Donald E. Craven
Kathleen Steger Craven
Robert A. Duncan
Introduction
Hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and healthcare-associated pneumonia (HCAP) remain important causes of morbidity and mortality despite recent advances in antimicrobial therapy, better supportive care modalities, and the use of a wide range of prevention measures [1,2,3]. HAP is an infectious disease of lung parenchyma that occurs ≥48 hours after admission and was not incubating at the time of admission. VAP refers to pneumonia that arises more than 48–72 hours after endotracheal intubation. HCAP includes patients who were hospitalized in an acute care hospital for ≥2 days within 90 days of the infection, resided in a long-term care facility, and received recent intravenous antibiotic therapy, chemotherapy, or wound care within the past 30 days of the current infection or attended a hospital or hemodialysis clinic. Although this document focuses more on HAP and VAP, many of the principles are relevant to HCAP.
Organisms causing HAP may originate from the host's endogenous flora, other patients, visitors, hospital staff, or environmental sources (Figure 31-1). Aspiration and leakage around the endotracheal tube cuff are major risk factors for bacterial entry into the lower respiratory tract [3,4]. Over the past decade, there has been an increase in HAP caused by multidrug-resistant (MDR) pathogens, such as Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, and methicillin-resistant Staphylococcus aureus (MRSA) [1,2,3,5].
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Figure 31-1 Sources of nosocomial respiratory tract pathogens: the environment, invasive devices, patients and hospital staff. |
This chapter highlights the changing epidemiology, pathogenesis, and treatment of HAP, VAP, and, to a lesser extent, HCAP. Our primary focus is on bacterial pathogens causing HAP in immunocompetent adults. Readers are referred to other chapters for specific information on pulmonary infections related to immunodeficiency, mycobacteria, viruses, and fungal pathogens. Our major emphasis is on patient management (diagnosis and treatment), effective prevention strategies, and improved methods for implementing evidence-based risk reduction strategies to improve patient outcomes. New concepts and publications from the past 5 years are prioritized.
Epidemiology
Each year there are between 5 and 10 episodes of HAP/1,000 hospital admissions [1,2,3]. HAP accounts for 15%
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of all healthcare-associated infections (HAIs) and approximately 25% of all intensive care unit (ICU) infections. Clearly, HAP rates are influenced by decreasing lengths of stay and transfers from acute care facilities to other healthcare venues. Rates of HAP tend to be higher in university vs. nonteaching hospitals. Rates of VAP in the Centers for Disease Control and Prevention's (CDC) National Nosocomial Infections Surveillance (NNIS) system varied by type of ICU with a pooled mean of 7.3/1,000 ventilator-days for medical versus 13.2 for surgical ICUs. The 50th percentile (median) was 6.0 for medicine and 11.6/1,000 ventilator-days for surgical ICUs [5].
Crude rates of VAP vary by patient population and method of diagnosis [1,2,3]. Several studies have demonstrated that rates of VAP increase with the duration of mechanical ventilation, and attack rates have been estimated to be approximately 3% per day during the first 5 days and then 2% per day thereafter [6].
In an era of increased pressure to publicly report and compare HAI rates, Eggimann et al. examined several ways to report HAI rates and suggested some caveats for benchmarking rates of VAP. In a prospective cohort of 1,068 medical ICU patients, 127 episodes of VAP developed in 106 (23.5%) of 451 mechanically ventilated patients [7]. The incidence of first episode of VAP was 22.8/1,000 patient-days; 29.6/1,000 patient-days at risk, 35.7/1,000 ventilator-days, and 44.0/1,000 ventilator-days at risk. When considering all 127 episodes of VAP, infection rates increased from 22.8 to 27.3 episodes/1,000 ICU days and from 35.7 to 42.8 episodes/1,000 ventilator-days. These data demonstrate that, depending on the denominator chosen, the apparent incidence of infection reported by various hospitals may differ by as much as 40–60%. These differences support the use of a standardized calculation of HAI rates among ICUs and hospitals in our current competitive medical environment.
The crude mortality rates for VAP pneumonia range from 20–60%, reflecting, in large part, the severity of underlying disease, organ failure, and specific pathogen(s) and study populations [1,2,3,8,9]. Estimates of attributable mortality directly related to VAP vary by study design but are approximately 33%. In two major studies of VAP, the mortality rate varied between 4% in patients without prior antibiotic exposure to 73% in those with VAP due to MDR pathogens (e.g., P. aeruginosa or A. baumannii), and attributable mortality ranged from 6–14% [10,11].
Cost
Prevention programs can be “marketed” to hospital administrators and others involved in resource allocation by demonstrating that preventing VAP results in improved clinical outcomes, significantly reduced costs, and less adverse publicity and liability. In 2002, Rello et al. demonstrated that, on average, an episode of VAP increased hospitalization by 12 days, mechanical ventilation by 10 days, ventilator days by 6 days, and ICU stay by 6 days at a hospital cost of $40,000; similar results have been reported from a suburban hospital by Warren et al. [9,12]. In addition to these direct savings associated with preventing VAP, the growing trend toward public reporting of institution-specific HAI rates and other outcome data is steadily increasing and may eventually be tied to hospital reimbursement rates.
Pathogenesis
Pathogenesis of HAP involves the direct interaction between the pathogen(s) with the host and epidemiologic variables that facilitate this dynamic. There are several mechanisms that contribute to the pathogenesis of HAP, and the relative contribution of each pathway remains controversial and varies by population at risk and the infecting pathogen(s) (Figure31-2) [1,2]. Microaspiration in nonventilated patients is the primary route of bacterial entry into the lower respiratory tract [1,2]. Dental plaque has also been implicated as a contributing factor. In addition, patients who are sedated, postoperative, or have abnormal swallowing are at higher risk for aspiration [1,2]. Direct inoculation, bacteremic spread, or translocation of bacteria from the gastrointestinal tract are less well documented routes.
High concentrations of bacteria refluxed from the gastric reservoir or infected sinuses may be aspirated and increase levels of bacteria colonizing the oropharynx, but the relative contribution of these sites remains controversial. Bacterial adherence and colonization of the oropharynx clearly is the primary source of bacterial entry into the lung and a conduit for gastric colonization [2,13,14]. The contributory role of the stomach in the pathogenesis of pneumonia may be related to patient position, type of stress ulcer prophylaxis, gastric pH, and underlying gastrointestinal diseases [2,15]. Retrograde colonization of the oropharynx from the stomach may increase the risk of oropharyngeal colonization and lower respiratory tract infection, also known as the “gastropulmonary route of infection.”
In the mechanically ventilated patient, inhalation of aerosols, contaminated tubing condensate, and leakage of bacteria and oral secretions around the endotracheal cuff are routes of bacterial entry into the lower respiratory tract (Figure 31-3) [16,17]. In addition, local trauma and inflammation from the endotracheal tube increase tracheal colonization and reduce clearance of organisms and secretions from the lower respiratory tract. The development of biofilm-encased bacteria over time on the endotracheal tube lumen may increase the risk of bacterial embolization into the alveoli following suctioning or bronchoscopy [18].
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Colonization of the Oropharynx
In contrast to healthy people, critically ill patients and those with VAP have high rates of oropharyngeal colonization with bacterial pathogens [1,2]. Colonization with gram-negative bacilli was present in 16% of moderately ill patients vs. 57% of critically ill patients, and rates of pneumonia were increased sixfold in ICU patients with bacterial colonization [13]. Host factors, types of bacteria colonizing the pharynx, and the use of antibiotics may alter colonization and adherence of gram-negative bacilli. Oral epithelial cells rich in fibronectin bind gram-positive organisms, such as streptococci and S. aureus; conversely, those poor in fibronectin preferentially bind gram-negative bacilli such as P. aeruginosa [19].
