HIREN POKHARNA AND ANNE Y. CHEN
Introduction
HEALTHCARE-ASSOCIATED INFECTIONS (HAIS): THE EVOLUTION
Although the modern-day concepts of prevention and control of hospital-associated infections originated in the middle of the nineteenth century, the history regarding knowledge about hospital-related infections dates back to the sixteenth century. Ambroise Pare (1517–1590), a surgeon at Hotel-Dieu in Paris, was one of the first physicians to describe increased frequency and severity of wound infections in hospitalized patients compared to nonhospitalized patients. The phrase hospital disease was first used in the eighteenth century. Hungarian physician Ignaz Philipp Semmelweiss (1818–1865) introduced the concept of hand washing while Sir Joseph Lister (1827–1912), a British surgeon, pioneered the concept of asepsis. Over the years, the Center for Disease Control and Prevention (CDC) has published several sets of definitions for Nosocomial Infections. Definitions used during the Comprehensive Hospital Infections Project (CHIP) (1969–1972) and in the National Nosocomial Infectious Study (NNIS) (1970–1974) were first used in the Proceedings of the First International Conference on Nosocomial Infection organized by CDC in 1970. Definitions were further extended in 1974 for hospitals participating in NNIS. Definitions for nosocomial infections were again modified by CDC in 1988. The term HAI was officially introduced in 2008 to reflect infections acquired by patients while receiving treatment for any surgical or medical conditions. It was defined as a localized or systemic condition resulting from an adverse reaction to the presence of an infectious agent(s) or its toxin(s) without any evidence that the infection was present or incubating at the time of admission to the acute care setting. HAIs can occur in acute care settings within hospitals or in ambulatory outpatient care settings, including same-day surgical centers or dialysis center. HAIs are increasingly associated with long-term facilities such as nursing homes and rehabilitation centers.
Healthcare-associated infections (HAIs) are a major cause of morbidity and mortality in the United States. It is estimated that there were 1.7 million HAI in 2002 which resulted in around 99,000 deaths, making it among the most common healthcare-associated adverse event. HAIs can occur in patients at any age and in any healthcare setting, but the most commoninfections are seen among adultsand children in the non-ICUsetting. According to National Nosocomial Infections Surveillance (NNIS) system data from 1990 to 2002, out of an estimated 98,987 deaths associated with HAI in the United States hospitals, 35,967 were due to pneumonia, 30,665 were related to bloodstream infections, 13,088 were related to UTIs, 8205 were due to for surgical site infections (SSI), and 11,062 due to infections from other sites.
HAIs have significant economic implications as well. They increase the healthcare burden on the society by $35.7–45 billion every year.
PATHOGENS
Bacteria remain the most common pathogens and source of HAIs. HAI are typically associated with Gram-positive pathogens including methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative Staphylococci, and glycopeptide (vancomycin)resistant Enterococci spp. (15–20). More recently, there are increasing reports of glycopeptide intermediate and glycopeptide-resistant S. aureus. Clostridium difficile, a normal intestinal flora in 3% of healthy adults and 20–30% of hospitalized adults, is responsible for 25–30% of antibiotic-associated diarrhea and is being increasingly recognized as a major nosocomial pathogen. There is increasing resistance among Gram-negative organisms. Among Enterobacteriaceae pathogenic isolates, resistance to fluoroquinolones, extended-spectrum cephalosporins, and carbapenems is increasing. There is also an increasing carbapenem resistance among Acinetobacter spp. (14, 28) and Klebsiella pneumoniae. MDR Pseudomonas spp., Klebsiella spp. and Enterobacter spp. are concerning as well. Emerging resistance to carbapenems conferred by New Delhi metallo-B-lactamase 1 (NDM-1) in countries such as India, Pakistan, and United Kingdom is a potential global health problem that will require coordinated international surveillance.
Candida species remain the most common healthcare-associated pathogens among fungi; and although less common, viruses including Adenovirus, Rotavirus, Norovirus, and hepatitis B have been recognized as nosocomial pathogens.
Common HAIS
URINARY TRACT INFECTION (UTI)
UTIs are the most common HAIs in both acute care setting and long-term care facilities. A major cause of septicemia and mortality, rates are similar in adult and pediatric patients and account for 36% of all HAIs. Intrinsic risk factors associated with UTIs include: advanced age, female gender, and severity of underlying illness (e.g., diabetes mellitus (DM)). Duration of indwelling catheterization is by far the most important extrinsic risk factor for UTIs. Indwelling urinary catheters are used in nearly all hospital nursing units, unlike ventilators and many other devices. Various studies have emphasized that catheter use is frequently inappropriate; inattention to both the proper indications for catheter use and catheter status in patients seems to be an important factor.
