Hospital infection prevention for pediatric transplant recipients and oncology patients

General principles

Children with deficient immune mechanisms, immunologic disorders, or those receiving immunosuppressive therapy (e.g., radiation, cytotoxic chemotherapy, antirejection medication, and steroids) are identified as high-risk patients with the greatest risk of acquiring healthcare-associated infections. Patients in this subset include those who are severely neutropenic for prolonged periods of time (i.e., an absolute neutrophil count ≤500 cells/mL), allogeneic hematopoietic stem cell transplantation (HSCT) patients, and those who have received intensive chemotherapy. Treatment of infection is usually difficult, making prevention strategies paramount.

Handwashing remains the simplest, most effective method of preventing infections, and efforts should be made to optimize proper hand hygiene using soap and water or alcohol-based sanitizers among patients, healthcare workers (HCWs), and visitors, including families. Hands should be washed at hospital room entry and exit. Hand hygiene should also be performed before and after manipulating catheters or performing procedures. Standard precautions, including the use of gloves while handling body fluids, respiratory etiquette, and safe injection practices, should be instituted as part of routine care for hospitalized patients.

Other infection prevention strategies incorporate personal protective equipment (PPE) to minimize modes of pathogen transmission that may vary based on pathogen class. These strategies may be transmission based (i.e., acute clinical syndromes such as diarrhea, meningitis and respiratory tract infections) and should trigger contact and/or droplet isolation precaution that typically includes donning of PPE (i.e., barrier gowns, gloves, and/or masks) when appropriate. The important routes of transmission include contact (i.e., direct transmission from infected person to uninfected person with or without an intermediary object or person, such as contaminated hands of HCWs or contaminated surfaces of hospital equipment) droplet (i.e., a more extensive form of contact transmission that involves exposure to infected respiratory droplets >5 μm in size from expectorated sputum, coughs, or sneezes), and airborne (i.e., transmission of either airborne droplet nuclei or small particles that remain infective over time and distance). ^,

Although some pathogens can be transmitted by more than one route, some of the more common examples of organisms transmitted via contact include Staphylococcus aureus and Clostridium difficile, whereas most respiratory viruses (e.g., influenza) are transmitted via droplet. Mycobacterium tuberculosis is a common example of an infection with airborne transmission. Airborne transmission could also occur with environmental pathogens such as fungal spores. Other environmental sources of infection include aerosolized water or ingestion of contaminated water, food, or medications, although standard hospital safety practices should limit these exposures. Numerous guidelines exist to assist with developing appropriate transmission-based precautions and duration of isolation for immunocompromised patients within a healthcare system. Extending the period of isolation for the duration of the hospital stay or until documented clearance of infection may be necessary for respiratory viruses or other transmissible infections owing to prolonged shedding of viruses that can occur in immunocompromised patients. Prevention of vector-borne infections that might spread within a healthcare system or in limited-resource settings is beyond the scope of this chapter.

Close collaboration with a healthcare epidemiologist is important to achieve the shared aims of improving patient safety, performing active monitoring, reporting healthcare-associated infections (HAIs) and promoting strategies that support quality, evidence-based medical care. Within an established culture of safety, the infrastructure for hospital epidemiology should have the capacity for investigation and management of HAIs and should be optimized for rapid outbreak identification. ^, Ideal programs incorporate HAI surveillance and antibiotic stewardship. Instituting a culture of safety where all members of the workforce combine efforts to prevent infections, avoid system errors, and adhere to infection prevention practices is pivotal to successfully preventing transmission of healthcare-associated pathogens to immunocompromised patients.

Importance of healthcare-associated infections surveillance

The Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN) has determined that certain preventable healthcare-associated infections should be actively monitored and reported to federal agencies with a potential to impact reimbursement. ^, Surgical site infections and C. difficile infections can be consistently determined for hospitalized patients regardless of immune status.

Indwelling catheter use is almost ubiquitous in the oncology and transplant populations owing to their chronic medication administrations and laboratory assessment needs. Stringent adherence to established practices for maintaining central catheters and urinary catheters is advised. Nevertheless, central line–associated bloodstream infections (CLABSIs) continue to rank among the most common of HAIs reported to the NHSN. Providers for immunocompromised pediatric patients have often argued that NHSN surveillance definitions may not appropriately characterize the nature of bloodstream infections in immunocompromised hosts, given underlying mucosal and immune defects. To accommodate for some of these concerns, the NHSN adjusted surveillance definitions to incorporate Mucosal Barrier Injury Laboratory-Confirmed Bloodstream Infection. This surveillance definition incorporates risk factors, such as allogeneic hematopoietic stem cell transplant recipients within the past year with high-grade gastrointestinal (GI) graft-versus-host-disease [GI GVHD], recent onset of voluminous (such as ≥1 L stool measured in a 24-hour period), and ongoing neutropenia (defined as at least 2 separate days with absolute neutrophil count and/or white blood cell values less than 500 cells/mm ³ collected within a 7-day period.) These criteria allow infection prevention professionals the ability to determine if bloodstream infections in certain individuals may not be entirely preventable.

