Nosocomial infections in the intensive care unit: Epidemiology and prevention

INTRODUCTION — Although intensive care units (ICUs) account for fewer than 10 percent of total beds in most hospitals, more than 20 percent of all nosocomial infections are acquired in ICUs [1]. ICU-acquired infections account for substantial morbidity, mortality, and expense.

The general epidemiology of nosocomial infections and antimicrobial resistance in ICUs will be discussed here. The epidemiology, management, and prevention of specific nosocomial infections in the ICU, namely catheter-related bloodstream infections (CRBSIs), ventilator-associated pneumonia (VAP), and catheter-associated urinary tract infections (CAUTIs), will be discussed briefly here and in more detail separately:

●(See "Intravascular catheter-related infection: Epidemiology, pathogenesis, and microbiology" and "Intravascular non-hemodialysis catheter-related infection: Treatment" and "Routine care and maintenance of intravenous devices".)

●(See "Epidemiology, pathogenesis, microbiology, and diagnosis of hospital-acquired and ventilator-associated pneumonia in adults" and "Treatment of hospital-acquired and ventilator-associated pneumonia in adults" and "Risk factors and prevention of hospital-acquired and ventilator-associated pneumonia in adults".)

●(See "Catheter-associated urinary tract infection in adults" and "Complications of urinary bladder catheters and preventive strategies".)

Issues related to surgical site infection are discussed separately. (See "Antimicrobial prophylaxis for prevention of surgical site infection in adults" and "Overview of control measures for prevention of surgical site infection in adults".)

Infection prevention and ICU care of patients with COVID-19 are also presented elsewhere. (See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection" and "COVID-19: Management of the intubated adult".)

EPIDEMIOLOGY OF NOSOCOMIAL INFECTIONS

Common noscomial infections — The most common and clinically important infections acquired in the ICU are those associated with the supportive devices that patients in the ICU often require. These include intravascular catheter-related bloodstream infection (CRBSI), ventilator-associated pneumonia (VAP), and catheter-associated urinary tract infection (CAUTI).

●Intravascular catheter-related infections – Arterial and central venous catheters are frequently used in critical care patients because of the need for hemodynamic monitoring and intravenous therapeutics. Bloodstream infections involving these catheters are common in ICUs and are associated with significant morbidity and mortality [2]. In addition, in the United States, the cost burden of these infections on health care facilities was exacerbated after the Centers for Medicare and Medicaid Services stopped reimbursing hospitals for catheter-related bloodstream infections (CRBSIs) in October 2008. These infections are discussed in detail elsewhere. (See "Intravascular catheter-related infection: Epidemiology, pathogenesis, and microbiology" and "Intravascular non-hemodialysis catheter-related infection: Clinical manifestations and diagnosis" and "Intravascular non-hemodialysis catheter-related infection: Treatment".)

●Ventilator-associated pneumonia – Ventilator-associated pneumonia (VAP) is infection of lung tissue that develops 48 hours or more after intubation in mechanically ventilated patients. Nosocomial pneumonia occurs frequently in the setting of endotracheal intubation and mechanical ventilation [3]. These issues are discussed in detail separately. (See "Epidemiology, pathogenesis, microbiology, and diagnosis of hospital-acquired and ventilator-associated pneumonia in adults" and "Risk factors and prevention of hospital-acquired and ventilator-associated pneumonia in adults" and "Treatment of hospital-acquired and ventilator-associated pneumonia in adults".)

●Catheter-associated urinary tract infection – Urinary tract infections (UTIs) are among the most common nosocomial infections [4]. While most catheter-associated UTIs do not cause severe morbidity and mortality or significantly increase hospital costs, the cumulative impact of these frequent infections is large [5]. In the United States, CAUTIs are responsible for 900,000 additional hospital days per year and contribute to >7000 deaths [6,7]. CAUTIs are the second most common cause of nosocomial bloodstream infection (ie, urosepsis), which have an attributable mortality of approximately 15 to 25 percent [8-12]. The Centers for Medicare and Medicaid Services does not reimburse hospitals for CAUTIs, which further increases the cost burden of these infections on hospitals in the United States.

In addition to actual infection, asymptomatic bacteriuria often leads to significant laboratory testing and inappropriate antimicrobial utilization in the absence of an established infection [11,13]. Inappropriate treatment of asymptomatic bacteriuria has been associated with adverse clinical outcomes [14]. The urinary tract in catheterized patients also serves as a reservoir for multidrug-resistant bacteria, which can cause either infection or asymptomatic bacteriuria [11]. Issues related to CAUTIs are discussed separately. During the work-up of a patient for suspected infection, if a non-urinary source of infection is suspected, routine urine culture should be avoided. (See "Catheter-associated urinary tract infection in adults" and "Placement and management of urinary bladder catheters in adults".)

Prevalence — Most studies of ICU-associated nosocomial infections come from industrialized countries. According to the United States Centers for Disease Control and Prevention (CDC), ICU patients accounted for 55,870 of 78,342 total device-related infections (71 percent) in US acute care hospitals in 2020 [15]. Specifically, 50 percent of CRBSIs, 49 percent of CAUTIs, and 96 percent of ventilator-associated events (VAEs) occurred in patients in the ICU.