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Figure 31-2 Pathogenesis of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) with possible targets for prevention strategies. Stage 1: colonization and invasion of the lower respiratory tract; Stage II: bacterial-host defense interactions (bacterial numbers and virulence versus host mechanical, humoral, and cellular defenses) and Stage III: outcomes (colonization, tracheobronchitis or pneumonia). |
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Figure 31-3 An intubated patient with oropharyngeal and gastric colonization; note subglottic secretions pooled above the endotracheal tube cuff. The endotracheal tube prevents mechanical clearance of bacteria and secretions from the trachea and bacteria encased biofilm form in the lumen of the endotracheal tube over time. Endotracheal and gastric tubes are in oropharynx and are potential sources for colonization by multidrug-resistant pathogens. |
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Gastric Colonization
In mechanically ventilated patients, the stomach and gastrointestinal tract may contribute to oropharyngeal and tracheal colonization with gram-negative bacilli, although some investigators question their importance (Figure 31-3) [2,14,15,20,21,22,23]. The stomach often is sterile when the pH is <2 because of the potent bactericidal activity of hydrochloric acid. An increase in gastric colonization occurs with achlorhydria, and various gastrointestinal diseases, malnutrition, or the use of antacids or histamine-2 (H2) blockers. In mechanically ventilated patients, colonization may reach 1–100 million gram-negative bacilli/ml of gastric juice when the pH is >4 [20].
Immune Defenses in the Lung
The response of pulmonary host defenses to invading microorganisms plays an integral part in the pathogenesis and outcome of infection, yet our understanding is limited and needs further elucidation (Figures 31-2 and 31-3) [1,3,23,24,25]. Mucociliary and mechanical clearance in the upper airway are important factors in the defense against infection. Bacterial antigens and cytokines that alter the activity and efficacy of ciliary cells in clearing bacteria from the lower airway need further study. The ability of macrophages and polymorphonuclear leukocytes to eliminate bacterial pathogens and the interaction of these cells with inflammatory cytokines probably play important roles in the pathogenesis of pneumonia. Cell-mediated immune response is controlled by a complex array of lipids, peptides, and cytokines, including interleukin-1 and -2, interferons, growth factors, and chemotactic factors. Leukotrienes, complement components, and platelet-activating factor also assist in the inflammatory response and contribute to the pathogenesis of pneumonia. Based on an improved understanding of the molecular interaction between bacteria cell walls, toxins, and host defenses, strategies should be considered to enhance host defenses and supplement current antimicrobial regimens.
Etiologic Agents
The wide spectrum of etiologic agents causing HAP varies with time, by hospital, type of ICU, and patient population studied, emphasizing the importance of current local surveillance data (Table 31-1) [1,2,3,5,9,26,27]. Bacteria causing HAP may originate from various sources, including the patient's endogenous flora, other patients, staff, contaminated devices, or the environment [4,28,29] (Figure 31-1). Prior hospitalization, exposure to chronic care facilities, and antibiotic therapy also are important predisposing factors for MDR pathogens [30,31,32,33]. In the absence of these factors, early onset HAP occurring during the first 5 days of the hospital stay is usually caused by Streptococcus pneumoniae, Moraxella catarrhalis, Hemophilus influenzae, or anaerobic bacteria (Table 31-1) [1,3]. In comparison, late onset HAP is commonly caused by MDR gram-negative bacilli (Klebsiella pneumoniae, A. baumannii, P. aeruginosa) or MRSA [34].
Gram-negative bacilli have been implicated in >60% of reported episodes of HAP, and S. aureus (often MRSA) accounts for 20–40% of episodes and is increasing [2,5,35]. Isolation rates of these bacteria vary considerably, depending on the population at risk, location, hospital size, ICU type, and method of diagnosis. However, overall rates of MDR pathogen infections are increasing in the United States [35,36,37].
Most episodes of bacterial nosocomial pneumonia are caused by >1 species of bacteria [1,2,3,9]. The specific etiologies of pneumonia vary by hospital, the presence of an endotracheal tube, and the method used for diagnosis. For example, critically ill patients who often have both acute and chronic underlying diseases are often exposed to numerous invasive procedures and more antibiotics and devices. All of these factors increase the risk of colonization and infection with MDR gram-negative bacilli, MRSA, and vancomycin-resistant or vancomycin-intermediate-resistant (VRSA/VISA) isolates of S. aureus [9,36,38,39,40].
Very few data are available about the bacteriology and risk factors for specific pathogens in patients with HAP and HCAP who are not mechanically ventilated. Unpublished data from a comprehensive hospitalwide surveillance of HAIs at the University of North Carolina described the pathogens causing both VAP and HAP from 2000–2003 (personal communication Dr. David Weber and Dr. William Rutala) [1]. Pathogens were isolated from 92% of mechanically ventilated patients with infection, and 77% of nonventilated patients with infection. Non-ventilated patients had very similar bacteriology to ventilated patients, including infection with MDR pathogens (e.g., MRSA, P. aeruginosa, Acinetobacter spp., or K. pneumoniae). In fact, MRSA and K. pneumoniae were more common in nonventilated than ventilated patients, but MDR gram-negative bacilli (e.g., P. aeruginosa, Stenotrophomonas maltophilia, orAcinetobacter spp.) were more common in VAP.
More recently, pneumonia due to community-acquired MRSA (CA-MRSA) has emerged in children and adults [39,40,41,42]. In contrast to healthcare-associated (HA)-MRSA, CA-MRSA isolates are genetically distinct and almost uniformly carry the Panton-Valentine leukocidin (PVL) that may be associated with greater virulence. These strains also have been identified as an emerging source of infection spreading within hospitals. There also is concern over the evolution of VISA/GISA isolates of S. aureus that have been increasing [38,39]. Although a smaller number of VRSA isolates have been reported to date, rates may increase with the lowering of the vancomycin minimum inhibitory concentrations (MICs) from 4 mcg/ml to 2 mcg/ml.
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Common Pathogens
Streptococcus pneumoniae and Haemophilus influenzae
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TABLE 31-1 |
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Klebsiella, Enterobacter, and Serratia Species
Klebsiella spp. are intrinsically resistant to ampicillin and other aminopenicillins and can acquire resistance to cephalosporins and aztreonam by the production of extended-spectrum β-lactamases (ESBLs) [1]. Plasmids encoding ESBLs often carry resistance to aminoglycosides and other drugs, but these usually remain susceptible to carbapenems. Enterobacter spp. has a chromosomal AmpC β-lactamase that is inducible and easily expressed at a high level by mutation with consequent resistance to oxyimino-β-lactams and α-methoxy-β-lactams, such as cefoxitin and cefotetan, but continued susceptibility to carbapenems. Citrobacter and Serratia spp. have the same inducible AmpC β-lactamase and the same potential for resistance development. Plasmid-mediated resistance, such as ESBL production, is a more common mechanism for β-lactam
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resistance in HAI isolates and is increasingly recognized, not only in isolates of K. pneumoniae and E. coli but also Enterbacter spp.
Pseudomonas aeruginosa
Acinetobacter baumannii, Stenotrophomonas maltophilia, Burkholderia cepacia
Although generally less virulent than P. aeruginosa, Acinetobacter spp. have nonetheless become problem pathogens because of increasing resistance to commonly used antimicrobial agents [1,44]. More than 85% of isolates are susceptible to carbapenems, but resistance is increasing due either to IMP-type metallo-enzymes or carbapenemases of the OXA-type. An alternative for therapy is sulbactam, usually employed as an enzyme inhibitor, but with direct antibacterial activity against Acinetobacter spp. S. maltophilia, which shares with B. cepacia a tendency to colonize the respiratory tract rather than cause invasive disease, is uniformly resistant to carbapenems because of a ubiquitous, metallo-β-lactamase. S. maltophilia and B. cepacia are most likely to be susceptible to trimethoprim/sulfamethoxazole, ticarcillin/clavulanate, or a fluoroquinolone. B. cepacia usually is susceptible to ceftazidime and carbapenems.
