Joseph T. DiPiro and Thomas R. Howdieshell
LEARNING OBJECTIVES
Upon completion of the chapter, the reader will be able to:
1. Define and differentiate between primary and secondary intra-abdominal infections.
2. Describe the microbiology typically seen with primary and secondary intra-abdominal infections.
3. Describe the clinical presentation typically seen with primary and secondary intra-abdominal infections.
4. Describe the role of culture and susceptibility information for diagnosis and treatment of intra-abdominal infections.
5. Recommend the most appropriate drug and nondrug measures to treat intra-abdominal infections.
6. Recommend an appropriate antimicrobial regimen for treatment of a primary and a secondary intra-abdominal infection.
7. Describe the patient-assessment process during the treatment of intra-abdominal infections.
KEY CONCEPTS
Most intra-abdominal infections are “secondary” infections that are caused by a defect in the GI tract that must be treated by surgical drainage, resection, and/or repair.
Primary peritonitis generally is caused by a single organism (Staphylococcus aureus in patients undergoing continuous ambulatory peritoneal dialysis [CAPD] and Escherichia coli in patients with cirrhosis).
Secondary intra-abdominal infections usually are caused by a mixture of enteric gram-negative bacilli and anaerobes. This mix of organisms enhances the pathogenic potential of the bacteria.
For peritonitis, early and aggressive IV fluid resuscitation and electrolyte replacement therapy are essential. A common cause of early death is hypovolemic shock caused by inadequate intravascular volume expansion and tissue perfusion.
Cultures of secondary intra-abdominal infection sites generally are not useful for directing antimicrobial therapy. Treatment generally is initiated on a “presumptive” or empirical basis.
Antimicrobial regimens for secondary intra-abdominal infections should include coverage for enteric gram-negative bacilli and anaerobes. Antimicrobial agents that may be used for treatment of secondary intra-abdominal infections include the following: (a) a β-lactam–β-lactamase-inhibitor combination, (b) a carbapenem, and (c) a quinolone plus metronidazole or an aminoglycoside plus clindamycin (or metronidazole).
Treatment of primary peritonitis for CAPD patients should include an antistaphylococcal antimicrobial such as a first-generation cephalosporin (cefazolin) or vancomycin, usually given by the intraperitoneal (IP) route.
The duration of antimicrobial treatment should be for a total of 5 to 7 days for most intra-abdominal infections.
Intra-abdominal infections are those contained within the peritoneal cavity or retroperitoneal space. The peritoneal cavity extends from the undersurface of the diaphragm to the floor of the pelvis and contains the stomach, small bowel, large bowel, liver, gallbladder, and spleen. The duodenum, pancreas, kidneys, adrenal glands, great vessels (aorta and vena cava), and most mesenteric vascular structures reside in the retroperitoneum. Intra-abdominal infections may be generalized or localized. They may be contained within visceral structures, such as the liver, gallbladder, spleen, pancreas, kidney, or female reproductive organs. Two general types of intra-abdominal infection are discussed throughout this chapter: peritonitis and abscess.
Peritonitis is defined as the acute inflammatory response of the peritoneal lining to microorganisms, chemicals, irradiation, or foreign-body injury. This chapter deals only with peritonitis of infectious origin.
Patient Encounter 1, Part 1
A 67-year-old man presents to the emergency room in acute distress with abdominal pain, nausea, and vomiting. The patient was in a reasonably good state of health until yesterday evening when he had a sudden onset of excruciating abdominal pain. During the night, he had a few episodes of vomiting, and the pain did not diminish. His physical exam is completely normal and no focal neurologic deficits were observed.
The patient is taking glyburide for noninsulin-dependent diabetes mellitus and has been treated in the past for peptic ulcer disease with ranitidine and omeprazole. He has a history of allergy to various types of pollen but reports no allergies to drugs. He reports moderate consumption of alcohol and smoking two packs of cigarettes per day.
What other information would you like to have about this patient before beginning treatment?
What are the goals of treatment?
An abscess is a purulent collection of fluid separated from surrounding tissue by a wall consisting of inflammatory cells and adjacent organs. It usually contains necrotic debris, bacteria, and inflammatory cells. Peritonitis and abscess differ considerably in presentation and approach to treatment.