Device-specific rates of nosocomial infections in United States ICUs were as follows [15]:

●CRBSI: 0.86 cases per 1000 catheter-days

●Ventilator-associated events (VAEs, including VAP): 9 cases per 1000 ventilator-days [16]

●CAUTI: 1 case per 1000 catheter-days

The rates of ICU-associated infection may even be higher in resource-limited countries, as illustrated by a multicenter prospective cohort surveillance study of 46 hospitals in Central and South America, India, Morocco, and Turkey [17]. An overall rate of 14.7 percent (or 22.5 infections per 1000 ICU days) was observed. The following rates were found for specific devices:

●CRBSI: 12.5 cases per 1000 catheter-days (range 7.8 to 18.5 cases)

●VAP: 24.1 cases per 1000 ventilator days (range 10.0 to 52.7 cases)

●CAUTI: 8.9 cases per 1000 catheter days (1.7 to 12.8 cases)

A subsequent study by the same international group reported results from 98 ICUs from Latin America, Asia, Africa, and Europe [18]. Despite the fact that device utilization was remarkably similar to that reported from ICUs in the United States, rates of device-associated nosocomial infection were markedly higher in the ICUs from resource-limited countries.

Risk factors — Several factors contribute to the high incidence of these infections in the ICU:

●Compared with patients in the general hospital population, patients in ICUs have more chronic comorbid illnesses and more severe acute physiologic derangements. These clinical factors are felt to lead to relative immunosuppression among ICU patients [19].

●The high frequency of indwelling catheters among ICU patients provides a portal of entry of organisms into vital body organs and sites. The use and maintenance of these catheters necessitate frequent contact with health care personnel, which predispose patients to colonization and infection with nosocomial pathogens. In addition, equipment associated with the proper maintenance of these devices might serve as reservoirs and vectors for pathogens and be related to horizontal patient-to-patient transmission of pathogens [20].

●Multidrug-resistant pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), Acinetobacter baumannii, Enterobacteriaceae that produce extended-spectrum beta-lactamases and/or carbapenemases (eg, ESBLs and CREs, respectively), and carbapenem-resistant Pseudomonas aeruginosa, are all being isolated with increasing frequency in ICUs [21,22]. Infections caused by these resistant pathogens are difficult to treat and are associated with increased morbidity, mortality, and costs [23,24]. (See 'Prevalence' below.)

●Compared with patients in the general hospital population, patients in ICUs are subjected to increased selective pressure due to extensive antibiotic use in ICUs, which often favors one microorganism's survival over others. Increased colonization pressure is also present in ICUs and occurs when one microorganism becomes increasingly prevalent in the ICU environment and on healthcare workers and patients, thereby making containment of spread more difficult. [19,25].

EPIDEMIOLOGY OF ANTIBIOTIC-RESISTANT ORGANISMS

Prevalence — The rate of resistance among bacterial pathogens recovered in intensive care units (ICUs) has steadily risen over the years. Among isolates reported to the United States Centers for Disease Control and Prevention (CDC) from hospital wards and ICUs between 2015 and 2017, resistance was common in pathogens that caused device-related infections [26]:

●34 percent of Enterococcus were vancomycin-resistant (ie, VRE).

●48 percent of S. aureus isolates were methicillin-resistant (ie, MRSA).

●43 percent of A. baumannii isolates were resistant to carbapenems. An additional 43 percent were multidrug-resistant (ie, resistant to at least three of the following classes: extended-spectrum cephalosporins, fluoroquinolones, aminoglycosides, carbapenems, piperacillin-tazobactam, and ampicillin-sulbactam).

●21 percent of P. aeruginosa isolates were resistant to carbapenems. Significant resistance was also reported to fluoroquinolones (26 percent), cephalosporins (eg, cefepime; 20 percent), piperacillin-tazobactam (15 percent), aminoglycosides (14 percent), and combinations of agents from at least three different classes (14 percent).

●21 percent of E. coli isolates were resistant to cephalosporins (eg, ceftriaxone or cefepime) and an additional 10 percent were resistant to at least three different classes. Resistance to fluoroquinolones was 38 percent and was 0.7 percent to carbapenems.

●21 percent of selected Klebsiella spp were resistant to cephalosporins (eg, ceftriaxone or cefepime) and an additional 13 percent were resistant to at least three different classes. Resistance to carbapenems was 7 percent.

●11 percent of Enterobacter spp were resistant to cefepime and an additional 7 percent were resistant to at least three of the following agents: cefepime, fluoroquinolones, aminoglycosides, carbapenems, and piperacillin-tazobactam. Resistance to carbapenems was 6 percent.

The emergence of broad-spectrum resistance among gram-negatives (A. baumannii, P. aeruginosa, and some Enterobacterales) is particularly worrisome since therapeutic options are scarce, and sometimes no effective antimicrobial agent is available at all [27]. Additional emerging threats are the non-glucose fermenting gram-negative bacilli that are intrinsically resistant to carbapenems (eg, Stenotrophomonas maltophilia, Burkholderia cepacia, Achromobacter xylosoxidans) [28]. (See "Extended-spectrum beta-lactamases", section on 'Treatment options' and "Carbapenem-resistant E. coli, K. pneumoniae, and other Enterobacterales (CRE)", section on 'Approach to treatment' and "Principles of antimicrobial therapy of Pseudomonas aeruginosa infections", section on 'Management of multidrug-resistant organisms'.)