The most common etiologic agents for catheter-associated UTI (CAUTI) as reported to the NHSNat CDC, 2006–2007, are E. coli (21%), Candida spp. (20%) [C. albicans (14%)], Enterococcus spp. (15%), P. aeruginosa (10%), K. pneumoniae (8%), Enterobacter spp. (4%), coagulase-negative Staphylococci (3%), S. aureus (2%), A. baumannii (1%), and K. oxytoca (1%).
Hospitals and Long-Term Care Facilities (LTCF) should develop, maintain, and propagate policies regarding indications for catheter insertion and removal. Education of staff, use of condom catheters where appropriate, and consideration of intermittent catheterization and suprapubic catheterization as an alternative to short-term or long-term indwelling urethral catheterization have all been recommended to reduce the risk of nosocomial UTIs.
PNEUMONIA
Pneumonia is the third most common HAI, the second most common in the ICU, and the most common cause of mortality among all HAIs. It is associated with considerably increased healthcare costs and hospitalization days. Hospital-acquired pneumonia (HAP) is defined as pneumonia that occurs 48 hours or more after admission, which was not incubating at the time of admission. Ventilator-associated pneumonia (VAP) refers to pneumonia that arises more than 48–72 hours after endotracheal intubation. Healthcare-associated pneumonia (HCAP) includes any patient who was hospitalized in an acute care hospital for two or more days within 90 days of the infection; resided in a nursing home or long-term care facility; received recent intravenous antibiotic therapy, chemotherapy, or wound care within the past 30 days of the current infection; or attended a hospital or hemodialysis clinic. Most current data, including microbiological, have been collected from patients with VAP but can be extrapolated to HAP and HCAP patients as well. Tracheal intubation and mechanical ventilation are the strongest risk factors, with 3- to 21-fold increase in risk for nosocomial pneumonia.
Among etiologic agents, S. aureus (24%) is the most common pathogen, followed by Gram-negative organisms: P. aeruginosa (16%), Enterobacter spp. (8%), A. baumannii (8%), K. pneumoniae (7%), and E. coli (5%).
Various infection control measures can help modify the risk factors for pneumonia. Intubations and reintubations should be avoided if possible, and noninvasive modes of ventilation should be used whenever possible. Orotracheal intubations and orogastric tubes, semirecumbent position rather than supine position, continuous aspiration of subglottic secretions, adequate endotracheal cuff pressures to prevent leakage of bacterial pathogens into the lower respiratory tract, and passive humidifiers or heat-moisture exchangers can all help decrease the risk for VAP.
SURGICAL SITE INFECTIONS (SSIS)
SSIs are second only to UTIs in frequency, accounting for 22% of all HAIs (5). It is estimated that SSI develop in 2–5% of the 27 million patients undergoing surgical procedures each year. Healthcare personnel and operating room environment have been implicated as common sources of pathogens for SSIs. Prolonged preoperative stay, preoperative shaving, length of surgery, and skill of surgeons are well-documented risk factors for SSIs. Intrinsic host-related risk factors include: severity of underlying illness (e.g., high American Society for Anesthesiology score, DM), obesity, advanced age, malnutrition, trauma, loss of skin integrity (e.g., psoriasis), and presence of remote infections at time of surgery.
Most common etiologic agents are: S. aureus (30%), coagulase-negative Staphylococcus (14%), Enterococcus spp. (11%), E. coli (10%), P. aeruginosa (6%), Enterobacter spp. (4%), K. pneumoniae (3%), and Candida spp. (2%).
Various pre-, intra- and postoperative measures will help minimize the risk of SSI. Preoperative bathing with an antimicrobial has been advocated to reduce skin colonization. Removing hair from the site of surgery and preoperative skin preparation reduces contamination of the operative site. Clipping with clippers or using cream to remove hair results in fewer surgical site infections than shaving. Intraoperatively, appropriate barrier devices, good skills, adequate hemostasis to prevent hematomas and seromas, and adequate debridement of dead tissue are some ways to reduce transmission of microorganisms. Postoperatively, adequate wound care will help prevent infections.
BLOODSTREAM INFECTIONS (BSIS)
Bloodstream infections (BSIs) are the fourth common cause of HAIs. Both the incidence and prevalence of BSIs have increased over the past several decades. An estimated 350,000 nosocomial BSIs are reported in the United States every year. Differentiating a clinically significant BSI from a blood culture contaminant remains a constant challenge for physicians. Because many patients receive home healthcare, including intravenous infusions and chemotherapy that until the recent past would have been administered in inpatient settings, the distinction between nosocomial and community-acquired BSIs has been difficult. Friedman et al. and Siegman-Igra et al. described 37% and 39% BSIs, respectively, that occurred in settings traditionally classified as community acquired and could be more accurately classified as healthcare-associated. The term nosohusial has been proposed to describe infections occurring in homecare subjects.