EPIDEMIOLOGY AND ETIOLOGY
Peritonitis may be classified as primary, secondary, or tertiary. Primary peritonitis, also called spontaneous bacterial peritonitis, is an infection of the peritoneal cavity without an evident source of bacteria from the abdomen.1,2 In secondary peritonitis, a focal disease process is evident within the abdomen. Secondary peritonitis may involve perforation of the GI tract (possibly because of ulceration, ischemia, or obstruction), postoperative peritonitis, or post-traumatic peritonitis (e.g., blunt or penetrating trauma). Tertiary peritonitis occurs in critically ill patients; and it is an infection that persists or recurs at least 48 hours after apparently adequate management of primary or secondary peritonitis.
Primary peritonitis develops in 10% to 30% of patients with alcoholic cirrhosis.3 Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) average one episode of peritonitis every 2 years.4Secondary peritonitis may be caused by perforation of a peptic ulcer; traumatic perforation of the stomach, small or large bowel, uterus, or urinary bladder, appendicitis, pancreatitis, diverticulitis, bowel infarction, inflammatory bowel disease, cholecystitis, operative contamination of the peritoneum, or diseases of the female genital tract such as septic abortion, postoperative uterine infection, endometritis, or salpingitis. Appendicitis is one of the most common causes of intra-abdominal infection. In 2006, 341,000 appendectomies were performed in the United States for suspected appendicitis.5
Patient Encounter 2, Part 1
A 28-year-old woman, who has been undergoing peritoneal dialysis for chronic renal failure and reports to her doctor’s clinic with cloudy dialysate and generalized abdominal pain and cramping.
HPI: The abdominal pain began about two days ago.
PMH: The patient has had renal failure since 22 years of age as a result of diabetes. She has been on peritoneal dialysis for the past three years. She also has hyperlipidemia. She reports two prior episodes in the past year similar to the present one.
Meds: She usually takes a combination of NPH and regular human insulin which controls her blood sugar. She takes simvastatin for dyslipidemia.
SOC: The patient is married with no children. She does not smoke or drink alcohol. There is no history of renal disease in her family.
PE: The abdomen is found to be tender. Bowel sounds are hypoactive. The remainder of the physical exam in not contributory.
VS: T 99°F (37.2°C), BP 128/82 mm Hg, P 96 bpm, wt 76 kg (167 lb), ht 5′7″ (170 cm), RR 20 per minute.
Labs: Hct 40%, Hgb 13.4 g/dL (134 g/L or 8.3 mmol/L), WBC 9.2 × 103/mm3 (9.2 × 109/L), serum: glucose 256 mg/dL (14.2 mmol/L), serum creatinine 3.2 mg/dL (283 μmol/L), BUN 43 g/dL (15.4 mmol/L), Na 138 mEq/L (138 mmol/L), K 4.2 mEq/L 4.2 mmol/L), Cl 103 mEq/L (103 mmol/L), CO2 23 mEq/L (23 mmol/L), total bilirubin 0.3 mg/dL (5.13 μmol/L), albumin 3.9 g/dL (39 g/L).
What is the likely diagnosis?
How does this type of infection differ from secondary peritonitis?
What are the likely pathogens? Should a culture be performed in this patient? If so, what sites?
What else would you want to know about this patient?
Primary peritonitis in adults occurs most commonly in association with alcoholic cirrhosis, especially in its end stage, or with ascites caused by postnecrotic cirrhosis, chronic active hepatitis, acute viral hepatitis, congestive heart failure, malignancy, systemic lupus erythematosus, and nephrotic syndrome. It also may result from the use of a peritoneal catheter for dialysis with renal failure or CNS ventriculoperitoneal shunting for hydrocephalus. Abscesses are the result of chronic inflammation and may occur without preceding generalized peritonitis. They may be located within the peritoneal cavity or in a visceral organ and may vary in size, taking a few weeks to years to form.
The causes of intra-abdominal abscess overlap those of peritonitis and, in fact, may occur sequentially or simultaneously. Appendicitis is the most frequent cause of abscess.
PATHOPHYSIOLOGY
Intra-abdominal infection results from bacterial entry into the peritoneal or retroperitoneal spaces or from bacterial collections within intra-abdominal organs. In primary peritonitis, bacteria may enter the abdomen via the bloodstream or the lymphatic system by transmigration through the bowel wall, through an indwelling peritoneal dialysis (PD) catheter, or via the fallopian tubes in females. Hematogenous bacterial spread (through the bloodstream) occurs more frequently with tuberculosis peritonitis or peritonitis associated with cirrhotic ascites. When peritonitis results from PD, skin-surface flora are introduced via the peritoneal catheter. In secondary peritonitis, bacteria most often enter the peritoneum or retroperitoneum as a result of perforation of the GI or female genital tracts caused by diseases or traumatic injuries.
