Bennett & Brachman's Hospital Infections, 5th Edition

24B

The Intensive Care Unit: Part B. Antibiotic Resistance and Prevention of CVC-BSIs, Catheter-Associated Urinary Tract Infections and C. Difficile*

Nasia Safdar

Dennis G. Maki

Introduction

Intensive care units (ICUs) have revolutionized the care of critically ill patients with trauma, shock states, and other life-threatening conditions, leading to greatly improved outcomes [1,2]. However, nosocomial (ICU-acquired) infection remains a major challenge in the ICU patient; rates of infection in the ICU are 3–5 times higher than rates in other hospital wards [3,4]. Although patients in the ICU represent only 10% of all hospital admissions, they account for nearly 50% of all healthcare-associated infections (HAIs) in U.S. hospitals. Major advances in our understanding of the epidemiology and pathogenesis of ICU-acquired infections have occurred over the past two decades leading to the development of measures to greatly reduce or prevent HAIs.

Epidemiology

Currently, HAIs affect more than 2 million patients in U.S. hospitals annually and are associated with approximately 90,000 deaths each year [5].

Surveillance of HAIs, especially in high-risk hospital settings, such as the ICU, has become an integral feature of infection control and quality assurance in all U.S. hospitals. The Centers for Disease Control and Prevention (CDC) Study of the Efficacy of Nosocomial Infection Control

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(SENIC) Project, showed that surveillance can help prevent HAIs [6].

The National Nosocomial Infections Surveillance (NNIS) system was established in the early 1970s to measure the impact of HAIs, better understand their associated risk factors, and develop effective strategies for their control [7]. NNIS, the only national system for tracking HAIs, includes approximately 350 hospitals. The NNIS system is currently being redesigned to cover new areas of patient safety monitoring and evaluation and will soon be called the National Healthcare Safety Network (NHSN). Surveillance of HAIs has been standardized by the NNIS System by providing simple unambiguous definitions, especially for device-associated infections [8]. Targeted surveillance and calculation of device-associated infection rates per 1000 device days allows benchmarking with similar hospitals and detection of unique institutional problems that need redress and a mechanism for assessing institutional trends and even HAI outbreaks.

Since the length of stay heavily impacts the HAI risk, infection rates should be expressed per 1000 patient-days. Device utilization affects device-associated infection rates, and the CDC recommends surveillance of device-associated infection and calculation of rates of device-associated infection per 1000 device days. Rates of HAI vary among the different types of ICUs and are highest in neonatal, surgical, and burn units followed by medical ICUs; Patients in coronary care units have a very low risk of infection (Table 24B-1) [9,10,11].

TABLE 24B-1 RATES OF DEVICE-ASSOCIATED INFECTIONS PER 1000 DEVICE-DAYS BY TYPE OF ICU IN NNIS HOSPITALS, JANUARY 2002–JUNE 2004

Type of ICU Infection Medical rate, mean (25%, 75%) Medical-Surgical rate, mean (25%, 75%) Surgical rate, mean (25%, 75%) Coronary rate, mean (25%, 75%) (Adapted from [11]) Catheter-associated urinary tract infection 5.1 (2.5, 7.1) 3.9 (2.1, 5.2) 4.4 (2.3, 6.5) 4.5 (2.6, 7.5) Central line-associated bloodstream infection 5.0 (2.4, 6.4) 4.0 (2.6, 5.1) 4.6 (2.0, 5.9) 3.5 (1.5, 7.0) Ventilator-associated pneumonia 4.9 (2.1, 6.2) 5.4 (2.6, 7.2) 9.3 (4.7, 12.2) 4.4 (1.9, 6.8)

The epidemiology of ICU-acquired infection in developing countries has recently been characterized by a new large multinational surveillance system in developing countries in South and Central America, Asia, Africa, and the Middle East using NNIS definitions of HAI. In a recent report, overall rates of device-associated infection in 55 ICUs of the consortium were 22.5 infections per 1000 ICU-days; 41% of infections were ventilator-associated pneumonia (VAP), followed by CVC-related bloodstream infection (CVC-BSIs; 12.5 episodes per 1000 catheter-days) and catheter-associated urinary tract infections (CA-UTIs 8.9 episodes per 1000 catheter-days) [12]. These rates are two- to threefold higher than reported in North American ICUs and highlight the extraordinary vulnerability to HAIs in ICUs around the world.

Aerobic gram-negative bacilli, especially Pseudomonas aeruginosa account for 50% of ICU infections; gram-positive cocci (20%) and candida species (10%) make up the remainder [3,4]. Figures 24B-1,24B-2,24B-324B-4 show the microbiology of ICU infection overall and with VAP, CVC-BSIs, and CA-UTIs [4].

General Aspects of Infection Control

The U.S. Joint Commission on Accreditation of Healthcare Organizations (JCAHO) and similar regulatory agencies in many other countries mandate that every hospital have an active program for surveillance, prevention, and control of HAIs [13]. Surveillance is the cornerstone of an effective control program. In most institutions, surveillance focuses on infections caused by antibiotic-resistant bacteria and infections that greatly increase morbidity and mortality (e.g., surgical site infections [SSIs], BSIs and VAP).

Although it is unclear whether environmental contamination with resistant bacteria translates into greater infections in patients, the inanimate environment may be a reservoir of resistant HAI pathogens. Several studies have shown that methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE), Clostridium difficile, and gram-negative bacteria can be recovered from a variety of hospital surfaces. Although the ICU environment cannot be made microbe free, certain architectural and environmental issues warrant attention. ICUs should be located in areas that limit traffic flow to essential ICU personnel. An adequate number of sinks and dispensers of waterless alcohol hand rub or antimicrobial soap must be available for all entering personnel who will have contact with the patient and the immediate

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environment. Separate areas and sinks should be used for cleaning, for storage, and for reprocessing contaminated equipment. All ICUs should have airborne infection isolation rooms for patients with tuberculosis or other airborne infections. For ICUs involved in the care of bone marrow transplant patients or hematologic malignancy, positive-pressure isolation rooms using high efficiency particulate air (HEPA) filtration should be available. All surfaces contiguous to the ICU patient should be wiped down with the general hospital disinfectant at least daily, and urine measuring devices, a frequent reservoir of gram-negative bacilli, should be rinsed with a disinfectant after each use. Each ICU patient should have a dedicated stethoscope and sphygmomanometer.

