Didier Pittet
Stephan J. Harbarth
The care of critically ill patients in specialized high-technology units is a primary component of modern medicine, although the efficacy and long-term benefit of critical care has been established for only a few conditions. Invasive diagnostic and therapeutic procedures are essential for the diagnosis and treatment of critically ill patients. However, life support systems often disrupt normal host defense mechanisms, affecting patients with already impaired immune response. Given the severity of the illnesses affecting patients in intensive care units (ICUs), it is not surprising that mortality rates can exceed 25%. In addition, more than one-third of the patients admitted to ICUs experience unexpected complications of medical care [1]. Healthcare-associated infection (HAI) is one of the most common medical complications affecting ICU patients. Although ICUs make up only 5–10% of hospital beds, infections acquired in these units account for >20% of HAIs [2,3,4]. Fortunately, systematic studies of the determinants of HAIs, HAI surveillance, and adherence to protocols for preventing HAIs have been effective in reducing the risk for patients admitted to ICUs.
ICU-Acquired HAIs
Pathogenesis
The dynamics of ICU-acquired HAIs are complex and depend on the contribution of the host's underlying conditions, the infectious agents, and the unique environment of the ICU. The following discussion considers the role of each component in the development of HAIs.
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Host Defenses
The ability of patients in ICUs to ward off infections is seriously compromised. Natural host defense mechanisms may be impaired by underlying diseases or as a result of medical or surgical interventions. All patients admitted to an ICU will have at least one, often several, indwelling devices that break the normal skin barriers and establish direct access between the external environment and normally sterile body sites. Natural chemical barriers in the stomach are neutralized by administering H2-blockers or antacids that reduce acidity and allow growth of enteric flora. Physiologic mechanisms for evacuating and cleansing hollow organs are disrupted and circumvented by insertion of endotracheal tubes, nasogastric tubes, or urinary catheters.
Specific host defense mechanisms also may be impaired by the underlying diseases. Patients with malignant disorders may have abnormal immune responses as a result of their disease or from therapies that diminish the number of effective phagocyte cells and blunt the normal immune response. ICU patients who are at the extremes of age exhibit selected impairments in natural and specific defense mechanisms that increase the HAI risk [5,6].
Because of the precarious condition of ICU patients, normal food intake often is suspended, leading to under- or malnutrition [7]. Injured tissue, perfusion deficits, and infection cause fever and tachycardia through mechanisms mediated by hormones and cytokines, such as endotoxin. The physiologic response to these mediators is an increase in oxygen consumption stemming from an increase in metabolic demand. This response results in breakdown of muscle to meet the body's demand for energy. The lean body mass declines, resulting in deficits in substrates necessary for recovery [8].
Although its clinical significance in hospitals is not well established, malnutrition has been associated with increased complication rates and delayed wound healing [9,10]. Several studies suggest that poor nutritional status is a predisposing factor for HAIs [11,12,13]. Recent studies have confirmed that the use of enteral nutrition vs. total parenteral nutrition (TPN), early initiation of enteral nutrition, and use of enteral and parenteral glutamine and intensive insulin therapy are all associated with reduced infectious morbidity in critically ill patients [14,15,16]. For instance, early or glutamine-enriched enteral nutrition in critically ill patients has been reported to decrease HAIs and other complications [17,18]. Conversely, a meta-analysis including 26 studies that examined the relationship between TPN and mortality rates in critically ill patients showed that TPN had no effect on mortality and only lowered complication rates in malnourished patients [19]. In a meta-analysis of trials comparing enteral nutrition to TPN in ICU patients, Simpson et al. reported that TPN was associated with an increase in infectious complications (odds ratio [OR] = 1.47; 95% confidence intervals [CI] = 0.90 to 2.38) [20].
Important alterations in T- and B-cell function affecting host defense and resistance to infection are found in critically ill and traumatized patients [21]. Alterations in T-cell activation and cytokine production are frequently associated with trauma and hemorrhage. Injury and blood loss result in activation of CD8 T-cell populations capable of altering bacterial antigen-specific B-cell repertoires and suppressing the function of other T-cells.
Systemic hypoxia and hypovolemia also are significant contributors to the development of infection. However, significant changes in perioperative care have been suggested in recent years [22,23]. The maintenance or restoration of normal physiologic characteristics after surgery becomes the key to preventing complications [24].
Medical Devices
The results of the European Prevalence of Infection in Intensive Care (EPIC) study [25] highlighted the relative importance of medical devices as risk factors for HAIs compared with other factors. Factors were collected from >10,000 ICU patients, of whom 2,064 had ICU-acquired HAIs. Among the seven independent risk factors identified, four were associated with medical devices commonly used in ICUs: central venous catheters (CVC) (OR = 1.35, 95% CI = 1.60 to 1.57), pulmonary artery catheters (OR = 1.20, 95% CI = 1.01 to 1.43), urinary catheters (OR = 1.41, 95% CI = 1.19 to 1.69), and mechanical ventilation (OR = 1.75, 95% CI = 1.51 to 2.03). Other independent risk factors for ICU-acquired HAIs were stress ulcer prophylaxis (OR = 1.38, 95% CI = 1.20 to 1.60), the presence of trauma on admission (OR = 2.07, 95% CI = 1.75 to 2.44), and the length of ICU stay. The latter constituted the strongest predictor of HAIs and showed a linear increase in the odds for HAI with time spent in the ICU [25].
In a recently published study [26], McLaws and Berry analyzed the rate for CVC-associated bloodstream infection (BSI) in 1,375 patients who were monitored for 7,467 days of CVC use. They found significant differences in the BSI rate depending on the length of catheterization (Figure 24A-1). The probability of BSI with a CVC in place was 6% by day 15, 14% by day 25, 21% by day 30, and 53% by day 320. Thus, the risk of BSI is not homogenous and increases substantially after prolonged CVC-insertion (>2 wks).
Underlying Diseases
ICUs, by design, serve patients with severe illnesses that compromise host defense. Each patient must be assessed individually to determine how the underlying illness might interfere with host defense mechanisms. A simple assessment of the severity of underlying illness was developed by McCabe and Jackson [27], who stratified patients according to whether the underlying disease was fatal, ultimately fatal, or nonfatal. Subsequent studies by Britt et al. [28] demonstrated the utility of this simple assessment for estimating the risk of nosocomial BSI.
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Numerous studies have found increasing rates of HAIs among patients with more severe illnesses [29].