If bacteria that enter the abdomen are not handled by cellular and humoral defense mechanisms, bacterial dissemination occurs throughout the peritoneal cavity, resulting in peritonitis. This is more likely to occur in the presence of a foreign body, hematoma, necrotic tissue, large bacterial inoculum, continuing bacterial contamination, and contamination involving a mixture of synergistic organisms.
The fluid and protein shift into the abdomen (called third spacing) may be so dramatic that circulating blood volume is decreased, which causes decreased cardiac output and hypovolemic shock. Accompanying fever, vomiting, or diarrhea may worsen the fluid imbalance. A reflex sympathetic response, manifested by sweating, tachycardia, and vasoconstriction, may be evident. With an inflamed peritoneum, bacteria and endotoxins are absorbed easily into the bloodstream (translocation), and this may result in septic shock.1 Other foreign substances present in the peritoneal cavity potentiate peritonitis, notably feces, dead tissues, barium, mucus, bile, and blood.
Many of the manifestations of intra-abdominal infections, particularly peritonitis, result from cytokine activity. Inflammatory cytokines are produced by macrophages and neutrophils in response to bacteria and bacterial products or to tissue injury, resulting from the surgical incision.1 These cytokines produce wide-ranging effects on the endothelium of organs, particularly the liver, lungs, kidneys, and heart. With uncontrolled activation of these mediators, sepsis may result.6 Peritonitis may result in death because of the effects on major organ systems.
An abscess occurs if peritoneal contamination is localized but bacterial elimination is incomplete. The location of the abscess often is related to the site of primary disease. For example, abscesses resulting from appendicitis tend to appear in the right lower quadrant or the pelvis; those resulting from diverticulitis tend to appear in the left lower quadrant or pelvis. A mature abscess may have a fibrinous capsule that isolates bacteria and the liquid core from antimicrobials and immunologic defenses.
Microbiology of Intra-Abdominal Infection
Primary bacterial peritonitis is often caused by a single organism. In children, the pathogen is usually Streptococcus pneumoniae or a group A Streptococcus, E. coli, S. pneumoniae, or Bacteroides species.4,7 When peritonitis occurs in association with cirrhotic ascites, E. coli and Klebsiella are isolated most frequently.8 Other potential pathogens are Haemophilus pneumoniae, Klebsiella, Pseudomonas, anaerobes, and S. pneumoniae.9 Occasionally, primary peritonitis may be caused by Mycobacterium tuberculosis. Peritonitis in patients undergoing PD is caused most often by common skin organisms such as S. epidermidis, S. aureus, Streptococci, and diphtheroids. Occasionally, aerobic gram-negative bacilli may cause infections, particularly in patients undergoing dialysis during hospitalization. Death from primary peritonitis caused by gram-negative bacteria occurs much more frequently than from gram-positive bacteria.10
Because of the diverse bacteria present in the GI tract, secondary intra-abdominal infections are often polymicrobial.2,11 The mean number of different bacterial species isolated from infected intra-abdominal sites ranged from 3 when infection involves the small intestine to 26 with the colon.11
Bacterial Synergism
A combination of aerobic and anaerobic organisms appears to increase the severity of infection. Facultative bacteria (such as E. coli) may provide an environment conducive to the growth of anaerobic bacteria.2 Although many bacteria isolated in mixed infections are nonpathogenic by themselves, their presence may be essential for the pathogenicity of the bacterial mixture.3 Facultative bacteria in mixed infections have the ability to:
• Promote an appropriate environment for anaerobic growth through oxygen consumption
• Produce nutrients necessary for anaerobes
• Produce extracellular enzymes that promote tissue invasion by anaerobes.
Bacteria such as E. coli appear responsible for the early mortality from peritonitis, whereas anaerobic bacteria are major pathogens in abscesses, with B. fragilis predominating.12 Enterococcus can be isolated from many intra-abdominal infections in humans, but its role as a pathogen is not clear.13
Clinical Presentation of Primary Peritonitis
General
Patients may not be in acute distress, particularly with peritoneal dialysis.
Symptoms
Patient may complain of nausea, vomiting (sometimes with diarrhea), and abdominal tenderness.
Signs
• Temperature may be only mildly elevated or not elevated in patients undergoing peritoneal dialysis.
