Healthcare-associated infections

  • Hand hygiene is foundational to infection control in the pediatric intensive care unit (PICU), including the prevention of healthcare-associated infections (HAIs); units should be relentless in pursuing compliance with recommended practices.

  • Daily review of invasive devices should become ingrained in the culture of the PICU, with prompt removal performed when a device is no longer indicated.

  • A comprehensive and multifaceted approach is required to prevent HAIs in the PICU, including organizational leadership and resources to support surveillance and frontline staff, antibiotic stewardship programs to guide appropriate antimicrobial use and curb spread of multidrug-resistant microbes, and robust quality improvement initiatives aimed at compliance with care bundles, infection control practices, and isolation precautions.

Healthcare-associated infections (HAIs) account for significant morbidity and mortality. For example, there are approximately 2 million HAIs every year in the United States alone, which lead to approximately 100,000 deaths every year. HAIs cost the US healthcare system between $5 billion to $10 billion on an annual basis. More than half of these infections are considered preventable with current evidence-based interventions. , Worldwide, approximately 3% to 19% of hospitalized children will develop at least one HAI each year. Children admitted to an intensive care unit (ICU) are at greater risk of developing an HAI, with an estimated 5% to 24% of children admitted to pediatric intensive care units (PICUs) developing an HAI at some point during their hospital stay. Aside from their impact on the overall healthcare system, HAIs significantly increase morbidity and mortality, hospital length of stay (LOS), and cost of hospitalization in both children and adults.

Healthcare-associated bloodstream infections and healthcare-associated lower respiratory tract infections, particularly central line–associated bloodstream infections (CLABSIs) and ventilator-associated pneumonia (VAP), comprise the vast majority of HAIs in children. As such, quality improvement efforts have primarily focused on the reduction of CLABSI and VAP. Within the last decade, HAI rates have had a continuous reduction, with CLABSI rates in the PICU declining from 8.5 per 1000 central-line days beginning in 1997 to 4.7 per 1000 in 2007 and eventually 1.0 per 1000 central-line days by 2012. , Similarly, PICU VAP rates have decreased from 3.7 per 1000 ventilator days in 1997 to 1.9 per 1000 in 2007 to 0.7 per 1000 in 2012. , These reductions resulted in millions of dollars in healthcare savings and, more importantly, decreased mortality. The experience with these two HAIs in particular, has shown that the most effective improvement efforts require a multidimensional team approach and should include education, surveillance, uniform and optimized care, engagement of staff, and follow-up. This chapter reviews basic infection control and prevention strategies as emphasized in the national efforts to reduce HAIs outlined by the US Department of Health and Human Services (HHS) and the Centers for Disease Control and Prevention (CDC) and provides an in-depth review of the most common and problematic HAIs in critically ill children.


The epidemiology of HAIs varies by country, the country’s socioeconomic conditions, available resources, and infection control experience. Direct comparisons are challenging given that data are reported as prevalence by some authors and rates per device or patient days by others. , , The prevalence of pediatric HAIs across the European Union is 4.2%. Individual country prevalence ranges from 1.2% to 10.4%, and the PICU population has the highest prevalence at 15.5%. In the United States, the prevalence of HAIs in PICU patients ranges from 5.7% to 11.9%. , The prevalence of HAIs in Canadian acute care hospitals is 8.7%, and in PICU populations specifically, 17.7%. Bloodstream infections (BSIs) are the most common HAIs in Europe, the United States, and Canada, ranging from 31% to 45% of all HAIs, with a prevalence of 2% to 6%. , , Most BSIs are associated with a central venous catheter (CVC), that is, CLABSIs. , However, a 2009 Canadian point prevalence study revealed that only 34% of BSIs were associated with CVCs, which was a significant difference from the earlier 2002 point prevalence study in which 83% of BSIs were CVC associated. , Lower respiratory tract infections are the second most common HAI, accounting for 16% to 23% of all HAIs, with a prevalence of 1.0% to 3.3%, and similar to BSI, most are device associated. , , In comparison, urinary tract infections (UTIs) and surgical site infections (SSIs) make up a smaller proportion of pediatric HAIs; the reported prevalence of each is 0.2% to 2.0% and 0.2% to 0.4%, respectively. , , The most common pathogens causing HAIs in Europe are Enterobacteriaceae, specifically Escherichia coli , Klebsiella spp., and Enterobacter species, followed by coagulase-negative staphylococci, and Staphylococcus aureus . In the United States, the organisms are very similar, with E. coli and S. aureus being most common, followed by Klebsiella spp., and coagulase-negative staphylococci.