Figure 24B-1 Microbiology of infections in the ICU. (Adapted from [4])

Figure 24B-2 Microbiology of bloodstream infections in the ICU. (Adapted from [4])

Figure 24B-3 Microbiology of healthcare-associated pneumonia in the ICU. (Adapted from [4])

Figure 24B-4 Microbiology of catheter-associated urinary tract infections in the ICU. (Adapted from [4])

Hand Hygiene

Infected or colonized patients represent the main reservoir of HAIs in the ICU, and the major mechanism of spread of HAI pathogens in the ICU is by carriage on the hands, apparel, or equipment of healthcare workers (HCWs). This has been most clearly shown in outbreak settings and for gram-positive pathogens in studies predating the advent of novel agents such as waterless alcohol-based hand rubs for hand hygiene; the role played by HCWs in horizontal transmission of gram-negative bacilli in the ICU in the presence of waterless alcohol-containing hand rubs remains to be elucidated. In a recent well-conducted cohort study, Waters et al. sought to determine whether or not hand carriage of gram-negative bacilli by neonatal nurses was associated with endemic HAIs caused by gram-negative bacilli in neonates cared for by those nurses [14]. The investigators found that 192/2935 neonates enrolled acquired an infection caused by gram-negative bacilli; 70% of the isolates were available for molecular typing, and 9% (11/119) of strains causing infection were recovered from the hands of neonatal ICU nurses. An additional 33% (39/119) of strains were shared among infants providing indirect evidence of hand carriage by HCWs. In this study, sampling of nurses' hands was performed quarterly immediately after hand hygiene using waterless alcohol-containing hand rubs, and because carriage is typically transient, it is possible that more frequent culturing would have yielded a larger number of shared strains. It is

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important that the role of the environment as a reservoir of HAI gram-negative pathogens was not assessed in this study.

Given the importance of hands as a major vehicle of horizontal transmission, hand hygiene remains the fundamental measure advocated to prevent HAIs [15,16,17,18,19,20]. Despite universal acknowledgement of hand washing as a cornerstone of HAI control programs, compliance rates >50% have been difficult to achieve, and hand-washing rates have ranged from 9% to 50% in HCW studies [21,22].

Recent investigations have strived to better understand the reasons for poor compliance in the face of the compelling evidence of the importance of hand washing for HAI prevention [21], identifying cutaneous irritation, inconvenient sink location, time constraints, high workload, and understaffing. Of concern, risk factors for noncompliance with hand hygiene include being a physician (rather than a nurse), working in an ICU, and, paradoxically, engaging in patient-care activities with a high risk of cross-transmission [21]. Interventions to redress these deficiencies have included targeted education; feedback; convenient location of sinks and hand-hygiene agents; use of alternative, less irritating hand-hygiene agents; and patient education [17]. Table 24B-2 summarizes strategies to enhance compliance with hand hygiene [23].

TABLE 24B-2 STRATEGIES TO IMPROVE HAND-HYGIENE COMPLIANCE

(Adapted from [23]). Healthcare worker education Routine observation and feedback Engineering controls Easy, convenient availability of alcohol-based hand rub Patient education Reminders in workplace Administrative sanctions or rewards Improved skin care for healthcare workers Active participation at individual and institutional level

Hygienic hand care with antiseptics is clearly more effective than conventional hand washing with soap and water; the advantage is most pronounced when contamination is heavy [24,25]. Conventional handwashing with plain soap and water results in minimal reduction or even, paradoxically, an increase in bacterial counts oxcompared to the baseline count before the hand oxwashing (Figure 24B-5) [18,26]. The increase is probably caused by promotion of bacterial release and dispersal through shedding of colonized skin squames [27,28]. In addition to superior antimicrobial activity, some antiseptics, such as chlorhexidine, bind to the stratum corneum, producing long-term anti-infective activity on the skin surface [29].

Figure 24B-5 Immediate bacterial removal with three hand-washing agents. Each agent was studied in 10 individuals with one week between tests. Cultures were obtained immediately before (B) and after (A) hand-washing with the agent. The bacterial count increased after hand washing with soap alone. (Adapted from [18].)

Antiseptics commercially available in the United States in a variety of formulations include chlorhexidine, iodophors, triclosan, Para-chloro-meta-xylenol, and alcohol based products [17]. A number of before–after studies using time-series analysis and HAIs as the primary outcome in ICUs [15,16,30,31,32,33,34] have shown that alcohol-containing waterless hand rubs were associated with oxsignificant HAI reductions. Three large, well-conducted, randomized trials assessing the efficacy of

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oxchlorhexidine-containing hand-hygiene products showed a 27–47% relative reduction in HAIs [30,33,34]. CDC recommendations for hand hygiene have recently been published [35], emphasizing hand antisepsis with an antiseptic containing-soap or detergent, or an alcohol-based hand rub: (1) before and after direct contact with patients or the environment and equipment in the immediate vicinity of the patient and (2) before performing invasive procedures, such as insertion of an intravascular device or urinary catheter. Alcohol-based, waterless hand rubs are now widely used in U.S. hospitals for hand hygiene because of their convenience and broadspectrum activity [17]. However, all have limited efficacy with gross soilage so that visibly soiled hands should always be washed with antiseptic soap and water [36].

The major factor limiting acceptance of alcohol products for hand antisepsis in the past was desiccation and irritation of skin. This is now obviated by incorporating emollients into alcohol-based hand rubs, which has enhanced HCW acceptance and may augment antibacterial activity by slowing the evaporation of alcohol [37]. A recent randomized clinical trial in 50 ICU HCWs compared a conventional 2% chlorhexidine gluconate wash with water to a waterless alcohol-based hand rub (61% ethanol with emollients) and showed that use of the waterless alcohol-based product produced significantly less skin scaling and irritation [38]; unfortunately, degerming was not assessed.

The recent CDC guidelines have been endorsed by the American Medical Association [39] and the American Society for Microbiology [40], both of which have played an active role in emphasizing hand hygiene in all areas of health care. Institutional commitment is essential to improve compliance with recommended hand-hygiene practices. The CDC guideline recommends that institutions (1) monitor and record adherence to hand hygiene by ward or service, (2) provide feedback to HCWs about their performance, and (3) monitor the volume of alcohol hand rub used per 1000 patient-days. Table 24B-3 summarizes the recommendations for hand hygiene in the 2002 CDC Guideline [41].

TABLE 24B-3 HANDWASHING AND HAND ANTISEPSIS RECOMMENDATIONS FROM THE CDC/HICPAC GUIDELINE ON HAND HYGIENE.

Strength of recommendationa (Adapted from [41]) a Categorization of recommendations: IA: strongly supported for implementation and strongly supported by well-designed experimental, clinical or, epidemiologic studies. IB: strongly recommended for implementation and supported by certain clinical or epidemiologic studies and by strong theoretical rationale. II: suggested for implementation and supported by suggestive clinical or epidemiologic studies or by strong theoretical rationale. When hands are visibly dirty or contaminated with proteinaceous material or are visibly soiled with blood or other body fluids, wash hands with either a nonantimicrobial soap and water or an antimicrobial soap and water IA If hands are not visibly soiled, use an alcohol-based hand rub or wash hands with an antimicrobial soap and water for the following situations: IB Before direct contact with patients Before putting on sterile gloves when inserting a central vascular catheter Before inserting a urinary catheter, peripheral vascular catheter, or other invasive procedure not requiring surgery After contact with patient's intact skin After contact with body fluids, mucous membranes, and wound dressings if hands are not visibly soiled Moving from a contaminated body site to a clean body site during patient care After contact with inanimate objects in the immediate vicinity of the patient After removing gloves Before eating and after using a restroom, wash hands with a nonantimicrobial soap and water or with an antimicrobial soap and water IB Antimicrobial-impregnated wipes are not a substitute for using an alcohol-based hand rub or antimicrobial soap IB If exposure to bacillus anthracis, wash hands with nonantimicrobial soap and water or antimicrobial soap and water II

Antimicrobial Resistance in the ICU

The global crisis in antimicrobial resistance has had a huge impact in the ICU where antibiotic pressure, critically ill patients, invasive devices, and procedures all contribute to increase nosocomial spread of multidrug-resistant pathogens (Figures 23B-6 and 23B-7) [42,43,44]. Stemming the tide of antimicrobial resistance mandates a multifaceted approach, encompassing antimicrobial stewardship, hand hygiene, and barrier precautions for HCWs in contact

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with high-risk patients. The CDC's Campaign to Prevent Antimicrobial Resistance aims to prevent antimicrobial resistance in healthcare settings [45]. The campaign centers on four main strategies: prevent infection, diagnose and treat infection, use antimicrobials wisely, and prevent transmission.