MRSA
In the United States, >50% of the ICU infections caused by S. aureus are methicillin-resistant organisms [35,36]. MRSA produces a penicillin-binding protein with reduced affinity for β-lactam antibiotics that is encoded by the mecA gene, which is carried by one of a family of four mobile genetic elements [1]. Strains with mecA are resistant to all commercially available β-lactams and many other antistaphylococcal drugs with considerable geographic variability worldwide. Although VISA with a minimal inhibitory concentration (MIC) of 8–16 µg/ml and high-level VRSA with MIC ≥32-1024 µg/ml have been isolated from clinical specimens, all of these isolates have been sensitive to linezolid [38,39]. Although linezolid resistance has emerged in S. aureus, it is currently rare. Daptomycin resistance has also been reported, but this drug is not indicated for treatment of pneumonia because of its inactivation by lung surfactant. MRSA now accounts for >50% of the ICU-acquired staphylococcal HAIs in the United States [45]. MRSA is associated with significant morbidity and mortality, making it a challenge for infection control. The introduction of new virulence factors from CA-MRSA strains into HA-MRSA strains may have important clinical and infection control consequences [46].
A recent outbreak of VISA infections in a French ICU may be a harbinger of future problems for other hospitals [38]. Aggressive antibiotic stewardship must focus on more judicious use of all antibiotics, especially fluoroquinolones, which have been shown to increase the chance of acquisition of MRSA three to fivefold. Also, more aggressive infection control measures, such as active surveillance cultures, patient isolation, and eradication of MRSA or “a search and destroy” strategy may be needed [40,41,47].
Legionella pneumophila
Rates of HAP due to L. pneumophila vary among hospitals but are increased in immunocompromised patients (e.g., organ transplant recipients or patients with human immunodeficiency virus [HIV] disease) and in those with diabetes mellitus, underlying lung disease or end-stage renal disease [2,48,49]. Serotype 1 is most common and can be cultured on special media but may be more rapidly diagnosed by urinary antigen testing. HAP due to Legionella spp. is more common in hospitals where the organism is present in the water supply or may surge during construction. Due to the widespread use of Legionella urinary antigen rather than culture for the diagnosis of Legionella, infection due to serotypes other than serotype 1 may be underdiagnosed. Detailed strategies for prevention of Legionella spp. infection and eradication procedures for Legionella spp. in cooling towers and the hospital water supply are outlined elsewhere [2] (see Chapter 44).
Diagnosis
Accurate data regarding etiologic agents, epidemiology, and treatment of HAP are limited by the lack of a diagnostic gold standard. Although clinical criteria and semiquantitative criteria for the diagnosis of HAP are the current standard for most U.S. hospitals, there are concerns about lack of diagnostic specificity [1,3,50,51,52,53,54,55]. Atelectasis, pulmonary edema, pulmonary emboli, neoplastic processes, and some autoimmune diseases can mimic the clinical presentation of HAP. In addition, chest radiographic changes may be difficult to evaluate due to adult respiratory disease syndrome (ARDS) or congestive heart failure, making the clinical diagnosis of pneumonia more difficult. The use of a computerized tomographic (CT) scan may provide
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improved imaging, but obtaining quality sputum samples for Gram stain and culture is of paramount importance. Finally, sputum may be produced spontaneously, induced by nebulized saline or obtained by bronchoscopy in the nonintubated patient or by endotracheal aspirates, bronchoscopy, or non-bronchoscopic methods in the intubated patient.
For mechanically ventilated ICU patients, there has been considerable controversy regarding the benefits and risks of clinical diagnosis, use of semiquantitative endotracheal aspirates, or use of quantitative diagnosis with either bronchoscopic bronchoalveolar lavage (B-BAL) or protective specimen brush (B-PSB) or “blind” non-bronchoscopic methods (NB-BAL or NB-PSB). The two diagnostic approaches for HAP discussed in detail in the recent American Thoracic Society (ATS)–Infectious Diseases Society of America (IDSA) Guideline are briefly summarized next [1].
Clinical-Semiquantitative Approach
The clinical diagnosis of pneumonia is defined as the presence of a new or progressive radiographic infiltrate plus at least 2 of 3 clinical features (fever >38°C, leukocytosis or leukopenia, and purulent secretions). While sensitivity for the presence of pneumonia is increased if only one criterion is used, specificity is reduced, leading to significantly increased antibiotic administration. Requiring all three clinical criteria is too insensitive, resulting in underprescribing for patients with HAP.
The clinical approach uses semiquantitative cultures of endotracheal aspirates or sputum with initial microscopic examination. Most microbiology laboratories report sputum culture results in a semiquantitative fashion, describing growth as light, moderate, or heavy. Moderate to heavy growth is most consistent with a diagnosis of HAP. It is rare that a sputum culture or tracheal aspirate culture does not contain a pathogen(s) found by invasive methods, but endotracheal aspirates consistently have more microorganisms than quantitative cultures (less specificity) (Table 31-2), frequently resulting in unnecessary treatment and excessive antibiotic use.
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TABLE 31-2 |
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Careful examination of a Gram stain is of critical importance to improve diagnostic accuracy, both quantifying polymorphonuclear leukocytes, macrophages, and squamous epithelial cells and looking at the morphology and staining of bacteria. Findings should then be correlated with culture results. Conversely, a negative tracheal aspirate (absence of bacteria or inflammatory cells) in a patient without a recent (within 72 hours) change in antibiotics has a strong negative predictive value (94%) for VAP. A reliably performed Gram stain of tracheal aspirates should reduce the incidence of inappropriate, initial empiric antibiotic therapy and may be helpful in monitoring response to treatment.
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Use of the clinical strategy for diagnosis allows prompt empiric therapy for all patients suspected of having HAP and prevents delays in initiating appropriate antibiotic therapy, which may increase mortality. Therapy can be modified or de-escalated based on clinical response at days 2 and 3 and on the results of semiquantitative cultures. Thus, the clinical approach is easy, inexpensive, and reduces delays in initiating therapy. The major limitation is overuse of antibiotics because semiquantitative cultures do not reliably separate pathogens from colonizers.
In an effort to improve the specificity of clinical diagnosis, Pugin et al. developed the clinical pulmonary infection score (CPIS), which combines clinical, radiographic, physiologic (Pao2/FiO2) and microbiologic data into a single numerical result [34]. When the CPIS score was >6, good correlation was found with the presence of pneumonia as defined by quantitative cultures of nonbronchoscopic BAL [50]. Singh et al. used a modified CPIS score that did not rely on culture data to guide clinical management [51]. Patients with a low clinical suspicion of VAP (CPIS ≤6) were randomized to therapy with ciprofloxacin compared to conventional therapy. The ciprofloxacin group had antibiotics discontinued after 3 days if there was no deterioration in their clinical status or CPIS score [51]. The modified CPIS score appears to be an objective measure to define patients who can receive shorter courses of therapy (3 days), achieving better overall outcomes.
Quantitative Approach
The bacteriologic approach uses quantitative cultures of lower respiratory secretions (endotracheal aspirates, BAL, or PSB collected with or without a bronchoscope) to define both the presence of HAP and the specific etiologic agent(s) [1,3]. Growth above the defined threshold concentration (moderate to heavy) is required to diagnose HAP/VAP whereas growth below the threshold is assumed to be due to colonization or contamination. The quantitative approach has been used to guide decisions about initiating antibiotic therapy, targeting specific pathogens, selecting antimicrobial therapy, and determining whether to continue therapy.
The quantitative approach avoids overtreatment with antibiotics by trying to delineate between colonizing and infecting pathogens. As a result, compared to the clinical approach, this method has consistently led to reduced numbers of bacteria treated, use of a narrower spectrum of antibiotics, and reduced numbers of patients treated [53]. For patients with negative cultures, a search for other diagnoses can be initiated. Furthermore, the use of quantitative measures may provide a better standard for comparison of VAP rates among hospitals.
The major limitations of the quantitative approach are that a false-negative culture can lead to a failure to treat and that the results may not always be consistent and reproducible [1]. A major factor causing false-negative quantitative cultures is recent initiation or a change in antibiotic therapy, especially in the preceding 24 hours but also up to 72 hours. Therefore, for BAL, the use of a threshold one log lower than usual may avoid some false-negative results in patients given antibiotics before culturing.
Finding a “Gold Standard”
A major problem with all studies of HAP is the absence of a “gold standard” to which diagnostic results can be compared. Some clinicians are concerned about the safety of withholding therapy in some patients until quantitative results are available [1,3,54]. Thus, most clinicians believe that patients with signs of infection, especially those who are clinically unstable, should receive early, appropriate, and adequate antibiotic therapy as outlined here.
