Regulatory bodies have also focused on HAIs. Goal 7 of the National Patient Safety Goals developed by the Joint Commission is to reduce the risk of HAIs in hospitals as well as ambulatory care/office-based surgery, long-term care, and assisted living settings [19]. Perhaps the most aggressive campaign against HAIs has come from CMS, which has suspended reimbursement of hospital costs related to three categories of HAIs it considers "reasonably preventable:" catheter-related urinary tract infection, vascular catheter-associated infection, and various surgical site infections [16,17,21]. However, studies have shown that this policy has not been a contributor to any decrease in the rate of HAIs, and a survey indicated that adherence to only a few prevention strategies has increased as a result of the policy [22,23]. The policy also has the potential to lead to increased unnecessary use of antimicrobials in an effort to prevent infections [24]. Additionally, one study found that many acute care hospitals commonly listed the reimbursement restricted HAIs as "present on admission," which mitigated the impact intended by CMS [25].

The results of the CDC Study of Efficacy of Nosocomial Infection Control 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" [29,30]. A later review estimated that as many as 65% to 70% of cases of catheter-associated infections and 55% of cases of surgical site infections are preventable [31].

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. These guidelines have been developed primarily by the CDC and the World Health Organization (WHO), infection-related organizations, and other professional societies. Some specialty organizations and quality improvement groups have summarized the guidelines for easier use in practice [2,28,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53]. Adherence to individual guidelines varies but, in general, is low. Historically, 87% of hospitals have failed to implement all of the recommended guidelines for preventing HAIs [54]. Hand hygiene is the most basic and single most important preventive measure, yet compliance rates among healthcare workers have averaged only 30% to 50% [3,25,42,55,56,57,58]. Decreasing the number of HAIs will require research to better understand the reasons behind lack of compliance with guidelines and to develop strategies that target those reasons.

A healthy human body has several defenses against infection: the skin and mucous membranes form natural barriers to infection, and immune responses (nonspecific and specific) are activated to resist micro-organisms that are able to invade. The skin can effectively protect the body from most micro-organisms unless there is physical disruption. For example, the human papillomavirus can invade the skin, and some parasites can penetrate intact skin, but bacteria and fungi cannot [63]. Other disrupters of the natural barrier are lesions (e.g., chapped, abraded, affected by dermatitis), injury, or in the healthcare setting, invasive procedures or devices [64].

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 [65]. 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 [2].

HAIs are commonly caused by bacteria, but can also be caused by viruses, fungi, and parasites. These types of infection occur less frequently and often do not carry the same risks of morbidity and mortality as bacterial infections. Viral infections are more common in children than in adults and carry a high epidemic risk [1]. Fungal infections frequently occur during prolonged treatment with antibiotics and in patients who have compromised immune systems [2]. Various pathogens have different levels of pathogenicity, virulence, and infectivity.

HAIs are commonly caused by bacteria, but can also be caused by viruses, fungi, and parasites. These types of infection occur less frequently and often do not carry the same risks of morbidity and mortality as bacterial infections. Viral infections are more common in children than in adults and carry a high epidemic risk [1]. Fungal infections frequently occur during prolonged treatment with antibiotics and in patients who have compromised immune systems [2]. Various pathogens have different levels of pathogenicity, virulence, and infectivity.

Percutaneous exposures may occur through the handling, disassembly, disposal, or reprocessing of contaminated needles and other sharp objects. They may also be related to the performance of procedures in which there is poor visualization (e.g., blind suturing, placing the nondominant hand next to or opposing a sharp, or performing procedures where bone spicules or metal fragments are produced). Data from the CDC National Surveillance System for Hospital Health Care Workers (NaSH) have shown that approximately 70% of percutaneous injuries occur during use of a sharp, 15% occur after use and before disposal, and 3% occur during or after disposal [70].

The CDC guideline for isolation precautions in hospitals, last updated in 2007, synthesizes a variety of recommendations for precautions based on the type of infection, the route of transmission, and the healthcare setting [28]. 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 they contain visible blood; nonintact skin; and mucous membranes [28]. 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 professionals 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 [28].

In addition to wearing a mask as outlined under Standard Precautions, wear a mask when working within 3 feet of the patient. (Logistically, some hospitals may want to implement a policy of wearing a mask to enter the room.)

Despite the simplicity of the intervention, its substantial impact, and wide dissemination of the guideline, compliance with recommended hand hygiene has ranged from 16% to 81%, with an average of 30% to 50% [3,42,54,56,57,58]. Among the reasons given for the lack of compliance are inconvenience, understaffing, and damage to skin [1,42,56,72]. The development of effective alcohol-based handrub solutions addresses these concerns, and studies have demonstrated that these solutions have increased compliance [57,73,74]. The CDC guideline recommends the use of such solutions on the basis of several advantages, including [42]:

The guideline suggests that healthcare facilities promote compliance by making the handrub solution available in dispensers in convenient locations (e.g., entrance to patients' room, at the bedside) and provide individual pocket-sized containers [42]. In one small survey of hand hygiene practices, healthcare workers indicated that they would be more likely to clean their hands as recommended if alcohol-based handrub solution was located near the patient [75]. 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 [1,42,56]. 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 [76]. Single interventions are unlikely to be effective [76]. Studies indicate that multimodal interventions (e.g., education, observation, provision of supplies, administrative support, reminders, surveillance, performance feedback) may be more effective in raising compliance [76,77,78].