Various automated blood cultures systems that are reasonably comparable to each other are being used by most laboratories. To ensure appropriate identification of the pathogen, all efforts should be made to avoid contamination of the sample. Skin preparation plays a major role. Various methods have been used for skin preparation. This includes cleaning venipuncture site with alcohol followed by an iodophor or iodine tincture and povidone iodine. More recently, Mimoz et al. showed that alcoholic chlorhexidine may be more efficacious in preventing skin contamination compared to povidone iodine. Reliability of blood culture results also depends on various other factors including amount of blood volume sampled, timing of blood cultures, and site from where blood cultures are obtained.
Bloodstream infections (BSIs) are associated with various risk factors. In the past, 75% of healthcare-associated (nosocomial) BSIs were secondary to SSIs, UTIs, intra-abdominal infections, pneumonia, or skin and soft tissue infections (62, 63). Over the years, the proportion of primary nosocomial BSIs has increased and most episodes without an obvious source are thought to be related to intravascular catheters (57, 64). Age (<1 year and >65 years) is a known predisposing factor for BSI (32, 57, 6567). Patients with underlying malignancies and/or neutropenia are long known to be at risk for BSI (6870). Notably, patients with hematologic malignancies are at higher risk than those with solid tumors. Other risk factors include patient with chronic liver disease (71), hemodialysis patients (72), burn patients (73), spinal cord injury patients (74, 75), transplant patients (76), and patients admitted to the ICU (77).
The pathogens differ in patients with various risk factors. Based on most recent studies, the common pathogens associated with central line associated BSI are coagulase-negative Staphylococcus (34%), S. aureus (15%), Enterococcus spp. (12%), Candida spp. (11%), E. coli (10%), P. aeruginosa (8%), K. pneumoniae (6%), Enterobacter spp. (5%), and A. baumannii (3%)(14).
Various recommendations have been made to prevent catheter-related BSI (78). Use of an all-inclusive catheter cart kit and barrier devices, chlorhexidine-based antiseptic for skin preparations, disinfecting catheter hubs, needleless connectors, and injection ports before accessing the catheter and appropriate surveillance are a few of the recommendations made by the Society for Healthcare Epidemiology of America/Infectious Disease Society of America (SHEA/IDSA).
Epidemiology of Infectious Disease and the Hospital and Ambulatory Care Environment
Epidemiology is defined as the study of the determinants and distribution of health and disease in populations. It is well recognized that health and disease occur due to the complex interactions between an agent, the host that is the target of agent actions, and the environment. In relation to HAIs, agent refers to the various healthcare-associated microorganisms, the host comprises the patients or/and the healthcare workers, and the environment would include different healthcare components such as acute care hospital, intensive care units, hemodialysis centers, ambulatory clinics, and so on.
Various models and equations have been used to describe these multifarious interactions. The simplest epidemiologic model described is the triangle model (79) (Figure 1.1). It signifies, in the most simplified manner, the complex yet close interaction between the agent, host and environment. The Seesaw model (Figure 1.2) is another way by which the interplay between the three components (agent, host, environment) has been described (80). By introducing the Seesaw model, Fox et al. (80) has illustrated the role that environment plays to keep an equilibrium between the agent and the host. Conversely, any disequilibrium results in adverse events. Therefore, the environment provides platform upon which the interaction between host and agent takes place. An equation of infection has been used to determine the probability of a microbial agent to cause infection in the host (81):
IP = D x S x T x V Hd
where Ip is the probability of infection, D is the dose (number of microorganisms) transmitted to the host, S is the receptive host site of contact with the agent, T is the time of contact (sufficient for attachment and multiplication or not), V is the virulence (the intrinsic characteristics of the microorganism that allow it to infect), and Hd is the force of the combined host defenses attempting to prevent the infection. Thus, if there is any compromise in the host's defense system, as may happen in the case of an immunocompromised patient, there may be a propensity to cause infection with lesser quantity of the microorganisms. Similarly, the host site may be one that may have otherwise been an unlikely site. The time required for the agent to cause infection and the virulence of the agent may be variable as well. For example, in a patient with febrile neutropenia secondary to chemotherapy, an organism such as Propionebacterium acnes may be able to cause a BSI compared to an unlikely possibility of the same agent to cause an infection in a healthy host.
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Excerpted from Molecular Techniques for the Study of Hospital Acquired Infection Copyright © 2011 by John Wiley & Sons, Ltd. Excerpted by permission of John Wiley & Sons. All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
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