To date, three randomized single-center studies have demonstrated no differences in mortality when invasive techniques (PSB and/or BAL) were compared to either quantitative or semiquantitative endotracheal aspirate culture techniques [1,54]. However, these studies included few patients, and antibiotics were continued in all patients, even those with negative cultures, thereby negating one of the potential advantages of the bacteriologic strategy. Several prospective studies have concluded that antibiotics can be safely stopped in patients with negative quantitative cultures with no adverse impact on mortality.
In one large, prospective, randomized trial of 413 patients with suspected VAP, patients receiving invasive management compared to those managed clinically had a lower mortality rate at day 14 (16% and 25%; p = 0.02, but not at day 28), lower mean sepsis-related organ failure assessment scores (p = 0.04), and significantly more antibiotic-free days (11 ± 9 vs. 7 ± 7; p < 0.001) [53]. Multivariate analysis demonstrated significantly reduced mortality (hazards ratio, 1.54 [CI, 1.10 to 2.16]; p = 0.01). Although a high percentage of patients received in both arms adequate initial antibiotics, more patients in the invasive group received adequate therapy than in the clinical group, and the impact of this difference on the observed mortality is of concern. This study suggests that the quantitative approach is safe, leads to less antibiotic use, and may potentially reduce mortality, but use of antibiotics was variable, and it is notable that approximately 10% of the patients managed with a quantitative strategy received antibiotic therapy regardless of bronchoscopic findings because of clinical instability or signs of sepsis.
On the contrary, a recent randomized study by the Canadian Critical Care Trials group compared quantitative and semi-quantitative techniques for diagnosing VAP in 740 patients who were randomized to specifically target antibiotic therapy [55]. Although there were many patients excluded from the study, including those with MRSA and P. aeruginosa colonization, the clinical outcomes in terms of length of stay in the hospital/ICU and the 28-day mortality were similar between the two groups.
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Currently, clinical signs of pneumonia (fever, leukocytosis and purulent sputum with the presence of more than 50% neutrophils on analysis of lower respiratory tract secretions and the presence of a new and persistent infiltrate on chest x-ray coupled with a pathogen having moderate to heavy growth on a semiquantitative culture of an endotracheal aspirate or quantitative BAL with >104 CFU/ml or protected specimen brush sample with >103 CFU/ml provides the most diagnostic sensitivity and specificity for VAP [50,52].
Antimicrobial Management using Early, Appropriate, and Adequate Initial Empiric Antibiotic Therapy
The 2005 ATS/IDSA Guidelines for the management of HAP are outlined in Figure 31-3 and Table 31-2 [1]. New principles of therapy include the use of initial empiric, broadspectrum antibiotic therapy that is likely effective against the infecting pathogen(s) and then de-escalating or streamlining therapy, and limiting the duration of therapy to 7 to 8 days [1].
Choosing an initial, appropriate intravenous antibiotic regimen depends on the likelihood of infection with MDR pathogens, such as P. aeruginosa, A. baumannii., ESBL+ K. pneumoniae, or MRSA (Figure 31-3). Risk factors for MDR pathogens include prior hospitalization, late onset infection, prior antibiotic therapy, chronic dialysis, residents of chronic care facilities, and immunocompromized patients.
Patients without MDR risk factors and early onset HAP or VAP usually can be treated with a more limited spectrum of antibiotics, such as ceftriaxone plus azithromycin, a third- or fourth-generation quinolone, such as levofloxacin or moxifloxacin or ampicillin-sulbactam (Table 31-3). Those with known risk factors for MDR pathogens often need broader initial antibiotic coverage. The selection of empiric antibiotics for MDR-pathogens may vary with the patient's risk factors, medical history, and the prevalence and types of endemic MDR-pathogens present in the healthcare facility or specific ICU. For example, patients with no known risk factors for MRSA or those in facilities with a low prevalence of MRSA may not require initial treatment with vancomycin or linezolid. It is important to use doses of antibiotics that will achieve adequate concentrations in the lung parenchyma that are outlined in the ATS/IDSA Guideline [1].
Assessing Clinical Response, Cultures, and Streamlining Therapy
While initial antibiotic coverage should be liberal and broad enough to cover all suspected pathogens, de-escalation or streamlining antibiotic therapy based on the patient's clinical response and microbiologic data is of critical importance to improve patient outcomes by minimizing unnecessary exposure to antibiotics (Figure 31-4) [1,51,56]. Patients without evidence of HAP or VAP, such as those without quantitative microbiologic evidence of infection, should have their antibiotics stopped, and if necessary, further workup and treatment for other sources of fever should be pursued.
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Figure 31-4 Approach to initial antibiotic therapy and management. Appropriate therapy is associated with improved outcomes in terms of morbidity and mortality. Adapted from American Thoracic Society & Infectious Diseases Society of America Guideline Committee. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. 2005;171:388–415. |
Limiting Duration of Therapy
In a recent randomized trial of patients with VAP, patients randomized to 8 days of antibiotic therapy had fewer recurrences and less resistance overall than those randomized to 15 days of therapy [58]. No significant differences were noted in mortality or clinical response parameters, but rates of recurrence for those patients with VAP due to P. aeruginosainfection were higher in the group treated for 8 rather than 15 days. The ATS/IDSA Guideline recommends 7–8 days of therapy for uncomplicated HAP or VAP with close follow-up for any signs of relapse, especially for patients with HAP or VAP due to P. aeruginosa (Figure 31-4) [1]. Evaluation of procalcitionin kinetics may be helpful in determining patients who may need further therapy [60].
Prevention
Detailed, evidence-based prevention measures are well summarized in the 2004 CDC (Healthcare Infection Control Prevention Advisory Committee [HICPAC]) and ATS/IDSA Guidelines, as well as several review articles and in Table 31-3 [1,2,61,62]. Unfortunately, prevention programs have often taken a back seat to diagnosis and treatment strategies. Prevention is cost effective, and use of a model team led by a champion is shown in Figure 31-5.
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Furthermore, some essential ingredients and evidence-based prevention strategies are shown in Table 31-3 and Figures 31-6 and 31-7.
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TABLE 31-3 |
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Figure 31-5 Possible “model” multidisciplinary team to formulate goals for prevention of HAP and VAP. Adapted from Craven DE. Preventing ventilator-associated pneumonia: Sowing seeds of change. Chest 2006;130:251–260. |
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Figure 31-6 Evidence-based hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) prevention program aimed at preventing infection and improving patient outcomes. Adapted from Craven DE. Preventing ventilator-associated pneumonia: Sowing seeds of change. Chest 2006;130:251–260. |
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Figure 31-7 Summary of risk-reduction strategies and their potential impact patient outcomes. |
General Prevention Strategies
Staff Education
Staff education is needed for all clinicians and staff who manage HAP and VAP. The ICU should be the cornerstone for initial efforts to reduce the incidence of VAP. Zack et al. initially reported a successful VAP educational prevention program carried out in five ICUs [63]. The program developed by a multidisciplinary team targeted respiratory care providers and ICU nurses who completed a self-study module on risk factors for VAP with evaluation both at baseline and after the program interventions. In-service teaching programs were coordinated with ICU staff meetings, and fact sheets and posters were placed in the ICU and Respiratory Care departments. Rates of VAP dropped nearly 58% to 5.7/1,000 ventilator days, and cost savings were estimated to be between $425,606 to >$4,000,000. Using an extension of this program in an Integrated Health Care System involving four hospitals, Babcock et al. reported a 46% reduction in VAP over an 18-month period [64].
Staffing Levels
Perhaps one of the most important and underappreciated prevention strategies is adequate staffing, particularly in ICUs [2,65]. Staffing must be sufficient to allow patient care to be provided while ensuring that staff are able to comply with essential infection control practices and other prevention strategies [64,66].
