HAI is one of the leading causes of death and increased morbidity for hospitalized patients. About 1 in 20 patients hospitalized has at least one healthcare-associated infection, a complication estimated to affect more than 1 million patients each year who reside in hospitals or other inpatient care facilities [1,2]. Historically, these infections have been known as nosocomial infections or hospital-acquired infections because they develop during hospitalization. As health care has increasingly expanded beyond hospitals into outpatient settings, nursing homes, long-term care facilities, and even home care settings, the more appropriate term has become healthcare-acquired or healthcare-associated infection. Many factors have contributed to an increase in HAIs. Advances in medical treatments have led to more patients with decreased immune function or chronic disease. The increase in the number of these patients, coupled with a shift in health care to the outpatient setting, yields a hospital population that is both more susceptible to infection and more vulnerable once infected. In addition, the increased use of invasive devices and procedures has contributed to higher rates of infection; more than 80% of HAIs are caused by four types of infection: catheter-related urinary tract infection, intravascular device-related bloodstream infection, surgical site infection, and ventilator-associated pneumonia [1]. These HAIs, along with infections caused by C. difficile and drug-resistant micro-organisms (especially methicillin-resistant Staphylococcus aureus [MRSA]), have garnered the most attention and research because of their impact in terms of morbidity, mortality, economic costs, and potential for prevention. Based on Centers for Disease Control and Prevention (CDC)-sponsored hospital surveillance data from 2018, about 3% to 4% of inpatients are infected and an estimated 633,000 hospitalized patients develop an HAI each year [3]. These infections lead to excess mortality and add billions of dollars in total direct medical costs annually [1,4].

Evidence-based guidelines are at the heart of strategies to prevent and control HAIs and drug-resistant infections and address a wide range of issues from architectural design of hospitals to hand hygiene (Table 3) [16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39]. Adherence to individual guidelines varies but, in general, is low. For example, hand hygiene is the most basic and single most important preventive measure, yet compliance rates among healthcare workers have averaged 30% to 50% [27,40,41,42,43]. Decreasing the number of HAIs will require research to better understand the reasons behind lack of compliance with guidelines and to develop education and interventions that target those reasons.

"Zero tolerance" of HAIs became a common catch-phrase as a call to improve prevention strategies and eliminate HAIs. Zero tolerance for HAIs is a worthy goal, but the complete elimination of all HAIs is not feasible, primarily because interventions address only exogenous sources of infection and do not address many other important factors, such as host response, patient case mixes, pathogen virulence, and lack of specificity in definitions and diagnostic criteria [44,45]. Furthermore, the literature has not supported the complete elimination of HAIs with enhanced compliance to prevention protocols. The results of the CDC's Study of Efficacy of Nosocomial Infection Control (SENIC) suggested that 6% of all HAIs could be prevented by minimal infection control efforts and 32% by "well organized and highly effective infection control programs" [46,47]. A later review of 30 studies suggested that an estimated 20% of HAIs are preventable [48]. A 2011 study estimated that approximately 65% to 75% of central line-associated bloodstream infections and catheter-associated urinary tract infections were preventable using current evidence-based strategies; 55% of ventilator-associated pneumonia and surgical site infections were estimated to be preventable [49]. Furthermore, complete elimination is not needed to reap substantial benefit. The U.S. Department of Health and Human Services estimates that a 40% decrease in preventable HAIs (compared with the 2010 rate) would result in 1.8 million fewer injuries and more than 60,000 lives saved over 3 years [9]. A 70% decrease in the rate of HAIs would save an estimated $25 to $31.5 billion [1].

In response to a call for mandatory reporting of HAIs, several states passed legislation requiring the mandatory reporting of specific HAIs, and reporting requirements vary by state. The number of states with mandates for public reporting grew from 3 in 2004 to 36 (and the District of Columbia) in 2021 [68,69].

In addition to breaks in the skin, other primary entry points for micro-organisms are mucosal surfaces, such as the respiratory, gastrointestinal, and genitourinary tracts. The membranes lining these tracts comprise a major internal barrier to micro-organisms due to the antimicrobial properties of their secretions. The respiratory tract filters inhaled micro-organisms, and mucociliary epithelium in the tracheobronchial tree moves them out of the lung. In the gastrointestinal tract, gastric acid, pancreatic enzymes, bile, and intestinal secretions destroy harmful micro-organisms. Nonpathogenic bacteria (commensal bacteria) make up the normal flora in the gastrointestinal tract and act as protectants against invading pathogenic bacteria. Commensal bacteria are a source of infection only if they are transmitted to another part of the body or if they are altered by the use of antibiotics [16].