• Bowel sounds are hypoactive
• Cirrhotic patients may have worsening encephalopathy.
• There may be cloudy dialysate fluid with peritoneal dialysis.
Laboratory Tests
• The WBC may be only mildly elevated.
• Ascitic fluid usually contains more than 0.3 × 103/mm3 (0.3 × 109/L) leukocytes, and bacteria may be evident on gram stain of a centrifuged specimen.
Other Diagnostic Tests
Culture of peritoneal dialysate or ascitic fluid should be positive.
CLINICAL PRESENTATION AND DIAGNOSIS
Intra-abdominal infections have a wide spectrum of clinical features. Peritonitis usually is easily recognized, but intra-abdominal abscess often may continue unrecognized for long periods of time. Patients with primary and secondary peritonitis present quite differently.
TREATMENT
Desired Outcomes
The primary goals of treatment are correction of the intra-abdominal disease processes or injuries that have caused infection and drainage of collections of purulent material (abscess). A secondary objective is to resolve the infection without major organ system complications (e.g., pulmonary, hepatic, cardiovascular, or renal failure) or adverse drug effects. Ideally, the patient should be discharged from the hospital with full function for self-care and routine daily activities.
Clinical Presentation of Secondary Peritonitis
General
Patients may be in acute distress.
Symptoms
• Patients may complain of nausea, vomiting, and generalized abdominal pain.
• Patients may demonstrate abdominal guarding and a “boardlike abdomen.”
Signs
• Tachypnea and tachycardia are present.
• Temperature is normal initially, then may increase to 100°F to 102°F (37.7–38.9°C) within the first few hours, and may continue to rise for the next several hours.
• Hypotension and shock may develop if intravascular volume is not restored.
• Decreased urine output may develop owing to dehydration.
• Bowel sounds are faint initially and eventually cease.
Laboratory Tests
• The WBC is high (WBCs 15–20 × 103/mm3 [15–20 × 109/L]), with neutrophils predominating and an elevated percentage of immature neutrophils (bands).
• The hematocrit and blood urea nitrogen increase because of dehydration.
• Hyperventilation and vomiting result in early alkalosis, which changes to acidosis and lactic academia to reduced intravascular volume and diminished tissue perfusion.
Other Diagnostic Tests
Abdominal radiographs may be useful because free air in the abdomen (indicating intestinal perforation) or distension of the small or large bowel is often evident.
General Approach to Treatment
The treatment of intra-abdominal infection most often requires the coordinated use of three major modalities: (a) prompt drainage; (b) support of vital functions; and (c) appropriate antimicrobial therapy to treat infection not eradicated by surgery.14 Antimicrobials are an important adjunct to drainage procedures in the treatment of secondary intra-abdominal infections; however, the use of antimicrobial agents without surgical intervention usually is inadequate. For most cases of primary peritonitis, drainage procedures may not be required, and antimicrobial agents become the mainstay of therapy.
Patient Encounter 1, Part 2: Physical Examination and Diagnostic Tests
PE:
The patient is found responsive but in acute distress. He is lying on the examination table with knees drawn up to his chest. There is involuntary abdominal guarding with a rigid abdomen. There are no audible bowel sounds. He is alert and oriented times 3. Neurologic function is intact. Mucous membranes are dry. Stool is heme-negative.
VS: T 101°F (38.3°C), BP 105/70 mm Hg, P 132 bpm, wt 82 kg (180 lb), ht 5′7″ (170 cm), RR 24 per minute.
Labs: Hct 46% (0.46 volume fraction), Hgb 15.4 g/dL (154 g/L or 9.5 mmol/L), WBC count 15.2 × 103/mm3 (15.2 × 109/L) (45% neutrophils, 20% bands)
Serum: Glucose 213 mg/dL (11.8 mmol/L), serum creatinine 1.9 mg/dL (168 μmol/L), BUN 42 g/dL (15 mmol/L), Na 138 mEq/L (138 mmol/L), K 3.7 mEq/L (3.7 mmol/L), Cl 101 mEq/L (101 mmol/L), CO2 21 mEq/L (21 mmol/L), calcium 9.8 mg/dL (2.45 mmol/L), magnesium 2.0 mEq/L (1.0 mmol/L), total bilirubin 0.4 mg/dL (6.84 μmol/L), albumin 4.2 g/dL (42 g/L), lactic acid 3.2 mEq/L (3.2 mmol/L)
KUB: An upright abdominal x-ray shows dilated loops of small bowel and free air under the diaphragm.