Obtaining routinely scheduled surveillance blood cultures is not recommended and may cause more long-term harm if it leads to recovery of skin contaminants and subsequent inappropriate use of antibiotics. Outside NHSN-defined surveillance, medical providers and infection prevention professionals should be aware that there may be atypical clinical presentations of infectious diseases in immunocompromised patients. Each healthcare facility should have a low internal threshold to initiate an investigation if there is an increased number of common infections or unique pathogens within transplant and oncology patients. For example, a single case of Legionella pneumonia acquired during a hospitalization or two cases of adenovirus conjunctivitis in immunocompromised hosts within a short period should warrant an immediate investigation to mitigate a possible outbreak.

Pathogen-specific infection prevention strategies

Infections in immunocompromised patients are often derived from pathogens colonizing the skin, such as S. aureus or Streptococcus species; colonizing the GI tract, such as Escherichia coli and Pseudomonas aeruginosa ; and from the environment, such as Aspergillus species. Although emerging pathogens (e.g., Candida auris ) or imported highly transmissible pathogens (e.g., viral hemorrhagic fevers) can infect HSCT, oncology, and organ transplant patients, aligning prevention efforts with the institution’s infection prevention department should help with preparation for and mitigation of these possible exposures. Efforts to decrease the risk of invasive infections in immunocompromised hosts should focus on areas in which interventions have been shown to decrease exposure or colonization with these microorganisms. Table 12.1 provides a summary of guidelines to prevent HAIs in pediatric immunocompromised patients.

TABLE 12.1

Summary of Recommendations to Prevent Healthcare-Associated Infections in Pediatric Immunocompromised Patients

Patient Population	Healthcare-Associated Pathogens	Infection Prevention Recommendations
Hematopoietic stem cell transplant	Viruses Aspergillus C. difficile MDROs	Handwashing Visitor restriction Herd immunization Water quality HEPA filtration Effective environmental cleaning Limitation of aerosolized water, use of carpets, exposure to animals. and live plants Positive-pressure rooms and ≥12 air exchanges/hour
Solid organ transplant	Viruses Candida MDROs	Handwashing Herd immunization Effective environmental cleaning
Oncology	Viruses MDROs C. difficile	Handwashing Visitor restriction Herd immunization Effective environmental cleaning

C. difficile, Clostridium difficile; HEPA, high-efficiency particulate air; MDROs, multidrug-resistant organisms.

Legionella

This pathogen is the prototypical microbe to highlight transmission of water-borne infections to the immunocompromised host. Legionella is a water-borne gram-negative pathogen associated with symptoms that range from a mild febrile illness to pneumonia with respiratory distress. Healthcare-associated transmission of laboratory-confirmed Legionnaires’ disease, defined as infection in patients hospitalized for 10 days or longer before confirming diagnosis, has been described among HSCT recipients. ^, Transmission occurs through inhalation of aerosolized water particles or exposure to contaminated water. Many published reports note that fountains, showers, water fixtures, and nonaerated faucets have been implicated as the source of outbreaks of water-borne illness. Other organisms with similar transmission routes include P. aeruginosa, Burkholderia cepacia, and Stenotrophomonas maltophilia . Methods to mitigate risk and curtail outbreaks are detailed in the “Water Quality” section later in the text.

Staphylococcus aureus and vancomycin-resistant Enterococci

S. aureus and Enterococci species are ubiquitous in the healthcare environment. The clinical impact of these bacteria includes severe infections in immunocompromised patients, although there remain conflicting data on whether these high-risk populations have increased mortality compared with immunocompetent children.

S. aureus , including methicillin-resistant S. aureus (MRSA), is an important cause of morbidity in pediatric immunocompromised patients. Staphylococcal infections in pediatric oncology and HSCT patients are predominately invasive and catheter associated, with a high rate (18%) of complications, not specifically associated with MRSA. In up to 5% of pediatric solid organ transplant (SOT) recipients in whom S. aureus infections developed, half of the isolates were identified as MRSA. Despite these reported infections, studies are not entirely supportive of the necessity or timing of MRSA screening and decolonization to reduce infections.