The transmission of infection follows the cycle that has been described for all diseases, and humans are at the center of this cycle [16]. In brief, a micro-organism requires a reservoir (a human, soil, air, or water), or a host, in which to live. The micro-organism also needs an environment that supports its survival once it exits the host and a method of transmission. Inherent properties allow micro-organisms to remain viable during transmission from a reservoir to a susceptible host, another essential factor for transmission of infection. The primary routes of transmission for infections are through the air, blood (or body fluid), contact (direct or indirect), fecal-oral route, food, animals, or insects. Once inside a host, micro-organisms thrive because of adherent properties that allow them to survive against mechanisms in the body that act to flush them out. Bacteria adhere to cell surfaces through hair-like projections, such as fibrillae, fimbriae, or pili, as well as by proteins that serve as adhesions [71]. Fimbriae and pili are found on gram-negative bacteria, whereas other types of adhesions are found with both gram-negative and gram-positive bacteria. Receptor molecules in the body act as ligands to bind the adhesions, enabling bacteria to colonize within the body. The virulence of the micro-organism will determine whether only colonization occurs or if infection will develop. With colonization, there is no damage to local or distant tissues and no immune reaction; with infection, bacterial toxins that break down cells and intracellular matrices are released, causing damage to local and distant tissues and prompting an immune response in the host. Bacteria continue to thrive within a host through strategies that enable them to acquire iron for nutrition and to defend against the immune response. These virulence factors enhance a micro-organism's potential for infection by interrupting or avoiding phagocytosis or living inside phagocytes [71].

Several risk factors for HAI caused by multidrug-resistant organisms have been identified [78,79]:

The most common drug-resistant HAI is MRSA, which emerged as a significant problem in the 1980s and increased steadily in prevalence, with a rate of approximately 59% of S. aureus infections in U.S. intensive care units (ICUs) in 2004 [79]. Since that time, however, the rate of MRSA associated with HAIs has decreased, most likely because of increased preventive strategies [79,82]. Overall, the rate of HAIs attributable to antimicrobial-resistant pathogens has not changed substantially since 2010 [82]. According to data on HAIs reported to the NHSN in 2009–2010, 20% of the infections were with antimicrobial-resistant phenotypes: MRSA (8.5%); vancomycin-resistant Enterococcus (VRE) (3%); extended-spectrum cephalosporin-resistant Klebsiella pneumoniae and K. oxytoca (2%); Escherichia coli (2%); Enterobacter spp. (2%); and carbapenem-resistant Pseudomonas aeruginosa (2%) [82]. The discovery of carbapenem-resistant Enterobacteriaceae as a new threat led the CDC to issue a guidance for control of infections with carbapenem-resistant or carbapenemase-producing Enterobacteriaceae in the healthcare setting [83,84]. Data from the 2015 NHSN network survey report showed that 45% of S. aureus isolates were methicillin-resistant, and among E. coli, Enterobacter, and Klebsiella isolates, 5% were carbapenem-resistant [3].

Droplets containing micro-organisms can be transmitted in the air, causing infection in patients either directly or indirectly (through contamination of devices or equipment). Cleaning activities, such as sweeping, dry mopping, dusting, or shaking linen, can contribute to the transmission of airborne micro-organisms. Bacteria in the air primarily consist of gram-positive cocci from the skin, and they can be eliminated with appropriate ventilation and circulation of air [89]. Many airborne viruses, such as influenza and other respiratory viruses and measles, do not carry far from the source; others, such as tuberculosis and varicella zoster, may be spread over long distances [16]. The most common fungal spore to be transmitted through air is Aspergillus, which is carried through dust particles, can survive for long periods, and is easily inhaled [90]. Under normal circumstances, the level of contamination with this airborne fungus' spores is not high enough to cause disease in otherwise healthy individuals. However, in the healthcare setting, the fungus causes respiratory infection, primarily pneumonia, in susceptible hosts.

The prevalence of infection with Aspergillus within a healthcare setting has been strongly associated with Aspergillus spore counts. Consequently, air conditioning systems with high-efficiency particulate air (HEPA) filters are needed to minimize contamination [91]. HEPA filters are especially needed to prevent infection with Aspergillus in patients at high risk for infection due to a suppressed immune system [92]. In one study, the risk of transplant-related mortality and overall mortality in the first 100 days after transplantation were significantly lower among patients treated in rooms with HEPA and/or laminar flow units than among patients treated in conventional isolation units [93]. In these units, the air exchange rate should be high (more than 15 exchanges per hour), rooms should be tightly sealed, and the air pressure in the rooms should be positive in relation to the hallway [91,94,95]. HEPA filters are also used in the hoods in microbiology laboratories and pharmacies, laminar flow units in ICUs, and unidirectional flow units in operating room suites [16].

