CHAPTER 17: INFECTIONS ACQUIRED IN HEALTH CARE FACILITIES

The costs of hospital-acquired (nosocomial) and other health care–associated infections are great. These infections have affected as many as 1.7 million patients at a cost of ~$28–33 billion and 99,000 lives in U.S. hospitals annually. Although efforts to lower infection risks have been challenged by the numbers of immunocompromised patients, antibiotic-resistant bacteria, fungal and viral superinfections, and invasive devices and procedures, a prevailing viewpoint—often termed “zero tolerance”—is that almost all health care–associated infections should be avoidable with strict application of evidence-based prevention guidelines (Table 17-1). In fact, rates of device-related infections—historically, the largest drivers of risk—have fallen steadily over the past few years. Unfortunately, at the same time, antimicrobial-resistant pathogens have risen in number and are estimated to contribute to ~23,000 deaths in and outside of hospitals annually. This chapter reviews health care–associated and device-related infections as well as basic surveillance, prevention, control, and treatment activities.

The standards of the Joint Commission require all accredited hospitals to have active programs for surveillance, prevention, and control of nosocomial infections. Education of physicians in infection control and health care epidemiology is required in infectious disease fellowship programs and is available in online courses. Concerns over “patient safety” have led to federal legislation that prevents U.S. hospitals from upgrading Medicare charges to pay for hospital costs resulting from at least 14 specific nosocomial events (Table 17-2) and have prompted national efforts to publicly report on processes of patient care (e.g., timely administration and appropriateness of perioperative antibiotic prophylaxis) and patient outcomes (e.g., surgical wound infection rates). Neither the carrot (pay-for-performance) nor the stick (nonpayment for preventable infections) appears to have impacted infection rates. The effect of public attention may be more positive; in 2009, the U.S. Department of Health and Human Services released a major interagency Action Plan to Prevent Healthcare-Associated Infections, including a list of 5-year national prevention targets that are mostly on track (Table 17-3).

Traditionally, infection preventionists have surveyed inpatients for infections acquired in hospitals (defined as those neither present nor incubating at the time of admission). Surveillance most often requires review of microbiology laboratory results, “shoe-leather” epidemiology on nursing wards, and application of standardized definitions of infection. Progressively more infection-control programs use computerized hospital databases for algorithm-driven electronic surveillance (e.g., of vascular catheter and surgical wound infections) that removes observer bias and, by so doing, provides data that are more reliable for interfacility comparisons. Although infection surveillance in nursing homes and some long-term acute-care hospitals (LTACHs) is still in its formative stage, the role of these facilities in the transmission of antimicrobial-resistant pathogens will require their increased attention to infection surveillance and control.

Most hospitals aim surveillance at infections associated with high-level morbidity or expense. Quality-improvement activities in infection control have led to increased surveillance of personnel compliance with infection control policies (e.g., adherence to influenza vaccination recommendations). In the spirit of “what is measured improves,” the majority of states now require public reporting of processes for prevention of health care–associated infection and/or patient outcomes. As a result, in some locales, the surveillance pendulum is swinging back to use of “house-wide” surveillance, and many states now require that hospitals use the Centers for Disease Control and Prevention’s (CDC’s) National Healthcare Safety Network (NHSN) reporting system to provide uniform definitions and to facilitate transmission of data. Increasing reliance on the NHSN by states to facilitate public reporting has led to participation by more than 12,000 facilities (~4700 of the ~5700 acute-care hospitals in the United States, ~540 LTACHs, ~270 inpatient rehabilitation facilities, ~6000 outpatient dialysis facilities, ~300 ambulatory surgery centers, ~150 long-term-care facilities). This level of participation provides a nationwide view of health care–associated infections and represents a watershed in potential access to national rates of antimicrobial use and resistance.

Results of surveillance are expressed as rates. In general, for example, 5–10% of patients develop nosocomial infections. However, such broad statistics have little value unless qualified by duration of risk, by site of infection, by patient population, and by exposure to risk factors. To account for some of these variables, the CDC now uses a Standardized Infection Ratio (SIR; www.cdc.gov/hai/national-annual-sir/) as part of NHSN rate reporting. Meaningful denominators for infection rates include the number of patients exposed to a specific risk (e.g., patients using mechanical ventilators) or the number of intervention days (e.g., 1000 patient-days on a ventilator). As use of invasive devices such as indwelling bladder catheters has purposely been decreased, the denominators have become smaller, but the fact that patients who still require such devices may be those at intrinsically higher risk (potential numerators) may paradoxically increase rates when device-days account for the denominator. Temporal trends in rates should be reviewed, and rates should be compared with regional and national benchmarks that incorporate the SIR. Interhospital comparisons still may be misleading because of the wide range in risk factors and severity of underlying illnesses. Process measures (e.g., adherence to hand hygiene) do not usually require risk adjustment, and outcome measures (e.g., cardiac surgery wound-infection rates) can identify hospitals with outlier infection rates (e.g., in the top deciles) for further evaluation. Moreover, temporal analysis of a hospital’s infection rates can help to determine whether control measures are succeeding and where increased efforts should be focused.