Two additional common and significant pathogens in ICU infections are Clostridioide difficile and Candida auris. These are not "traditional" multidrug-resistant organisms but risk factors for infections due to these pathogens are similar to those associated with multidrug-resistant organism infections, and thus the affected populations are similar [29,30]. These pathogens are discussed in detail elsewhere. (See "Clostridioides difficile infection in adults: Clinical manifestations and diagnosis" and "Clostridioides difficile infection in adults: Treatment and prevention" and "Overview of Candida infections".)

Risk factors — Certain characteristics increase the risk of infections with multidrug-resistant pathogens in ICUs by contributing to increased selective pressure and/or increased colonization pressure [25,31,32]. Specifically, risk factors for resistant infections reported from ICUs include the following [33-39]:

●Older age.

●Lack of functional independence and/or decreased cognition.

●Presence of underlying comorbid conditions (eg, diabetes, renal failure, malignancies, immunosuppression) and higher severity of acute illness indices.

●Long duration of hospitalization prior to the ICU admission, including interinstitutional transferring (particularly from nursing homes).

●Frequent encounters with health care environments (eg, hemodialysis units, ambulatory daycare clinics).

●Frequent contact with health care personnel concurrently caring for multiple patients, whose hands can serve as vehicles for transfer of pathogens between patients. Shared equipment and contaminated environments can also serve as reservoirs and/or vectors that contribute to acquisition of infections in the ICU.

●Presence of indwelling devices such as central venous catheters, urinary catheters, and endotracheal tubes, which bypass natural host defense mechanisms and serve as portals of entry for pathogens.

●Recent surgery or other invasive procedures.

●Receipt of antimicrobial therapy prior to the ICU admission, which creates selective pressure promoting the emergence of multidrug-resistant bacteria.

The association between prior receipt of antibiotics and infection with drug-resistant organisms has been demonstrated in several studies and by various methodologies. In case-control studies, exposure to antibiotics has consistently been associated with the emergence of resistance to that same or a different class of antimicrobial agent [40]. As an example, receipt of fluoroquinolones has been linked to the emergence of piperacillin-resistant P. aeruginosa [41]. One study demonstrated that even a relatively short exposure to imipenem in ICU patients was associated with a significant increase in carriage of imipenem-resistant gram-negative bacilli [42]. In a separate study, antibiotic exposure was the strongest single predictor for infection with extensively drug-resistant gram-negative pathogens [40]. The association between certain antibiotic use and emergence of resistance has also been supported by studies that used longitudinal time-series analyses to determine rates of resistance when various antibiotic agents were more commonly used at a particular institution [43] and studies that demonstrate reductions in multidrug-resistant pathogens with the implementation of antimicrobial stewardship programs and various strategies to minimize unnecessary antimicrobial use [44].

Prognosis — Infections caused by multidrug-resistant pathogens are associated with increased mortality, length of hospital stay, and hospital costs [45-51]. Patients with infections due to multidrug-resistant organisms usually are chronically or acutely ill and at risk of dying from underlying serious and complex medical illnesses. However, a number of factors related to the difficulties of choosing antibiotics for multidrug-resistant bacteria independently predispose to poor outcomes. These include the following:

●Multidrug-resistant pathogens are more frequently resistant to empiric antimicrobial regimens than are susceptible organisms. Thus, there are often delays in initiation of appropriate, effective antimicrobial therapy in the treatment of multidrug-resistant organisms [52]. These delays are independent predictors of mortality in severe sepsis and thus contribute to the increased mortality rates associated with resistant infections [47,53-58]. As an example, in a study of patients with septic shock, each hour of delayed appropriate therapy in the first six hours of infection was associated with an average decrease in survival of 7.6 percent [59]. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Choosing a regimen'.)

●Antimicrobial resistance often precludes the use of optimal "first-line" antimicrobial agents and necessitates the use of "second-line" agents with inferior bactericidal activity and unfavorable pharmacokinetic and/or pharmacodynamic properties [55]. When "second line" agents are required to treat a resistant organism, adverse patient outcomes sometimes result [49,50,60-64]. As an example, vancomycin is commonly used to treat MRSA since anti-staphylococcal penicillins (eg, nafcillin) and first-generation cephalosporins (eg, cefazolin) are not active against the organism. However, vancomycin does not possess strong bactericidal activity and is associated with an increased risk for renal insufficiency compared with beta-lactams. In several clinical studies, vancomycin was inferior to beta-lactam agents in treating methicillin-susceptible S. aureus infections [65]. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of bacteremia".)

Another factor that may contribute to poor outcomes among patients with infections due to certain multidrug-resistant pathogens is the virulence properties of the organism. In clinical studies, it is often unclear whether worse outcomes in patients with multidrug-resistant infections are due to increased virulence of the organism or to the higher rate of serious comorbidities and suboptimal antibiotic therapy in patients with multidrug-resistant pathogens [66,67].

PREVENTION — Strategies to prevent the emergence and spread of multidrug-resistant bacteria in intensive care units (ICUs) can be divided into two major categories: strategies that attempt to improve the efficacy and utilization of antimicrobial therapy (reducing selective pressure) and infection control measures (reducing colonization pressure) [55,68-70]. It is most efficacious to combine the two approaches [68].

Antibiotic utilization controls — Incorporating antibiotic stewardship programs (often involving clinicians, infectious diseases experts, and pharmacists) into specific hospital settings such as the ICU can comprehensively address the goal of reducing infections of resistant bacterial strains. The programs promote the effective and safe use of antimicrobial agents, evaluate and guide formulary decisions, and implement educational programs to improve antimicrobial utilization [70-74]. The specifics of antibiotic stewardship programs are discussed in detail elsewhere. (See "Antimicrobial stewardship in hospital settings".)