The most common pathogen identified in tap water is P. aeruginosa [79]. In one study, researchers evaluated the association between tap water from faucets in a surgical ICU and patients with colonization or infection with P. aeruginosa [98]. The pathogen was found in 58% of water samples taken from individual faucets but was not identified in the main water supply. The genotypes of the micro-organism in 21 of the 45 patients were identical to those found in the tap water from the sink in the patient's room (15 patients) or in the adjacent room (6 patients). According to epidemiologic analysis, transmission of the pathogen had occurred from faucet to patient as well as from patient to faucet. P. aeruginosa is also the primary bacterial pathogen found in bath water [99]. The effect of infection with P. aeruginosa may be mild, as in folliculitis and external otitis, but wound infection may be more severe. Greater morbidity is associated with infection in individuals who have a compromised immune system or who have another health condition, such as diabetes [16].

Patient-related risk factors for HAIs include age, general health status, and the type of procedure to be carried out, and risk can be classified as minimal, medium, or high [16]. Patients are at minimal risk if they have no significant underlying disease, have an intact immune system, and will not undergo an invasive procedure. Medium risk is assigned to older patients who are susceptible to disease for a variety of reasons, including decreased immune function, comorbid conditions, and low nutritional status. Medium risk also refers to patients who are to have a nonsurgical invasive procedure, such as a peripheral venous catheter or a urinary catheter.

Advances in medical treatments have led to longer lives for individuals of all ages who have had organ transplantation, cancer, or infection with human immunodeficiency virus (HIV), and their compromised immune system puts them at high risk for HAI. High risk is also assigned to patients with multiple trauma or severe burns, or those who have surgery or an invasive procedure that is considered to be high risk, such as endotracheal intubation or insertion of a central venous catheter.

Most HAIs can be attributed to devices in the critical and semicritical categories, including intravascular catheters, surgical drains, urinary catheters, and endoscopic instruments [89]. Discussion here is limited to endoscopic instruments, as infections related to the other devices are addressed in detail later. In general, the transmission of pathogens on endoscopic devices has been attributed to noncompliance with appropriate reprocessing (cleaning, disinfection, sterilization, and drying) [17,32,105,106]. In particular, appropriate drying has been overlooked as an integral component of reprocessing, and guidelines have been inconsistent in recommendations on drying [107].

Bronchoscopes and gastrointestinal endoscopes are the primary diagnostic scopes used in healthcare settings. Both types of devices are associated with a low risk of infection transmission. Approximately 500,000 flexible bronchoscopies are done in the United States each year [17,108]. Few studies, however, have been carried out to evaluate the risk of infection; nosocomial infection related to bronchoscopy is difficult to detect and is likely under-recognized and under-reported [109]. In 2003, there were two reports of multiple pseudoinfections and true infections, primarily with P. aeruginosa, associated with bronchoscopes that had been reprocessed according to current standards [110,111]. However, in both reports, loose fittings over the valve stem for the working channel of the bronchoscope were thought to have prevented effective mechanical cleaning and disinfection [109]. Overall, the pathogens associated with bronchoscopy-related infection have been P. aeruginosa, Serratia marcescens, nontuberculous mycobacteria, and environmental fungi [109]. In 2014, the U.S. Food and Drug Administration (FDA) received 50 medical device reports that mentioned infection or device contamination associated with reprocessed flexible bronchoscopes [108]. During the course of investigating these reports, the FDA identified two recurrent themes that contributed to device contamination or device-associated infection: failure to meticulously follow the manufacturer's instructions for reprocessing (e.g., failure to perform thorough manual cleaning before high-level disinfection), and continued use of devices, despite integrity, maintenance, and mechanical issues (e.g., persistent channel kinks or bends).

More studies have evaluated the risk of infection associated with gastrointestinal endoscopy, which is performed on approximately 10 to 20 million people each year [112]. The American Society for Gastrointestinal Endoscopy (ASGE) estimates that infectious organisms are transmitted in 1 of 1.8 million gastrointestinal endoscopies [105]. Furthermore, all instances of infection during endoscopy have been the result of noncompliance with established guidelines for reprocessing of endoscopy equipment, highlighting the importance of adhering to these recommendations [32,112,113,114].