In a study of abdominal aortic surgery patients by Dang et al., decreased nursing staff was associated with significantly higher rates of respiratory and cardiac complications than in patients who had higher intensity nursing care [67]. Currently, this is of critical importance due to severe nursing shortages and staffing reductions because of budget constraints. Nurse-to-patient ratios should be 1:1 for high-risk, complicated ICU patients or 2:1 for patients with lower disease acuity. Currently, efforts to establish legislation that would cap the number of patients per nurse are underway in some states.
Infection Control
Effective targeted surveillance for high-risk patients coupled with staff education, the use of proper isolation techniques, and effective infection control practices are cornerstones for prevention of HAP [2,4,66]. Previous studies have indicated
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that hospitals with effective surveillance and infection control programs have rates of pneumonia 20% lower than hospitals without such programs (see Chapters 3, 5).
Infection control programs have repeatedly demonstrated efficacy in reducing infection and colonization due to MDR-organisms [2,28,65,68,69,70]. Unfortunately, staff compliance with proven infection control measures, such as hand hygiene, remains inconsistent in many hospitals. Thus, staff education on infection control must be inclusive, frequent, and reiterative. Special attention should be directed toward house staff, students, volunteers, and visitors, and compliance should be monitored periodically.
Surveillance of ICU infections to identify and quantify endemic and new MDR-organisms with timely feedback of data is critical [7,59,68,71,72]. Timely communication of current data among clinicians, laboratory, pharmacy, and infection control staff is essential. Organism-specific strategies for specific MDR-pathogens may be appropriate. For MRSA, VISA (or GISA) isolates, active surveillance cultures and isolation are recommended along with more aggressive eradication methods [38,40,73].
Cross-colonization and cross-infection are important mechanisms in the pathogenesis of HAI [2,4,68] (Figure 31-1). Gram-negative bacilli and S. aureus often are present in high concentrations as indigenous flora in critically ill patients, the hospital environment, and on the hands or gloves of hospital personnel [4,74]. Hand washing before and after patient contact is an effective means of removing transient bacteria, but because of the inadequacy of hand-washing practices among hospital personnel, some investigators have advocated the use of barrier precautions (gloves and gowns) for contact with all patients. This practice has been associated with significantly decreased HAI rates in pediatric ICUs [1]. If gloves are used, care must be taken to change them between patients.
Nasal carriage of S. aureus is common among healthcare workers (HCWs), and outbreaks are often associated with HCWs with dermatitis or nasal or rectal colonization [2]. Bassetti et al. emphasize the importance of viral respiratory tract infections in the transfer of airborne MRSA from a physician to patients in an ICU [75]. Molecular typing was performed to confirm the source of the outbreak, and experimental induction of rhinovirus infection and its role in airborne dispersion of bacteria was demonstrated (the “cloud adult”). Without the use of surgical masks, the dispersal of S. aureus increased transmission 40-fold. These data underscore the importance of upper respiratory tract infection in the dissemination ofS. aureus and the importance of masks in preventing transmission.
Antibiotic Stewardship Strategies
Antibiotic stewardship programs play an extremely important role in the overall effort to control healthcare-associated infections, reduce emergence of MDR-organisms, and control spiraling healthcare costs. For example, reduced use of fluoroquinolones has been associated with reduced rates of MRSA infection [47]. Antibiotic stewardship is complex and should be focused, dynamic, and carefully monitored and may vary by type of MDR-pathogen. For example, control of specific types of MDR Gram-negative bacilli may require “squeezing the balloon at multiple sites” to prevent the emergence of other MDR-pathogens, as nicely summarized by Rahal et al [22,76]. Adding an infectious disease pharmacist to the ICU team or a computerized decision support program to optimize drug regimens should be considered [1,2].
Data from antibiotic cycling or rotation programs are difficult to evaluate, but this approach has been advocated by some for reducing MDR-pathogens [1,76,77,78,79]. In theory, a class of antibiotics or a specific antibiotic is withdrawn from use for a defined time period and re-introduced at a later point in time in an attempt to limit bacterial resistance to the cycled antimicrobial agents.
When outbreaks of infection with a specific strain of resistant bacteria have occurred, restricted access to specific antibiotics has successfully managed the problem with generally no impact on the overall frequency of resistance. However, if disproportionate use of another antibiotic results, resistance rates may be affected. Rahal et al. restricted use of third-generation cephalosporins to combat an outbreak of ESBL (+) Klebsiella infections [76]. Restriction of cephalosporins was accompanied by a 44% reduction in infection and colonization with the ESBL (+) Klebsiella. However, the use of imipenem increased by 140% during the intervention year and was associated with a 69% increase in the incidence of imipenem-resistant P. aeruginosa throughout the medical center. The clinical impact of shifting resistance from one pathogen to another was not assessed.
Gerding et al. evaluated cycling of aminoglycosides over 10 years at the Minneapolis Veterans Affairs Medical Center, cycling amikacin and gentamicin. Using cycle times of 12 to 51 months, these investigators found significantly reduced resistance to gentamicin when amikacin was used [80]. Gentamicin resistance recurred with the rapid re-introduction of gentamicin while subsequent more gradual re-introduction of gentamicin occurred without increased levels of resistance. This experience suggests that cycling antibiotics within the same drug class in some circumstances could be an effective strategy for curbing antimicrobial resistance.
Gruson et al. observed a reduction in the incidence of VAP after introducing an antimicrobial program that consisted of supervised rotation and restricted use of ceftazidime and ciprofloxacin [81]. The antibiotic selection was based on monthly reviews of the pathogens isolated from the ICU and their antibiotic susceptibility patterns. The decreased incidence of VAP was primarily due to a reduction in the number of episodes attributed to antibiotic-resistant jGram-negative bacteria including P. aeruginosa, B. cepacia, S. maltophilia, andA. baumanii, which was sustained over a 5-year time period [82].
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Environmental Issues
MDR bacteria are commonly found in the environment (Figure 31-1) [38,66]. Although it is widely appreciated that the environment is swarming with microorganisms, this does not necessarily directly result in infection; therefore, widespread routine environmental sampling is not recommended. For example, despite studies showing that Legionella spp. can be recovered from 12–70% of hospital water systems, this source of nosocomial outbreaks remains underappreciated [49].
Studies are beginning to implicate the inanimate environment as an indirect contributor to pathogen acquisition [66]. Special interventions, including targeted environmental sampling and more aggressive environmental disinfection, may be indicated during outbreaks, particularly those involving MDR-organisms or organisms that are more resistant to routine cleaning [74].
Modifiable Risk Factors
Risk factors for the development of HAP can be differentiated into modifiable and nonmodifiable conditions. Some modifiable strategies that are feasible, effective, and cost effective have been recommended and are discussed here.
Aspiration, the primary route of bacterial entry into the lung, is commonly increased during hospitalization, with sedation, neuromuscular blockers, head trauma, intubation, enteral feeding, and following surgery [2,83,84,85,86,87]. Supine patient positioning may facilitate aspiration, which can be decreased by maintaining a semirecumbent patient position. With the use of radioactive-labeled enteral feeding, cumulative numbers of endotracheal radioactivity counts were higher when patients were placed in a completely supine position (0°) as compared to a semirecumbent position (45°) [88,89]. One randomized trial demonstrated a threefold reduction in the incidence of ICU-acquired VAP in patients kept in a semirecumbent position vs. supine [90]. VAP rates reached 50% in patients maintained in the supine position while receiving enteral nutrition. These data support maintaining patients in semirecumbent positions, particularly during enteral feeding. In contrast to rotational beds, semirecumbent patient position is a low-cost, easily accessible intervention and may be a more practical and more tolerable approach than rotational beds or prone body position [91,92].