Antimicrobial stewardship programs in the ICU setting have been impactful and associated with decreases in drug-resistant bacteria in some settings. As an example, in a study of two ICUs in the United States that implemented a comprehensive antimicrobial stewardship program, the proportion of hospital-acquired infections caused by certain multidrug-resistant gram-negative bacilli, including P. aeruginosa, A. baumannii, and extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales, decreased from 37.4 percent in 2001 to 8.5 percent in 2008 [44]. The rate of hospital-acquired infections per 1000 patient-days that were caused by these multidrug-resistant organisms declined by 0.78 per year. Similarly, in a study of an ICU in Melbourne, Australia, which implemented an antimicrobial stewardship program, 2838 gram-negative bacilli were isolated from clinical cultures over seven years, and, over this time, there were significant increases in susceptibility of P. aeruginosa to imipenem (18.3 percent per year, p = 0.009) and gentamicin (11.6 percent per year, p = 0.02) compared with trends recorded prior to the stewardship program [75]. Improvements in the rates of gentamicin and ciprofloxacin susceptibility were also noted among Enterobacter spp.

There may be concerns that antibiotic stewardship may result in a delay in the initiation of appropriate antimicrobial therapy, which has been associated with poor clinical outcomes with infections caused by multi- and extensively drug-resistant infections [52,53]. However, a meta-analysis of five studies found that implementation of antimicrobial stewardship programs in ICUs was not associated with increased mortality (pooled relative risk 1.03, 95% CI 0.93-1.14), thus providing some reassurance that there is no clear evidence of unintended deleterious effects of stewardship programs on mortality in the ICU setting [76].

There is no role for rotating antibiotic prescription practices by changing empiric regimens in an attempt to curb emergence of resistance [77,78].

Infection control measures — Strategies to prevent the emergence of multidrug-resistant organisms that do not involve changes in antimicrobial utilization (which impacts selective pressure) primarily involve infection control measures (which impact colonization pressure and patient-to-patient transmission). Careful attention to these activities has been used to contain outbreaks of resistant organisms [79-82]. Adherence to hand hygiene, daily bathing with chlorhexidine, and implementation of device-specific strategies to decrease infection should be performed on a routine basis for all patients in an ICU [69]. For targeted reduction of methicillin-resistant S. aureus (MRSA), intranasal mupirocin can be used [83]. Use of chlorhexidine dressings are effective in reducing central line-associated bloodstream infection (CLABSI), including CLABSI due to resistant pathogens [84]. Contact precautions are warranted for patients infected or colonized with resistant organisms, patients with wound drainage that cannot be contained by dressings, and for patients with diarrhea. Surveillance for drug-resistant organisms is also important for identification and control of epidemic and endemic rates of resistance. Enhancing the regulation, the monitoring, and the processes for environmental cleaning is an additional established measure to contain the spread of multidrug-resistant organisms in the ICU [85]. New technologies (eg, ultraviolet light, hydrogen peroxide vapor) to reduce contamination of room air and surfaces are emerging; some such interventions can be performed while the room is occupied, but none negate the need for thorough cleaning, and data are scarce regarding their ultimate impact on preventing ICU infections or multidrug-resistant organism acquisitions [86].

Hand hygiene — There is no substitute for good hand hygiene compliance. Alcohol-based hand hygiene is more effective than traditional soap and water in cleansing hands of bacteria; in addition, no sink or towels are necessary, and alcohol foam is no more abrasive to hands than antiseptic soap and water [86,87]. Alcohol gel/foam is not appropriate for hands that are visibly soiled or for health care personnel caring for patients with C. difficile infection (or other spores-forming organisms) since the foam does not inactivate C. difficile toxins and does not kill the spores themselves. Antiseptic soap and water are also recommended while caring for patients with diarrhea or for patients with noncontained wounds. (See "Infection prevention: Precautions for preventing transmission of infection", section on 'Hand hygiene'.)

Contact precautions, cohorting, and dedicated staff — Wearing gown and gloves when entering a patient room and removing them prior to or shortly after exiting (but still adjacent to patient's close environment) may decrease transmission of multidrug-resistant bacteria, including MRSA, vancomycin-resistant enterococci (VRE), and carbapenem-resistant and ESBL-producing gram-negative organisms (A. baumannii, P. aeruginosa, Enterobacterales). These precautions should be routinely implemented when caring for ICU patients who have a history of or are found to have infection or colonization with resistant organisms. Evidence supporting this practice is discussed elsewhere. (See "Vancomycin-resistant enterococci: Epidemiology, prevention, and control", section on 'Contact precautions' and "Extended-spectrum beta-lactamases", section on 'Infection control and antibiotic stewardship' and "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Prevention and control".)

The issue of whether to use universal contact precautions for every patient in the ICU, regardless of colonization history, is a matter of ongoing debate. Although this may be a reasonable practice in outbreak settings or in institutions that have a high rate of colonization or infection with drug-resistant bacteria, routine use of universal contact precautions is not yet supported by strong scientific evidence.

During the COVID-19 pandemic, despite widespread usage of universal contact precautions in some ICUs, device-related hospital-acquired infections rates increased [88]. The increase may have been due to altered device maintenance practices and lack of adherence to infection control practices and procedures, executed as well by replacing nonsufficiently trained personnel during the pandemic.