Figure 24B-6 The epidemiology of nosocomial infection. Transmission occurs mainly by contact spread to a much lesser extent by the airborne route. Aspiration, surgical wounds, exposure to invasive devices and antimicrobial use amplify transmission, colonization, and susceptibility to infection. (Adapted from [100] with permission.)

Control of Antimicrobial Resistance: Optimizing Antimicrobial Usage

Antimicrobial use drives antimicrobial resistance [46,47]. Studies have shown that inappropriate antimicrobial use is common in healthcare institutions [48,49]. Antimicrobial stewardship is essential to limit unnecessary antimicrobial use, optimize patient outcomes, and reduce the problem of antimicrobial resistance [50]. Various strategies have been proposed to improve antimicrobial use and limit emergence of resistance [43]. These include the use of protocols or guidelines, formulary restriction of key drugs, infectious disease consultation, computerized physician order entry, and increased use of diagnostics to confirm the presence of an infection (Table 24B-4).

Figure 24B-7 Major antimicrobial resistant pathogens associated with nosocomial infections in ICUs in 1989, 1993, 1997 and 2002. (Adapted from National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 to June 2002, issued August 2002 and [4].)

Prevention of Nosocomial Spread of Resistant Organisms

Isolation of infected or colonized patients is widely regarded as the most important measure to prevent spread of

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resistant pathogens through the healthcare institution [51]. The most recent CDC guideline categorizes isolation precautions: (1) standard precautions and (2) transmission-based precautions [52]. Standard precautions specify the use of gloves for any anticipated contact with blood, any body fluid, secretions or excretions (except sweat), nonintact skin, and mucous membranes. Gowns are recommended if patient-care activities are likely to generate splashes of blood, body fluids, and secretions. Hand hygiene is expected after removing gloves and between patients. Standard precautions apply to all patients without regard to clinical diagnosis.

TABLE 24B-4 ANTIMICROBIAL USAGE STRATEGIES FOR REDUCING THE EMERGENCE OF ANTIMICROBIAL RESISTANCE IN THE INTENSIVE CARE UNIT

Recommendation Strength of recommendationa (Adapted from [43]). a Level I, supported by randomized controlled trials; Level II, supported by nonrandomized trials and observational studies. Limit unnecessary antibiotic administration Develop hospital-based guidelines for antibiotic use II Create an antibiotic use quality improvement team II Provide professional education and detailing on antibiotic use for physicians II Restrict hospital formulary II Use quantitative cultures for nosocomial pneumonia I Optimize antimicrobial effectiveness Avoid inadequate treatment by using automated guidelines II Use combination antimicrobial treatment II Consult with infectious diseases staff II Cycling antibiotics II Automatic stop orders for surgical prophylaxis I Avoid routine selective digestive decontamination I Computer–assisted provider order entry II

Transmission-based precautions include contact, droplet, and airborne precautions, each based on the mode of transmission of the infectious agent within the healthcare setting. Acknowledging that multidrug-resistant HAI pathogens, particularly MRSA or VRE, are spread primarily by direct (and indirect) contact with HCWs, the guideline specifies that patients known to be colonized or infected by resistant bacteria are to be placed in contact isolation, which requires a private room for the patient (or cohorting the patient in a semiprivate room with another patient who is also colonized or infected by the same organism). HCWs are expected to wear gloves on entry to the room and gowns if substantial contact with the patient or the environment is anticipated. Gloves and gowns should be removed and hands treated with a medicated hand-hygiene product while still in the isolation room. Noncritical patient-care items should be dedicated; if reused, they must be disinfected between patients.

Unfortunately, the existent paradigm for preventing spread of resistant organisms in the hospital—waiting until colonization or infection by MRSA, VRE or some other resistant organism is serendipitously identified by the clinical laboratory, following which the patient is placed in isolation, usually in a single room, requiring the use of gloves, with or without a gown, for all contacts with the patient—is failing dismally, viewing the inexorable growth in antimicrobial resistance [53].

A recent guideline from the Society for Healthcare Epidemiology of America [54] recommends that surveillance cultures to detect silent VRE or MRSA carriage be performed in roommates of VRE- or MRSA-colonized or infected patients and other high-risk patients at the discretion of infection control staff; patients found to be colonized must also be placed in contact isolation [54]. If these measures fail to contain spread, efforts should be intensified in the highest risk areas, such as the ICU. Cohorting of staff and screening of staff for carriage, if epidemiologic data point to a link, is recommended. Verification that environmental disinfection procedures are effective by environmental surveillance cultures before and after cleaning areas containing VRE- or MRSA-colonized or infected patients also is recommended.

We believe that a simpler strategy for preventing spread of all types of multidrug-resistant bacteria is the preemptive use of barrier isolation precautions (gowns and gloves) and dedicated patient-care items (e.g., stethoscopes and sphygmomanometers) for all high-risk patients from the time of admission to prevent HCWs from acquiring

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hand contamination by multidrug-resistant organisms when they have contact with patients with unrecognized colonization or infection and block transmission to other as yet uncolonized patients. Numerous studies have shown that the preemptive use of barrier precautions, also called “protective isolation,” can effectively prevent the spread of multidrug-resistant organisms, such as MRSA or VRE, in an epidemic setting [55], and other studies have shown the effectiveness of protective isolation in high-risk populations, such as patients in an ICU, for prevention of endemic HAIs, including by multidrug-resistant organisms [56,57,58,59]. Three prospective randomized trials have been conducted to assess the efficacy of preemptive barrier precautions [56,57,60]; two showed benefit with a reduction in all HAIs in ICU patients (relative risk reduction, 52–81%) [56,57].

Specific Infections

Intravascular Device-Related Bloodstream Infections

The use of intravascular devices has become an essential component of delivering care to patients with cancer. Unfortunately, vascular access is associated with substantial and generally underappreciated potential for producing iatrogenic disease, particularly BSIs originating from infection of the percutaneous device used for vascular access. Nearly 40% of all nosocomial BSIs derive from vascular access in some form [61] and can be associated with excess mortality approaching 35% [62], increased length of hospitalization, and excess healthcare costs [63,64].