As with bronchoscopy, the pathogen with the highest rate of transmission associated with gastrointestinal endoscopy is P. aeruginosa [112,114]. As is true for other pathogens associated with endoscopy, infection with P. aeruginosa has resulted from nonadherence to reprocessing guidelines; however, this pathogen differs from the others because of its predilection for a moist environment. Many cases of infection with P. aeruginosa have been linked to the water supply to the endoscope and to failure to completely dry the endoscope channels with a 70% alcohol solution and forced air [107,112,114]. Salmonella species have also been associated with endoscopy, but no cases have been reported since the publication of the 1988 guidelines for standardized cleaning and disinfection of the devices [112,114]. Infection with Helicobacter pylori has also been related to suboptimal cleaning and disinfection [112]. Low rates of hepatitis B and C virus transmission have been reported, and most cases of infection with hepatitis C were found to be related to the inappropriate use of multiple-dose vials and/or syringes rather than to the endoscope itself [32,112].

As with bronchoscopy, the pathogen with the highest rate of transmission associated with gastrointestinal endoscopy is P. aeruginosa [112,114]. As is true for other pathogens associated with endoscopy, infection with P. aeruginosa has resulted from nonadherence to reprocessing guidelines; however, this pathogen differs from the others because of its predilection for a moist environment. Many cases of infection with P. aeruginosa have been linked to the water supply to the endoscope and to failure to completely dry the endoscope channels with a 70% alcohol solution and forced air [107,112,114]. Salmonella species have also been associated with endoscopy, but no cases have been reported since the publication of the 1988 guidelines for standardized cleaning and disinfection of the devices [112,114]. Infection with Helicobacter pylori has also been related to suboptimal cleaning and disinfection [112]. Low rates of hepatitis B and C virus transmission have been reported, and most cases of infection with hepatitis C were found to be related to the inappropriate use of multiple-dose vials and/or syringes rather than to the endoscope itself [32,112].

HAI is clearly defined by the CDC in the NHSN as a "localized or system condition (1) that results from adverse reaction to the presence of an infectious agent(s) or its toxin(s); and (2) that was not present or incubating at the time of admission to the hospital" [127]. Thus, an infection is considered to be healthcare associated if it is unrelated to the admitting diagnosis and develops within 48 hours after admission. The CDC notes that an infection should be considered healthcare associated if it is thought that the infection was acquired in the hospital but did not become evident until after discharge 127]. The diagnosis of infection is made on the basis of a combination of clinical findings and the results of laboratory studies or other diagnostic testing [127]. The NHSN provides comprehensive details about the criteria for infection at 13 major anatomic sites and has developed clinical and biologic criteria for 48 specific sites or types of infection [127]. The WHO has simplified the criteria to facilitate infection control in healthcare institutions with limited resources [16].

The risk factors for each of these HAIs have been delineated in many studies (Table 7) [20,79,135,136,137,138,139,140,141,142]. Yet, predicting which patients are at risk can be difficult. In one study, physicians in a surgical ICU were asked to assess at admission the individual risk of major HAI during the patient's stay in the unit. The investigators found that the physicians could not accurately predict risk, with positive predictive values that ranged from 8.4% to 14.5% and negative predictive values that ranged from 92.1% to 100% [143].

HAIs are predominantly caused by bacteria. Between January 2015 and December 2017, 355,633 pathogens (311,897 HAIs) were reported to the NHSN [144]. Surgical site infections contributed to the highest proportion of HAIs (42.4%), followed by catheter-associated urinary tract infections (29.7%), central-line associated bloodstream infections (25.3%), and ventilator-associated pneumonia (2.6%). E. coli was the most common pathogen across all HAIs, accounting for nearly 18% of reported pathogens. Approximately 69% of the reported pathogens belonged to one of nine main pathogen groups [144]:

Urine specimens for culture should not be obtained from the drainage bag; instead, a sample should be taken through the catheter port with use of aseptic technique [30]. If there is no port, a needle and syringe can be used to puncture the catheter tubing and collect the specimen [30]. For patients with a long-term indwelling catheter, the IDSA recommends replacing the catheter and collecting the specimen from the newly placed catheter [30].