Some observational studies prior to the COVID-19 pandemic have suggested a decrease in transmission rates of drug-resistant organisms with universal contact precautions [89-91]. However, a large cluster-randomized trial failed to demonstrate a statistically significant benefit of universal use of contact precaution measures [92]. In this trial, 20 medical and surgical ICUs were randomly assigned to practice universal gown and glove use for all patients (intervention) or standard care with gown and glove use for only those patients known to be infected or colonized with antibiotic-resistant bacteria (control). Overall, 26,180 patients were followed over the three-month baseline period prior to implementation of the intervention and the 10-month study period following it. Compliance with gown and glove use was high, ranging from 80 to 86 percent. The intervention did not reduce the primary combined endpoint of MRSA or VRE acquisitions compared with baseline rates to a greater extent than the control (reduction from 21.4 to 16.9 versus 19.0 to 16.3 acquisitions per 1000 patient days in the intervention and control groups, respectively). The intervention did reduce MRSA acquisitions by 2.98 acquisitions per 1000 patient days (95% CI 0.38-5.58) more than the control; however, the baseline rate of MRSA acquisition was higher in the intervention group, so acquisition rates at the end of the study period were comparable between the two groups. Universal use of contact precaution measures has not been demonstrated to significantly reduce the acquisition of other drug-resistant organisms including gram-negative bacilli and C. difficile [93,94].

In the trial, universal gown and glove use led to one fewer health care personnel visit per patient on average, but there was no excess of adverse patient events with this practice. This is in contrast with earlier observational studies that had reported adverse effects associated with implementation of universal contact precautions (eg, increased rates of falls, pressure ulcers, dissatisfaction of patients with their treatment, and less documented care safety) [95,96]. Long-term consequences of contact isolation precautions are yet unknown.

In another multicenter trial, contact isolation practices were observed among health care workers; as the proportion of patients in contact isolation increased, compliance with contact isolation precautions decreased [97]. A threshold for staff compliance (approximately 40 percent of patients on contact precautions) was noted.

Gowns and gloves should always be worn while caring for patients with wound drainage that cannot be contained by dressings. In addition, gown and gloves should always be removed prior to or immediately after leaving a patient's room/unit.

An additional potential control measure is geographically cohorting carriers of the same multidrug-resistant organism and assigning dedicated nursing staff to such patients. In one outbreak of carbapenem-resistant Enterobacteriaceae, the outbreak was contained only after implementation of dedicated cohorting [98]. However, a single unit for care of patients with multiple different types of multidrug-resistant organisms should be avoided, since genes conferring resistance can cross between species [99].

Patient bathing/decolonization

Patient bathing — We suggest daily chlorhexidine bathing for all ICU patients. Bathing patients daily with chlorhexidine gluconate (CHG), an antiseptic agent with broad-spectrum activity against many organisms, is an effective method of decreasing both hospital-acquired infections (ie, bloodstream infections, urinary tract infections [UTIs], surgical-site infections, and ventilator-associated pneumonia [VAP]) and colonization with drug-resistant organisms among patients in the ICU, as demonstrated in many studies [83,100-114]. Despite limitations of some of these studies, our recommendation is based on the apparent benefits, the low rate of associated adverse effects, and the relative ease of implementation.

Chlorhexidine-impregnated cloths or chlorhexidine soaked washcloths should be firmly massaged over all patient body surfaces and skin folds below the jaw line except for the face. Most larger trials that evaluated chlorhexidine bathing used this approach with impregnated cloths [83,104]. It is uncertain whether bathing with a washcloth soaked with liquid chlorhexidine would result in similar effects, but this may be more accessible and less expensive than premade cloths. If a soaked washcloth is used, large amounts of water should be avoided (in order to retain an effective CHG concentration [ie, approximately 4 percent]), and care should be taken to avoid getting catheter dressing wet, which may be associated with an increased rate of catheter exit-site infections [115]. Reusable basins have been demonstrated to be a reservoir for multidrug-resistant organisms and should be mechanically disinfected between uses [116].

Although slightly mixed, studies on chlorhexidine bathing generally support its efficacy. In a meta-analysis of two controlled trials and 10 observational studies of ICU patients, daily chlorhexidine bathing was associated with a decrease in health care-associated bloodstream infections compared with soap and water or no bath (odds ratio [OR] 0.44, 95% CI 0.33-0.59) [103]. Similarly, in a subsequent randomized trial that included over 7000 patients in ICUs and bone marrow transplant units, there was a 28 percent reduction in the rate of hospital-acquired bloodstream infections (4.8 versus 6.6 cases per 1000 patient-days, respectively) [104]. The reduction in bloodstream infections with chlorhexidine was greatest for coagulase-negative staphylococci and fungal infections. Some studies suggest a trend towards reduced gram-negative infections [117]. Given the broad in vitro activity of chlorhexidine, and lack of significant adverse impacts associated with chlorhexidine bathing, it could be used as a measure to contain the spread of currently endemic ICU multi-drug resistant organisms.