In limited-resource countries, device-associated HAI rates are higher than those in resource-rich countries such as the United States, Canada, and Western Europe. The International Nosocomial Infection Control Consortium (INICC) is analogous to the CDC’s National Health Surveillance Network (NHSN) in the United States, and was established to measure, prevent, and control HAIs in limited-resource countries. From 2010 to 2015, 76 PICUs reported device-associated HAIs to the INICC. The pooled mean rates per 1000 device days were 8.5 for CLABSI, 8.2 for VAP, and 5.5 for catheter-associated urinary tract infection (CAUTI). In contrast, the 2013 NHSN rates for these same HAIs in US PICUs were 1.2, 0.7, and 2.5, respectively. In its Report on the Burden of Endemic Health Care-Associated Infection Worldwide , the World Health Organization (WHO) described device-associated HAI densities up to 13 times greater, and ICU-acquired infections 2 to 3 times greater in low- and middle-income countries compared with high-income countries such as the United States. The HAI rate difference between developing countries and the United States may be due to the lack of national surveillance systems or the government will or laws mandating such systems or infection prevention programs. Additionally, limited resources, including medical supplies, hospital beds (capacity), and sufficient numbers of trained healthcare workers in some cases, impacts HAI rates. Last, most developing countries lack mandatory hospital accreditation or it is not available. A few studies from PICUs in developing countries reported VAP as the most common HAI rather than CLABSI in contrast to Europe, the United States, and Canada. , ,

Risk factors

Many critically ill neonates and children have weakened or immature immune systems, which increases their risk for infection if exposed to potential pathogens. Children admitted to the PICU frequently require invasive devices, such as CVCs and endotracheal tubes, to deliver life-saving therapies. While necessary, these devices provide surfaces for potential pathogens to grow and as entry points for invasion, which can result in HAI. The National Nosocomial Infections Surveillance System collected data from 1992 to 1997 showing that 91% of pediatric BSIs occurred in children with a CVC, 95% of hospital-acquired pneumonias were in children who were mechanically ventilated, and 77% of hospital-acquired UTIs were in children with urinary catheters. , Many have identified the presence of an invasive device as one of the greatest risk factors for developing any HAI. , Days of ventilator use, in particular, is independently associated with HAI development, with an attributable risk of nearly 14%.

Many studies have reported that severity of illness, as reflected by Pediatric Risk of Mortality (PRISM and PRISM III) and McCabe scores, is a risk factor for HAI. , LOS in the PICU prior to development of an HAI is a time-dependent risk factor associated with HAIs. Specifically, patients with a PICU LOS of 14 or more days are nearly 15 times more likely to develop an HAI. Younger age, particularly less than 2 years, is also associated with HAI. , Interestingly, a recent post-hoc analysis of the Critical Illness Stress-Induced Immune Suppression (CRISIS) prevention trial database found that increasing age, cardiac arrest, and lymphopenia at admission predisposed long-stay, immunocompetent PICU patients to HAI. Last, correlations between HAI risk and blood product exposure, corticosteroid use, total parenteral nutrition administration, or H2 blockers have been inconsistent in the pediatric literature. Collectively, the single most important risk factor for HAI is the presence of an indwelling invasive device, such as a CVC, endotracheal tube, or urinary catheter. ,

Pathogen transmission and isolation practices

To fully understand isolation and prevention strategies, it is important to understand how infectious diseases are transmitted. Transmission occurs via direct or indirect contact. Direct contact involves the transfer of a potentially infectious agent from one person to another via physical contact. Indirect contact involves the transfer of the infectious agent from a person to a surface or inanimate object, which creates a contaminated surface/object, and then to another person when a second person comes into contact with the contaminated surface/object. Modes of transmission include contact, droplet, and airborne. Descriptions of transmission modes, examples of infectious agents, and recommended isolation practices are outlined in Table 109.1 .

TABLE 109.1

Modes of Transmission of Infectious Agents

Mode Definition Examples/Infectious Agents Isolation Recommendations

  • Direct : Physical contact with infected or colonized person by susceptible host

  • Indirect : Contact with contaminated surface or object by a susceptible host

  • Herpes simplex virus

  • Infectious diarrhea

  • MDRO

  • Scabies

  • Noncontained abscess, cellulitis, or decubitus ulcer

  • Standard precautions + gown and gloves

  • Single room preferred


  • Form of contact transmission

  • Respiratory droplet carrying infectious agent from infected person to mucous membrane of susceptible host

  • Transfer over a short distance

  • ≥5 μm in size

  • Bordetella pertussis

  • Adenovirus

  • Rhinovirus

  • Mycoplasma pneumoniae

  • Neisseria meningitides

  • Group A Streptococcus

  • Influenza virus

  • Standard precautions + surgical mask

  • Single room preferred


  • Aerosolization of infectious agent in form of droplet nuclei or small particles inhaled by susceptible host

  • Particles are <5 μm in size

  • Mycobacterium tuberculosis

  • Rubeola virus (measles)

  • Varicella zoster virus (chicken pox)

  • Airborne infection isolation room

  • NIOSH certified level N95 or higher respirator

MDRO, Multidrug-resistant organisms; NIOSH, National Institute for Occupational Safety and Health.