According to National Hospital Discharge Survey data, 51.4 million inpatient surgical procedures were performed in 2010, creating a large population at risk for surgical site infections [162]. The CDC healthcare-associated infection (HAI) prevalence survey found that there were an estimated 157,500 surgical site infections associated with inpatient surgeries in 2011 [163]. Infection will develop postoperatively in approximately 2.6% of all patients who have surgery [164]. During 2015–2017, surgical site infections contributed the highest proportion of pathogens (43%) compared with all other HAIs [144]. The rate has decreased since the 1990s, but the lower rate is not thought to be an accurate representation because of the increased number of operations done on an outpatient basis; a decrease in the length of the postoperative hospital stay; and a wound infection incubation period of 5 to 7 days [40]. This potential for underestimation of the number of surgical site infections is reflected in the findings of a study in which one-third of healthcare-associated wound infections were detected after the patient had been discharged [165]. Surgical site infections are associated with extended lengths of stay, a high rate of readmissions, excess hospital costs, and a mortality rate of 3%, with a higher mortality rate reported for patients 70 years of age and older [166,167].

Among the most common surgery-related factors are anesthesia score, duration of the operation, the use of drains, and inadequate aseptic technique [89]. In a study to determine the influence of risk factors on complications after colorectal surgery, body mass index, duration of the operation, and the surgeon who performed the operation were the three most important factors influencing surgical site infections [171].

Before surgery, patients should be advised to shower or bathe (full body) with soap (antibacterial or non-antibacterial) or an antiseptic agent on at least the night before the operative day [29]. Antimicrobial prophylaxis should be administered only when indicated based on published clinical practice guidelines and timed such that a bactericidal concentration of the agents is established in the serum and tissues when the incision is made [29]. Antibiotic prophylaxis need not be maintained longer than a few hours after the incision has been closed. Additional guidance is provided in reference to specific surgical procedures and specialty operations (e.g., prosthetic joint arthroplasty) [29].

Based on expert opinion, the IDSA recommends opening an infected surgical site, removing the infected material, and continuing dressing changes until the wound heals by secondary intention [164]. Although treatment with antibiotics is commonly started when a surgical site infection is diagnosed, the IDSA notes that little evidence has supported this approach [164]. A short course (24 to 48 hours) of antibiotics may be indicated for patients with a temperature higher than 38.5 degrees Centigrade or a pulse rate of more than 100 beats/min [164]. The guidelines add that treatment is usually empirical but may be selected according to results of wound culture [164]. IDSA offers guidance on the selection of antibiotics according to the operative site [164].

The rate of ventilator-associated pneumonia is higher than that for hospital-acquired pneumonia, with a reported rate of 1 to 4 cases per 1,000 ventilator-days, and rates as high as 10 cases per 1,000 in some neonatal and surgical populations [18,192]. An estimated 10% of patients requiring mechanical ventilation will develop pneumonia as a complication, and the mortality rate directly attributable to ventilator-associated pneumonia is estimated at 13% [18]. Excess cost of care resulting from prolongation of hospital stay is estimated to range from $30,000 to $40,000 per patient [18].

In a systematic review, the American College of Physicians found several patient-related and surgery-related factors that increased the risk of postoperative pulmonary complications. The most common patient-related factors were the presence of COPD and an age older than 60 years [141]. Other significant factors were an American Society of Anesthesiologists (ASA) class 2 (defined as a patient with mild systemic disease) or higher, functional dependence, and congestive heart failure. Cigarette use was associated with a modest increase in risk, and obesity and mild or moderate asthma were not found to increase risk [141]. Use of a PPI or histamine-2 receptor antagonist is also thought to be a risk factor [142]. Surgery-related factors included prolonged duration of surgery (more than three to four hours), emergency surgery, and surgical site, with abdominal surgery, thoracic surgery, neurosurgery, head and neck surgery, vascular surgery, and aortic aneurysm repair being associated with the greatest risks [141].

The risk of ventilator-associated pneumonia correlates with the duration of intubation; the risk has been estimated to be 3% per day during the five-day period after intubation, decreasing to 2% per day for days 5 through 10 and to 1% per day for longer durations [193]. Nearly half of all cases of ventilator-associated pneumonia develop within the first four days of mechanical ventilation [190]. In addition to duration of ventilation, several other risk factors among adults have been identified, including a supine head position; use of a nasogastric tube, paralytic agents, or PPI or histamine-2 receptor antagonists; patient age; chronic lung disease; and head trauma [20,142]. In one study, ventilator-associated pneumonia was most frequently associated with ICU admission diagnoses of postoperative care, neurologic conditions, sepsis, and cardiac complications [194].