Nosocomial infections follow basic epidemiologic patterns that can help to direct prevention and control measures. Nosocomial pathogens have reservoirs, are transmitted by largely predictable routes, and require susceptible hosts. Reservoirs and sources exist in the inanimate environment (e.g., residual Clostridium difficile spores on frequently touched surfaces in patients’ rooms) and in the animate environment (e.g., infected or colonized health care workers, patients, and hospital visitors). The mode of transmission usually is either cross-infection (e.g., indirect spread of pathogens from one patient to another on the inadequately cleaned hands of hospital personnel) or autoinoculation (e.g., aspiration of oropharyngeal flora into the lungs along an endotracheal tube). Occasionally, pathogens (e.g., group A streptococci and many respiratory viruses) are spread from person to person via large infectious droplets released by coughing or sneezing. Much less common—but often devastating in terms of epidemic risk—is true airborne spread of small or droplet nuclei (as in nosocomial chickenpox) or common-source spread (e.g., by contaminated IV fluids). Factors that increase host susceptibility include underlying conditions, abnormalities of innate defense (e.g., due to genetic polymorphisms), and medical-surgical interventions and procedures that compromise host defenses.

Hospitals’ infection-control programs must determine general and specific control measures. Given the prominence of cross-infection, hand hygiene is cited traditionally as the most important preventive measure. Health care workers’ rates of adherence to hand-hygiene recommendations are abysmally low (often <50%). Reasons cited include inconvenience, time pressures, and skin damage from frequent washing. Sinkless alcohol rubs are quick and highly effective and actually improve hand condition since they contain emollients and allow the retention of natural protective oils that would be removed with repeated rinsing. Use of alcohol hand rubs between patient contacts is recommended for all health care workers except when hands are visibly soiled or after care of a patient who is part of a health care facility outbreak of infection with C. difficile, whose spores resist killing by alcohol and require mechanical removal. In these cases, washing with soap and running water is recommended. A number of innovative systems have been developed to track hand-hygiene adherence in real time and to provide feedback; although this approach is exciting, sustained improvements in rates remain to be seen.

The fact that >25–50% of nosocomial infections are due to the combined effect of the patient’s own flora and invasive devices highlights the importance of improvements in the use and design of such devices. Intensive education, “bundling” of evidence-based interventions (Table 17-4), and use of checklists to facilitate adherence have reduced infection rates (Table 17-3) through improved asepsis in handling and earlier removal of invasive devices. It is especially noteworthy that turnover or shortages of trained personnel jeopardize safe and effective patient care and have been associated with increased infection rates.

URINARY TRACT INFECTIONS

Urinary tract infections (UTIs) account for ~30–40% of nosocomial infections; up to 3% of bacteriuric patients develop bacteremia. Although UTIs contribute at most 15% to prolongation of hospital stay and may have an attributable cost in the range of only $1300, these infections are reservoirs and sources for spread of antibiotic-resistant bacteria. Most nosocomial UTIs are associated with preceding instrumentation or indwelling bladder catheters, which create a 3–7% risk of infection each day. UTIs generally are caused by pathogens that spread up the periurethral space from the patient’s perineum or gastrointestinal tract—the most common pathogenesis in women—or via intraluminal contamination of urinary catheters, usually due to cross-infection by caregivers who are irrigating catheters or emptying drainage bags. Pathogens come occasionally from inadequately disinfected urologic equipment and rarely from contaminated supplies.

Hospitals should monitor essential performance measures for preventing nosocomial UTIs (Table 17-4). Prompts to clinicians to assess a patient’s need for continued use of an indwelling bladder catheter can improve removal rates and lessen the risk of UTI. Guidelines for managing postoperative urinary retention (e.g., with bladder scanners) also may limit the use or duration of catheterization. Other approaches to the prevention of UTIs have included the use of topical meatal antimicrobial agents, drainage bag disinfectants, and anti-infective catheters. None of the latter three measures is considered routine.

Administration of systemic antimicrobial agents for other purposes decreases the risk of UTI during the first 4 days of catheterization, after which resistant bacteria or yeasts emerge as pathogens. Prophylactic antibiotic administration at the time of catheter removal has been reported to decrease the risk of UTI. Selective decontamination of the gut also is associated with a reduced risk. Again, however, none of these approaches is routine.

Irrigation of catheters, with or without antimicrobial agents, may actually increase the risk of infection. A condom catheter for men without bladder obstruction may be more acceptable than an indwelling catheter and may lessen the risk of UTI if maintained carefully. The role of suprapubic catheters in preventing infection is not well defined.

Treatment of UTIs is based on the results of quantitative urine cultures (Chap. 33). The most common pathogens are Escherichia coli, nosocomial gram-negative bacilli, enterococci, and Candida. Several caveats apply in the treatment of institutionally acquired infection. First, in patients with chronic indwelling bladder catheters, especially those in long-term-care facilities, “catheter flora”—microorganisms living on encrustations within the catheter lumen—may differ from actual urinary tract pathogens. Therefore, for suspected UTI in the setting of chronic catheterization (especially in women), it is useful to replace the bladder catheter and to obtain a freshly voided urine specimen. Second, as in all nosocomial infections, at the time treatment is initiated on the basis of a positive culture, it is useful to repeat the culture to verify the persistence of infection. Third, the frequency with which UTIs occur may lead to the erroneous assumption that the urinary tract alone is the source of infection in a febrile hospitalized patient. Fourth, recovery of Staphylococcus aureus from urine cultures may result from hematogenous seeding and may indicate an occult systemic infection. Finally, although Candida is now the most common pathogen in nosocomial UTIs among patients on intensive care units (ICUs), treatment of candiduria is often unsuccessful and is recommended only when there is upper-pole or bladder-wall invasion, obstruction, neutropenia, or immunosuppression.