Individual types of intravascular devices (IVDs) pose different risks of infection. In a recent systematic review of 200 prospective studies, we showed that point incidence rates of IVD-related BSI were lowest with peripheral Intravenous (0.1%, 0.5 per 1000 IVD-days) or midline catheters (0.4%, 0.2 per 1000 catheter-days). Far higher rates were seen with short-term noncuffed and nonmedicated central venous catheters (CVCs) (4.4%, 2.7 per 1000 catheter-days). Arterial catheters used for hemodynamic monitoring (0.8%, 1.7 per 1000 catheter-days) and peripherally inserted central catheters (PICCs) used in hospitalized patients (2.4%, 2.1 per 1000 catheter-days) posed risks approaching those seen with short-term conventional CVCs used in the ICU. Surgically implanted long-term central venous devices—cuffed and tunneled catheters (22.5%, 1.6 per 1000 IVD-days) and central venous ports (3.6%, 0.1 per 1000 IVD-days)—appear to have high rates of infection when risk is expressed as BSIs per 100 IVDs but actually pose much lower risk when rates are expressed per 1000 IVD-days [65].

Figure 24B-3 summarizes the microbial profile of IVD-related BSIs (IVDR-BSIs) [4]. As might be expected from knowledge of the pathogenesis of these infections, skin microorganisms account for the largest proportion of IVDR-BSIs.

Recent evidence-based guidelines provide the best current information on the evaluation of the ICU patient with fever or other signs of sepsis [66]. Before any decision regarding initiation of antimicrobial therapy or removal of an IVD, the patient must be thoroughly examined to identify all plausible sites of infection, including ventilator-assisted pneumonia (VAP), CA-UTI, SSI, antibiotic-associated colitis, or line sepsis.

Despite the challenge of identifying the source of a patient's signs of sepsis [66], several clinical, epidemiologic, and microbiologic findings point strongly toward an IVD as the source of a septic episode. Patients with abrupt onset of signs and symptoms of sepsis without any other identifiable source should prompt suspicion of infection of an IVD. The presence of inflammation or purulence at the catheter insertion site is now uncommon in patients with IVDR-BSI [67]. However, if purulence is seen in combination with signs and symptoms of sepsis, it is highly likely the patient has IVDR-BSI and should prompt removal of the IVD. Finally, recovery of certain microorganisms in multiple blood cultures (e.g., Staphylococci,Corynebacterium or Bacillus species, or Candida or Malassezia spp.) strongly suggests infection of the IVD.

It is indefensible to start anti-infective drugs for suspected or presumed infection in the critically ill patient without first obtaining blood cultures from two separate sites, at least one of which is drawn from a peripheral vein by percutaneous venipuncture. In adults, if at least 30 milliliter (mL) of blood is cultured, 99% of detectable bacteremias should be identified [68,69,70]. Similar operating characteristics are achieved in the pediatric population using a weight-based graduated volume approach to blood cultures [71]. Standard blood cultures drawn through CVCs provide excellent sensitivity for diagnosis of BSI but are less specific than cultures obtained from a peripheral vein [72,73]. If the patient has a long-term multilumen catheter, a specimen should be obtained from each lumen of the catheter because studies have found a high rate of discordance (~30%) between cultures obtained from different lumens of the same catheter [74].

Short-term IVDs should be removed from the outset in unstable patients with suspected IVDR-BSI (as follows); however, it often is undesirable or difficult to do this in patients with surgically implanted IVDs, such as Hickman and Broviac catheters. Only 15–45% of long-term IVDs that are removed for suspected infection are truly colonized or infected at the time of removal [75,76,77]. To avoid unnecessary removal of IVDs, methods have been developed to identify infection while allowing the device to stay in place: (1) paired quantitative blood cultures drawn from the IVD and percutaneously from a peripheral vein [78], (2) differential time to positivity (DTP) of paired standard blood cultures, one drawn from the IVD, the second from a peripheral vein [79], and (3) gram stain [80] or acridine orange staining of blood samples drawn through the IVD [81,82].

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Quantitative blood cultures are labor intensive and cost almost twice as much as standard blood cultures. The DTP of paired blood cultures, one drawn through the IVD and the second concomitantly from a peripheral vein, has been shown to reliably identify IVDR-BSI of both short-term and long-term IVDs if the blood culture drawn from the IVD turns positive ≥2 hours before the culture drawn peripherally [83].

If a short-term vascular catheter is suspected of being infected because the patient has no obvious other source of infection to explain fever, there is inflammation at the insertion site, or cryptogenic staphylococcal sp. BSI or candidemia has been documented, blood cultures should be obtained and the catheter should be removed and cultured. Failure to remove an infected catheter puts the patient at risk of developing septic thrombophlebitis with peripheral IV catheters, septic thrombosis of a great central vein with CVCs [84], or even endocarditis. Continued access, if necessary, can be established with a new catheter inserted in a new site. Although small studies have found some utility of guidewire exchange in the management of CVCs suspected of being infected [85,86,87,88], we believe that, in the absence of randomized studies demonstrating its safety, guidewire exchange generally should not be performed if there is suspicion of IVDR-BSI, especially if there are signs of local infection such as purulence or erythema at the insertion site or signs of systemic sepsis without a source. In these instances, the old catheter should be removed and cultured and a new catheter should be inserted in a new site.

Prevention of IVDR-BSI

An updated guideline for the prevention of IVDR-BSIs was published in 2002 by the CDC's Healthcare Infection Control Practices Advisory Committee (HICPAC) (Table 24B-5) [89].

Ventilator-Associated Pneumonia

Mechanical ventilation is an essential feature of modern ICU care. Unfortunately, mechanical ventilation is associated with a substantial risk of VAP, the most common HAI in the ICU with an incidence ranging from 9–40% [90,91,92]; it is associated with prolonged hospitalization [93,94,95], increased healthcare costs [96], and a 15–45% attributable mortality [97,98,99].

Understanding the pathogenesis of VAP is essential to devising strategies for prevention of these infections [100]. Advances in our understanding of pathogenesis have led to the development of specific measures that can greatly reduce the risk of VAP [101,102,103,104].

In the mechanically ventilated patient, a number of factors conspire to compromise host defenses: critical illness, co-morbidities [105], and malnutrition impair the immune system [106], and, most important, endotracheal intubation thwarts the cough reflex [107], compromises mucociliary clearance [108], injures the tracheal epithelial surface [109], and provides a direct conduit for rapid access of bacteria from above into the lower respiratory tract [110,111]. It probably would be more accurate pathogenetically to rename VAP as “endotracheal intubation-related pneumonia.” Invasive devices and procedures and antimicrobial therapy create a favorable milieu for antimicrobial-resistant HAI pathogens to colonize the aerodigestive tract [112]. This combination of impaired host defenses and continuous exposure of the lower respiratory tract to large numbers of potential pathogens through the endotracheal tube (Figure 24B-8) [113] put the mechanically ventilated patient at great jeopardy of developing VAP.