DPL (diagnostic peritoneal lavage: examination of fluid in peritoneal cavity): No blood is found, but WBCs are evident.
Develop a care plan for this patient for the first 7 days of his hospitalization. This plan should include specific drug recommendations, and monitoring parameters to evaluate outcome.
In the early phase of serious intra-abdominal infections, attention should be given to preserving major organ system function. With generalized peritonitis, large volumes of IV fluids are required to maintain intravascular volume, to improve cardiovascular function, and to ensure adequate tissue perfusion and oxygenation. Adequate urine output should be maintained to ensure appropriate fluid resuscitation and to preserve renal function. A common cause of early death is hypovolemic shock caused by inadequate intravascular volume expansion and tissue perfusion.
An additional important component of therapy is nutrition. Intra-abdominal infections often involve the GI tract directly or disrupt its function (paralytic ileus). The return of GI motility may take days, weeks, and occasionally, months. In the interim, enteral or parenteral nutrition as indicated facilitates improved immune function and wound healing to ensure recovery.
Patient Encounter 2, Part 2
A sample of dialysate fluid was found to be cloudy. A spun specimen had numerous white cells and gram-positive cocci on gram stain.
Suggest an initial regimen for this patient (agent, dose, and route of administration).
What are some factors that would be considered when deciding the route of antimicrobial administration for this patient?
How long should the antimicrobial be continued?
What can be done to prevent future infections like this?
Nonpharmacologic Therapy
Drainage Procedures
Primary peritonitis is treated with antimicrobials and rarely requires drainage. Secondary peritonitis requires surgical removal of the inflamed or gangrenous tissue to prevent further bacterial contamination. If the surgical procedure is suboptimal, attempts are made to provide drainage of the infected or gangrenous structures.
The drainage of purulent material is the critical component of management of an intra-abdominal abscess. This may be performed surgically or with percutaneous image-guided techniques.15 Without adequate drainage of the abscess, antimicrobial therapy and fluid resuscitation can be expected to fail. The most valuable microbiologic information may be obtained at the time of percutaneous or operative abscess drainage.
Fluid Therapy
In patients with peritonitis, hypovolemia is often accompanied by acidosis and large volumes of a solution such as lactated Ringer’s may be required initially to restore intravascular volume. Maintenance fluids should be instituted (after intravascular volume is restored) with 0.9% sodium chloride and potassium chloride (20 mEq/L [20 mmol/L]) or 5% dextrose and 0.45% sodium chloride with potassium chloride (20 mEq/L [20 mmol/L]). The administration rate should be based on estimated daily fluid loss through urine and nasogastric suction, including 0.5 to 1.0 L for insensible fluid loss. Potassium would not be included routinely if the patient is hyperkalemic or has renal insufficiency. Aggressive fluid therapy often must be continued in the postoperative period because fluid will continue to sequester in the peritoneal cavity, bowel wall, and lumen.
Pharmacologic Therapy
Antimicrobial Therapy
The goals of antimicrobial therapy are as follows:
• To control bacteremia and prevent the establishment of metastatic foci of infection
• To reduce suppurative complications after bacterial contamination
• To prevent local spread of existing infection
After suppuration has occurred (e.g., an abscess has formed), a cure by antibiotic therapy alone is difficult to achieve; antimicrobials may serve to improve the results with surgery.
An empirical antimicrobial regimen should be started as soon as the presence of intra-abdominal infection is suspected and before identification of the infecting organisms is complete. Therapy must be initiated based on the likely pathogens, which vary depending on the site of intra-abdominal infection and the underlying disease process. Cultures of secondary intra-abdominal infection sites generally are not useful for directing antimicrobial therapy. Table 77–1 lists the likely pathogens against which antimicrobial agents should be directed.
Antimicrobial Experience
Many studies have been conducted evaluating or comparing the effectiveness of antimicrobials for treatment of intra-abdominal infections. Substantial differences in patient outcomes from treatment with a variety of agents generally have not been demonstrated.16
Important findings from the last 25 years of clinical trials regarding selection of antimicrobials for intra-abdominal infections are as follows:
• Antimicrobial regimens for secondary intra-abdominal infections should cover a broad spectrum of aerobic and anaerobic bacteria from the GI tract.