Maintaining mechanically ventilated and/or enterally fed patients in a 30° to 45° semirecumbent position, particularly during enteral feeding, continues to be strongly recommended [1,2,90]. However, recent studies have not only questioned the results of previous studies but also suggested that maintaining semiupright patient position may not be practical, at least at the levels currently recommended. A study by van Nieuwenhoven et al. in which mechanically ventilated patients were randomly assigned to backrest elevation of 45° vs. the standard of 10° demonstrated barriers to implementing this strategy [93]. Backrest elevation was measured continuously during the first week of ventilation with a monitoring device. The targeted backrest elevation of 45° was not reached; the actual achieved difference was 28° vs. 10°, which did not reduce VAP. Similarly, Grap et al. monitored patient position in ICU patients using a bed frame elevation gauge or electronic bed readout and found very low compliance with maintaining semirecumbent patient position with a mean backrest elevation of only 19.2° with 70% of subjects maintained in a supine position [94,95]. Perhaps further studies measuring the impact of maintaining ventilated and/or enterally fed patients in a semirecumbent position may needed to evaluate more attainable targets. Until this issue is resolved, prevention guidelines recommend elevating the head of the bed for ventilated and/or enterally fed patients.
Enteral Feeding Issues
Enteral nutrition has been considered a risk factor for the development of HAP, mainly secondary to the increased risk of aspiration of gastric contents [2,96]. Parenteral nutrition is associated with a higher risk of intravascular-device associated infection, complications from central venous catheter insertion, higher costs, and loss of intestinal villous architecture, which may facilitate enteral microbial translocation. Some have advised feeding critically ill patients enterally as early as possible, but early (day 1 of intubation and ventilation) enteral feeding was associated with a higher risk of VAP when compared to later enteral feeding (day 5 of intubation) [97].
Seven studies have evaluated the risks for ICU-acquired HAP in patients randomized to either gastric or postpyloric feeding [98]. Although significant differences were not demonstrated in any individual study, a meta-analysis demonstrated that postpyloric feeding was associated with a significant reduction in ICU-acquired HAP (relative risk = 0.76, 95% confidence interval 0.59 to 0.99) [99].
Accurate assessment of the patient's nutritional status and the use of enteral feeding, rather than parenteral nutrition, appear to reduce the risk of HAP [2,98]. Early initiation of enteral feeding may help maintain the gastrointestinal epithelium and prevent bacterial translocation, but it is not without risk. Because enteral feedings can be contaminated during preparation, we recommend the routine use of aseptic technique and sterile water for their preparation and for nasogastric tube flushes because we are concerned that tap water may be a source of legionellae and other nosocomial Gram-negative bacilli (see section on Legionella pneumophila) [2,49].
Enteral feeding protocols have been suggested to reduce complications [65,100]. Bowman et al. instituted an evidence-based, enteral feeding protocol in which 78–85% of patients reached their enteral feeding goal. Aspiration pneumonia rates decreased from 6.8 to 3.2/1,000 patient-days [100]. Such protocols should be reviewed by
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multidisciplinary committees to standardize enteral nutrition protocols and risk reduction for VAP.
Early gastrostomy for enteral feedings has been suggested as a strategy to reduce VAP in patients with head injury and stroke [101]. In a small, randomized clinical trial of 20 patients with gastrostomy vs. 21 controls, rates of VAP were reduced (10% vs. 38%, respectively) and most of the VAP episodes were late onset VAP (>5 days). Additional studies with higher enrollment are needed to further assess this strategy in these high-risk patients.
Modulation of Bacterial Colonizaton
Oral Care
Oral care has been studied and recommended to prevent VAP [102,103,104,105]. In a recent study, Mori et al. compared rates of VAP in a nonrandomized group compared to historic controls [106]. The incidence of VAP in the oral care group was 3.9 episodes/1,000 days vs. 10.4 in the control group. Although there are concerns about the study design, oral care has intuitive benefits and limited cost, but more randomized controlled studies are needed.
Antibiotic Prophylaxis with Selective Decontamination of the Digestive Tract (SDD)
Modulation of oropharyngeal colonization by combinations of oral antibiotics, with or without systemic therapy (selective decontamination of the digestive tract) also is effective in significantly reducing the frequency of HAP, although the methodologic study quality, specific regimens used, study populations, and clinical impact differ widely among studies [1,2,14,102,107,108].
In two recently published prospective randomized trials, SDD was associated with a higher ICU survival among patients [109,110]. In the first study, a subpgroup of patients with a mid-range acute physiology and chronic health evaluation (APACHE) II score on admission had a lower ICU mortality, although ICU mortality rates of all included patients did not differ significantly [109]. In the largest study performed so far, SDD administered to 466 patients in one unit was associated with relative risk for ICU mortality of 0.65 and of hospital mortality of 0.78 when compared to 472 patients admitted in a control ward [110]. In addition, infections due to antibiotic-resistant microorganisms occurred more frequently in the control ward. Importantly, levels of antibiotic-resistant pathogens were low in both wards with complete absence of MRSA. Moreover, a small pre-existing difference in outcome between two wards and the absence of a crossover design warrant confirmation of these beneficial effects of SDD.
In two meta-analyses and one additional study, decreased mortality was demonstrated in critically ill surgical patients receiving SDD, including both systemic and local prophylactic antibiotics [107,109,111], raising questions about the relative importance of systemic rather than nonabsorbed antibiotics.
The preventive effects of SDD for HAP and VAP also have been considerably lower in ICUs with high endemic levels of MDR-pathogens [2]. Although SDD reduces HAP, routine prophylactic use of antibiotics should be undertaken cautiously, especially in hospital settings where there are high levels of antibiotic resistance [112,113].
Moreover, antibiotics clearly predispose patients to subsequent colonization and infection with antibiotic-resistant pathogens [30,114]. In contrast, prior antibiotic exposure conferred protection (risk ratio 0.37, 95% CI 0.27–0.51) for ICU-acquired HAP in another study [6]. Preventive effects of intravenous antibiotics were evaluated in only one randomized trial: administration of cefuroxime for 24 hours at the time of intubation, which reduced the incidence of early onset HAP in patients with closed head injury [115]. The role of the gastrointestinal tract in the pathogenesis of VAP and the clinical evidence for the efficacy of SDD were recently reviewed by Kallet and Quinn [116] and in a Cochrane review by Liberati et al. [107]. In the latter study, the authors conclude that for topical and systemic antibiotic prophylaxis, 5 patients would need to be treated to prevent one infection, and 21 patients would need to be treated to prevent one death. No recommendation was made for topical prophylaxis. In a recent large study of SDD by de Jonge et al in 2003, SDD was highly effective in preventing pneumonia without an increase in antibiotic resistance [110]. However, citing concerns over rapid increases in antimicrobial resistance in the hospital setting coupled with the association between MDR-pathogens and poorer patient outcomes, recent guidelines have suggested that SDD should be considered for selected ICU populations and in targeted clinical scenarios but not employed “routinely” for VAP prevention [1,2,112].
Antiseptics
Oropharyngeal colonization is the primary source of pathogens causing HAP and VAP, and thus reducing levels of colonization or eliminating potential pathogens is an obvious risk reduction strategy. In a randomized trial, DeRiso et al. demonstrated that the use of the oral antiseptic chlorhexidine (CHX) significantly reduced rates of HAI in patients undergoing coronary artery bypass graft surgery [117]. Athough topical antiseptics, such as CHX, provide an attractive alternative to antibiotics, the initial reported success in cardiac surgery patients could not be confirmed by other studies. A recent study by Koeman et al. provides important data from a multicenter, double-blind, randomized, clinical trial of VAP outcomes for subjects treated with 2% CHX paste vs. patients randomized to 2% CHX + 2% colistin (COL) paste to provide more activity against Gram-negative bacilli compared to placebo [118]. Compared to the placebo group, the daily risk of VAP was
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reduced by 65% in the CHX group (p = 0.01) and 55% in the CHX-COL group (p < 0.03). This impressive result for an inexpensive, nontoxic, topically applied modality warrants further attention but is difficult to reconcile with the absence of effect on ventilator-days, length of stay, or mortality. It is important to measure how prophylactic use of CHX and CHX-COL complement other effective prevention strategies, and resistance could become an important issue over time.
Colonization Blockers—Protegrins
Iseganan, a topical antimicrobial peptide active against aerobic and anaerobic Gram-positive and Gram-negative bacteria and yeasts, was evaluated in a randomized, double-blind trial to prevent VAP [119]. Although there was a significant reduction in colonization in the treatment group, the rates of VAP among survivors (16% vs. 20%) and 14-day mortality were similar (22% vs. 18%). Although protegrins are ubiquitous antimicrobial peptides and in human trials were able to reduce oral colonization by two logs, these results raise several questions about iseganan efficacy and why it failed.