Chlorhexidine bathing has also been studied in critically ill pediatric patients. In a large trial including more than 6000 pediatric ICU patients older than two months, there was a nonsignificant reduction in the incidence of bacteremia with daily chlorhexidine bathing compared with standard bathing practices in the intention-to-treat analysis (3.5 versus 4.9 per 1000 days) [110]. In the per-protocol population, the incidence of bacteremia was lower among patients who received chlorhexidine bathing (3.3 versus 4.9 events per 1000 days, adjusted relative risk 0.64, 95% CI 0.42-0.98).

Although one cluster-randomized, crossover study including 9340 adults in ICUs noted that daily chlorhexidine bathing did not demonstrate a reduced incidence of health care-associated infections, the study was underpowered to detect such differences due to the rarity of events, which limits the generalizability of the results [118,119]. A Cochrane systematic review that included this trial and seven others, comprising greater than 24,000 patients, noted reductions in rate of nosocomial infection (rate difference 1.70 fewer infections per 1000 patient-days, 95% CI 0.12-3.29) and mortality (OR 0.87, 95% CI 0.76-0.99) with chlorhexidine bathing but deemed the evidence to be of very low quality [120].

Reported adverse effects of chlorhexidine bathing are rare and predominantly mild skin reactions [103,110]. It is also relatively inexpensive.

However, emergence of resistance to chlorhexidine is an important consideration [105,121]. In a study including two 15-bed ICUs over a four-year period, introduction of a chlorhexidine-based surface antiseptic protocol was associated with a 70 percent reduction in MRSA transmission, although transmission of strains carrying the plasmid-born qacA/B gene (which codes for multidrug efflux pumps and can lead to chlorhexidine resistance) was not reduced [105]. Resistance to triclosan, an ingredient in some antimicrobial soaps, has also emerged among dermal, intestinal, and environmental microorganisms, including S. aureus [122,123].

Patient bathing plus decolonization — Although not universally recommended, decolonization with mupirocin and chlorhexidine is recommended by some expert guidelines, and there is growing evidence supporting this practice [124]. It is unclear whether the addition of decolonization to chlorhexidine bathing is more effective than chlorhexidine alone (except in cases of a targeted intervention to reduce S. aureus acquisitions and/or infections), although the addition of chlorhexidine has been demonstrated to be more effective than nasal iodophors.

Nasal decolonization with twice-daily mupirocin combined with daily chlorhexidine bathing may be particularly beneficial in ICUs with high rates of S. aureus infections, including MRSA. In a large, multicenter trial that involved over 74,000 patients, universal decolonization with chlorhexidine and twice daily intranasal mupirocin reduced both MRSA-positive clinical cultures and bloodstream infections due to any pathogen (HRs 0.63 and 0.56 compared with baseline rates) to a greater extent than screening and isolation (HRs 0.92 and 0.99) or targeted decolonization of carriers (HRs 0.75 and 0.78) [83]. The number of patients requiring decolonization to prevent one MRSA infection or one bloodstream infection was 181 or 54, respectively. Since both chlorhexidine and mupirocin were used for decolonization, the clinical effect in this study cannot reliably be attributed to chlorhexidine or mupirocin alone.

Resistance of S. aureus to mupirocin has been well described, and varies by region [125]. Some centers have elected to substitute intranasal iodophore (eg, povidone-iodine) for mupirocin because iodophors exhibit less resistance and are often less costly [126]. However, in an open-label cluster-randomized trial in over 230 adult ICUs in 137 hospitals whose ICUs provide daily bathing to all patients, universal use of nasal iodophore was associated with an increase of S. aureus clinical cultures by 18 percent compared with mupirocin [127]. Based on the results of this study, we suggest that centers electing to perform universal decolonization in their ICUs choose nasal mupirocin ointment be used rather than nasal iodophors.

The use of targeted decolonization for patients with confirmed MRSA is discussed in detail elsewhere. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Prevention and control", section on 'Targeted decolonization'.)

Digestive and oropharyngeal decontamination — Decontamination of the digestive and oropharyngeal tracts has been proposed as a method to reduce HAIs and mortality in critically ill patients by reducing microorganism colonization.

Decontamination methods include oropharyngeal decontamination with antiseptics (eg, chlorhexidine), selective oropharyngeal decontamination (SOD) with antibiotics, and selective digestive decontamination (SDD) with antibiotics.

●Oropharyngeal decontamination with antiseptics – Oral care of ventilated patients in the ICU using antiseptic mouthwash or gel (usually chlorhexidine) has been a common intervention in ICUs in the United States and Europe [128]. Multiple systematic reviews and meta-analyses have suggested that VAP rates may be decreased by this intervention, but when analyses were limited to double-blinded studies, VAP rates were not improved [128-139]. Due to lack of clear reduction in VAP rates and in mortality, and some data that suggest increased mortality, updated American guidelines recommend against using chlorhexidine for oral care [128,133,134,139-143]. European guidelines purposely did not issue a recommendation for this practice until more safety data become available [144]. However, as depicted below, mouth hygiene is of paramount importance among mechanically ventilated patients, and practices should be standardized and monitored.

●Selective oral decontamination (SOD) and selective digestive decontamination (SDD) – These interventions use antibiotics instead of antiseptics to attempt to decontaminate the oropharynx (SOD) or the entire digestive tract (SDD). SOD involves applying an oral paste of nonabsorbable antibiotics (often a combination of colistin, tobramycin, and an antifungal) to the mouths of ventilated patients. SDD involves SOD plus administration of nonabsorbable antibiotics directly into the GI tract via the stomach; in some protocols, a few doses of intravenous antibiotics are also administered.