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Figure 24A-1 Kaplan–Meier survival curve of a nonuniform hazard for the development of bloodstream infection (BSI) beginning with all patients (cumulative survival, 1.00) free of BSI. By day 5, 99% of the patients remained free of BSI. By day 16, 94% remained free of BSI. CVL-central venous catheter. (Adapted from McLaws ML, Berry G. Nonuniform risk of bloodstream infection with increasing central venous catheter-days. Infect Control Hospital Epidemiol 2005; 26:715–719 with permission.) |
Although McCabe's classification has been useful, it was not designed to assess ICU patients. Therefore, several severity-of-illness scoring systems have been proposed to estimate a patient's risk of death in ICUs objectively. Great progress has been observed in the last 10 years in the accuracy of statistical models to assess critically ill patients and predict survival [30,31]. Customized or modified versions of the most frequently used scoring systems (e.g., simplified acute physiology score [SAPS] III and Acute Physiology, Age, and Chronic Health Evaluation [APACHE] III) have been proposed to provide satisfactory estimates of the probability of death in ICU patients, which depends on the severity of illness, the number of acute organ failures, and the characteristics of underlying disease [32,33,34,35]. Nevertheless, limitations persist about the capacity of these scoring systems to integrate differences in overall quality of care [36]. Moreover, older versions of these scores, which were developed in the early 1990s, have shown a decline in predictive accuracy as the models age. Therefore, mortality tends to be overpredicted when older models are applied to more contemporary data, which, in turn, leads to biased benchmarking data of different ICUs [37]. Thus, care should be taken when using outdated severity scoring models to contemporary populations.
A group of critical care physicians developed, by consensus, the so-called “Sepsis-Related Organ Failure Assessment” (SOFA) score in December 1994, a severity scoring system that targets septic patients [38]. Because the score is not specific for sepsis, it was later called “Sequential Organ Failure Assessment.” The SOFA score is composed of scores from six organ systems, graded from 0 to 4 according to the degree of dysfunction [39]. While primarily designed to describe morbidity, several analyses showed a relationship between the SOFA score and mortality [40,41]. These analyses indicated a good correlation of the score with survival and a good distribution of patients among the different score values.
Infectious Agents and Antimicrobial Resistance
In ICUs where antibiotics are used more frequently and in larger amounts than in almost any other hospital area, antimicrobial resistance ensures the survival of some HAI pathogens [42]. Moreover, the close proximity of patients facilitates transfer of resistant organisms from patient to patient [43,44]. It is noteworthy that trends in the pathogens responsible for HAIs in the ICU have shown an increase in infections due to multiply-resistant gram-positive bacteria (e.g., coagulase-negative staphylococci, S. aureus, E. faecium), gram-negative bacteria (GNB)(e.g., Enterobacter spp, Acinetobacter baumannii) and fungi such as Candida spp. [4,45,46]. The emergence of these pathogens is due, at least in part, to patterns of antibiotic use and selection pressure and to the development of antibiotic resistance among these isolates [47].
Recent data from the Center for Disease Control and Prevention's (CDC's) National Nosocomial Infections Surveillance (NNIS) system shows alarming trends in the nosocomial transmission rates of multiresistant organisms in the United States [48]. This voluntary surveillance system receives monthly reports of HAIs data from a nonrandom sample of >300 hospitals in 42 U.S. states. The microbiological data include antimicrobial susceptibility test results on all nonduplicate clinical isolates processed
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by the microbiology laboratories during each month stratified by patients' hospital location. The most recent NNIS report [48] shows that in 2003, 60% of all Staphylococcus aureusisolates in the participating U.S. ICUs were methicillin resistant, 29% of all enterococci were vancomycin resistant, and 89% of all coagulase-negative staphylococci were methicillin resistant. More than 30% of all Pseudomonas aeruginosa isolates from ICU patients were resistant to fluoroquinolones or ceftazidime. Of note, there has been a nearly 50% increase in nonsusceptible Klebsiella pneumoniae isolates to third-generation cephalosporins between 2002 and 2003. Likewise, methicillin-resistant S. aureus (MRSA) account for ≥30% of S. aureus isolates in most European ICUs and are a growing problem, especially in southern Europe, where rates of antibiotic resistance are alarmingly high with a prevalence of methicillin resistance among S. aureus isolates of ≥50% [49,50].
Organisms such as Klebsiella spp. and Escherichia coli are important sources of transferable antibiotic resistance, and multiresistant Enterobacteriaceae are now endemic in many countries and settings [45,51,52,53,54]. Numerous reports have demonstrated spread of antibiotic resistance from ICUs to other hospital units and vice versa [55,56,57]. D'Agata et al. [56,58] prospectively examined sporadic and endemic colonization with resistant GNB in a Boston ICU. The study showed that most resistant GNB were imported from outside but detected within the ICU by intensive microbiologic surveillance. Routine clinical cultures would have detected multiresistant GNB in only 5% (3/60) of patients. The most important risk factor for colonization with resistant GNB except for severity of illness and previous hospitalization was the duration of exposure to antibiotic prophylaxis with first-generation cephalosporins [56]. The authors concluded that inappropriate antibiotic use outside the ICU increases the chances of developing resistant GNB for patients admitted to the ICU.
Another HAI pathogen that is increasingly colonizing and infecting patients is A. baumannii. Patients with debilitating conditions are at especially high risk of acquiring pneumonia or bacteremia with this pathogen [59,60,61,62]. Observational studies may help to identify modifiable risk factors for A. baumannii HAI so that preventive measures can be implemented. The wide use of broad-spectrum antibiotics may be one of the most important risk factors for A. baumannii colonization and infection [63,64]. Villers et al. [65] illustrated the complex relation between the use of fluoroquinolones and the occurrence of A. baumannii infections in a French ICU. They showed that epidemic infections coexisted with endemic infections favored by the selection pressure of intravenous fluoroquinolones.
Different types of epidemiological studies have been used to quantify the association between antibiotic exposure and resistance in critically ill patients [66,67,68,69,70]. These studies included outbreak reports, laboratory-based surveys, randomized trials, and prospective or retrospective cohort studies based on analyses of individual patient data or aggregated data. The different methodological approaches are not mutually transposable, and the lack of uniformity makes the comparison of different studies difficult. For instance, aggregated data may be limited by “ecologic bias,” which is the failure of group-level estimates to reflect the biological effect of antibiotic use at the individual-patient level. This bias is a result of the fact that, unlike individual-level studies, ecologic studies do not link individual outcome events to individual antibiotic exposure histories. Notwithstanding these difficulties, the majority of studies confirm that dramatic differences exist in the pattern of antimicrobial usage and antimicrobial resistance between different hospitals and ICUs. Use of antimicrobials may show important variations between institutions facing similar prevalences of highly resistant organisms, confirming that efforts to control resistance should focus on both antimicrobial use and infection control practices [71].
Sources of Colonization
Host colonization is a prerequisite for the development of infection. This process involves adherence of organisms to epithelial or mucosal cells, proliferation, and persistence at the site of attachment. Although the factors promoting the progression from colonization to infection are not well understood, almost 50% of ICU-acquired HAIs are preceded by host colonization with the same organism. Factors associated with microbial colonization are similar to those associated with development of infection. These risk factors include the duration of hospitalization and length of ICU stay, invasive devices, prolonged antibiotic therapy, and elimination of normal pharyngeal or bowel flora through the use of broad-spectrum antimicrobial agents [72]. Other factors promoting colonization of patients in ICUs include disruption of normal mechanical defense mechanisms (i.e., the bronchial mucociliary “escalator”) by drugs or tracheal intubation, changes in protective antibacterial secretions (i.e., lysozyme, lactoferrin, saliva, and gastric acid) in response to stress and therapeutic agents, or disruption of “colonization resistance.”