Probiotics—Lactobacillus GG (LGG)
Interesting data from a double-blind pilot study of subjects randomized to oral and gastric LGG (2 × 109 colony forming units twice daily) (n = 19) versus placebo (n = 21) were presented by Morrow et al. at the 2005 American Thoracic Society Annual Meeting Symposium [120]. Demographics and APACHE II scores were similar in the two groups, but the LGG group had significantly higher rates of colonization with normal flora (p < 0.03), fewer oral pathogens, less clinical VAP (26% vs. 45%. p = 0.20), lower microscopic VAP (11% vs. 33%, p= 0.08), and a lower mortality rate (0% vs. 10%, p = 0.17). Further studies are in progress.
Mechanical Ventilation and Associated Devices
Several devices have been identified as risk factors for HAP. Many of these devices are used in mechanically ventilated patients and increase the risk of VAP; intervention strategies are summarized in several review articles and in Table 31-3 [1,2,121].
Noninvasive Positive Pressure Ventilation (NPPV)
NPPV provides ventilatory support without the need for intubation and for earlier removal of the endotracheal tube to reduce complications related to prolonged intubation. NPPV using a face mask is an attractive alternative for patients with acute exacerbations with chronic obstructive pulmonary disease (COPD), acute hypoxemic respiratory failure, for some immunosuppressed patients with pulmonary infiltrates and respiratory failure [1,2]. In a recent Cochrane review, Burns et al reported significant benefits: decreased mortality (RR 0.41, 95% CI 0.22–0.76), lower rates of VAP (RR 0.28, 95% CI 0.90 to 0.85), decreased length of ICU and shorter hospital stays, and lower duration of mechanical support [122]. The impact of NPPV is greater in patients with COPD exacerbations or congestive heart failure than for patients with VAP. Recent data also indicate that NPPV may not be a good strategy to avoid re-intubation after initial extubation and is recommended for hospitals with staff who are experienced in this technique [123].
Ventilator Management: Sedation and Weaning
Attention to the specific type of endotracheal tube, its maintenance, and the site of insertion also may be valuable. The use of oral endotracheal and orogastric tubes rather than nasotracheal or nasogastric tubes can reduce the frequency of nosocomial sinusitis and possibly HAP, although causality between sinusitis and HAP has not been firmly established [124]. Efforts to reduce the likelihood of aspiration of oropharyngeal bacteria around the endotracheal tube cuff into the lower respiratory tract include limiting the use of sedative and paralytic agents that depress cough and other host protective mechanisms and maintaining endotracheal cuff pressure at >20 cm H2O [125]. Re-intubation should be avoided, if possible, because it increases the risk of VAP [126]. Efforts to reduce acute lung injury by using smaller tidal volumes and lower pressures have been suggested [127].
Other strategies to reduce the duration of mechanical ventilation include improved methods of sedation and the use of protocols to facilitate and accelerate weaning [2,128,129,130]. These interventions clearly depend on adequate ICU staffing [131,132]. Dries et al., using a standardized weaning protocol, reduced the proportion of days of mechanical ventilation (total ICU days) from 0.47% to 0.33%, number of patients failing extubation (25 vs. 43), and rates of VAP (15% to 5%) [133]. Schweickert et al. evaluated seven complications in 128 patients receiving mechanical ventilation and continuous infusions of sedative drug who were randomized to daily interruption of sedative infusions (N = 66) vs. sedation directed by the MICU team without this strategy (N = 60) [49,128]. Daily interrupted sedative infusions reduced ICU length of stay (6.2 days vs. 9.9, p < 0.01), duration of mechanical ventilation (4.8 vs. 7.3 days, p < 0.003) and the incidence of complications per patient (13/12 patients vs. 26/19 patients, p < 0.04).
Subglottic Secretion Drainage
Continuous aspiration of subglottic secretions (CASS) through the use of especially designed endotracheal
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tubes with a wider, elliptic hole helps facilitate drainage (Figure 31-3) and has significantly reduced the incidence of early onset VAP in several studies [1,2], In a recent metaanalysis, CASS reduced the incidence of VAP by half (risk ratio 0.51, 95% CI 1.7 to 2.3), shortened ICU stay by 3 days (95% CI 2.1 to 3.9), and delayed the onset of VAP by 6 days. CASS also was cost effective saving $4,992/episode of VAP prevented or $1,872/patient, but mortality was not affected [134]. However, when CASS was combined with semirecumbent positioning, no clinical benefit was observed, underscoring the importance of interactive prevention strategies [135].
Ventilator Circuits, Condensate and Heat Moisture Exchangers
VAP also may be related to colonization of the ventilator circuit tubing (Figure 31-8) [136]. Frequency of circuit changes do not prevent VAP, an area for substantial cost savings [120,137]. Condensate collecting in the ventilator circuit can become contaminated from patient secretions or by opening the circuit; vigilance is needed to prevent inadvertently flushing the condensate into the lower airway or in-line nebulizers at the bedside and during patient transport [136,138]. Furthermore, metered dose inhalers (MDI) may be safer for the delivery of bronchodilators than nebulizers, which, if contaminated, may produce bacterial aerosols [17]. In addition, high-level disinfection of tubing temperature sensors is recommended to prevent cross-contamination between patients [2].
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Figure 31-8 Mechanically ventilated patient in the upright position. Humidified air is carried through the inspiratory tubing to the patient's lower respiratory tract. Contaminated condensate may form in the ventilator circuit and should not be allowed to relux into the patient's endotracheal tube. Use of a heat–moisture exchanger (HME) eliminates humidifier and circuit condensate. Adapted from Craven DE, Steger KA. Hospital-acquired pneumonia: perspective for the epidemiologist. Infect Control Hosp Epidemiol 1997;18:783–795, with permission. |
There have been conflicting reports on the use and benefits of heat moisture exchangers (HME) compared to heated humidifiers for preventing VAP [2,137]. Heat moisture exchangers reduce the risk of contaminated condensate entering the lower airway but may not provide sufficient humidity or may become occluded by secretions in some patients. A recent meta-analysis by Kola et al. demonstrated a reduction in the relative risk of developing VAP in the HME group (relative risk 0.7) but may have been affected by the large difference in outcomes in one of the studies [139]. For patients with a mean ventilation of >7 days, the relative risk for VAP fell to 0.57 in the HME group (95% CI = 0.38–0.83). A more recent, large, randomized study by Lacherade et al. found no benefit for the HME group. In another study of HMEs using historic controls, patients who were ventilated >2 days reported a significant reduction in VAP (p = 0.01) [140].
Bronchoscopy
Mechanically ventilated patients may undergo bronchoscopy for diagnostic purposes or for removal of mucus plugs or excessive secretions. In one study, bronchoscopy was identified as a risk factor for HAP [2]. This could be related to several factors, including the use of large volumes of BAL that impede the host's removal of bacteria in the lower airway and the introduction of HAI pathogens into the lower airway by releasing bacteria encased in biofilm on the endotracheal tube. As discussed previously, when bacteria encased in biofilm embolize to different areas of the lung, they may be particularly difficult for host defenses to clear effectively. Although these pathogenic mechanisms are hypothetical, they are of concern.
Miscellaneous Strategies
Intensive Insulin Therapy
Hyperglycemia, relative insulin deficiency, or both may directly or indirectly increase the risk of complications and
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poor outcomes in critically ill patients. Van den Berghe et al. randomized surgical ICU patients to receive either intensive insulin therapy to maintain blood glucose levels between 80 and 110 mg per deciliter or to receive conventional treatment [141]. The group receiving intensive insulin therapy had reduced mortality (4.6% vs. 8%, p < 0.04), and the difference was greater in patients who remained in the ICU >5 days (10.6% vs. 20.2%, p = 0.005). When compared to the control group, those treated with intensive insulin therapy had a 46% reduction of bloodstream infections, 41% decreased frequency of acute renal failure requiring dialysis, fewer antibiotic treatment days, and significantly shorter length of mechanical ventilation and ICU stay. While the same degree of benefit may not be seen in VAP as in other populations, aggressive treatment of hyperglycemia has both theoretical and clinical support for SICU patients.