PNEUMONIA

Historically, pneumonia has accounted for ~10–15% of nosocomial infections; ventilator-associated pneumonia (VAP) occurred in 1 to >4 patients per 1000 ventilator-days, and these infections were reported as responsible for a mean of 10 extra hospital days and $23,000 in extra costs per episode. Most cases of bacterial nosocomial pneumonia are caused by aspiration of endogenous or hospital-acquired oropharyngeal (and occasionally gastric) flora. Nosocomial pneumonias are associated with more deaths than are infections at any other body site. However, attributable mortality rates suggest that the risk of dying from nosocomial pneumonia is affected greatly by other factors, including comorbidities, inadequate antibiotic treatment, and the involvement of specific pathogens (particularly Pseudomonas aeruginosa or Acinetobacter). Surveillance and accurate diagnosis of pneumonia have been problematic in hospitals because many patients, especially those in the ICU, have abnormal chest roentgenographs, fever, and leukocytosis potentially attributable to multiple causes. This diagnostic uncertainty has led to a refocus from VAP to “ventilator-associated events” (VAEs), conditions, and complications, for which worsening physiologic parameters, such as oxygenation, are key metrics. Early data suggest that ~5–10% of patients using mechanical ventilators develop VAEs. Viral pneumonias, which are particularly important in pediatric and immunocompromised patients, are discussed in the virology section and in Chap. 21.

Risk factors for nosocomial pneumonia include those events that increase colonization by potential pathogens (e.g., prior antimicrobial therapy, contaminated ventilator circuits or equipment, or decreased gastric acidity); those that facilitate aspiration of oropharyngeal contents into the lower respiratory tract (e.g., intubation, decreased levels of consciousness, or presence of a nasogastric tube); and those that reduce host defense mechanisms in the lung and permit overgrowth of aspirated pathogens (e.g., chronic obstructive pulmonary disease, extremes of age, or upper abdominal surgery).

Control measures for pneumonia (Table 17-4) are aimed at frequent testing of readiness for extubation, remediation of risk factors in patient care (e.g., minimizing aspiration-prone supine positioning), and aseptic care of respirator equipment (e.g., disinfecting or sterilizing all inline reusable components such as nebulizers, replacing tubing/breathing circuits only if required because of malfunction or visible soiling—rather than on the basis of duration of use—to lessen the number of breaks in the system, and teaching aseptic technique for suctioning). Although the benefits of selective decontamination of the oropharynx and gut with nonabsorbable antimicrobial agents and/or use of short-course postintubation systemic antibiotics have been controversial, a randomized multicenter trial demonstrated lowered ICU mortality rates among patients on mechanical ventilation who underwent oropharyngeal decontamination.

Among the logical preventive measures that require further investigation are placement of endotracheal tubes that provide channels for subglottic drainage of secretions, which has been associated with reduced infection risks during short-term postoperative use, and noninvasive mechanical ventilation whenever feasible. Use of silver-coated endotracheal tubes may lessen risk of VAP but is not considered routine. It is noteworthy that reducing the rate of VAP often has not reduced overall ICU mortality; this fact suggests that this infection is a marker for patients with an otherwise-heightened risk of death.

The most likely pathogens for nosocomial pneumonia and treatment options are discussed in Chap. 21. Several considerations regarding diagnosis and treatment are worth emphasizing. First, clinical criteria for diagnosis (e.g., fever, leukocytosis, development of purulent secretions, new or changing radiographic infiltrates, changes in oxygen requirement or ventilator settings) have high sensitivity but relatively low specificity. These criteria are most useful for selecting patients for bronchoscopic or nonbronchoscopic procedures that yield lower respiratory tract samples protected from upper-tract contamination; quantitative cultures of such specimens have diagnostic sensitivities in the range of 80%. Second, early-onset nosocomial pneumonia, which manifests within the first 4 days of hospitalization, is most often caused by community-acquired pathogens such as Streptococcus pneumoniae and Haemophilus species, although some studies have challenged this view. Late-onset pneumonias most commonly are due to S. aureus, P. aeruginosa, Enterobacter species, Klebsiella pneumoniae, or Acinetobacter. When invasive techniques are used to diagnose VAP, the proportion of isolates accounted for by gram-negative bacilli decreases from 50–70% to 35–45%. Infection is polymicrobial in as many as 20–40% of cases. The role of anaerobic bacteria in VAP is not well defined. Third, one multicenter study suggested that 8 days is an appropriate duration of therapy for nosocomial pneumonia, with a longer duration (15 days in that study) when the pathogen is Acinetobacter or P. aeruginosa. Finally, in febrile patients (particularly those who have endotracheal or gastric tubes inserted through the nares), occult respiratory tract infections, especially bacterial sinusitis and otitis media, should be considered.