A vast literature exists regarding the development of colonization and subsequent infection [73]. A few important studies are summarized. The classic article [74] of Johanson et al, written in 1969, showed that severe illness predisposes to oropharyngeal GNB colonization. In 1974, Schimpff et al. [75] suggested that in critically ill patients, the origin of infection usually is the endogenous flora. Several studies have subsequently confirmed that patients are rapidly colonized by GNB after ICU admission and later develop infection with the same organisms [76,77,78,79,80].
In a recently published landmark study, Grundmann et al. [44] prospectively studied HAIs in patients admitted to five ICUs in Germany. During 28,498 patient days, 431 ICU-acquired HAIs and 141 episodes of nosocomial transmission were identified. A total of 278 HAIs were
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caused by the 10 species that were genotyped; only 41 (14.5%) could be associated with transmissions between patients. Thus, modern typing methods confirmed that the patients' endogenous flora is probably the most important source of HAI in the ICU setting.
The central role of gastric colonization in the pathogenesis of HAI and pneumonia has been called into question. Based on studying sequences of colonization in ICU patients, Bonten et al. [81] concluded that the stomach is unlikely to be an important source of pathogens leading to nosocomial pneumonia as diagnosed by bronchoalveolar lavage (BAL) or protected specimen brush (PSB). Furthermore, the initial site and route of colonization might not be the same for all organisms [81]. These results were confirmed in a large, observational cohort study conducted in two medical ICUs where specimens for culture were taken daily from nares, oropharynx, trachea, and stomach from the time of admission to the first signs of nosocomial pneumonia [82]. The stomach was an uncommon source of organisms that cause pneumonia in ventilated patients. Preventive regimens should thus be mainly directed against colonization of the oropharynx and trachea [83].
Epidemiology
Infection Sites and Types of ICU
In 1992, a total of 1,417 ICUs in 17 countries in Western Europe participated in a one-day point prevalence study [25]. The prevalence of ICU-acquired HAIs was 20.6% (2,064/10,038) and markedly varied from country to country, ranging from 9.7–31.6%. Trends toward higher ICU-acquired HAI prevalence paralleled trends toward higher mortality [84]. These differences are likely to reflect differences in ICU care practice between countries and underline the importance of controlling for case mix when interpreting and comparing HAI rates between hospitals or countries [85,86].
Not only at a national or international level, the frequency differs with which HAIs occur but also at different sites in the ICU and within a hospital. The annual NNIS report and data from the German ICU surveillance system Krankenhaus Infections Surveillance System illustrate these differences in the incidence of HAIs in different types of wards and ICUs [48,87]. First, urinary tract infections (UTIs) predominate in general wards, whereas the most common HAIs in ICUs are lower respiratory tract infections (LRTIs). Second, rates of HAI tend to be higher in surgical than medical ICUs, and rates in the adult ICUs are generally higher than in pediatric ICUs (except neonatal ICUs) [88]. Third, in adult ICUs, the lower respiratory tract (LRT) is the most common site of infection, whereas in pediatric ICUs, BSIs predominate (Table 24A-1). High rates of pulmonary infections relative to other HAI sites are unique to adult ICUs where patients are frequently admitted because of respiratory distress and require mechanical ventilation. Although primary BSIs and infections stemming from the presence of vascular cannulas are less common than LRTIs, the morbidity and mortality associated with these infections are particularly high [89,90].
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TABLE 24A-1 |
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In 2000, the CDC briefly reported a decrease in HAI rates in the ICUs of participating NNIS hospitals from 1990 to 1999 [91]. Device exposure–adjusted HAI rates decreased for three body sites (LRTIs, UTIs, and BSIs). The greatest decrease was observed for BSI rates, which decreased in medical ICUs by 44%, in coronary ICUs by 43%, in pediatric ICUs by 32%, and in surgical ICUs by 31%. However, because of a progressively shorter ICU length of stay over the last 20 years, the overall, hospitalwide rate of HAIs per 1,000 patient-days has actually increased by 36%, from 7.2 in 1975 to 9.8 in 1995 [92]. The variable use of different denominators also may have an important effect on trend analyses and may bias benchmarking [93].
When HAI rates have been compared over shorter increments of time (i.e., by month) wide variations have been noted. Observations in different ICUs suggested that the level of skilled nursing care relative to patient census may be an important determinant of this variation [94,95]. Indeed, there are a large number of studies showing that overcrowding, understaffing, or a misbalance between workload and resources are important determinants of HAIs and cross-transmission of organisms in ICUs [96,97,98]. Importantly, not only the number of staff but also the level of their training affects outcomes. The causal pathway between understaffing and HAI is complex, and factors might include lack of time to comply with infection control recommendations, job dissatisfaction, job-related burnout, absenteeism, and a high staff turnover [95].
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In summary, rates of HAIs vary considerably within hospitals by type of ICU. Rates are generally lower in cardiac ICUs and higher in neonatal, surgical, trauma, and burn units, reflecting the higher risk of HAI of patients admitted to these latter types of units [48].
Impact of Infections Acquired in the ICU
HAIs in the ICU are harmful for the patients and expensive for society. Several studies suggest that nosocomial LRTIs and BSIs are associated with a two- to threefold increased risk of death in ICU patients [99,100]. Thus, in contrast to a widespread theory, a significant proportion of patients in the ICU dies due to HAIs.
Crude mortality rates in patients who acquire HAIs in the ICU are estimated to vary between 10% and 80%. The term attributable (or excess) mortality defines the mortality directly associated with the infection rather than the mortality attributable to underlying conditions. In ICU patients, underlying conditions other than HAI that may affect the outcome mainly include pre-existing comorbidities, severity of acute physiologic disturbance, and complications arising from these conditions [101].
Assessment of mortality attributable to HAIs in the ICU setting is difficult and not straightforward because HAIs and mortality attributable to other causes share common risk factors that may confound the cause-and-effect relationship. Thus, it is sometimes difficult to estimate whether the critically ill patient would have survived in the absence of HAI. The most often used approach to estimate the attributable mortality of HAIs in ICU patients is to conduct a matched cohort study. In this type of study design, cases are defined as patients in whom HAIs develop during their ICU stay. These case-patients are subsequently compared with noninfected controls. Case- and control-patients usually are matched for age, time of the year, underlying diseases, and additional variables that may contribute to excessive mortality rates of ICU stay independent of the HAI itself. In brief, the attributable mortality due to HAI defines the excess mortality due to the infection. As an example, Table 24A-2 summarizes estimates of excess mortality attributable to nosocomial pneumonia in ICU populations.
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TABLE 24A-2 |
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For the assessment of the economic burden associated with HAI in the ICU, matched cohort studies are not optimal. This study design has several limitations because of the time-varying nature of the exposure. One source of bias occurs when infected and uninfected patients are compared with regard to total hospital costs or total hospital length of stay [102]. For infected patients, only those costs incurred after the occurrence of the HAI are possibly secondary to infection. Before infection onset, patients are unexposed. The association between pre-infection outcome and HAI is entirely noncausal from the perspective of measuring the excess burden of infection. Therefore, combining pre-infection outcomes with postinfection outcomes dramatically amplifies confounding [103].