For microorganisms to cause VAP, they first must gain access to the normally sterile lower respiratory tract where they can adhere to the mucosa and produce sustained infection. Microorganisms gain access by one of four mechanisms: (1) aspiration of microbe-laden secretions, either from the oropharynx directly or, secondarily, by reflux from the stomach into the oropharynx and then into the lower respiratory tract [114,115,116], (2) direct extension of a contiguous infection, such as a pleural space infection, (3) inhalation of contaminated air or medical aerosols, and (4) hematogenous carriage of microorganisms to the lung from remote sites of local infection, such as CVC-BSI.

Outbreaks of VAP due to contamination of respiratory therapy equipment [117,118,119,120,121,122,123,124,125] and diagnostic equipment, such as bronchoscopes and endoscopes, have been well described [126,127,128,129,130,131,132]. For example, Takigawa et al. reported 16 episodes of hospital-acquired pneumonia due to Burkholderia cepacia caused by contamination of inhaled medication nebulizer reservoirs [125]. Likewise, Srinivasan et al. reported 28 episodes of pneumonia caused by P. aeruginosa linked epidemiologically to contaminated bronchoscopes with defective biopsy-port caps [132]. This outbreak occurred despite adherence to disinfection and sterilization guidelines [133].

Since the first reports of large outbreaks of severe acute respiratory syndrome (SARS) in 2003 in which more than 8,000 persons in China, Hong Kong, Singapore, Vietnam, Taiwan, and Canada ultimately became infected and 9.6% died [134], major advances have been made in our understanding of the epidemiology and mode of transmission of this new human Coronavirus [135]. SARS spreads almost exclusively through respiratory droplets from person to person, rarely by the airborne or contact route. The risk of SARS acquisition is far higher in the hospital than in the community, and nearly one-half of the early episodes involved HCWs or hospitalized patients infected secondarily upon admission [136]. Although SARS has been contained for now, if it returns, it will comprise an ongoing threat to patients and HCWs as a cause of nosocomial pneumonia. Outbreaks of other respiratory pathogens, such as Legionella spp., influenza A or respiratory syncytial virus, are well described in nosocomial settings [65,66,67,68,69,70,71].

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TABLE 24B-5 SUMMARY OF CDC/HICPAC GUIDELINE FOR PREVENTION OF INTRAVASCULAR DEVICE-RELATED BLOODSTREAM INFECTION

Strength of recommendationa (Adapted from [89]). Note: BSI, bloodstream infection; CVC, central venous catheter; IVD, intravascular device; PICC, peripherally inserted central catheters. a Taken from the CDC/HICPAC system of weighting recommendations based on scientific evidence. IA: strongly supported for implementation and strongly supported by well-designed experimental, clinical, or epidemiologic studies. IB: strongly recommended for implementation and supported by certain clinical or epidemiologic studies and by strong theoretical rationale. IC: required for implementation as mandated by federal or state regulation or standard. II: suggested for implementation and supported by suggestive clinical or epidemiologic studies or by strong theoretical rationale. NR: no recommendation for or against at this time; unresolved issue involves practices for which insufficient evidence or no consensus exists about efficacy. General measures Educate all healthcare workers involved in intravascular device (IVD) care and maintenance IA Ensure adequate nursing staff levels in intensive care units (ICUs) IB Surveillance Monitor institutional IVD infection rates of IVD-related bloodstream infection (BSI) IA Express rates of CVC-related BSIs per 1000 CVC days IB At catheter insertion Aseptic technique: Hand hygiene before insertion or manipulation of any IVD IA Clean or sterile gloves during insertion and manipulation of noncentral IVDs IC Maximal barrier precautions during insertion of central venous catheters (CVCs): mask, cap, sterile gown, gloves and drapes IA Dedicated IVD team strongly recommended IA Chlorhexidine first choice for cutaneous antisepsis IA Subclavian vein rather than internal jugular vein catheter insertion IA Use of sutureless securement device NR Sterile gauze or a semipermeable polyurethane dressing to cover site IA No systemic or topical antibiotics at insertion IA Maintenance Remove IVD as soon as no longer required IA Monitor IVD site daily IB Change dressing of CVC insertion site at least weekly II Do not use topical antibiotic ointments IA Change needleless IV systems at least as frequently as the administration set; replace caps no more frequently than every 3 days or per manufacturers' recommendations II Complete lipid infusions within 12 hours IB Replace administration sets no more frequently than every 72 hours. When lipid-containing admixtures or blood products are given, sets should be replaced every 24 hours; with propofol every 6–12 hours IA Replace peripheral IVs every 72–96 hours IB Do not routinely replace CVCs or PICCs solely because of fever unless IVD infection is suspected, but replace catheter if there is purulence at the exit site, especially if the patient is hemodynamically unstable and IVD-related-BSI is suspected IB Technology Use antimicrobial-coated or antiseptic-impregnated CVC in adult patients if institutional rate of BSI is high despite consistent application of preventive measures and catheter likely to remain in place >5 days IB Use chlorhexidine-impregnated sponge dressing for patients with uncuffed CVCs or other catheters likely to remain in place for >5 days NR Use prophylactic antibiotic lock solution only in patients with long-term IVDs who have continued to experience IVD-related BSIs despite consistent application of infection control practices II

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Figure 24B-8 of colonization/infection in mechanically ventilated patients. Colonization of the aerodigestive tract may occur endogenously (A and B) or exogenously (C–F). Exogenous colonization may result in primary colonization of the oropharynx or may be the result of direct inoculation into the lower respiratory tract during manipulations of respiratory equipment (D), during using of respiratory devices (E), or from contaminated aerosols (E). (From [113].)

In the mid-1980s, tuberculosis (TB) rates in the United States rose after half a century of decline, and large nosocomial outbreaks with multidrug-resistant strains occurred. In one such outbreak investigated by the CDC, six episodes of TB occurred following exposure to a source-patient who had spent several weeks in the hospital before being placed in respiratory isolation [137]. Transmission of Mycobacterium tuberculosis through contaminated bronchoscopes and respiratory equipment also has been reported [138,139].

Although reported pseudo-outbreaks with nontuberculous mycobacteria far outnumber epidemics of true disease, HAI outbreaks caused by these ubiquitous environmental organisms are well described, most often in association with contaminated hospital water [140,141,142].

For most endemic VAPs, the most important mechanism of infection is aspiration of oropharyngeal organisms into the distal bronchi followed by bacterial proliferation and parenchymal invasion. Inflammation of the bronchiole wall involves the alveolar septi and airspaces leading to bronchopneumonia.

Pathogens causing VAP may be part of the host's endogenous flora at the time of hospitalization or may be acquired exogenously after admission to the healthcare facility from the hands, apparel, and equipment of HCWs, the hospital environment, and the use of invasive devices.

Although most VAP epidemics have stemmed from direct infection of the lower airway by exogenous organisms, such as gram-negative bacilli, Legionella spp., and aspergillus spp., epidemics can be more insidious with colonization of the upper airway and episodes of VAP occurring days or weeks later.