SURGICAL WOUND INFECTIONS

Wound infections occur in ~500,000 patients each year, account for ~15–20% of nosocomial infections, contribute up to 7–10 extra postoperative hospital days, and result in $3000 to $29,000 in extra costs, depending on the operative procedure and pathogen(s). The average wound infection has an incubation period of 5–7 days—longer than many postoperative stays. For this reason and because many procedures are now performed on an outpatient basis, the incidence of wound infections has become more difficult to assess. These infections usually are caused by the patient’s endogenous or hospital-acquired skin and mucosal flora and occasionally are due to airborne spread of skin squames that may be shed into the wound from members of the operating-room team. True airborne spread of infection through droplet nuclei is rare in operating rooms unless there is a “disseminator” (e.g., of group A streptococci or staphylococci) among the staff. In general, the common risks for postoperative wound infection are related to the surgeon’s technical skill, the patient’s underlying conditions (e.g., diabetes mellitus, obesity) or advanced age, and inappropriate timing of antibiotic prophylaxis. Additional risks include the presence of drains, prolonged preoperative hospital stays, shaving of operative sites by razor the day before surgery, long duration of surgery, and infection at remote sites (e.g., untreated UTI).

The substantial literature related to risk factors for surgical-site infections and the recognized morbidity and cost of these infections have led to national prevention efforts and to recommendations for “bundling” preventive measures (Table 17-4). Additional measures include attention to technical surgical issues (e.g., avoiding open or prophylactic drains), operating-room asepsis, and preoperative therapy for active infection. Reporting surveillance results to surgeons has been associated with reductions in infection rates. Preoperative administration of intranasal mupirocin to patients colonized with S. aureus, preoperative antiseptic bathing, and intra- and postoperative oxygen supplementation have been controversial because of conflicting study results, but evidence seems mostly to favor these interventions.

The process of diagnosing and treating wound infections begins with a careful assessment of the surgical site in the febrile postoperative patient. Diagnosis of deeper organ-space infections or subphrenic abscesses requires a high index of suspicion and the use of CT or MRI. Diagnosis of infections of prosthetic devices, such as orthopedic implants, may be particularly difficult and often requires the use of interventional radiographic techniques to obtain periprosthetic specimens for culture. Cultures of periprosthetic joint tissue obtained at surgery may miss pathogens that are cloistered in prosthesis-adherent biofilms; cultures of sonicates from explanted prosthetic joints have been more sensitive, particularly for patients who have received antimicrobial agents within 2 weeks of surgery.

The most common pathogens in postoperative wound infections are S. aureus, coagulase-negative staphylococci, and enteric and anaerobic bacteria. In rapidly progressing postoperative infections manifesting within 24–48 h of a surgical procedure, the level of suspicion regarding group A streptococcal or clostridial infection (Chaps. 44 and 51) should be high. Treatment of postoperative wound infections requires drainage or surgical excision of infected or necrotic material and antibiotic therapy aimed at the most likely or laboratory-confirmed pathogens.

INFECTIONS RELATED TO VASCULAR ACCESS AND MONITORING

Intravascular device–related bacteremias cause ~10–15% of nosocomial infections; central vascular catheters (CVCs) account for most of these bloodstream infections. Past national estimates indicated that as many as 200,000 bloodstream infections associated with CVCs occurred each year in the United States, with attributable mortality rates of 12–25%, an excess mean length of hospital stay of 12 days, and an estimated cost of $3700 to $29,000 per episode; one-third to one-half of these episodes occurred in ICUs. However, infection rates have dropped steadily (Table 17-3) since the publication of guidelines by the Healthcare Infection Control Practices Advisory Committee (HICPAC) in 2002. With increasing care of seriously ill patients in the community, vascular catheter–associated bloodstream infections acquired in outpatient settings are becoming more frequent. Broader surveillance for infections—outside ICUs and even outside hospitals—will be needed.

Catheter-related bloodstream infections derive largely from the cutaneous microflora of the insertion site, with pathogens migrating extraluminally to the catheter tip, usually during the first week after insertion. In addition, contamination of the hubs of CVCs or of the ports of “needle-less” systems may lead to intraluminal infection over longer periods, particularly with surgically implanted or cuffed catheters. Intrinsic (during the manufacturing process) or extrinsic (on-site in a health care facility) contamination of infusate, although rare, is the most common cause of epidemic device-related bloodstream infection; extrinsic contamination may cause up to half of endemic bacteremias related to arterial infusions used for hemodynamic monitoring. The most common pathogens isolated from vascular device–associated bacteremias include coagulase-negative staphylococci, S. aureus (with ≥50% of isolates in the United States resistant to methicillin), enterococci, nosocomial gram-negative bacilli, and Candida. Many pathogens, especially staphylococci, produce extracellular polysaccharide biofilms that facilitate attachment to catheters and provide sanctuary from antimicrobial agents. “Quorum-sensing” proteins, a target for future interventions, help bacterial cells communicate during biofilm development.

Evidence-based bundles of control measures (Table 17-4) have been strikingly effective, eliminating almost all CVC-associated infections in one ICU study. Additional control measures for infections associated with vascular access include use of a chlorhexidine-impregnated patch at the skin-catheter junction; daily bathing of ICU patients with chlorhexidine; application of semitransparent access-site dressings (for ease of bathing and site inspection and protection of the site from secretions); avoidance of the femoral site for catheterization because of a higher risk of infection (most likely related to the density of the skin flora); rotation of peripheral catheters to a new site at specified intervals (e.g., every 72–96 h), which may be facilitated by use of an IV therapy team; and application of aseptic technique when accessing pressure transducers or other vascular ports.