Several recent studies have demonstrated the effect of this bias. Outcome analyses that did not account for the time before the occurrence of the HAI yielded different results than studies that did account for the time before the HAI. Schulgen et al. [104] tested different methods and showed that the use of unmatched or matched comparisons between non-infected and infected patients led to an overestimation of the excess length of stay due to nosocomial pneumonia compared to analyses based on a structural formulation of transitions between different states. In a recent study, Beyersmann et al. have confirmed the validity of this statistical approach [105]. They showed that HAI significantly reduced the discharge hazard (HR = 0.72; 95% CI = 0.63–0.82) (i.e., prolonged ICU stay). Prolongation of ICU length of stay due to HAI was estimated at 5.3 days (±1.6). Similarly, Asensio and Torres [106] found that regression models yielded lower estimates of the excess length of stay and cost due to HAI than a matched-pair comparison. Another approach to estimating cost and length of stay effects of adverse events is to apply survival models in which the adverse event is incorporated as a time-dependent variable. This strategy can be applied to costs and length of stay [103].
Even when the time-varying nature of the exposure is accounted for, it is still necessary to adequately adjust for traditional confounders, those factors that both increase the risk of HAI and affect the outcome of interest. For instance, Soufir et al. [107] investigated the excess risk of death due to catheter-related bloodstream infection (CR-BSI) in a cohort of critically ill patients. The crude case-fatality ratio
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was 50% and 21% in patients with and without CR-BSI, respectively. The statistical method of adjustment was based on Cox proportional hazards regression with inclusion of matching variables and prognostic factors for mortality. CR-BSI remained associated with mortality following adjustment for prognostic factors at ICU admission (HR = 2.0;P = 0.03). However, after controlling for severity scores calculated one week before CR-BSI, the increased mortality was no longer significant in the Cox model (HR = 1.4;P = 0.27).
In summary, HAIs in critically ill patients unquestionably have substantial impact on morbidity and mortality. However, the matched cohort study design may produce bias in the estimation of the effects of HAI on length of stay and costs. Cost effects or excess length of stay are likely to be overestimated if the interval to onset of HAI is not properly accounted for in the study design or analysis [103].
Causative Agents
Bacteria, fungi, and viruses have been reported as causative agents in HAIs, and many infections are polymicrobial. Data obtained from the NNIS System and the previously mentioned EPIC study (Table 24A-3) illustrate the trends in microbial etiology of HAIs responsible for disease in ICUs [25,108]. These data reflect a large geographic sample and are representative of ICUs in the industrialized world. Similar patterns of causative organisms have been noted in other studies [2,109,110,111]. For instance, recently reported data from the German KISS system identified the following as most commonly reported HAI pathogens [110]: S. aureus (16.5% of all HAIs), P. aeruginosa (14.2%), E. coli (13.9%), enterococci (13.4%), C. albicans (11.2%), Klebsiella spp. (9.1%), coagulase-negative staphylococci (9.1%), and Enterobacter spp. (7.4%). The recently published Sepsis Occurrence in Acutely ill Patients (SOAP) study [111] investigated a large cohort of septic patients in 198 ICUs in 24 European countries. Among the 279 patients with ICU-acquired HAIs, staphylococci, including MRSA, were most frequent (40%), followed by Pseudomonas spp. (21%), streptococci (19%), E. coli (17%), and C. albicans (16%). Patients with ICU-acquired HAIs had a higher incidence of mixed infections (23% vs. 16%) compared with those with non-ICU-acquired sepsis [111].
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TABLE 24A-3 |
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Table 24A-3 lists the most common HAI pathogens by infection site from U.S. or Western European ICUs. The leading pathogens causing nosocomial BSI and surgical site infections (SSIs) were staphylococci and enterococci. P. aeruginosa was the most common pathogen causing LRTI. Candida spp and E. coli were the most prevalent pathogens from UTIs. Overall, in contrast to the 1970s, major shifts in the etiology of HAIs occurred in the decades between 1980 and 2000 [29]. Gram-positive bacterial or fungal infections are becoming more common, and GNB such as Klebsiella spp. are becoming increasingly resistant to available antibiotics. Taken as a whole, the shifts are away from more easily treated pathogens toward more resistant pathogens with fewer options for therapy [108].
Clusters of Infections in the ICU
Although <10% of hospitalized patients are treated in ICUs, many outbreaks of HAIs occur in these units, frequently related to breaks in technique or noncompliance with infection control guidelines. Other epidemics are associated with specific strains of bacteria, usually related to a contaminated inanimate or animate reservoir from which the organism may be transmitted to the patients [112].
A literature search in the Web-based repository www.outbreak-database.com for outbreaks occurring in ICUs identified more than 800 hits. Table 24A-4 summarizes important features of selected outbreaks [113,114,115,116]. Leading pathogens of outbreaks in the ICU setting were MRSA and GNB.
Although there were unique factors in each epidemic, several generalizations can be made. Epidemics associated with specific pathogens often were associated with bacteria that were relatively resistant to antibiotics, relatively
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virulent when compared with normal endogenous and environmental flora, capable of withstanding variations in environmental conditions, and transmitted by hand from patient to patient [63]. Pathogens that exemplify these characteristics include S. aureus and Serratia, Klebsiella, and Enterobacter spp. Epidemics caused by unusual organisms, such asAcinetobacter spp, often were associated with contaminated equipment or with changes in the environment [117]. HAI outbreaks were more frequently reported from neonatal ICUs than from other types of ICUs [96]. It is important to remember that new equipment or a new procedure may introduce a new reservoir or mode of transmission into the ICU [118]. Finally, transplanted organs from infected donors also can serve as source of unusual HAIs in the critical care setting [119,120].
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TABLE 24A-4 |
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Clinical Aspects of Infections in the ICU
Critically ill patients are highly susceptible to HAIs. The importance of medical devices in catheter-associated UTIs, intravascular device–associated infections, and ventilator-associated pneumonia is discussed elsewhere. Only selected aspects of infections seen predominantly in ICU patients will be discussed in the following section.
Ventilator-Associated Pneumonia
Pneumonia is the most common ICU-acquired HAI, accounting for 25–50% of all HAIs in ICU patients [121]. In mechanically ventilated patients, pneumonia is associated with an excess mortality ranging between 0 and 30% (Table 24A-2) [104,122]. The attributable mortality varies according to underlying disease, type of pathogen, and adequacy of initial empiric antibiotic treatment [123,124,125]. For instance, in a matched cohort study conducted at Geneva University Hospitals, we analyzed 97 patients with ventilator-associated pneumonia (VAP) and observed an excess mortality rate of 7.3% (P = 0.26) [126]. Considering the studies shown in Table 24A-4 and the data generated by a recently published systematic review, critically ill patients who develop VAP appear to be 1.4–2.0 times as likely to die compared to patients without VAP [99]. In surviving patients, VAP causes substantial morbidity and extends hospital length of stay by at least 4 days.