The normal flora of the oropharynx in the nonintubated patient without critical illness is composed predominantly of viridans streptococci, hemophilus spp., and anaerobes. Salivary flow and content (immunoglobulin, fibronectin) are the major factors maintaining the normal flora of the mouth (and dental plaque). Aerobic gram-negative bacilli rarely are recovered from the oral secretions of healthy patients [143,144]. During critical illness, especially in ICU patients, the oral flora shifts dramatically to colonization by aerobic gram-negative bacilli and S. aureus [145]. Bacterial adherence to the oro-tracheal mucosa of the mechanically ventilated patient is facilitated by reduced mucosal IgA and increased protease production, exposed and denuded mucous membranes, elevated airway pH, increased numbers of airway receptors for bacteria due to acute illness, and antimicrobial use.

A large number of studies show that colonization of the oropharynx by aerobic gram-negative and gram-positive pathogens, such as S. aureus, is a near-universal

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occurrence in critically ill patients receiving mechanical ventilation [114,115,116,146,147,148,149]. In a study of 80 ventilated patients, Torres et al. found that in 19 patients with secondary tracheal colonization, 46% of the microorganisms isolated in the trachea already had been isolated in the pharynx [114]. George et al. reported similar findings with 42% of the pathogens isolated in 26 patients with VAP previously recovered from the oropharynx [116]. In a more recent study performed in 48 trauma patients, Ewig et al. found that upon admission to the ICU, patients were colonized mainly with S. aureus, H. influenzae, or Streptococcus pneumoniae. However, follow-up cultures showed replacement of the normal oropharyngeal flora by enteric gram-negative bacilli and P. aeruginosa. Oropharyngeal colonization was a powerful independent predictor of subsequent tracheobronchial colonization ([Odds Ratio] OR 23.9, 95% [Confidence Interval] CI 3.8–153.3) [115].

Aspiration of oropharyngeal contents containing a large bacterial inoculum overwhelms host defenses already compromised by critical illness and the presence of an endotracheal tube, thus leading to the development of VAP.

Understanding this sequence of pathophysiologic events, it would seem logical that reducing concentrations of oral microorganisms should have a beneficial effect on VAP prevention. Five studies have evaluated the use of scheduled oral care with a chlorhexidine antiseptic solution for prevention of VAP [150,151,152,153,154]; chlorhexidine oral care reduced the incidence of oral microbial colonization and VAP. The use of chlorhexidine for oral antisepsis warrants further study and consideration for application in clinical practice.

The stomach has been posited to be an important reservoir of organisms that cause VAP [155]. In healthy persons, few bacteria entering the stomach survive in the presence of gastric acid. Conditions that reduce the gastric pH (e.g., achlorhydria, H2 antagonists, and enteral nutrition) predispose to bacterial proliferation in the stomach [156,157,158,159]. Several studies have shown a powerful relationship between a high gastric pH and massive overgrowth of gastric bacteria [156,157,158,159]. Gastric microorganisms reflux up the esophagus abetted by recumbent position and the ever-present naso- or oro-gastric tube and are aspirated into the trachea. Direct and indirect evidence exists to implicate the stomach as a potential reservoir of bacteria causing VAP [160,161,162]. Numerous studies have shown that gastric contents can be aspirated into the lower airways despite the presence of an endotracheal cuff [163,164]. However, recent literature suggests that the stomach, although a reservoir for enteric gram-negative bacteria, is not the primary site for colonization of pathogens and that the gastropulmonary route is not a major pathogenic route for development of VAP [146,165]. In a prospective, randomized, double-blind study in ICU patients, Bonten et al. compared antacids and sucralfate and measured intragastric acidity. Colonization by Enterobacteriaceae occurred in the stomach, trachea, and oropharynx; however, intragastric acidity did not influence the incidence of VAP [166]. In another analysis of the same study, the same investigators showed that oropharyngeal colonization by Enterobacteriaceae was an important independent risk factor for VAP; in contrast, gastric colonization by Enterobacteriaceae was not found to increase the risk of VAP [167].

The diagnostic criteria and tests for VAP include clinical criteria, qualitative or quantitative endobronchial cultures, bronchoalveolar lavage (BAL) or culture of protected specimen brush samples obtained by bronchoscopic techniques, and specimens, including bronchial washings, mini-BAL, or protected specimen brush samples, obtained by blind non bronchoscopic procedures. Clinical criteria (e.g., fever, leukocytosis, purulent secretions, new or changing radiographic infiltrate) have high sensitivity but relatively low specificity. Clinical criteria are useful for initial screening for VAP and for selecting patients for invasive procedures that have sensitivities and specificities in the range of 80% [168]. The optimal methods for defining VAP in clinical practice and the impact of different diagnostic techniques on patient outcome are the subject of much debate [169].

NNIS data show that, based on clinical diagnosis, the most common pathogens isolated from pneumonia in patients in ICUs are S. aureus, P. aeruginosa, Enterobacter spp., andKlebsiella pneumoniae, with varying prevalences depending on the type of ICU [11] (Figure 24B-6). Early onset VAP, which manifests within the first 4 days of hospitalization, more often is caused by community-acquired pathogens, such as S. pneumoniae and Haemophilus spp.. When invasive techniques are used to diagnose VAP, the frequency of recovery of enteric gram-negative bacilli decreases from 50–70% of isolates to 35–45%. VAP is polymicrobial in as many as 20–40% of patients. A number of recent studies have shown that anaerobes do not play a major role in VAP [170].

Control Measures

A number of nonpharmacologic and pharmacologic preventive measures have been recommended for clinical use in ICUs (Table 24B-6) [171]. The use of nonabsorbable oral antibiotics to eradicate or reduce gastrointestinal carriage of pathogenic bacteria, a process widely termed selective digestive decontamination (SDD), has been extensively studied [172,173]. A short course of parenteral antimicrobials and a longer duration of topical antimicrobials have been used in most studies evaluating the efficacy of SDD for the prevention of VAP. More than 40 randomized controlled trials [174,175,176] and eight meta-analyses [177,178,179,180,181] have undertaken to determine the efficacy of SDD for reducing the incidence of VAP; most, but not all, have found a beneficial effect on VAP but an inconsistent effect on ICU mortality. Regardless of efficacy, a very real concern relates to the potential for antimicrobial resistance with long-term use of SDD [182,183]. Recent studies have justified this

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concern and further dampened enthusiasm for this approach. Moreover, most of the studies were not designed to assess the relative effect of the components of SDD (topical and systemic) on the prevention of VAP. Future studies need to more clearly evaluate antimicrobial resistance as a major endpoint, including the use of selective media for surveillance cultures to enhance recovery of nosocomial, antibiotic-resistant pathogens.