The incidence of infections secondary to vancomycin-resistant Enterococcus (VRE) is relatively low among immunocompromised patients and the impact on morbidity and mortality may vary according to the underlying medical or clinical condition. In one registry-based population study, HSCT recipients who experienced VRE bacteremia demonstrated decreased 1-year survival and increased nonrelapsed mortality compared with patients with non-VRE bacteremia, but study findings are limited by the exclusion of known contributing factors, such as GVHD, in the analysis. Among SOT recipients, a meta-analysis reviewing VRE colonization demonstrated that pre- and post-transplant VRE colonization portends a statistically significant risk for VRE infection among transplant recipients.

Accepted infection prevention practices to limit the transmission of multidrug-resistant organisms such as MRSA and VRE include use of PPE (i.e., donning gowns and gloves before caring for a colonized patient). One publication suggests that the routine use of contact isolation to prevent transmission of VRE may not be necessary, although study limitations (exclusion of noninvasive infection, adult population) preclude generalization of these findings to the pediatric population.

S. aureus decolonization, using topical antibiotics to eradicate nasal colonization, is recommended in critically ill patients admitted to the intensive care unit as it decreases the incidence of invasive S. aureus infections during their hospitalization. ^, There are few studies assessing the utility of screening and routine decolonization of transplant and oncology patients except in the case of preoperative decolonization. Case-by-case decision making for the use of mupirocin for decolonization may be warranted. Although the debate continues on the utility of contact isolation to limit transmission of MRSA and VRE, facilities housing immunocompromised patients should closely monitor for increased incidence of disease if contact isolation for MRSA and VRE is not routinely used.

Clostridium difficile

C. difficile is a bacteria that causes infections in patients with prolonged exposure to antibiotics or exposure to the healthcare system, most of whom are immunocompromised patients. C. difficile has been responsible for numerous healthcare-associated outbreaks, even within immunocompetent hosts. The particular strain, toxinotype III, North American pulsed-field type 1, and PCR ribotype 027 (NAP1/027), known to produce large amounts of toxin A and B, has been identified in these outbreaks across the globe. Reduction of antimicrobial use is the predominant modifiable risk factor that decreases the risk for C. difficile infection. An infrastructure that supports infection prevention and antibiotic stewardship to reduce HAIs such as C. difficile is ideal. In addition, appropriate hand hygiene with soap and water before and after contact with a patient is recommended. Some experts support the use of an alcohol-based hand sanitizer in non-outbreak settings. Contact precautions (i.e., PPE of gown and gloves) should be used by HCWs caring for transplant and oncology patients infected with C. difficile . ^,

C. difficile spores may persist within the healthcare environment; optimal cleaning of infected patient rooms using a bleach-containing disinfectant (5000 ppm) is advised. During endemic outbreaks or in hospital units with high rates of healthcare-associated C. difficile , terminal cleaning with a sporicidal agent and preferential use of soap and water for handwashing are recommended. Other modalities for cleaning and disinfection, such as ultraviolet germicidal irradiation and vaporized hydrogen peroxide, have shown promising results, but data are insufficient at this time to make firm conclusions for use in routine or outbreak settings. Compared to MRSA and VRE isolation, there is little debate and some evidence to support the necessity of contact isolation to decrease transmission of C. difficile .

Multidrug-resistant gram-negative organisms

Microorganisms resistant to one or more classes of commercially available antimicrobial agents are described as multidrug-resistant organisms (MDROs). Gram-negative organisms are emerging as epidemiologically important pathogens owing to the high rate of healthcare-associated transmission, the increasing number of outbreaks, and the increased mortality rates associated with invasive infections in children. Risk factors independently associated with developing a severe infection with an MDRO, specifically carbapenem-resistant Klebsiella pneumoniae, include recent organ or stem cell transplantation, prolonged length of hospital stay, and extensive use of antibiotics, all of which are often present in the pediatric immunocompromised population. A carbapenem-resistant Enterobacteriaceae (CRE) infection develops in up to 10% of SOT recipients if they reside in a CRE-endemic area. Preventing the spread of these pathogens has now been listed as an urgent priority by the CDC.