Unresolved issues include the role of gut translocation rather than vascular access sites as a cause of primary bacteremia in immunocompromised patients and the implications for surveillance definitions; the best frequency for rotation of CVC sites (given that guidewire-assisted catheter changes at the same site do not lessen and can even increase infection risk); the appropriate role of mupirocin ointment, a topical antibiotic with excellent antistaphylococcal activity, in site care; the relative degrees of risk posed by peripherally inserted central catheters (PICC lines); and the risk-benefit of prophylactic use of heparin (to avoid catheter thrombi, which may be associated with increased risk of infection) or of vancomycin or alcohol (as catheter flushes or “locks”—i.e., concentrated anti-infective solutions instilled into the catheter lumen) for high-risk patients.

Vascular device–related infection is suspected on the basis of the appearance of the catheter site or the presence of fever or bacteremia without another source in patients with vascular catheters. The diagnosis is confirmed by the recovery of the same species of microorganism from peripheral-blood cultures (preferably two samples drawn from peripheral veins by separate venipunctures) and from semiquantitative or quantitative cultures of the vascular catheter tip. Less commonly used diagnostic measures include (1) differential (faster) time to positivity (>2 h) for blood drawn through the vascular access device than for a sample from a peripheral vein and (2) differences in quantitative cultures (a threefold or greater “step-up”) for blood samples drawn simultaneously from a peripheral vein and from a CVC, which should show the step-up if infected. When infusion-related sepsis is considered (e.g., because of the abrupt onset of fever or shock temporally related to infusion therapy), a sample of the infusate or blood product should be retained for culture.

Therapy for vascular access–related infection is directed at the pathogen recovered from the blood and/or infected site. Important considerations in treatment are the need for an echocardiogram (to evaluate the patient for endocarditis), the duration of therapy, and the need to remove potentially infected catheters. In one report, approximately one-fourth of patients with intravascular catheter–associated S. aureus bacteremia who were studied by transesophageal echocardiography had evidence of endocarditis; this test may be useful in determining the appropriate duration of treatment.

Detailed consensus guidelines for the management of intravascular catheter–related infections have been published and recommend catheter removal in most cases of bacteremia or fungemia due to nontunneled CVCs. When attempting to salvage a potentially infected catheter, some clinicians use the “antibiotic lock” technique, which may facilitate penetration of infected biofilms, in addition to systemic antimicrobial therapy (see www.idsociety.org/Other_Guidelines/).

The authors of the consensus treatment guidelines advise that the decision to remove a tunneled catheter or implanted device suspected of being the source of bacteremia or fungemia should be based on the severity of the patient’s illness, the strength of evidence that the device is infected, the presence of local or systemic complications, an assessment of the specific pathogens, and the patient’s response to antimicrobial therapy if the catheter or device is initially retained. For patients with track-site infection, successful therapy without catheter removal is unusual. For patients with suppurative venous thrombophlebitis, excision of affected veins is usually required.

Written policies for the isolation of infectious patients are a standard component of infection control programs. To replace its prior pathogen-specific guidelines, the CDC published recommendations in 2006 for the control of multidrug-resistant organisms in health care settings; in 2007, the CDC published a revised edition of its basic isolation guidelines to provide updated recommendations for all components of health care, including acute-care hospitals and long-term, ambulatory, and home-care settings (see www.cdc.gov/hicpac/pdf/isolation/Isolation2007.pdf).

Standard precautions are designed for the care of all patients in hospitals and aim to reduce the risk of transmission of microorganisms from both recognized and unrecognized sources. These precautions include gloving as well as hand cleansing for potential contact with (1) blood; (2) all other body fluids, secretions, and excretions, whether or not they contain visible blood; (3) nonintact skin; and (4) mucous membranes. Depending on exposure risks, standard precautions also include use of masks, eye protection, and gowns.

Precautions for the care of patients with potentially contagious clinical syndromes (e.g., acute diarrhea) or with suspected or diagnosed colonization or infection by transmissible pathogens are based on probable routes of transmission: airborne, droplet, or contact, for which personnel don, at a minimum, N95 respirators, surgical face masks, or glove and gown, respectively. Sets of precautions may be combined for diseases that have more than one route of transmission (e.g., contact and airborne isolation for varicella).

Some prevalent antibiotic-resistant pathogens, particularly those that colonize the gastrointestinal tract (e.g., vancomycin-resistant enterococci [VRE] and even multidrug-resistant gram-negative bacilli such as carbapenemase-producing strains of K. pneumoniae [KPCs]), may be present on intact skin of patients in hospitals (the “fecal patina”). This issue has led some experts to recommend gloving for all contact with patients who are acutely ill and/or in high-risk units, such as ICUs or LTACHs. Wearing gloves does not replace the need for hand hygiene because hands sometimes (in up to 20% of interactions) become contaminated during wearing or removal of gloves.