Several single-institution studies have demonstrated that appropriate hand hygiene reduces overall rates of HAIs, including those caused by MRSA and vancomycin-resistant enterococci [57,58,73,74]. 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 [79]. One challenge in evaluating the impact of hand hygiene is that a variety of methodologies (e.g., surveys, direct observation, measurement of product use) have been used to assess compliance, each with its own advantages and disadvantages [80]. 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 [58]. Lastly, as noted previously, the development of HAIs is complex, with many contributing factors [58]. 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 is an element of every infection control guideline [2,28,36,37,39,40,42,43,44,47,49].

Various levels of cleaning and disinfection have been defined, and decontamination and cleaning must be carried out before any of the higher level processes (Table 2) [2,37,66]. The cleaning and disinfection of devices varies according to the Spaulding classification, which categorizes devices as critical (i.e., enters normally sterile tissue or the vascular system), semicritical (i.e., comes into contact with intact mucous membranes and does not ordinarily penetrate sterile tissue), or noncritical (i.e., does not ordinarily touch a patient or touches only intact skin) [66,83]. Critical devices require sterilization, and semicritical devices require high-level disinfection; noncritical devices may be cleaned with low-level disinfection [2,48,66,83].

Every healthcare facility should have a written housekeeping schedule for the routine cleaning of the environment. Routine cleaning removes so-called visible dirt, which can harbor micro-organisms. Soap and water can be used to remove visible dirt from most surfaces, such as walls, doors, ceilings, and floors. A disinfectant should be used when there are signs of contamination. The level of asepsis in cleaning depends on the likelihood of contamination. WHO suggests classifying areas within a healthcare facility into four zones [2]:

Cleaning according to this classification should be as follows [2]:

The following guidelines should be considered with regards to injection practices [28]:

If an occupational exposure to a bloodborne pathogen or infectious material occurs, employers should follow all federal (including the Occupational Safety and Health Administration) and state requirements for recording and reporting. The circumstances surrounding the exposure and postexposure management strategies should be recorded in the exposed person's confidential medical record and should include [93]:

All healthcare professionals experiencing fever, cough, rash, vesicular lesions, draining wounds, vomiting, or diarrhea require immediate evaluation by a licensed medical professional and possible restriction from patient care activities and return to work clearance [95]. The CDC recommends that all healthcare personnel obtain annual influenza vaccination to reduce infection of staff, patients, and family members and to decrease absenteeism [97]. Immunization against hepatitis B and pertussis (Tdap), in addition to all core vaccines, is also recommended [98]. Vaccination of healthcare personnel is considered an essential component of a patient safety program [97].

Recommendations for HBV postexposure management include initiation of the hepatitis B vaccine series to any susceptible, unvaccinated person who sustains an occupational blood or body fluid exposure. Postexposure prophylaxis with hepatitis B immune globulin (HBIG) and/or hepatitis B vaccine series should be considered for occupational exposures after evaluation of the hepatitis B surface antigen status of the source as well as the vaccination and vaccine-response status of the exposed person [93].

Immune globulin and antiviral agents (e.g., interferon with or without ribavirin) are not recommended for postexposure prophylaxis of HCV. In this instance, the HCV status of the source and the exposed person should be determined as soon as possible (preferably within 48 hours) after the exposure, using one of two options: test for HCV RNA (preferred), or test for anti-HCV and then if positive, test for HCV RNA [106]. If the source patient is known or suspected to have recent behavior risks for HCV acquisition (e.g., injection drug use), or if the risk cannot be reliably assessed, the initial testing should include a nucleic acid test for HCV RNA. Persons with recently acquired acute infection typically have detectable HCV RNA levels as early as one to two weeks after exposure [106]. For healthcare professionals exposed to an HCV-positive source, follow-up HCV testing should be performed to determine if infection develops [93,106]. The timing and type of follow-up testing recommended is included in guidance from the CDC published in 2020 [106].

Healthcare professionals exposed to hepatitis viruses should refrain from donating blood, plasma, organs, tissue, or semen [93]. When based only on exposure to HBV- or HCV-positive blood, modifications to an exposed healthcare professional's patient-care responsibilities are not necessary. Acutely infected healthcare professionals should be evaluated according to current guidelines; healthcare professionals chronically infected with HBV or HCV should follow all recommended infection control practices [93].

The CDC and HICPAC have also established postexposure protocols for mumps. The mumps vaccine should be administered to all personnel without documented evidence of mumps immunity, unless otherwise contraindicated [95,98]. Routine serologic screening is not necessary unless the healthcare professional considers screening cost-effective or requests it. Susceptible personnel who are exposed to mumps should not work from the 12th day after first exposure through the 26th day after last exposure or, if symptoms develop, until five days after onset of parotitis [95].

Healthcare-associated infections are a major cause of sepsis among severely ill patients. Increased risk of nosocomial infection is associated with the presence of underlying chronic disease, alteration in host defenses, prolonged hospital stay, and the presence of invasive catheters or monitoring devices [142]. Pulmonary, urinary tract, gastrointestinal, and wound infections predominate [143,144]. In hospitalized adult patients, the etiology of sepsis has shifted from being predominantly gram-negative nosocomial infections (Escherichia coli, Klebsiella spp., Enterobacter spp., and Pseudomonas aeruginosa) to gram-positive infections (Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes) [145]. The incidence of sepsis caused by gram-positive infections has increased by 26.3% per year over the last three decades [146]. Multidrug-resistant pathogens, such as S. aureus, now account for more than half of all sepsis cases. S. aureus is singly responsible for 40% of ventilator-associated pneumonia episodes and most cases of nosocomial pneumonia [146,147]. Group B streptococcus is a leading cause of neonatal sepsis in the United States [148].