Prevention strategies should incorporate efforts to delay the advent of resistance by promoting judicious broad-spectrum antimicrobial use in highly vulnerable patients. Performing surveillance cultures of the perianal and rectal regions of at-risk patients can identify patients colonized with MDROs and preemptive cohorting or contact isolation may prevent healthcare-associated exposures. Surveillance of CRE or carbapenem-resistant Klebsiella pneumoniae and ongoing implementation of bundled infection prevention practices, including hand hygiene, preemptive use of contact precautions for colonized patients, and multidisciplinary teams to monitor adherence to recommendations are part of a comprehensive program to minimize the impact of MDROs. ^,

Mycobacteria

Nontuberculous mycobacteria are ubiquitous in the environment and outbreaks have been well described in immunocompromised patients. Transmission may occur through contact with soil or contaminated water. Over a 10-year period, investigators at a U.S.-based cancer treatment institution described clinical risk factors associated with rapidly growing mycobacteria infections, typically within 7 days of culture incubation, in patients with cancer. Although few clinical cases occurred (2.9 per 100,000 patient-days), disease in 59% of patients was diagnosed from respiratory specimen cultures and most infections occurred in SOT patients. Continued assessment of air and water quality (see later text) is needed to decrease the burden of particulates or spores in healthcare areas housing immunocompromised patients. Screening HCWs for M. tuberculosis should be based on local prevalence and regulations.

Opportunistic mold

Opportunistic molds (such as Aspergillus ) cause significant morbidity and mortality in immunocompromised patients, although mortality rates are highly variable according to the underlying condition of the affected patient population and the advent of antifungal prophylaxis. Opportunistic molds are associated with dusty or moist environmental conditions, such as those found in construction areas. Contribution of the healthcare environment to an invasive fungal infection of a patient is hampered by the unknown incubation period of Aspergillus and the threshold spore count necessary for infection. Prevention strategies to protect patients against mold infections should include minimization of dust accumulation and dust disturbance.

Viruses

Pediatric patients are at high risk for transmissible viral infections, especially during seasonal outbreaks. The all-cause mortality among pediatric HSCT recipients who were hospitalized with a respiratory viral infection over a 3-year period was as high as 11%, suggesting significant contribution to outcomes after HSCT. Over a similar period and among more than 1000 pediatric SOT patients hospitalized with respiratory viral infections, intestinal/abdominal transplant recipients (38%) were most often affected; however, case fatality within 3 months of infection was lower (4%) than HSCT recipients. Reverse droplet precautions, where all HCWs wear masks before interactions with neutropenic patients during respiratory viral seasons, are used in various institutions, but no available evidence supports this practice. Early identification of immunocompromised hosts with viral infections and implementation of contact and droplet precautions may attenuate healthcare-associated viral transmission. Limiting exposure to ill HCWs and visitors may help with preventing respiratory viral infections. Routine surveillance for community-acquired respiratory viruses in asymptomatic immunocompromised patients is not advised.

Nonrespiratory viruses also affect the pediatric immunocompromised host. Gastrointestinal (GI) viruses may be acquired from the community (e.g., norovirus) or represent reactivation (e.g., adenovirus, cytomegalovirus). Healthcare-associated transmission of norovirus and adenovirus have been reported in patient populations with oncologic disease and recipients of HSCT and solid organs. ^, The presence of GI viruses in immunocompromised patients, regardless of clinical suspicion as to the primary etiology of a diarrheal illness or merely intestinal shedding, should prompt the appropriate isolation precautions to minimize transmission to other vulnerable patients. Although prolonged intestinal shedding is well known to occur in immunocompromised patients, it is unclear whether isolation needs to be extended past resolution of diarrheal symptoms to minimize transmission.

Transmission of viruses, historically known as blood-borne (human immunodeficiency virus, hepatitis B, hepatitis C), have largely been eliminated through national screening programs. Expansion of the screening panel (e.g., inclusion of West Nile Virus) or temporary inclusion of emerging pathogens (Zika virus) further ensures the safety of the blood supply to all patients.

Vaccine-preventable viruses, namely varicella-zoster and measles, can cause virulent infections in immunocompromised patients. Centers with declining community vaccine rates (and likely low herd immunity) may consider restricting incompletely vaccinated children from visiting pediatric transplant units. Sufficient data to support the use of airborne precautions and in tandem N95 masks by vaccinated HCWs to prevent transmission of measles and varicella-zoster viruses do not currently exist. Some have suggested that surgical masks and PPE may be sufficient. However, for consistency among HCWs and to avoid confusion, some facilities may opt to use airborne precautions for all patients being evaluated for or currently being treated for specific viral infections. To comply with airborne precautions and prevent inhalation of infected particles, HCWs should have scheduled fit testing to confirm their ability to use a respirator with N95 or higher filtration.

Good practice recommendations

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