For each prevention strategy, it is critical to assess the risk-benefit ratio. Using a retrospective outcome study, Egi et al. reported that hypoglycemia in surgical ICU patients receiving intensive insulin therapy varied from 1.4–2.7% and estimated that the number of patients needed to be treated to save one life varied from 38 to 113, whereas the rate of hypoglycemia (number needed to harm) varied from 7 to 13 patients [142].
A recent study of intensive insulin therapy in 1,200 medical ICU patients did not significantly reduce overall hospital mortality and actually increased mortality in patients with ICU stays <3 days [143]. However, the intensive insulin therapy group had reduced acquired renal failure, duration of mechanical ventilation, and length of ICU and hospital stay. Unfortunately, predicting length of stay is difficult; coupled with concerns about the risks of hypoglycemia and with increased resource implications, the benefit of intensive insulin therapy for specific hospital or MICU patients will require further evaluation.
Stress Bleeding Prophylaxis
Histamine type 2 (H2)-antagonists and antacids have been identified as independent risk factors for ICU-acquired HAP. Sucralfate has been used for stress bleeding prophylaxis because it does not increase intragastric acidity or gastric volume but is less effective in preventing gastrointestinal bleeding [1,2]. Numerous randomized trials using different doses and various study populations have provided controversial results on the benefits of specific stress bleeding prophylaxis agents in relation to the increased risk of VAP and bleeding [20,144]. One large randomized trial comparing antacids, H2 blockers, and sucralfate reported no differences in rates of early onset VAP, but rates of late onset VAP were lower in patients treated with sucralfate [20]. More recently, Bornstain et al. examined risk factors for early onset VAP (from 3–7 days) in 747 patients [145]. Several different variables were identified in the univariate analysis, but only sucralfate used in the first 48 hours of ICU stay and unplanned extubation were predictors of VAP in the multivariate analysis, and antibiotics were protective. In an earlier multicenter study of VAP in patients with ARDS, sucralfate and duration of exposure to sucralfate were associated with an increased risk of VAP [146].
A recent, large, double-blind, randomized trial comparing ranitidine to sucralfate demonstrated a trend toward lower rates of VAP with sucralfate, but clinically significant gastrointestinal bleeding was 4% higher in the sucralfate group [144]. Data indicate that H2 blockers and protein pump inhibitors are associated with lower rates of gastrointestinal bleeding when compared to sucralfate, which may be doubly important because transfusion also is a possible risk factor for VAP.
Transfusion Risk
A landmark prospective randomized trial comparing liberal and conservative “triggers” to transfusion in ICU patients not exhibiting active bleeding and without underlying cardiac disease demonstrated that awaiting a hemoglobin level of 7.0 g per deciliter as opposed to a level of 9.0 g per deciliter for initiating transfusion resulted in fewer transfusions and no adverse effects on outcome [147]. In fact, in those patients less severely ill, as judged by low APACHE II scores, mortality was improved in the “restricted transfusion” group, a result thought to be related to immunosuppressive effects of non-leukocyte depleted red blood cell units with a consequent increased risk of infection. Multiple studies have identified exposure to allogeneic blood products as a risk factor for postoperative infection and postoperative pneumonia, and the length of time of blood storage was another factor modulating risk [1]. In one prospective randomized control trial, the use of leukocyte-depleted red blood cell transfusions resulted in a lower incidence of postoperative infections and specifically a reduced incidence of pneumonia in patients undergoing colorectal surgery [148]. Routine red blood cell transfusion should therefore be conducted with a restricted transfusion trigger policy. Whether leukocyte-depleted red blood cell transfusions will further reduce the incidence of pneumonia in broad populations of patients at risk remains to be determined.
Supporting data were reported in a secondary analysis from a recent, large study of transfusions in which transfusion was identified as an independent risk factor for VAP [149]. These data suggest that transfusion may be a more important modifiable risk factor than previously appreciated. Furthermore, a recent study by Levy et al. reported that mechanically ventilated patients received transfusions at a higher pretransfusion hemoglobin level than nonventilated patients (8.7 vs. 8.2, p < .0001) [150].
Secondary Prevention Strategies at Discharge
The focus of prevention has been on ICU patients while in the ICU, but these patients are also at increased risk for relapse or re-infection during their rehabilitation. Therefore, efforts should be directed at risk reduction
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at discharge, such as routine vaccinations and patient education aimed at health promotion, such as smoking cessation, exercise, and weight control (Table 31-3).
Translating Prevention Guidelines into Practice Barriers
Prevention efforts for HAP should be evidence based and cost effective (Table 31-3) [1,2,61,151]. It may be more prudent to focus initially on a limited number of feasible, cost-effective strategies as suggested by the Institute for Healthcare Improvement (IHI) 100,000 Lives Campaign. IHI has challenged hospitals to adopt a series of measures to reduce HAIs [151]. The VAP or “ventilator bundle” initiative includes five components: elevation of the head of the bed to between 30° and 45°, daily “sedation vacation,” daily assessment for readiness to extubate, and prophylaxis for peptic ulcer disease and deep vein thrombosis and oral care. Some of the participating hospitals using this approach have reported no episodes of VAP over sustained periods of time [Donald Berwick, IHI National Forum, December 13, 2005]. Peer-reviewed publications of these dramatic results are needed. However, IHI's principles and approach have been major forces for stimulating interest and drawing national attention to HAIs and the need to place more emphasis on prevention.
Multidisciplinary Team Approach
Prevention efforts targeting VAP must be part of an evidence-based, multidisciplinary prevention program that has a “core” team with an agenda focused on patient safety and quality improvement (Figures 31-5 and 31-6) [61]. Optimally, the team should be led by a “champion” of the cause and include interested clinicians, respiratory care staff, administrators, risk management staff, and other stakeholders as “core” team members (Figure 31-5). This group's responsibilities include setting prevention benchmarks, establishing goals and timelines, providing appropriate education and training, and performing audits with feedback to the staff, all while continually updating themselves on the relevant clinical and prevention strategies (Figures 31-6 and 31-7). Prevention programs should be “marketed” to hospital administrators and others involved in resource allocation by demonstrating that preventing VAP results in improved clinical outcomes and significantly reduced costs.
Summary
Despite rapid technologic and treatment advances in medicine, dramatic reductions in rates of VAP, and effective use of complex prevention and management guidelines remain elusive [1,2]. Prevention outcomes are directly related to reducing risk in the areas suggested in Figure 31-7 and Table 31-4. Investing in prevention can pay great dividends in improved quality of life and reduced morbidity and mortality [61]. In addition, prevention can have a huge impact in reducing length of hospital stay and healthcare costs during acute care. Spreading the seeds of prevention into chronic care and rehabilitation facilities also is vitally needed in our increasing diversity of healthcare settings.
As described in a recent commentary by Berwick et al, the laudable goal set forth by the IHI to reduce deaths among hospitalized patients in the United States by 100,000 over 18 months through improving patient quality and safety set a very high bar [151]. Each of the six 100,000 Lives Campaign interventions that include VAP prevention is conceptually simple and feasible. Notably, each strategy included in the “VAP bundle” is not new or expensive.
The IHI's 100,000 Lives Campaign may be the call to action that is needed to disseminate prevention and safety information and to implement prevention guidelines consistently and broadly [151]. Preliminary data suggest that the campaign exceeded its goal by saving 122,000 lives and enrolled more than half of the nation's hospitals in this effort. This campaign provides a valuable infrastructure for sowing and disseminating seeds that will grow into trees and for measuring outcomes. This infrastructure coupled with endorsements of government agencies, such as Joint Commission on Accreditation of Healthcare Organizations (JCAHO) and Medicare, as well as medical, nursing, and public health groups translates into powerful lobby for the advancement of patient safety and quality care, and for obtaining the necessary resources to incorporate prevention into practice [152].
References
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