• Single-agent regimens (such as antianaerobic cephalosporins, extended-spectrum penicillins with β-lactamase inhibitors, or carbapenems) are as effective as combinations of aminoglycosides or fluoroquinolones with antianaerobic agents. This is also true for antimicrobial treatment of acute bacterial contamination from penetrating abdominal trauma.
• Clindamycin and metronidazole appear to be equivalent in efficacy when combined with agents effective against aerobic gram-negative bacilli (e.g., gentamicin or aztreonam).
• For most patients, antimicrobial treatment can be completed orally with amoxicillin–clavulanate or the combination of ciprofloxacin and metronidazole.
• Five to seven days of antimicrobial treatment are sufficient for most intra-abdominal infections of mild to moderate severity.
Intra-abdominal infection presents in many different ways and with a wide spectrum of severity. The antibiotic regimen employed and duration of treatment depend on the specific clinical circumstances (i.e., the nature of the underlying disease process and the condition of the patient).
Recommendations
For most intra-abdominal infections, the antimicrobial regimen should be effective against both aerobic and anaerobic bacteria.17 Although it is impossible to provide antimicrobial activity against every possible pathogen, agents with activity against enteric gram-negative bacilli, such as E. coli and Klebsiella, and anaerobes, such as B. fragilis and Clostridia spp., should be administered.
Table 77–2 presents the recommended agents for treatment of community-acquired and complicated intra-abdominal infections from the Infectious Diseases Society of America and the Surgical Infection Society.18,19 These recommendations were formulated using an evidence-based approach. Most community-acquired infections are “mild to moderate,” whereas health care–associated infections tend to be more severe and difficult to treat. Table 77–3presents guidelines for treatment and alternative regimens for specific situations. These are general guidelines; there are many factors that cannot be incorporated into such a table.
Table 77–1 Likely Intra-Abdominal Pathogens
Table 77–2 Recommended Agents for the Treatment of Community-Acquired Complicated Intra-Abdominal Infections
Table 77–3 Guidelines for Initial Antimicrobial Agents for Intra-Abdominal Infections
When used for intra-abdominal infection, aminoglycosides should be combined with agents that are effective against the majority of B. fragilis. Clindamycin or metronidazole is the agent of first choice, but others, such as antianaerobic cephalosporins (e.g., cefoxitin, cefotetan, or ceftizoxime), piperacillin, mezlocillin, and combinations of extended-spectrum penicillins with β-lactamase inhibitors, would be suitable alternatives. Patients receiving multiple broad-spectrum antimicrobial agents who are immunocompromised should receive an oral antifungal agent (nystatin) for prevention of fungal overgrowth in the mouth and GI tract. The benefits of systemic antifungal prophylaxis (with fluconazole) have not been established for intra-abdominal infection and should not be used routinely.
In immunocompromised patients or patients with valvular heart disease or a prosthetic heart valve, there is justification to provide specific antimicrobial activity against enterococci. Ampicillin or other penicillins that are active against enterococci (e.g., penicillin, piperacillin, and mezlocillin) should be used in patients at high-risk, patients with persistent or recurrent intra-abdominal infection, or patients who are immunosuppressed, such as after organ transplantation. Ampicillin remains the drug of choice for this indication because it is most active in vitro against enterococci and is relatively inexpensive. Vancomycin is active against most enterococci; however, resistance is increasing, and this agent should be reserved for established infections when first-line therapies cannot be used.
IP administration of antibiotics is preferred over IV therapy in the treatment of peritonitis that occurs in patients undergoing CAPD.20 The International Society of Peritoneal Dialysis (ISPD) revised its guidelines for the diagnosis and pharmacotherapy of PD-associated infections.21 The guidelines provide dosing recommendations for intermittent and continuous therapy based on the modality of dialysis (CAPD or automated peritoneal dialysis [APD]) and the extent of the patient’s residual renal function.
