-cell dysfunction may be a cause of failure to respond to vaccines.
· Common variable immunodeficiency is perhaps the most important primary immune deficiency of adults, and its etiology is based on various defects in B-cell differentiation and varying degrees of T-cell dysfunction.
· Other diseases in this class of deficiency include IgA deficiency (also quite common), hyper-IgM syndrome, Good syndrome, and individual IgG subclass deficiencies. The latter conditions tend to be relatively asymptomatic.
· When suspected, a simple screen of immunoglobulin levels can be helpful in identifying underlying processes. Additional testing of immune globulin subsets or specific vaccine responses can further delineate the diagnosis.
· Treatment by monthly intravenous immune globulin injections can reduce the number of recurrent infections.
OTHER IMMUNODEFICIENCIES
· Adults can present with primary deficiencies commonly uncovered in childhood such as adenosine deaminase deficiency, Job syndrome (hyper-IgE syndrome), chronic granulomatous disease, and leukocyte adhesion defects. Age should not be an absolute factor in ruling out such diseases.
· The presentation of these processes is quite diverse; however, recurrent pyogenic abscesses can be one clue.
· Opportunistic infections in HIV-negative patients may also prompt evaluation.
· Recurrent mycobacterial infections or Salmonella infections may lead one to suspect a deficiency in interferon-γ. This group of genetic disorders is quite rare.
· Testing of lymphocyte and neutrophil function may be necessary as defects in cytokine production or oxidative bursts can be easily identified and can uncover the deficiency.
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