Patients who have suffered severe trauma and those who have had major surgery are at particularly increased risk of subsequent LRTIs [127]. Exogenous infection is rare, but, on occasion, medication nebulizers, the endotracheal tube lumen, and other respiratory therapy equipment or
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contaminated hospital water can serve as sources for the inoculation of organisms into the lung [115].
Although mechanical ventilation is not a necessary prerequisite for the development of ICU-acquired pneumonia, it substantially increases the LRTI risk. Cook et al. found that the daily risk of pneumonia was not linear: It was highest during the first week (3% per day) and decreased thereafter [128]. In the third week of mechanical ventilation, pneumonia developed in ~1% of patients with each additional day of mechanical ventilation (Figure 24A-2).
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Figure 24A-2 Hazard rate for ventilator-associated pneumonia during the stay in the ICU. The hazard function presents the conditional probability of ventilator-associated pneumonia in the next day, given that a patient is event free. Estimation of the hazard function shows the event rate per day over the duration of ventilation. (Adapted from Cook et al. Incidence of and risk factors for ventillator-associated pneumonia in critically ill patients. Ann Intern Med 1998; 129:433–440 with permission.) |
Cultures of the LRT are important in the diagnosis of ICU-acquired pneumonia [129]. Because the oropharynx of critically ill patients is frequently colonized with potentially pathogenic bacteria, care must be taken to avoid contaminating cultures of the lower airways. Retrieval of culture specimens by bronchoscope using either a PSB or BAL has been helpful for this purpose [130]. Although numerous studies have evaluated the performance of bronchoscopic and nonbronchoscopic procedures for the diagnosis of VAP, controversy persists about the optimal diagnostic strategy [131]. Fever, leukocytosis, and lung consolidation, hallmarks of pneumonia in otherwise healthy patients, can result from other pathogenic mechanisms in intubated patients (e.g., pulmonary edema, contusion, atelectasis, pleural effusion, or acute respiratory distress syndrome) [132]. Therefore, several authorities encourage the use of invasive techniques to diagnose VAP, including BAL, nonbronchoscopic (“blind”) BAL, and “blind” PSB, to increase diagnostic accuracy and guide clinicians in their decision making [133]. Although diagnosis by invasive methods requires a considerable commitment of resources, it can potentially reduce cost of care and may even lower mortality due to VAP [134,135]. Whatever method chosen, the interpretation of the sensitivity and specificity of any given sampling technique may be severely hampered by the distorting effect of previous antibiotic exposure on the yield of bacterial cultures [136].
Early Onset Pneumonia
Early onset VAP accounts for at least one-third of pneumonias in the ICU. This entity should be distinguished from late-onset episodes because of their different microbiologic spectrum, risk factors, and outcome. Because the pathogens causing aspiration pneumonia reflect the oropharyngeal microbial flora at time of aspiration, the pathogens that bring about early onset pneumonia are more likely to reflect normal oral flora or pathogens responsible for community-acquired pneumonia (S. aureus, Streptococcus pneumoniae, orHemophilus influenzae). Nevertheless, antimicrobial-resistant pathogens also may be involved in early onset pneumonia, especially in settings with high prevalence of antibiotic overuse [137,138].
In a prospective cohort study of 747 critically ill patients, Bornstain et al. [139] reported that 80 patients (11%) experienced early onset pneumonia in their ICU. Aspiration of oropharyngeal flora was the presumed mode of inoculation. Male gender, impairment of reflexes that protect the airways, sucralfate use, or unplanned extubation were the most important risk factors. Use of certain antibiotics protected against early onset pneumonia. Other potentially modifiable risk factors for early onset and late-onset pneumonia have been summarized recently [140].
Nosocomial Sinusitis
Sinusitis frequently complicates nasotracheal or nasogastric intubation (2–25%) [141,142]. Mechanical obstruction of the maxillary sinuses usually initiates the process with subsequent spread to the ethmoid and sphenoid sinuses. Fever, leukocytosis, and purulent nasal discharge suggest the diagnosis, but their absence does not exclude it [143]. Conventional sinus radiographs and computed tomography scans are useful, but sinus aspirate allows confirmation of the diagnosis and identification of the causative agents [144]. In contrast to community-acquired sinusitis, GNB have predominated in this context. Pseudomonas spp., Enterobacteriaceae, and anaerobic bacteria have been the pathogens most commonly recovered [145,146]. In addition, S. aureus and Candida spp. also have been encountered, and polymicrobial infection has been documented in 40–100% of episodes. Nasotracheal intubation is associated with a significantly higher risk of infection than orotracheal intubation [147]. Complications include pansinusitis, orbital cellulitis, brain abscess, osteomyelitis, secondary BSI, and nosocomial pneumonia [142]. Treatment requires the removal of the device and adequate intravenous antibiotic therapy.
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In summary, the existing studies establish that sinusitis joins pneumonia, catheter sepsis, SSIs, and UTIs as one of the “five horsemen” of clinically important HAIs in ICU patients. Therefore, a sinus computed tomography scan is a necessary component of the evaluation of intubated patients with fever or signs of sepsis from unknown origin [148]. Sinus aspiration is essential to confirm the diagnosis, direct antimicrobial therapy, and help drainage.
Other ICU-Specific Infectious Problems
Acalculous cholecystitis, also called postoperative cholecystitis, commonly complicates both abdominal and nonabdominal surgery in critically ill patients [149,150]. P. aeruginosa, E. coli, and Enterobacter spp. are the most commonly isolated pathogens. Severe complications can occur, including gangrene of the gallbladder, perforation, secondary peritonitis, intrahepatic abscesses, and ipsilateral empyema. Abdominal ultrasound has been found to be a reliable method of early detection of acalculous cholecystitis and for follow-up of possible complications. Diagnostic laparoscopy might be another accurate method to establish the early diagnosis. Treatment of acalculous cholecystitis requires surgery and appropriate antimicrobial therapy. Other important ICU–specific problems include Pneumocystis jiroveci pneumonia in patients with the acquired immunodeficiency syndrome, meningitis, and antibiotic-associated colitis, which are discussed in other chapters of this textbook.
The differentiation of the causes of fever in ICU patients is a daily challenge for physicians. Not all fevers result from infection; nosocomial fever often does not signal HAI and may augur a wide variety of other conditions. The most common causes of noninfectious fever are listed in Table 24A-5.
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TABLE 24A-5 |
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Control and Prevention of HAIs
Surveillance
Two types of measures are needed to control HAIs. Engineering controls are those controls that are incorporated into the structural design of the unit or equipment and over which there is limited human control. Administrative controls are guidelines that must be learned and executed by healthcare workers (HCWs). The latter are effective only if appropriate changes in behavior are incorporated into the routine activities of HCWs. For instance, we experienced a cluster of invasive pulmonary aspergillosis in nonimmunocompromised patients associated with room air filter replacement [151]. Such fatal infection could have been prevented by the establishment and application of guidelines for this procedure.