In 2015–2017, the most common pathogens reported with ventilator-associated pneumonia in adults were S. aureus (29%) and P. aeruginosa (13%), followed by K. pneumonia/oxytoca (10%), Enterobacter spp. (8%), and H. influenzae (6%) [144]. Almost half of all cases of ventilator-associated pneumonia are caused by infection with more than one pathogen [190]. As with other forms of HAI, the percentage of S. aureus resistant to methicillin has decreased in recent years [3,163]. The percentage of vancomycin-resistant E. faecium has remained stable, but the percentage of vancomycin-resistant E. faecalis decreased from 10% in 2009–2010 to 7% in 2015–2017 [144]. In 2015–2017, the rates of resistance among Klebsiella spp. for extended-spectrum cephalosporins, carbapenems, multidrug were 21%, 7%, and 13%, respectively, and the rate of multidrug-resistant E. coli increased to nearly 10% [144].

Gram-negative enteric bacilli and Pseudomonas spp. rarely colonize the upper respiratory tract of healthy individuals, but often do so in persons with an underlying disease, such as alcohol use disorder, and in those who are hospitalized or reside in nursing homes. Most cases of pneumonia that develop in a healthcare facility are caused by aspiration of oropharyngeal or gastric secretions colonized with hospital bacterial flora. Consequently, the prevalent causation as well as the antibiotic sensitivity pattern of resident pathogens will vary from region to region in relation to the type of facility and burden of antimicrobial usage. The selection of initial antibiotic therapy in these cases is based on the patient's risk factors for infection with a multidrug-resistant organism, such as MRSA, P. aeruginosa, K. pneumoniae, or Acinetobacter. The infectious disease and pulmonary specialty societies (IDSA and American Thoracic Society [ATS]) list the following risk factors for multidrug-resistant pathogens in patients presenting with hospital-acquired or ventilator-associated pneumonia [18]:

Two guidelines were developed to focus specifically on the prevention of ventilator-associated pneumonia; one was jointly developed by the SHEA and IDSA, and the other was jointly developed by the Canadian Critical Care Trials Group and the Canadian Critical Care Society [20,36]. In addition, prevention of ventilator-associated pneumonia is addressed in the CDC's guidelines for preventing healthcare-associated pneumonia and in the IDSA/ATS guidelines on the management of healthcare-associated pneumonias [18; 25]. All of these agencies suggest a multicomponent strategy for prevention of pneumonia. Compliance with guidelines, however, has been slow; nursing surveys demonstrate rates of adherence to specific preventive measures ranging from 15% to 50% [192,196]. All of these agencies suggest a multicomponent strategy for prevention of pneumonia. Compliance with guidelines, however, has been slow; nursing surveys demonstrate rates of adherence to specific preventive measures ranging from 15% to 50% [192,196]. Education is beneficial, and training sessions are a proven means to enhance knowledge and practice among healthcare professionals caring for intubated patients [197].

The difficulty in diagnosing hospital-acquired or ventilator-associated pneumonia has been well established [18,193,218]. The clinical signs can resemble those of other, noninfectious conditions, and the specificity of clinical criteria is low [190]. According to the CDC definition, the diagnosis in adults is made on the basis of clinical signs and symptoms and results of laboratory testing or imaging and must meet one of two criteria [219,220].

Criterion 1

For any patient, at least one of the following:

AND at least two of the following:

Criterion 2

Two or more serial chest radiographs showing at least one of the following:

The nontunneled central venous catheter accounts for the majority of all intravascular device-related bloodstream infections [28]. Peripheral catheters (arterial and venous) are rarely associated with bloodstream infections, and totally implantable catheters are associated with the lowest risk [28]. A systematic review of 200 prospective studies of intravascular device-related bloodstream infections indicated that the level of risk associated with various types of devices can vary substantially depending on whether risk is expressed as the number of infections per 100 intravascular device-days or 1,000 intravascular device-days [244]. The risks associated with peripheral intravenous catheters were much higher when expressed over 1,000 intravascular device-days, pointing to the need for prevention strategies targeted to all types of devices [244].

There are several approaches to diagnosing an intravascular device-related bloodstream infection. A meta-analysis of 51 studies published between 1966 and 2004 was designed to identify which method was the most accurate [256]. The studies had involved the eight most commonly used diagnostic methods: culture (qualitative, semiquantitative, or quantitative) of a catheter segment; culture (qualitative or quantitative) of blood obtained through the catheter; paired quantitative cultures (blood obtained through the catheter as well as from a peripheral site); differential time to positivity (monitoring of cultures of blood obtained through the catheter and from a peripheral site); and acridine orange leukocyte cytospin. The paired cultures method was the most accurate, with a pooled specificity of 99%, followed by qualitative culture of blood drawn through the catheter and acridine orange leukocyte cytospin [256].