Antimicrobial agents effective against both gram-positive and gram-negative organisms should be used for initial IP empirical therapy for peritonitis in PD patients. The most important factors to take into consideration for initial antimicrobial selection are the dialysis center’s and the patient’s history of infecting organisms and their sensitivities. The use of cefazolin (loading dose [LD] 500 mg/L, maintenance dose [MD] 125 mg/L) plus ceftazidime (LD 500 mg/L, MD 125 mg/L) or cefepime (LD 500 mg/L, MD 125 mg/L) or an aminoglycoside (gentamicin-tobramycin LD 8 mg/L, MD 4 mg/L) is suitable for initial empirical therapy; if patients are allergic to cephalosporin antibiotics, vancomycin (LD 1,000 mg/L, MD 25 mg/L) or an aminoglycoside should be substituted. Another option is monotherapy with imipenem-cilastin (LD 500 mg/L, MD 200 mg/L) or cefepime. Antimicrobial doses should be increased empirically by 25% in patients with residual renal function (more than 100 mL/day urine output).21 Antimicrobial therapy should be continued for at least 1 week after the dialysate fluid is clear and for a total of at least 14 days. The reader is referred to these guidelines for additional information.21
After acute bacterial contamination, such as with abdominal trauma where GI contents spill into the peritoneum, combination antimicrobial regimens are not required. If the patient is seen soon after injury (within 2 hours) and surgical measures are instituted promptly, antianaerobic cephalosporins (such as cefoxitin or cefotetan) or extended-spectrum penicillins are effective in preventing most infectious complications. Antimicrobials should be administered as soon as possible after injury.22
For appendicitis, the antimicrobial regimen used should depend on the appearance of the appendix at the time of operation, which may be normal, inflamed, gangrenous, or perforated. Because the condition of the appendix is unknown preoperatively, it is advisable to begin antimicrobial agents before the appendectomy is performed. Reasonable regimens would be antianaerobic cephalosporins or, if the patient is seriously ill, a carbapenem or β-lactam–β-lactamase-inhibitor combination. If, at operation, the appendix were normal or inflamed, postoperative antimicrobials would not be required. If the appendix is gangrenous or perforated, a treatment course of 5 to 7 days with the agents listed in Table 77–2 is appropriate.
Acute intra-abdominal contamination, such as after a traumatic injury, may be treated with a short course (24 hours) of antimicrobials.22 For established infections (i.e., peritonitis or intra-abdominal abscess), an antimicrobial course limited to 5 to 7 days is justified. Under certain conditions, therapy for longer than 7 days would be justified, for example, if the patient remains febrile or is in poor general condition, when relatively resistant bacteria are isolated, or when a focus of infection in the abdomen still may be present. For some abscesses, such as pyogenic liver abscess, antimicrobials may be required for a month or longer.
OUTCOME EVALUATION
Whether diagnosed with primary or secondary peritonitis, monitor the patient for relief of symptoms. Once antimicrobials are initiated and the other important therapies described earlier are used, most patients should show improvement within 2 to 3 days. Successful antimicrobial therapy with resolution of infection will result in decreased pain, manifested as resolution of abdominal guarding and decreased use of pain medications over time. The patient should not appear in distress, with the exception of recognized discomfort and pain from incisions, drains, and a nasogastric tube.
Monitor vital signs and WBC count with differential; each should normalize as the infection resolves. At 24 to 48 hours, aerobic bacterial culture results should be available. If a suspected pathogen is not sensitive to the antimicrobial agents being given, the regimen should be changed if the patient has not shown sufficient improvement. If the isolated pathogen is extremely sensitive to one antimicrobial and the patient is progressing well, concurrent antimicrobial therapy often may be discontinued.
With anaerobic culturing techniques and the slow growth of these organisms, anaerobes often are not identified until 4 to 7 days after culture, and sensitivity information is difficult to obtain. For this reason, anaerobic culture information generally is not helpful for selection of the antianaerobic component of the antimicrobial regimen. A report indicating that anaerobes were not isolated should not be the sole justification for discontinuing antianaerobic drugs because anaerobic bacteria that were present in the infectious process may not have been transported properly to the microbiology laboratory, or other problems may have led to bacterial death in vitro.
Once the patient’s temperature is normal for 48 to 72 hours and the patient is eating, consider changing the IV antibiotic to an oral regimen for the duration of antibiotic treatment. Monitor the serum creatinine level to evaluate for renal complications as well as potential drug toxicity, especially if an aminoglycoside is a component of the antibiotic regimen. Bowel sounds should return to normal. Evaluate the patient daily for development of rash or other drug-related adverse effects.
For patients with primary peritonitis, if peritoneal dialysate cultures were positive initially, repeat cultures should be negative. For patients with secondary peritonitis, monitor the amount of fluid draining if a drain was placed. The volume of drainage should lessen as the infection resolves. Repeat abdominal radiographs should return to normal.