Engineering Controls
The contribution of the design of ICUs to the control of HAI is difficult to evaluate. However, it seems prudent to consider several issues when remodeling or designing new units [152]:
Administrative Controls for Medical Equipment
Medical technology is changing rapidly, and new diagnostic and therapeutic devices are constantly being introduced into ICUs. In many instances, the efficacy of the devices has not been adequately evaluated, and their effect on the HAI incidence is unknown. For example, vendors seeking to introduce new urinary catheters alleged to have antimicrobial activity should be challenged to provide data on the efficacy of their product [156].
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Cleaning protocols for invasive devices should be provided by the industry and be reviewed by infection control professionals or hospital epidemiologists to ensure the adequacy of the recommendations. Sufficient numbers of frequently used instruments should be available to allow time for cleaning, disinfection, and sterilization, when recommended. An increase in the initial outlay for equipment may reduce costs and morbidity in the long term. The routine application of guidelines for the appropriate use of medical devices contributes significantly to the control of HAIs. Guidelines for the use and control of urinary tract catheters, intravascular devices, respiratory devices, and other products have been published by the CDC.
The Role of the Environment
For more than two decades, infection control has focused on patients rather than the patients' environment as the most important source of HAI pathogens. This attitude was based on studies that failed to find improvement in the HAI rates after the units were moved into new, “clean” structures [157,158]. However, there is a growing body of literature emphasizing that some HAI pathogens are ubiquitous in the environment of patient-care areas, waiting to be cross-transmitted on HCWs' hands [159]. Therefore, the widespread transmission of antibiotic-resistant pathogens that survive for considerable periods in the environment (VRE, MRSA, A. baumannii, C. diffcile) and recent advances in our knowledge of the transmission of HAI pathogens requires a change in hospital hygiene practices [160]. Appropriate cleaning and disinfection procedures are essential to decrease microbial burden in the close patient environment and minimize the likelihood of cross-infection of multiresistant pathogens in this high-risk area [161].
Oelberg et al. published a spectacular experimental study using non-infectious DNA markers designed from a cauliflower mosaic virus as surrogate markers to illustrate microbial transmission pathways [162]. These investigators demonstrated the rapid spread of the DNA markers via the hands of HCWs in a neonatal ICU. The most consistently positive sites within all pods were the blood-gas analyzers, computer mouse, telephone handles, medical charts, ventilator knobs, door handles, radiant warmer control buttons, patient monitors, and, of course, personnel hands [162]. These experimental findings were extended by Foca et al. [163], who conducted an epidemiological and molecular investigation of endemic P. aeruginosa transmission among infants in a neonatal ICU that was associated with widespread environmental contamination and carriage of the organisms on the hands of HCWs. A history of the use of artificial fingernails or nail wraps was an additional risk factor for colonization of the hands. Transmission of P. aeruginosa was stopped after re-emphasis of good hand-hygiene practices, the importance of reliable cleaning techniques of inanimate surfaces and equipment, and the complete withdrawal of jewelry, cosmetic nail treatments, water baths, and unnecessary supplies kept by the patients' bedsides [163]. A recent investigation by Carling et al. corroborated the hypothesis that cleaning of the patients' close environment is suboptimal in most ICUs, which may play an important role as reservoir for transmitting HAI pathogens [164].
Administrative Controls for Healthcare Personnel
Staffing and Training
For the patient to benefit from technologic advances in medical care, HCWs must be well trained in state-of-the-art intensive care. Studies have documented that cooperation among critical care personnel can directly influence outcomes from intensive care, suggesting that the use of invasive technologies is important but not sufficient for optimal patient care [165,166]. Therefore, HCWs in ICUs should be involved in continuous postgraduate medical education to learn new technologies and the proper use of new medical devices and procedures [167]. They also need periodic updates on new disease entities peculiar to patients in ICUs, including psychologic problems and end-of-life issues associated with ICU hospitalization. Finally, the level of stress in ICUs exceeds that of most other areas of the hospital. As a result, rates of employee turnover are high. Loss of highly skilled healthcare workers requires extensive training of replacement workers, including in-depth training on infection control procedures. Changes in staff and unrecognized modifications in infection control procedures might contribute to HAI epidemics.
The extent and severity of illnesses afflicting ICU patients demand a high level of nursing care, and the high rate of HAIs mandate strict application of rigid barrier nursing techniques to control transmission. Breakdown in these techniques during periods of understaffing or overcrowding has been associated with HAI outbreaks [95]. A nurse-to-patient staffing ratio of 1:1 has been recommended to reduce lapses in techniques that lead to person-to-person transmission of pathogens within ICUs. A study from Geneva University Hospitals underlines the importance of an adequate nurse-to-patient ratio [96]. In this study, a low nurse-to-patient ratio was found to be an independent risk factor for transmission and acquisition ofEnterobacter cloacae in neonates (Figure 24A-3). Thus, reductions in nursing staff below a critical level may cause an increase in HAIs in ICUs by making adequate patient care difficult [168].
It is important that HCWs in ICUs understand their responsibility in preventing transmission of infectious agents. This responsibility includes prevention of spread of pathogens from patient to patient and from the healthcare worker to the patient. Therefore, it is important that the hospital provide adequate staffing to cover medical absences and personal benefits that will not punish employees who are responsible enough to avoid working when ill.
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Monitoring Quality of Care
The effectiveness of administrative controls will depend on compliance with established guidelines. Therefore, the performance and behavior of HCWs should be monitored [169]. Failure to comply with guidelines, whether on the part of physicians, nurses, or other support personnel, should be addressed promptly to prevent the establishment of bad habits that impose unnecessary risks on patients [170,171]. Monitoring the quality of medical care in ICUs is important, albeit controversial, given the complexity of the conditions of the patients and the procedures performed in these units [172].
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Figure 24A-3 Outbreak of Enterobacter cloacae at the neonatal ICU of Geneva University Hospitals, December 1996 to January 1997. Arrows indicate Enterobacter cloacaeisolates. The horizontal line indicates the supposed maximum capacity (15 infants) of the unit. |
Administrative Controls for Patients
Because of the risk of infection and other complications in ICUs, only patients who will benefit from high-intensity, high-risk care should be admitted to ICUs, and patients should be discharged from the ICU as soon as possible to lower the HAI risk. Unfortunately, there is little published information to assist the physician in making those important decisions. Surveillance for HAIs, monitoring HAI rates, and reporting results to personnel are important to ensure the quality of medical care in ICUs [173]. Properly conducted surveillance can identify behavioral, environmental, or treatment factors that, when corrected, will diminish endemic HAI rates in the unit [174]. Additional benefits of concurrent surveillance include early identification and intervention in epidemics [175].
Practical Aspects of Infection Control in the ICU
Methods for preventing HAIs are numerous. The principles are the same throughout the hospital, and many are discussed elsewhere in the text. Only selected measures of prime importance in the ICU will be discussed in this section.