The primary risk factors for infection with C. difficile are antibiotic use, older age, and hospitalization [33]. Exposure to antibiotic agents is the most modifiable risk factor, an association reported in more than 96% of hospitalized patients in one study [280]. Antibiotics increase the risk by suppressing or altering normal bowel microflora, thereby facilitating overgrowth of relatively dormant C. difficile organisms. Many antibiotics have been implicated, but fluoroquinolones, cephalosporins, carbapenems, and clindamycin have been found to confer high risk [33]. The likelihood of infection increases with longer hospitalizations, with a 15% to 45% risk of colonization among patients hospitalized for one to three weeks [280].

Guidelines developed by SHEA/IDSA in 2010, and updated in 2017 and 2021, offer recommendations for prevention, diagnosis, and management of C. difficile[33,281]. (The scope of the 2021 focused update is restricted to adults and includes new data for fidaxomicin and for bezlotoxumab, a monoclonal antibody targeting toxin B produced by C. difficile [281].)

Control measures include restriction of antibiotic use; isolation precautions for healthcare workers, patients, and visitors; and environmental cleaning and disinfection (Table 16) [33]. The guidelines note that the use of antibiotics should be minimized and that an antibiotic stewardship program should be developed and implemented by all hospitals [33]. Appropriate hand hygiene is essential, and soap and water should be used rather than alcohol-based handrubs, as alcohol is not effective at killing C. difficile spores [33]. Gowns, gloves, and contact precautions for the duration of diarrhea are also recommended. The guidelines suggest that removing environmental sources of C. difficile, such as replacing rectal thermometers with disposable ones, can help reduce the incidence of C. difficile infection. The guidelines also note that the following are not recommended: routine environmental screening for C. difficile (level III, C); routine identification of asymptomatic carriers for infection control purposes (level III, A); and use of probiotics to prevent infection (level I, B) [33].

The most important step in treating C. difficile-associated diarrhea is to discontinue the inciting antibiotic as soon as possible [33]. This approach alone will lead to resolution of diarrhea in approximately 15% to 25% of patients with mild infection [268,280]. Antibiotic treatment of the diarrhea should not begin until the culture or toxin assay results are known, as approximately 30% of hospitalized patients with antibiotic-associated diarrhea will have C. difficile infection [33]. However, if severe or complicated C. difficile infection is suspected, empirical treatment should be started as soon as the diagnosis is suspected (level III, C) [33]. The SHEA/IDSA guidelines recommend fidaxomicin rather than a standard course of vancomycin for an initial episode of C. difficile gastrointestinal infection, whether mild or moderately severe. Implementation of this recommendation depends upon available resources. Vancomycin remains an acceptable alternative [281]. For an initial episode of C. difficile, a dosage of fidaxomicin 200 mg orally twice daily for 10 days is recommended. Vancomycin 125 mg orally four times per day for 10 days is the recommended alternative regimen [281]. Table 17 outlines the guideline recommendations for treatment according to severity of illness [281].

Despite the simplicity of the intervention, its substantial impact, and wide dissemination of the guidelines, compliance with recommended hand hygiene has ranged from 16% to 81%, with an average of 30% to 50% [27,40,41,42,43]. A 2010 systematic review of studies on compliance with hand-hygiene guidelines in hospital care found an overall median compliance rate of 40%, with lower rates in ICUs (30% to 40%) than in other settings (50% to 60%), lower rates among physicians than among nurses (32% and 49%, respectively), and lower rates before (21%) rather than after (47%) patient contact [291]. Among the reasons given for the lack of compliance are inconvenience, understaffing, and damage to skin [27,41,89]. The development of effective alcohol-based handrub solutions addresses these concerns, and studies have demonstrated that these solutions, as well as performance feedback and accessibility of materials, have increased compliance [42,291,292,293]. The CDC guidelines recommend the use of handrub solutions on the basis of several advantages, including [27]:

The guidelines suggest that healthcare facilities promote compliance by making the handrub solution available in dispensers in convenient locations (such as the entrance to patients' room or at the bedside) and provide individual pocket-sized containers [27]. The handrub solution may be used in all clinical situations except for when hands are visibly dirty or are contaminated with blood or body fluids. In such instances, soap (either antimicrobial or nonantimicrobial) and water must be used.

However, there are many other reasons for lack of adherence to appropriate hand hygiene, including denial about risks, forgetfulness, and belief that gloves provide sufficient protection [27,41]. These reasons demand education for healthcare professionals to emphasize the importance of hand hygiene. Also necessary is research to determine which interventions are most likely to improve hand-hygiene practices, as no studies have demonstrated the superiority of any intervention [294,295]. Single interventions are unlikely to be effective [294,295].