Modest mortality benefits have been demonstrated among ICU patients treated with SOD or SDD in the Netherlands, a region with low baseline antimicrobial resistance [139-141,144-150]. However, these interventions have not found widespread favor outside the Netherlands, since no benefit for their use has yet been observed in ICUs with moderate to high levels of antibiotic resistance [139,141,144,145,147,151-153]. In addition, there is uncertainty regarding the long-term effects of SOD and SDD on emergence of antimicrobial resistance [146,147,152-160]. European and American guidelines recommend against using SOD or SDD in countries, regions, or ICUs with high prevalence of antibiotic resistance, although they state that SOD or SDD could be considered in ICUs with low prevalence of antibiotic-resistant organisms [139,141,144].

Basic oral hygiene using toothbrushes is recommended in all ventilated ICU patients [139]. A more detailed discussion of the impact of oropharyngeal chlorhexidine, SOD, and SDD on rates of VAP is discussed separately. (See "Risk factors and prevention of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Decontamination of the oropharynx and digestive tract'.)

Surveillance — Surveillance for infections with multidrug-resistant bacteria within the institution as a whole and within specific units is critical for the early identification and control of epidemic outbreaks and endemic increases of resistant bacteria. The incidence and prevalence of isolation of multidrug-resistant bacteria (eg, MRSA, VRE, and carbapenem-resistant gram-negative bacilli) should be monitored, and these data should be disseminated to nurses and clinicians who work in the ICU through a form that is easy to interpret. It is useful to compare data from different time periods for one ICU and to compare different units within the same hospital. The United States National Healthcare Safety Network System also provides comparisons of rates among participating hospitals [22]. Comparing rates among different institutions helps to identify hospitals or units where problems persist and can help to gauge the efficacy of interventions aimed at controlling rates of endemic and epidemic resistant organisms. (See "Vancomycin-resistant enterococci: Epidemiology, prevention, and control", section on 'Surveillance cultures' and "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Prevention and control".)

Positive surveillance culture results should be coupled with effective flagging systems and established routes of communication inside the facility and between neighboring facilities in order to be successful [161]. In theory, this measure can reduce patient-to-patient transmission rates.

Active surveillance cultures, or screening patients for asymptomatic colonization with resistant organisms, is widely performed but may not be as effective as universal decolonization at controlling the spread of MRSA. In a large multicenter trial described above, universal chlorhexidine bathing and nasal mupirocin reduced rates of MRSA clinical isolates and bloodstream infections from any pathogen to a greater extent than did screening for MRSA and isolating carriers [83] (see 'Patient bathing/decolonization' above). This study did not evaluate active screening for other drug-resistant organisms, such as VRE. (See "Vancomycin-resistant enterococci: Epidemiology, prevention, and control", section on 'Surveillance cultures'.)

Prior to this study, the efficacy of universal active surveillance cultures for MRSA was uncertain, as illustrated by the following studies with conflicting conclusions [162-165]:

●In a cluster-randomized trial involving more than 9000 patients admitted to 18 intensive care units, use of MRSA surveillance cultures and expanded use of barrier precautions (universal glove precautions while awaiting active surveillance culture results) were not effective in reducing transmission of MRSA compared with existing practice [164]. This finding was surprising given that surveillance cultures identified a sizable subgroup of colonized patients who were not otherwise recognized. The authors hypothesized that additional interventions such as antiseptic bathing and improved environmental decontamination may be needed. Limitations of the study included the long turn-around time of the active surveillance cultures and omission of gowns as part of the barrier precautions.

●In a Veterans Affairs system-wide quality improvement initiative including nearly two million patients in 150 hospitals, a MRSA "bundle" program (including universal MRSA surveillance, contact precautions for colonized or infected patients, hand hygiene, and institutional culture change) was implemented [165]. This program was temporally associated with a reduction in the rate of health care-associated MRSA infection in ICUs by 62 percent (from 1.64 to 0.62 infections per 1000 patient-days) and general units by 45 percent (from 0.47 to 0.26 infections per 1000 patient-days). However, as this study did not include control groups, it was not possible to determine whether MRSA surveillance was causally related to the observed drop in rates.

●A mathematical model demonstrated that the universal screen and isolate strategy could have contributed only marginally to the reduction in infections, since transmission rates before bundle implementation were already low and most patients with MRSA colonization were already colonized at admission [166].

However, there are other pathogens (such as VRE and carbapenem-resistant Enterobacterales) for which active surveillance may continue to be an important measure in the efforts to contain the spread of these organisms in health care settings [98]. Moreover, since decolonization may not be practical or effective for these pathogens, active surveillance and strict contact isolation for carriers is still important for limiting spread [167]. Screening for asymptomatic carriage of C. difficile is gaining interest but data are not yet conclusive [168]. There are no reliable surveillance techniques to detect carriage of P. aeruginosa; however, for A. baumannii, different techniques have been used to detect carriage [169-171]. (See "Vancomycin-resistant enterococci: Epidemiology, prevention, and control", section on 'Surveillance cultures'.)

Device-specific strategies — Preventing infections and decreasing the length of hospital stay of patients will decrease antimicrobial utilization and decrease the risk of becoming infected or colonized with resistant bacteria. Limiting unnecessary use of central venous catheter, bladder catheter, and endotracheal intubation decreases infection rates, decreases antibiotic use, and decreases selective antibiotic pressure on resident bacteria. Clinicians should assess on a daily basis the need to keep each of these invasive devices in place [172].