TABLE 24B-6 MEASURES FOR PREVENTION OF VENTILATOR-ASSOCIATED PNEUMONIA

Recommendation Strength of recommendationa (Adapted from [171]). Note: MDR, multidrug resistant; VAP, ventilator-associated pneumonia; HAP, hospital-acquired pneumonia. a Level I, supported by randomized controlled trials; Level II, supported by nonrandomized trials and observational studies. General prophylaxis Effective infection control measures: staff education, compliance with alcohol-based hand disinfection, and isolation to reduce cross-infection with MDR pathogens should be used routinely I Surveillance of ICU infections to identify and quantify endemic and new MDR pathogens and prepare timely data for infection control and to guide appropriate antimicrobial therapy in patients with suspected HAP or other nosocomial infection, are recommended II Intubation and mechanical ventilation Intubation and ventilation should be avoided, if possible, because it increases the risk of VAP I Noninvasive ventilation should be used whenever possible in selected patients with respiratory failure I Orotracheal intubation and orogastric tubes preferred over nasotracheal intubation and nasogastric tubes to prevent nosocomial sinusitis and to reduce the risk of VAP II Continuous aspiration of subglottic secretions can reduce the risk of early-onset VAP and should be used, if available I Endotracheal tube cuff pressure should be maintained >20 cm H2O to prevent leakage of bacterial pathogens around the cuff into the lower respiratory tract II Contaminated condensate should be carefully emptied from ventilator circuits and condensate should be prevented from entering either the endotracheal tube or inline medication nebulizers II Passive humidifiers or heat-moisture exchangers decrease ventilator circuit colonization but have not consistently reduced the incidence of VAP; thus, they cannot be regarded as a pneumonia prevention tool I Reduced duration of intubation and mechanical ventilation may prevent VAP and can be achieved by protocols to improve the use of sedation and to accelerate weaning II Maintaining adequate staffing levels in the ICU can reduce length of stay, improve infection control practices, and reduce duration of mechanical ventilation II Aspiration, body position, and enteral feeding Patients should be kept in the semirecumbent position I Enteral feeding is preferred over parenteral nutrition I Modulation of colonization: oral antiseptics and antibiotics Selective decontamination of the digestive tract is not recommended for routine use II Prior administration of systemic antibiotics has reduced the risk of nosocomial pneumonia in some patient groups, but if a history of prior administration is present at the time of onset of infection, there should be increased suspicion of infection with MDR pathogens II Prophylactic administration of systemic antibiotics for 24 hours at the time of emergent intubation has been demonstrated to prevent ICU-acquired HAP in patients with closed head injury, but routine use is not recommended until more data become available I Routine use of oral chlorhexidine is not recommended until more data become available I Use daily interruption or lightening of sedation to avoid constant heavy sedation and try to avoid paralytic agents II Stress bleeding prophylaxis, transfusion, and hyperglycemia If needed, stress bleeding prophylaxis with either H2 antagonists or sucralfate is acceptable Transfusion of red blood cell and other allogeneic blood products should follow a restricted transfusion trigger policy; leukocyte-depleted red blood cell transfusions can help to reduce HAP in selected patient populations Intensive insulin therapy is recommended to maintain glucose levels between 80 and 110 mg/dl in ICU patients I

Use of sucralfate rather than H₂ blockers for stress ulcer prophylaxis, with a goal of maintaining gastric pH and thereby suppressing gastric colonization by potential VAP pathogens, initially appeared to be a promising preventive strategy but was not effective in a large, multi-center, randomized trial [143]. Preventive measures aimed at reducing the risk of aspiration, particularly by semirecumbent positioning of patients, have been among

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the more successful and less costly strategies. Measures aimed at improving host and lung defenses against aspirated pathogens are not yet ready for implementation.

Clostridium difficile-Associated Diarrhea

Clostridium difficile is the major infectious cause of nosocomial diarrhea and is associated with prolonged hospitalization and increased hospital costs [184]. The incidence of infection with this organism is increasing in hospitals worldwide due to the widespread use of broadspectrum antibiotics, with reported rates ranging from 1 to 10 episodes per 1000 discharges and 17 to 60 episodes per 100,000 bed-days [185].

Clostridium difficile infection encompasses a spectrum of conditions ranging from asymptomatic colonization to fulminant disease with toxic megacolon [186]. The usual presentation is acute watery diarrhea with lower abdominal pain and fever occurring during or shortly after beginning antimicrobial therapy. The antibiotics that most predispose to C. difficileinfection are third- or fourth-generation cephalosporins, clindamycin, and penicillins [187]; however, virtually any antimicrobial may trigger C. difficile infection.

Diagnosis of C. difficile-associated diarrhea can be reliably made by detection of C. difficile toxins A and/or B by enzyme-linked immunoassay (ELlSA) in a stool sample [188]. If this test is negative and C. difficile infection is strongly suspected, cytotoxin testing, widely regarded as the reference standard, should be performed. This test, while 94–100% sensitive and 99% specific, takes at least 48–72 hours before results are available. In severely ill patients, flexible sigmoidoscopy provides a rapid means of diagnosis because 90% of episodes of pseudo mebranous colitis involve the left side of the colon; the visualization of colonic pseudo membranes is essentially pathognomonic for C. difficile infection. Computerized tomography (CT) of the abdomen, while useful for identifying bowel wall thickness, does not differentiate between C. difficile and other causes of bowel wall thickening, such as ischemic colitis [189].

Clostridium difficile has become a major HAI pathogen widely prevalent in healthcare facilities, and control of nosocomial transmission is essential. A growing body of literature suggests that the inanimate environment may contribute to nosocomial transmission of C. difficile. Commonly used hospital disinfectants are not germicidal against C. difficilespores, which may persist for very prolonged periods on surfaces. A recent before–after study using sodium hypochlorite solution to disinfect a bone-marrow transplant ward found that rates of C. difficile infection decreased from 8.3 per 1000 patient-days to 3.4 per 1000 patient-days; when hypochlorite disinfection was discontinued, rates returned to baseline levels [190].

The Society for Healthcare Epidemiology of America has published a guideline for prevention and treatment of C. difficile infections (Table 24B-7) [191]. Patients with C. difficile-associated diarrhea should be placed in private rooms, and staff should wear gowns and gloves for all contacts with the patient. Hand hygiene with an antiseptic agent is essential. It is important to note that alcohol-based hand rubs do not have activity against the spore form of C. difficile. Equipment such as stethoscopes and sphygmomanometers should be dedicated to the patient, and consideration should be given to disinfecting the environment with sodium oxhypochlorite.

Catheter-Associated Urinary Tract Infection

Each year, urinary catheters are inserted in >5 million patients in acute-care hospitals and extended-care facilities [192]. CA-UTI is the most common HAI in hospitals and nursing homes, comprising >40% of all institutionally acquired infections [11]. Nosocomial bacteriuria or candiduria develops in up to 25% of patients requiring a urinary catheter for ≥7 days with a daily risk of 5% [192]. CAUTI is the second most common cause of nosocomial bloodstream infection [193]; some studies also have found increased mortality associated with it [194]. Although most CAUTIs are asymptomatic [195], rarely extend hospitalization, and add only $500 to $1,000 to the direct costs of acute-care hospitalization [196], asymptomatic infections commonly precipitate unnecessary antimicrobial therapy [197]. CAUTIs comprise perhaps the largest institutional reservoir of nosocomial antibiotic-resistant pathogens, the most important of which are multidrug-resistant Enterobacteriacae other than Escherichia coli, such as Klebsiella, Enterobacter, Proteus, or Citrobacter; Pseudomonas aeruginosa; enterococci and staphylococci; and Candida spp [198].