Outbreaks are always big news but probably account for <5% of nosocomial infections. The investigation and control of nosocomial epidemics require that infection control personnel (1) develop a case definition, (2) confirm that an outbreak really exists (since apparent epidemics may actually be pseudo-outbreaks due to surveillance or laboratory artifacts), (3) review aseptic practices and disinfectant use, (4) determine the extent of the outbreak, (5) perform an epidemiologic investigation to determine modes of transmission, (6) work closely with microbiology personnel to culture for common sources or personnel carriers as appropriate and to type epidemiologically important isolates, and (7) heighten surveillance to judge the effect of control measures. Control measures generally include reinforcing routine aseptic practices and hand hygiene, ensuring appropriate isolation of cases (and instituting cohort isolation and nursing if needed), and implementing further controls on the basis of the investigation’s findings. Examples of some emerging and potential epidemic problems follow.

VIRAL RESPIRATORY INFECTIONS: PANDEMIC INFLUENZA

Infections caused by the severe acute respiratory syndrome (SARS)–associated coronavirus challenged health care systems globally in 2003 (Chap. 95), and in 2012 Middle East respiratory syndrome coronavirus (MERS-CoV) emerged as a more geographically localized problem (Chap. 95). For SARS, basic infection-control measures helped to keep the worldwide case and death counts at ~8000 and ~800, respectively, although the virus was unforgiving of lapses in protocol adherence or laboratory biosafety. The epidemiology of SARS—spread largely in households once patients were ill or in hospitals—contrasts markedly with that of influenza (Chap. 96), which is often contagious a day before symptom onset; can spread rapidly in the community among nonimmune persons; and, even in its seasonal variety, kills as many as 35,000 persons each year in the United States.

Control of seasonal influenza has depended on (1) the use of effective vaccines, with increasingly broad evidence-based recommendations for vaccination of children, the general public, and health care workers; (2) the use of antiviral medications for early treatment and for prophylaxis as part of outbreak control, especially for high-risk patients and in high-risk settings like nursing homes or hospitals; and (3) infection control (surveillance and droplet precautions) for symptomatic patients. Controversial infection-control issues have been the questionable role of airborne spread of influenza and the need to mandate influenza vaccination of health care workers because of the embarrassingly low rates of vaccination in this high-risk group.

With the occurrence of localized outbreaks of avian (H5N1) influenza in Asia over the past few years, concerns about potential pandemic influenza led to (1) recommendations for universal “respiratory hygiene and cough etiquette” (basically, “cover your cough”), as described and promoted in the CDC’s 2007 Guideline for Isolation Precautions, and for “source containment” (e.g., use of face masks and spatial separation) for outpatients with potentially infectious respiratory illnesses; (2) re-examinations of the value in the 1918–1919 influenza pandemic of nonpharmacologic interventions, such as “social distancing” (e.g., closing of schools and community venues); and (3) debate about the level of respiratory protection required for health care workers (i.e., whether to use the higher-efficiency N95 respirators recommended for airborne isolation rather than the surgical masks used for droplet precautions).

In the spring of 2009, a novel strain of influenza virus—H1N1 or “swine flu” virus—caused the first influenza pandemic in four decades. Recombinant events that create new strains (e.g., H7N9) continue to challenge global efforts at infection control and vaccine development (Chap. 96).

NOSOCOMIAL DIARRHEA

A new, more virulent strain of C. difficile—NAP1/BI/027—emerged in North America, and overall rates of C. difficile–associated diarrhea (Chap. 31) have increased, especially among older patients, in U.S. hospitals during the past few years. C. difficile control measures include judicious use of all antibiotics, especially fluoroquinolone antibiotics that have been implicated in driving these changes; heightened suspicion for “atypical” presentations (e.g., toxic megacolon or leukemoid reaction without diarrhea); and early diagnosis, treatment, and contact precautions. To improve diagnosis, use of more sensitive polymerase chain reaction–based rather than enzyme immunoassay–based testing of diarrheal stool is now recommended, with resultant artificial doubling of infection rates in some hospitals. Preliminary data suggest a role for probiotics in the prevention of C. difficile–associated diarrhea in patients in whom systemic antibiotic therapy is being initiated. Fecal transplantation has had dramatic results in the treatment of relapsing cases of C. difficile–associated diarrhea (Chap. 31). Successes with fecal transplants and probiotics have called attention to the potential role of manipulation of the intestinal microbiome as a broader infection-control strategy.

Outbreaks of norovirus infection (Chap. 98) in U.S. and European health care facilities appear to continue to increase in frequency or at least in reporting, with the virus often introduced by ill visitors or staff. This pathogen should be suspected when nausea and vomiting are prominent aspects of bacterial culture–negative diarrheal syndromes. Contact precautions may need to be augmented by aggressive environmental cleaning (given the persistence of norovirus on inanimate objects), prevention of secondary cases in cleaning staff through an emphasis on the use of personal protective equipment and hand hygiene, and active exclusion of ill staff and visitors.

CHICKENPOX

Infection control practitioners institute a varicella exposure investigation and control plan whenever health care workers have been exposed to chickenpox (Chap. 89) or have worked while having or during the 24 h before developing chickenpox. The names of exposed workers and patients are obtained; medical histories are reviewed, and (if necessary) serologic tests for immunity are conducted; physicians are notified of susceptible exposed patients; postexposure prophylaxis with a preparation of varicella-zoster immune globulin (VZIG) is considered for immunocompromised or pregnant contacts, with administration as soon as possible (but as long as 10 days after exposure) (Table 89-1); varicella vaccine is recommended or preemptive use of acyclovir is considered as an alternative strategy in other susceptible persons; and susceptible exposed employees are furloughed during the at-risk period for disease (8–21 days or, if VZIG has been administered, 28 days). Routine varicella vaccination of children and susceptible employees has made nosocomial spread less common and less problematic.