Patient Screening
Screening on ICU admission should be considered for control of highly transmissible HAI pathogens [176]. Patients colonized with multiresistant bacteria, such as MRSA or VRE, serve as a reservoir for spread within the healthcare environment, mainly through the hands of HCWs. Active surveillance by patient screening and intensive control measures attempt to decrease this reservoir with the ultimate goal of reducing infection rates [177]. Guidelines published by the CDC and Society for Healthcare Epidemiology of America (SHEA) are useful in this respect [178].
Nevertheless, the most efficient approach to control endemic MRSA in the ICU setting remains controversial [179,180,181]. Several authorities have suggested that screening on admission to ICUs and subsequent patient isolation may decrease the risk of cross-infection [182,183]. This may be particularly true when using a rapid screening test. We recently investigated the clinical usefulness of a rapid on-admission screening test for MRSA [184]. A substantial decrease in MRSA infections was seen in a medical ICU after increasing compliance with on-admission screening and implementing a strategy that linked the rapid test to pre-emptive isolation of MRSA patients. However, no effect on MRSA rates was observed in the surgical ICU, although a large number of unnecessary pre-emptive isolation-days could be saved by using the rapid MRSA test [184].
Despite the fact that culture-based MRSA screening techniques have proven inexpensive and sensitive if collected from several body sites, the time to report the results remains a major issue. Definitive identification and testing results are usually available only 48 to 96 hours after sample collection, a time delay that could allow MRSA cross-transmission if patients are not presumptively placed
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under contact precautions. This may be one of the reasons (besides low hand hygiene compliance) why the recently published study by Cepeda et al. did not show a significant effect of contact isolation for MRSA carriers identified by conventional methods [180].
Frequent transfers of patients through various units and levels of care increase the risk of transmission of resistant organisms throughout the hospital [54]. As mentioned earlier, colonized patients are important animate reservoirs of resistant organisms during interinstitutional or international transfers and probably account for the spread of multiresistant bacteria [61,185,186]. To control the spread of resistant organisms, it is important to document information regarding carriage of antibiotic-resistant microflora in the patient's medical record and to report it to receiving units and facilities. On-admission screening should be performed for any patient transferred from settings and institutions with endemic multiresistant pathogens.
Patient Isolation
More than 50% of patients admitted to ICUs are colonized at the time of admission with the organism responsible for subsequent infections. Patients who are readmitted to the hospital may carry and transmit resistant organisms acquired during previous hospitalizations [187]. Not infrequently, unrecognized infection contributes to the decision for entry into the unit. The early diagnosis of potentially transmissible disease requires vigilance on the part of ICU physicians. Patients with suspected infections should be appropriately screened and segregated at the time of admission [188]. The level of isolation should account for each of the following factors: the site of infection, the mode of transmission, the amount of secretions or excretions, and the virulence and antimicrobial susceptibilities of the causative agent.
Discussion of specific isolation techniques are beyond the scope of this chapter. It should be recognized that as the duration of stay increases, the frequency of colonization with resistant microflora also grows. Patients become animate reservoirs that facilitate transmission to susceptible incoming patients [44]. It may be wise, therefore, to separate long-stay patients from the short-stay patients who make up the major portion of the population in the unit. This segregation may be accomplished by moving chronically ill patients to single rooms or relocating groups of patients to a physically separate part of the unit. A dedicated nursing staff for the long-term patients would provide an added barrier to transmission, but this is frequently impossible to implement. Adequate hand antisepsis certainly constitutes the most appropriate, least expensive, and highly effective measure, but lack of compliance is an issue [189,190].
Hand Hygiene
Routine hand hygiene before and between contact with patients is the most important feature of infection control. Virtually all healthcare workers are aware of and agree with this concept [191]. It is dismaying, therefore, to see repeated reports of low levels of compliance with this simple and inexpensive technique. In ICUs, compliance usually does not exceed 40% and is frequently much lower [192]. Several reasons have been suggested to account for this low level of compliance, including lack of priority over other required procedures, insufficient time to accomplish hand hygiene, inconvenient placement of hand-hygiene tools, allergy or intolerance to the hand cleansing solutions, lack of leadership on the part of the senior medical staff, and lack of personal commitment to the routine of hand hygiene.
Grossly misleading impressions about the value of alcohol-based hand rubbing persisted widely during the 20th century [193]. Alcohol-based hand rubbing for HCWs has rarely been promoted systematically, and, consequently, sink-based handwashing with soap and water remained the predominant tool for reducing transient hand carriage of HAI pathogens in most ICUs. Only in the last five years has the strength of evidence in favor of alcohol-based hand rubbing become simply overwhelming so that infection-control experts around the world including the CDC and the World Health Organization (WHO) [153,192], have rewritten recommendations for hand hygiene in healthcare.
This breakthrough is due to the following important insights:
Barrier Precautions
There is currently little evidence that the addition of gloves in the routine intensive care setting has any benefit over
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regular hand hygiene in controlling HAIs. Major arguments against the routine use of gloves in ICUs rely on the fact that HCWs frequently do not remove gloves when moving from patient to patient and forget to clean their hands after glove removal.
Whereas a number of studies have investigated the role of sophisticated forms of protective isolation in reducing high HAI rates in patients with profound granulocytopenia or full-thickness burns, only a few have evaluated whether simple protective isolation would be beneficial for ICU patients. Klein et al. [201] conducted a prospective, randomized trial in a pediatric ICU, assessing the benefit of simple barrier precautions (disposable gown and gloves) on both colonization and subsequent infection. Colonization with ICU-acquired bacterial strains occurred an average of 5 days later in isolated patients. The daily HAI rate for isolated patients was 2.2 times lower than among patients provided standard care.
Although previous studies have reported conflicting results concerning the value of protective isolation in ICU patients, gowns and gloves may be effective in dealing with selected high-risk patients [202]. The recent Severe Acute Respiratory Syndrome (SARS) epidemic has shown that hospitals with high compliance with barrier precautions had a lower impact and less viral transmission compared to institutions that lacked this response [203]. Further studies are necessary to determine the cost effectiveness of this approach in the general ICU population. To draw definitive conclusions, compliance with isolation precautions also should be evaluated. Only a few studies have analyzed compliance with isolation precautions, and most reported low compliance and insufficient knowledge of precautions for pathogens [204,205,206].
Controversies Specific to the ICU Setting
Selective Digestive Decontamination
Because many HAIs are believed to arise from endogenous flora in the oropharyngeal tract, innovations in prevention have focused on the control (decontamination) of potential pathogens with oral antimicrobial therapy. The aim of selective digestive decontamination (SDD) is to prevent overgrowth of pathogenic GNB and yeasts. It involves the use of topical oral and intestinal antibiotics, often with a systemic antibiotic added for the first few days of the regimen, with the goal being the elimination of potential pathogens from the gastrointestinal tract. With eradication of endogenous bacterial sources, infection may be avoided [207,208].