Excluding rare hematogenously derived pyelonephritis, caused almost exclusively by S. aureus, most microorganisms causing endemic CAUTI derive from the patient's own colonic or perineal flora or from the hands of HCWs during catheter insertion or manipulation of the collection system [199]. Organisms gain access in one of two ways. Extraluminal contamination may occur early by direct inoculation when the catheter is inserted or later by organisms ascending from the perineum by capillary action in the thin mucous film contiguous to the external catheter surface. Intraluminal contamination occurs by reflux of microorganisms gaining access to the catheter lumen from failure to maintain closed drainage or contamination of urine in the collection bag. Recent studies suggest that CAUTIs most frequently stem from microorganisms gaining access to the bladder extraluminally [200], but both routes are important.

Most infected urinary catheters are covered by a thick biofilm containing the infecting microorganisms embedded in a matrix of host proteins and microbial exoglycocalyx [201]. A biofilm forms intraluminally, extraluminally, or both ways, usually advancing in a retrograde fashion. The role of biofilms in the pathogenesis of CAUTI has

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not been established. However, anti-infective-impregnated or silver-hydrogel catheters, which inhibit adherence of microorganisms to the catheter surface, significantly reduce the risk of CAUTI [202], particularly infections caused by gram-positive organisms or yeasts, which are most likely to be acquired extraluminally from the periurethral flora. These data suggest that microbial adherence to the catheter surface is important in the pathogenesis of many, but not all, CAUTIs. Infections in which the biofilm does not play a pathogenetic role probably are caused by mass transport of intraluminal contaminants into the bladder by retrograde reflux of microbe-laden urine when a catheter or collection system is moved or manipulated.

TABLE 24B-7 PREVENTION AND CONTROL OF CLOSTRIDIUM DIFFICILE-ASSOCIATED DIARRHEA (CDAD)

Recommendation Strength of recommendationa (Adapted in part from the 2002 Society for Healthcare Epidemiology of America guidelines for the prevention of Clostridium difficile associated diarrhea, [191], and [207]). Category: A = good evidence to support are commendation for use. B = moderate evidence to support are commendation for use. Quality of evidence: I = Evidence from ≥ properly randomized controlled trial. II = evidence from ≥1 well-designed observational study, multiple time-series, or dramatic results of uncontrolled experiments. III = expertopinion, descriptive studies. Surveillance and diagnosis Surveillance for CDAD should be performed in every institution B-III Appropriate and prompt diagnostic testing should be performed in patients with antibiotic-associated diarrhea A-II Diagnostic tests for C. difficile should be performed only on diarrheal (soft or unformed) stool specimens unless ileus is suspected B-III Testing of stool specimens from asymptomatic patients for C. difficile (including “test of cure” after treatment) B-II Prevention and control Implement policies to ensure prudent antimicrobial use A-II Surveillance of antimicrobial utilization in the facility should be conducted B-III Healthcare providers in the facility should be educated about the epidemiology of CDAD B-III Patients with CDAD and fecal incontinence should be in a private room. If possible, all patients with CDAD should be in private rooms B-III Meticulous hand hygiene with soap or an antiseptic agent is recommended after contact with patients, their body substances, or their potentially contaminated environment B-III Healthcare providers should wear gloves for contact with patients with CDAD A-I Use of disposable, single-use thermometers (rather than shared electronic thermometers) is recommended A-II Patient-care items, such as stethoscopes and sphygmomanometers, should be dedicated. If they must be shared, they should be disinfected between patients B-I Disinfection of the environment of a patient with CDAD should be done using sporocidal agents, such as a diluted sodium hypochlorite solution B-II Patients with CDAD may be removed from contact isolation when their diarrhea has resolved B-III

Several catheter-care practices are universally recommended to prevent or at least delay the onset of CAUTI (Table 24B-8) [199,203]: avoid unnecessary catheterizations, consider a condom or suprapubic catheter, have a trained HCW insert the catheter aseptically, remove the catheter as soon as no longer needed, maintain closed drainage, ensure dependent drainage, minimize manipulations of the system, and separate catheterized patients.

Technologic innovations to prevent HAIs are likely to be most effective if they are based on a clear understanding of the pathogenesis and epidemiology of the infection. Novel technologies must be designed to block CAUTI by either the extraluminal or intraluminal routes or both. Impregnated catheters, which reduce adherence of microorganisms to the catheter surface, may confer the greatest benefit for preventing CAUTI. Two catheters impregnated with anti-infective solutions have been studied in randomized trials, one impregnated with the urinary antiseptic nitrofurazone [204] and the other with a new broadspectrum antimicrobial combination of minocycline and rifampin [205]. Both catheters showed a significant reduction in bacterial CAUTIs; however, the studies were small, and selection of antimicrobial-resistant uropathogens was not satisfactorily resolved. Silver compounds also have been studied for coating urinary catheters. A meta-analysis of 8 randomized trials comparing silver oxide or silver alloy catheters with standard nonimpregnated catheters found that silver alloy but not silver oxide catheters were associated with a threefold reduced risk of CAUTI [206].

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TABLE 24B-8 CENTERS FOR DISEASE CONTROL AND PREVENTION GUIDELINE FOR PREVENTION OF CATHETER-ASSOCIATED URINARY TRACT INFECTION

Recommendation Strength of recommendationa (Adapted from [203]) Note: NR, no recommendation a Level I, supported by randomized controlled trials Level II, supported by nonrandomized trials and observational studies III Educate personnel in correct techniques of catheter insertion and care I Periodically reeducate personnel in catheter care II Catheterize only when necessary II Consider alternative techniques of urinary drainage before using an indwelling urethral catheter III Emphasize hand hygiene I Insert catheter using aseptic technique and sterile equipment I Use smallest bore catheter suitable II Secure catheter properly I Maintain closed sterile drainage I Replace the collecting system when sterile closed drainage has been violated III Avoid irrigation unless needed to prevent or relieve obstruction II Refrain from daily meatal care with povidone-iodine or soap and water II Obtain urine samples aseptically I Maintain unobstructed urine flow I Do not change catheters at arbitrary fixed intervals II Spatially separate infected and uninfected patients with indwelling catheters III Avoid routine bacteriologic monitoring III Medicated urinary catheters NR

Future Directions

It is clear that HAIs represent one of the most important causes of iatrogenic morbidity and mortality in patients who require prolonged life support in an ICU. Strategies to increase adherence to hand hygiene, to prevent patient colonization, and to prevention infection once colonization has occurred should be a major focus of ICU staff attention and a research priority. The importance of hand carriage of pathogens by HCWs, the role of airborne transmission in the ICU, and the relevance of contamination of the inanimate environment by mutidrug-resistant pathogens needs to be better delineated. More effective ways to enhance compliance with evidence-based guidelines for hand hygiene and to prevent VAP, IVDR-BSI, and CAUTI would have vast immediate benefits.

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