TUBERCULOSIS

Important measures for the control of tuberculosis (Chap. 74) include prompt recognition, isolation, and treatment of cases; recognition of atypical presentations (e.g., lower-lobe infiltrates without cavitation); use of negative-pressure, 100% exhaust, private isolation rooms with closed doors and at least 6–12 air changes per hour; use of N95 respirators by caregivers entering isolation rooms; possible use of high-efficiency particulate air filter units and/or ultraviolet lights for disinfecting air when other engineering controls are not feasible or reliable; and follow-up testing of susceptible personnel who have been exposed to infectious patients before isolation. The use of serologic tests, rather than skin tests, in the diagnosis of latent tuberculosis for infection control purposes has become common, mostly for logistic reasons. As tuberculosis once again is on the decline in the United States, we need to remember that the price of freedom—in this instance, from a communicable disease—is eternal vigilance.

GROUP A STREPTOCOCCAL INFECTIONS

The potential for an outbreak of group A streptococcal infection (Chap. 44) should be considered when even one or two nosocomial cases occur. Most outbreaks involve surgical wounds and are due to the presence of an asymptomatic carrier in the operating room. Investigation can be confounded by carriage at extrapharyngeal sites such as the rectum and vagina. Health care workers in whom carriage has been linked to nosocomial transmission of group A streptococci are removed from the patient-care setting and are not permitted to return until carriage has been eliminated by antimicrobial therapy.

FUNGAL INFECTIONS

Fungal spores are common in the environment, particularly on dusty surfaces. When dusty areas are disturbed during hospital repairs or renovation, the spores become airborne. Inhalation of spores by immunosuppressed (especially neutropenic) patients creates a risk of pulmonary and/or paranasal sinus infection and disseminated aspergillosis (Chap. 116). Routine surveillance among neutropenic patients for infections with filamentous fungi, such as Aspergillus and Fusarium, helps hospitals to determine whether they are facing environmental risks. As a matter of routine, hospitals should inspect and clean air-handling equipment, review all planned renovations with infection control personnel and subsequently construct appropriate barriers, remove immunosuppressed patients from renovation sites, and consider the use of high-efficiency particulate air intake filters for rooms housing immunosuppressed patients.

A major multistate iatrogenic outbreak of meningitis, localized spinal or paraspinal infection, and arthritis due to Exserohilum rostratum was recognized in 2012 and traced to contamination of an injectable preservative-free steroid product produced by a single compounding pharmacy.

LEGIONELLOSIS

Nosocomial Legionella pneumonia (Chap. 56) is most often due to contamination of potable water and predominantly affects immunosuppressed patients, particularly those receiving glucocorticoid medications. The risk varies greatly within and among geographic regions, depending on the extent of hospital water contamination and on specific hospital practices (e.g., inappropriate use of nonsterile water in respiratory therapy equipment). Laboratory-based surveillance for nosocomial Legionella should be performed, and a diagnosis of legionellosis should probably be considered more often than it is. If nosocomial cases are detected, environmental samples (e.g., tap water) should be cultured. If cultures yield Legionella and if typing of clinical and environmental isolates reveals a correlation, eradication measures should be pursued. An alternative approach is to periodically culture tap water in wards housing high-risk patients. If Legionella is found, a concerted effort should be made to culture samples from all patients with nosocomial pneumonia for Legionella.

ANTIBIOTIC-RESISTANT BACTERIA

Emerging multidrug-resistant bacteria like KPCs are harbingers of a potential “postantibiotic” era. Control of antibiotic resistance depends on close laboratory surveillance, with early detection of problems; on aggressive reinforcement of routine asepsis; on implementation of barrier precautions for all colonized and/or infected patients; on use of patient-surveillance cultures to more fully ascertain the extent of patient colonization; on antimicrobial stewardship to lessen ecologic pressures; and on timely initiation of an epidemiologic investigation when rates increase. Molecular typing (e.g., pulsed-field gel electrophoresis and, most recently, whole-genome sequencing) can help differentiate an outbreak due to a single strain (which necessitates an emphasis on hand hygiene and an evaluation of potential common-source exposures) from a polyclonal outbreak (which requires an emphasis on antibiotic prudence and device bundles; Table 17-4). Continuing emergence of multidrug-resistant organisms suggests that control efforts have been insufficient and that regional or broader (national and global) strategies and interventions are urgently needed (see www.cdc.gov/drugresistance/threat-report-2013/ and www.gov.uk/government/publications/uk-5-year-antimicrobial-resistance-strategy-2013-to-2018/).

Currently, several antibiotic resistance problems are of particular concern. First, over the past decade or so, the emergence of community-associated methicillin-resistant S. aureus (CA-MRSA) has been dramatic in many countries, with as many as 50% of community-acquired “staph infections” in some U.S. cities now caused by strains resistant to β-lactam antibiotics (Chap. 43). The incursion of CA-MRSA into hospitals is well documented and has impacted surveillance and control of nosocomial MRSA infections.