The role of SDD in preventing ICU-acquired HAI and mortality remains one of the most controversial issues in critical care medicine [209,210]. More than 30 randomized controlled trials that evaluated the efficacy of SDD in preventing VAP and reducing mortality have been published. Several meta-analyses of these studies showed a positive treatment effect, although the effect appeared to be smaller when considering only high-quality studies [211,212]. The crucial concern associated with the use of SDD is the development and spread of antibiotic resistance; whether SDD contributes to or reduces antibiotic selection pressures by reducing the incidence of infection remains an open question. Nevertheless, some evidence supports the use of SDD as an effective strategy that may reduce morbidity and mortality in selected groups of critically ill patients hospitalized in those units where cross-transmission of multiresistant organisms (e.g., MRSA or Acinetobacter spp.) is not a predominant problem [213,214,215,216].
In spite of the data from many clinical trials and systematic reviews, it seems difficult to recommend that SDD be either abandoned or used routinely in the ICU setting. It may be premature to ignore the potential benefits of SDD because the results of most clinical trials have been encouraging in terms of reducing infection rates. Additional studies are clearly needed, especially about the overall mortality benefit of SDD [217]. It may be more practical to administer oropharyngeal decontamination without systematic antibiotic treatment; however, whether this approach has an impact on ICU-mortality remains to be shown [83,218,219,220]. Recently, a multicenter study investigated the potential preventive efficacy of an antimicrobial peptide (Iseganan) [221]. Although preliminary studies with this new agent were promising, the overall results of the clinical trial showed that the study drug was not effective in improving outcome in patients on prolonged mechanical ventilation.
Another potential role for SDD may be in the control of HAI outbreaks. Brun-Buisson et al. [222] reported that intestinal decontamination by oral nonabsorbable antibiotics was important in resolving an outbreak of multiresistant Enterobacteriaceae infections in a medical ICU. In units where routine infection control measures fail to control outbreaks, careful application of SDD, including the selection of appropriate oral antimicrobial agents and diligent monitoring for the emergence of new resistant strains, might be an important adjunct to conventional infection control procedures.
In summary, the use of SDD is more a question of philosophy and art rather than an exact science. We believe that SDD should be restricted to subgroups of patients at high risk of nosocomial pneumonia or to situations in which efficacy and cost effectiveness have been established. If used, surveillance for antimicrobial resistance must be done. Table 24A-6summarizes situations and high-risk patients in which SDD may be beneficial.
Other Measures to Prevent VAP
Coma, prolonged mechanical ventilation through an endotracheal tube, repeated intubation, micro-aspiration events, and permanent supine position increase the risk of VAP [140]. A variety of strategies is recommended to prevent aspiration associated with enteral feeding:
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discontinuation of enteral-tube feeding; removal of endotracheal devices as soon as possible; routine verification of the placement of the feeding tube and the patient's intestinal motility; and elevation of the head at an angle of 30°–45° [223,224]. The latter preventive measure has recently been questioned by a well-performed study by van Nieuwenhoven et al. [225] who showed that placing a patient into a semirecumbent position may be more difficult to achieve than previously thought. In that multicenter study, a 45° patient position did not appear to be achievable, and only a mean position of about 30° was achieved, which was not associated with a reduced VAP incidence [225].
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TABLE 24A-6 |
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Installation of effective drainage of subglottic secretions may reduce the risk for aspiration and VAP, as shown in several randomized trials [226,227]. Aspiration of subglottic secretions requires the use of specially designed endotracheal tubes containing a separate dorsal lumen that opens into the subglottic region. It is a promising new strategy for VAP prevention and should be considered in patients requiring prolonged mechanical ventilation. However, these specialized endotracheal tubes should be part of an organized VAP prevention strategy and should not be used in place of such efforts. In any case, the pressure of the endotracheal tube cuff should be adequate to prevent the leakage of colonized subglottic secretions into the lower airway.
Additional controversial issues surrounding VAP prevention, such as stress ulcer prophylaxis, postpyloric feeding, noninvasive positive-pressure ventilation, and ventilator circuit changes have been addressed in recently published reviews and position papers [140,223,224].
Preemptive Treatment of Fungal Infections
Candida spp infections in ICU patients have become increasingly important, particularly among surgical patients [4,228]. Infections mainly evolve from endogenous colonization facilitated by the use of broad-spectrum antibiotics [229,230]. It has been confirmed that sequential spread of candida spp. colonization from the abdominal cavity to other body sites takes place before candidemia occurs [231]. In heavily colonized surgical ICU patients, Candida spp. colonization was patient specific and always preceded infection with a genotypically identical strain [232]. The intensity of Candida spp. colonization constitutes a strong predictor of subsequent infection [233]. In recognition of the high morbidity and mortality rates associated with those infections [100], an aggressive approach to suspected Candida spp. infections seems justified. Pre-emptive therapy in patients at high risk of infection has been tested in controlled clinical trials [234,235,236].
Multimodal Interventions Under Routine Working Conditions
It is unclear what proportion of ICU-associated HAIs is potentially preventable under routine working conditions. We recently performed a systematic review to describe multimodal intervention studies to provide a crude estimate of the proportion of potentially preventable HAIs [237]. The evaluation of 30 reports suggests that great potential exists to decrease HAI rates from a minimum reduction effect of 10% to a maximum effect of 70%, depending on the study design, baseline infection rates, and type of infection. The most important reduction effect was identified for CR-BSIs, whereas a smaller but still substantial potential for prevention seems to exist for other types of infections.
Although the optimal approach to reducing HAIs in critically ill patients is unclear, recent studies and quality improvement initiatives have shown that education-based programs with multiple interventions can substantially decrease infection rates in different ICUs and settings [238]. For instance, Berenholtz et al. [239] have shown that multifaceted interventions that helped to ensure adherence with evidence-based guidelines nearly eliminated CR-BSIs in a surgical ICU in Baltimore. Education, process control, and feedback also were associated with significant reductions in rates of catheter-related infections in an ICU in Mexico [240]. Use of maximal barrier precautions during CVC insertion is a central part of these interventions and has been shown to be cost effective [241].
The “Bundle Approach”: New Fashion or an Approach for Sustained HAI Prevention?
Approximately 50% of all U.S. hospitals have now joined the Institute for Healthcare Improvement (IHI) initiative, which is a nationwide quality improvement initiative to decrease HAIs and increase patient safety. As defined by IHI (www.ihi.org),
care bundles, in general, are groupings of best practices with respect to a disease process that individually improve care, but when applied together result in substantially greater improvement. The science supporting the bundle components is sufficiently established to be considered standard of care.
Preliminary results posted on the IHI Web site indicate that this initiative has been successful in reducing infection and mortality rates in U.S. hospitals and ICUs.
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Conclusions
Considerable progress has been made in providing intensive care and life support to patients who are acutely ill. Unfortunately, each new technologic advance is accompanied by potential risks for the patient, including HAIs. Clinical research is needed to address the benefits and risks associated with these new interventions. To achieve these objectives, collaboration is needed among critical care physicians, nursing staff, epidemiologists, and infection control professionals to design appropriate studies, interventions, and policies. Administrative and peer support is critical to the success of interventions to reduce HAI rates and improve patient safety. The challenge is to avoid undoing the benefits of intensive care by minimizing risk of complications.
References
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