Several single-institution studies have demonstrated that appropriate hand hygiene reduces overall rates of HAIs, including those caused by MRSA and VRE [43,292,293]. However, rigorous evidence linking hand hygiene alone with the prevention of HAIs is lacking, making it difficult to evaluate the true impact of hand hygiene alone in reducing HAIs [57]. One challenge in evaluating the impact of hand hygiene is that a variety of methodologies have been used to assess compliance (e.g., surveys, direct observation, measurement of product use), each with its own advantages and disadvantages [296]. Measuring the effect of appropriate hand hygiene alone is also difficult because the intervention is often one aspect of a multicomponent strategy to reduce infection [43]. Lastly, as noted previously, the development of HAIs is complex, with many contributing factors. Although more research is needed to assess the individual impact of appropriate hand hygiene, this basic prevention measure is the essential foundation of an effective infection control strategy and an element of every infection control guideline.

The vaccination status of healthcare workers has been found to have a direct effect on transmission of the influenza virus to patients. Outbreaks of influenza in healthcare settings have been associated with low rates of vaccination among healthcare workers, and lower rates of nosocomial influenza have been related to higher vaccination rates among healthcare workers [297,298]. Because of these findings, several organizations have addressed the need for vaccination. The CDC and the Advisory Committee on Immunization Practices recommends annual influenza vaccination for all healthcare workers [299]. CDC guidelines include four Level I recommendations to help increase rates of vaccination [300]:

In addition, the Joint Commission began including vaccination programs in its accreditation standards in 2007 [301].

The CDC guidelines for isolation precautions in hospitals, updated in 2007, synthesize a variety of recommendations for precautions based on the type of infection, the route of transmission, and the healthcare setting [23]. As defined by the CDC, Standard Precautions represent measures that should be followed for all patients in a healthcare facility, regardless of diagnosis or infection status. Standard Precautions apply to blood; all body fluids, secretions, and excretions except sweat, regardless of whether or not they contain visible blood; nonintact skin; and mucous membranes [23]. For patients who are known to have or are highly suspected to have colonization or infection, Contact Precautions should be followed. This type of precaution is designed to reduce exogenous transmission of micro-organisms through direct or indirect contact from healthcare workers or other patients. Airborne Precautions are used for patients who have or are highly suspected of having infection that is spread by airborne droplet nuclei, such as tuberculosis, measles, or varicella. Droplet Precautions target infections that are transmitted through larger droplets generated through talking, sneezing, or coughing, such as invasive Haemophilus influenzae type b disease, diphtheria (pharyngeal), pertussis, group A streptococcal pharyngitis, influenza, mumps, and rubella [23].

Most outbreaks of group A streptococci involve surgical wounds, and the source can usually be traced to an asymptomatic carrier in the operating room or on the wound care team [89,337]. Standard Precautions are sufficient if the wound is minor; if it is major, Contact Precautions should be instituted and followed for 24 hours after initiation of effective therapy [23]. The healthcare worker should receive antimicrobial therapy as appropriate and leave the setting until completion of therapy.

Dealing with pulmonary tuberculosis involves prompt identification of the disease and determining the susceptible individuals who were exposed to the patient before isolation [89]. Airborne Precautions should be instituted and remain in place until the patient is receiving effective therapy, is improving clinically, and the culture results for three consecutive sputum specimens, collected on different days, are negative. Comprehensive information is available in the CDC guidelines for preventing the transmission of tuberculosis in healthcare facilities [338].

The source of HAI with Legionella pneumonia is usually contaminated water [89]. Implementation of Standard Precautions for the patient is sufficient [23]. Laboratory-based surveillance for nosocomial Legionella should be performed, and samples of tap water should be obtained for culture. If the culture is positive, it is best to obtain cultures from patients who have healthcare-associated pneumonia. There are more than 40 known types of Legionella species, but most outbreaks are caused by Legionella pneumophila serotypes 1 and 6.

Outbreaks of antibiotic resistance have involved MRSA, VRE, and, most recently, vancomycin-resistant S. aureus [339]. In such outbreaks, it is important to identify patients with colonization or infection early and isolate them or cohort them. Contact Precautions should be implemented and carried out until antibiotic therapy has been completed and cultures are negative [23]. The importance of adhering to proper hand hygiene and other elements of Contact Precautions should be emphasized. Healthcare workers who were involved with patients before isolation should be evaluated for colonization and infection and treated appropriately.