In addition, as many of the multidrug-resistant infections in the ICU are associated with indwelling devices, specific strategies for placement and care of such devices, as well as additional adjunctive measures, are effective in reducing the risk of catheter-associated urinary tract infections (CAUTIs), VAP (table 1), and intravascular catheter-related bloodstream infection (table 2). These strategies are discussed in detail elsewhere:

●(See "Placement and management of urinary bladder catheters in adults" and "Complications of urinary bladder catheters and preventive strategies", section on 'Prevention of complications'.)

●(See "Risk factors and prevention of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Prevention'.)

●(See "Routine care and maintenance of intravenous devices".)

Environmental cleaning — Environmental cleaning, disinfection, and sterilization are basic and important measures used to prevent or reduce infections in the intensive care unit, as in the rest of the hospital environment. Innovative but as yet experimental techniques for environmental decontamination include ultraviolet light sterilization lamps, hydrogen-peroxide vapor decontamination devices, and other technologies, which might contribute to future attempts at reducing colonization pressure. However, these new technologies will not replace the necessity of proper manual "terminal" cleaning that should be established by a written protocol in every ICU, and adherence to the protocol must be regularly monitored. (See "Infection prevention: General principles", section on 'Health care environment: Cleaning and disinfection'.)

SUMMARY AND RECOMMENDATIONS

●Factors contributing to ICU infections – Infections are especially frequent in intensive care units (ICUs) because the patients are likely to have chronic illnesses and acute physiologic derangements, indwelling catheterization is common, and multidrug-resistant pathogens that are difficult to eradicate are isolated with increasing frequency due to enhanced selective antimicrobial pressure and enhanced colonization pressure. (See 'Epidemiology of nosocomial infections' above and 'Epidemiology of antibiotic-resistant organisms' above.)

●Multi-drug resistant organisms – The most common multi- and extensively drug-resistant pathogens isolated in ICUs include methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales. Carbapenem-resistant Enterobacterales are also increasing in prevalence. Clostridioides difficile, Candida auris, and intrinsically carbapenem-resistant nonglucose fermenting gram-negatives (eg, Stenotrophomonas maltophilia) are an emerging threat. (See 'Epidemiology of antibiotic-resistant organisms' above.)

•Risk factors for multi-drug resistant organisms – Comorbid conditions, long hospital courses, frequent contact with health care personnel, indwelling catheterization, and receipt of antimicrobial therapy all increase the risk of colonization and infection with multidrug-resistant pathogens. Infections with such organisms are associated with increased mortality, length of stay, and hospital costs. (See 'Risk factors' above and 'Prognosis' above.)

•Infection control – Good hand hygiene compliance, contact precautions for patients who harbor epidemiologically relevant drug-resistant organisms, and minimizing unnecessary hospitalization and interventions are critical for preventing infection and the spread of resistant organisms in the ICU. Adequate and standardized approaches to environmental cleaning and disinfection is an additional established measure to contain the spread of multidrug-resistant organisms. More intensive infection control interventions to reduce colonization pressure include cohorting with dedicated staff, chlorhexidine bathing, selective decontamination, active surveillance for certain pathogens, and reduction of catheterization utilization. (See 'Infection control measures' above and "Infection prevention: Precautions for preventing transmission of infection".)

•Antibiotic stewardship – Restricted and judicious antibiotic utilization, often implemented as part of a global institutional antimicrobial stewardship program, can decrease selective pressure that promotes emergence of resistant bacterial strains. Infection control measures such as hand hygiene prevent the spread of multidrug-resistant organisms. (See 'Prevention' above.)

●Chlorhexidine bathing and nasal decolonization – For all patients in an ICU, we suggest daily chlorhexidine bathing (Grade 2C). Daily chlorhexidine bathing decreases the risk of colonization and infection with drug-resistant and other organisms and is associated with minimal adverse effects. Additionally, it may be more effective in controlling certain infections than an active surveillance policy. (See 'Prevention' above.)

For hospitals that elect to add nasal decolonization to daily chlorhexidine bathing in their ICUs, we suggest nasal mupirocin rather than nasal iodophors (Grade 2C). Nasal decolonization with mupirocin combined with daily chlorhexidine bathing may be particularly beneficial in ICUs with high rates of S. aureus infections, including MRSA.

●Types of infections in the ICU – The most common infections in the ICU are those associated with indwelling devices, namely intravascular catheter-related bloodstream infection, ventilator-associated pneumonia (VAP), and catheter-associated urinary tract infection. Apart from minimizing their use, certain strategies regarding placement and care of indwelling devices can decrease the risk of infection (table 2 and table 1). The epidemiology, management, and prevention of these infections are discussed in detail elsewhere.

•(See "Catheter-associated urinary tract infection in adults" and "Complications of urinary bladder catheters and preventive strategies".)

•(See "Epidemiology, pathogenesis, microbiology, and diagnosis of hospital-acquired and ventilator-associated pneumonia in adults" and "Treatment of hospital-acquired and ventilator-associated pneumonia in adults" and "Risk factors and prevention of hospital-acquired and ventilator-associated pneumonia in adults".)

•(See "Intravascular catheter-related infection: Epidemiology, pathogenesis, and microbiology" and "Intravascular non-hemodialysis catheter-related infection: Treatment" and "Routine care and maintenance of intravenous devices".)