Second, in the ongoing global reemergence of nosocomial multidrug-resistant gram-negative bacilli, new problems include plasmid-mediated resistance to fluoroquinolones, metallo-β-lactamase-mediated resistance to carbapenems, KPCs, and panresistant strains of Acinetobacter. The problematic New Delhi metallo-β-lactamase (NDM) is plasmid-mediated, has been highly successful in inter-genus transmission, and has quickly become a global threat (see www.nc.cdc.gov/eid/article/17/10/11-0655_article.htm). For several years, KPCs were a very focal problem in the United States (predominantly in Brooklyn, NY), but more recently these strains have become a national threat. Many multidrug-resistant gram-negative bacilli are susceptible only to colistin, a drug that is consequently being “rediscovered,” or to no available agents.

Third, there has been renewed recognition of the role of nursing homes, and now LTACHs, in the spread of resistant gram-negative bacilli such as KPCs. In some LTACHs, as many as 30–50% of patients may be colonized with KPCs.

Fourth, there has been increasing community-based spread of E. coli strains harboring an enzyme, CTX-M, that renders them broadly resistant to β-lactam antibiotics. Given the community focus of spread, these strains may be seen as a gram-negative version of CA-MRSA.

Finally, clinical infections with MRSA strains exhibiting high-level vancomycin resistance due to VRE-derived plasmids have been reported in a few patients—almost all in the United States and most in Michigan—in the setting of prolonged or repeated treatment with vancomycin and/or VRE colonization. Much more common is vancomycin “MIC creep”: an increasing prevalence of MRSA strains that exhibit upper-limit susceptibility to vancomycin.

Colonized personnel who are implicated in nosocomial transmission of multidrug-resistant pathogens and patients who pose a threat can be decontaminated, depending on the pathogen. In a few ICUs, nonabsorbed antimicrobial agents for gastrointestinal decontamination of patients have been used successfully as a temporary emergency control measure for outbreaks of infection due to gram-negative bacilli. Potentially, manipulation of patients’ intestinal microbiome could be a more durable strategy to control outbreaks of multidrug-resistant pathogens that have a gastrointestinal reservoir.

In several trials over the past 10 years, source control—i.e., removal of patients’ fecal patina—by daily bathing with chlorhexidine has reduced the risk of bacteremia in ICU patients. “Search-and-destroy” methods—i.e., active surveillance cultures to detect and isolate the “resistance iceberg” of patients colonized with MRSA—in nonoutbreak settings are credited with elimination of nosocomial MRSA in the Netherlands and Denmark. In a recent multicenter trial in the United States, universal source control with chlorhexidine and nasal mupirocin was significantly more effective for controlling MRSA than was a search-and-destroy approach and led to control of other pathogens as well, providing a broad (“horizontal”) rather than a narrower (“vertical”) intervention (see www.ahrq.gov/professionals/systems/hospital/universal_icu_decolonization/). For some pathogens, such as VRE, enforcement of environmental cleaning also reduces cross-transmission risk.

Because the excessive use of broad-spectrum antibiotics underlies many resistance problems, “antibiotic stewardship” has been promulgated actively. The main tenets are to restrict the use of particular agents to narrowly defined indications in order to limit selective pressure on the nosocomial flora and, when broad-spectrum therapy is begun empirically in critically ill patients, to “de-escalate” treatment as soon as possible on the basis of the results of culture and susceptibility tests.

BIOTERRORISM AND OTHER “SURGE-EVENT” PREPAREDNESS

The horrific attack on the World Trade Center in New York City on September 11, 2001; the subsequent mailings of anthrax spores in the United States; the Boston Marathon bombing in 2013; and ongoing revelations of terrorist plans and activities in many other countries as well as the United States have made bioterrorism a prominent source of concern to hospital infection-control programs. The essentials for hospital preparedness entail education, internal and external communication, and risk assessment. Up-to-date information is available from the CDC (see www.bt.cdc.gov).

An institution’s employee health service is a critical component of its infection control efforts. New employees should be processed through the service, where a contagious-disease history can be taken; evidence of immunity to a variety of diseases, such as hepatitis B, chickenpox, measles, mumps, and rubella, can be sought; immunizations for hepatitis B, measles, mumps, rubella, varicella, and pertussis (the only vaccine-preventable childhood disease that is on the rise again in the United States) can be given as needed; baseline tuberculosis testing can be performed; and education about personal responsibility for infection control can be initiated. Evaluations of employees should be codified to meet the requirements of accrediting and regulatory agencies.

The employee health service must have protocols for dealing with workers exposed to contagious diseases (e.g., influenza) and those percutaneously or mucosally exposed to the blood of patients infected with HIV or hepatitis B or C virus. For example, postexposure HIV prophylaxis (PEP) with combination antiretroviral agents is recommended, as indicated; free consultation is available from the CDC-funded PEPLine (888-HIV-4911). Protocols are also needed for dealing with caregivers who have common contagious diseases (such as chickenpox, group A streptococcal infection, influenza or another respiratory infection, or infectious diarrhea) and for those who have less common but high-visibility public health problems (such as chronic hepatitis B or C or HIV infection) for which exposure-control guidelines have been published by the CDC and by the Society for Healthcare Epidemiology of America.