If symptoms do not improve, the patient should be evaluated for persistent infection. There are many reasons for poor patient outcome with intra-abdominal infection; improper antimicrobial selection is only one. The patient may be immunocompromised, which decreases the likelihood of successful outcome with any regimen. It is impossible for antimicrobials to compensate for a nonfunctioning immune system. There may be surgical reasons for poor patient outcome. Failure to identify all intra-abdominal foci of infection or leaks from a GI anastomosis may cause continued intra-abdominal infection. Even when intra-abdominal infection is controlled, accompanying organ system failure, most often renal or respiratory, may lead to patient demise.
The outcome from intra-abdominal infection is not determined solely by what transpires in the abdomen. Unsatisfactory outcomes in patients with intra-abdominal infections may result from complications that arise in other organ systems. Infectious complications commonly associated with mortality after intra-abdominal infection are urinary tract infections and pneumonia.23 Reasons for antimicrobial failure may not always be apparent. Even when antimicrobial susceptibility tests indicate that an organism is susceptible in vitro to the antimicrobial agent, therapeutic failures may occur. Possibly there is poor penetration of the antimicrobial agent into the focus of infection, or bacterial resistance may develop after initiation of antimicrobial therapy. Also, it is possible that an antimicrobial regimen may encourage the development of infection by organisms not susceptible to the regimen being used. Superinfection in patients being treated for intra-abdominal infection can be caused by Candida; however, Enterococci or opportunistic gram-negative bacilli such as Pseudomonas and Serratia may be involved.
Patient Care and Monitoring
1. A thorough patient medication history should be taken at the time of admission to document all recent medication use, including nonprescription medications and use of complementary or alternative medicines. Any drug allergies or intolerances also should be documented.
2. The initial antimicrobial regimen should conform to standard guidelines unless an appropriate justification for an alternative regimen is evident. With the first few doses of antimicrobial, assess the patient for hypersensitivity reactions or other acute intolerances.
3. Review the dosages of all medications to be sure that they are appropriate for age, weight, and major organ function Verify that the drugs selected are not contraindicated in the patient with allergies or other intolerances.
4. Confirm that all necessary acute and chronic medications are continued postoperatively.
5. Monitor vital signs (i.e., temperature and heart rate) and laboratory assessments (i.e., WBC count) daily to assess resolution of infection and efficacy of pain medications. When possible, interview the patient to obtain additional information about pain control.
6. Evaluate fluid status to ensure that the patient is not hypovolemic. In a seriously ill patient, assess intravascular volume by monitoring blood pressure and heart rate, but do so more accurately by measuring central venous pressure or urinary output via a urinary bladder catheter. Urine output should equal or exceed 0.5 mL/kg of body weight per hour.
7. Review results of cultures obtained preoperatively or during the surgical procedure. Evaluate the appropriateness of antibiotic therapy based on susceptibility information. Although some investigators suggest that routine culturing of patients with community-acquired intra-abdominal infections contributes little to their management, other investigators suggest that antimicrobial therapy should be based on susceptibility of the bacteria collected from the operative site because this has been shown to correlate with clinical outcome.24
8. Assess serum creatinine and aminoglycoside serum concentrations if the patient is being treated with an aminoglycoside. Adjust aminoglycoside dose based on serum concentrations; target peak concentration with multiple doses per day = 6 mcg/mL (12.5 μmol/L gentamicin or 12.8 μmol/L tobramycin).
9. On the fifth day of antimicrobial treatment or when GI function returns, determine if parenteral antimicrobial agents can be switched to oral agents to complete therapy.
10. Assess nutritional needs and recommend appropriate supplementation. When the patient is tolerating an oral diet, determine if any parenteral medications can be switched to the oral route.
11. Monitor the patient for the development of potential complications of treatment such as delayed hypersensitivity reactions, antibiotic-induced diarrhea, pseudomembraneous colitis, or fungal superinfections (manifested as oral thrush).
12. Provide information to the patient concerning the medications administered in the hospital as well as any new medications prescribed for use at home. Advise the patient to contact his or her doctor or pharmacist if he or she experience any adverse effects from medications.
Treatment regimens for intra-abdominal infection can be judged as successful if the patient recovers from the infection without recurrent peritonitis or intra-abdominal abscess and without the need for additional antimicrobials. A regimen can be considered unsuccessful if a significant adverse drug reaction occurs, reoperation or percutaneous drainage is necessary, or patient improvement is delayed beyond 1 or 2 weeks.
Abbreviations Introduced in This Chapter
Self-assessment questions and answers are available at http://www.mhpharmacotherapy.com/pp.html.
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