Standard precautions include hand hygiene, use of the appropriate personal protective equipment (PPE) if contact with bodily fluid is anticipated (gloves, gown, mask, eye protection), and safe injection practices. , Safe injection practices and respiratory hygiene/cough etiquette are newer additions to standard precautions, designed to protect both the caregiver and patient. Last, it is recommended that healthcare workers wear masks when inserting catheters or injecting materials into spinal or epidural spaces to decrease the risk of introducing infection during these procedures. Standard precautions should be used whenever contact with a patient is anticipated and should be appropriately tailored to each interaction. ,

Respiratory hygiene/cough etiquette was introduced by the CDC as a way to reduce both direct and indirect respiratory pathogen transmission. , Education of healthcare workers, patients, families, and visitors regarding disease transmission is the first step. Included in this education is the key reminder to cover the nose and mouth when coughing or sneezing, either with a tissue when available, or in the antecubital fossa portion of the shirt sleeve when a tissue is not available. Tissues should be disposed of after use, preferably in no-touch receptacles, and proper hand hygiene should be performed immediately after. Last, any person who is symptomatic should wear a surgical mask if tolerated. If unable to tolerate a mask, the CDC recommends spatial separation, defined as staying more than 3 feet away from others. ,

Some hospitals use reverse-isolation precautions for patients who are immunocompromised. In some hospitals, this simply means following standard precautions unless the healthcare worker or visitor has symptoms of an acute illness. Visitors are usually encouraged to visit only if healthy, and ideally, healthcare providers are not working when ill. However, if a healthcare worker has symptoms of a respiratory infection, appropriate precautions to protect the patient should be used, for example, droplet precautions. In other hospitals, reverse-isolation precautions may imply that all healthcare workers and visitors wear a gown, gloves, and a mask in addition to following standard precautions whenever entering the patient room.

Infection prevention strategies

Care bundles

The Institute of Healthcare Improvement developed the concept of a care bundle, defined as “a small, straightforward set of evidenced-based practices—generally three to five—that, when performed collectively and reliably, have been proven to improve patient outcomes.” Current pediatric research focuses largely on prevention bundles for CLABSI and VAP. The bundle elements vary from study to study. Despite these variances, nearly all studies conclude an association between implementation of care bundles and infection rate reductions. Nationally standardized care bundles for PICUs could facilitate randomized controlled trials to further assess the efficacy of individual bundle elements, as some might prove unnecessary, that is, bundle “fine-tuning.” Both pediatric and adult studies have shown that optimal bundle efficacy toward infection reduction requires measurement of bundle practice compliance and that higher compliance is associated with increased infection prevention outcomes. Last, sustained and ongoing reduction in HAIs is possible when a standardized care bundle is implemented and consistent attention to practice compliance is maintained.

Hand hygiene

Proper hand hygiene is a simple and cost-effective measure to decrease HAI rates. In 2002, the CDC issued evidence-based hand hygiene recommendations that the WHO used to develop global guidelines. Recommendations include performing hand hygiene in any of the following situations, using either alcohol-based hand sanitizers or washing with soap and water:

  • 1.

    Immediately before or after contact with a patient or the patient’s environment

  • 2.

    When moving from a soiled body site to a clean body site on the same patient

  • 3.

    Before performing an aseptic task or handling invasive medical devices

  • 4.

    After contact with blood, bodily fluids, or contaminated surfaces

  • 5.

    Immediately before putting on or after removing gloves

Medical professionals prefer alcohol-based hand sanitizers for their ease of use, including not requiring a sink. In addition, in some cases, the sanitizers cause less skin irritation than soap and water. This has contributed to increased hand hygiene compliance; thus, alcohol-based hand sanitizers are recommended over soap and water by the CDC. , Exceptions to this include when hands are visibly soiled or when alcohol-based hand sanitizers are ineffective, for example, in the case of patients infected with spore-forming organisms such as Clostridium difficile . ,

Personal protective equipment

The required PPE varies based on infection type. The most common forms of PPE are gloves, gowns, masks, and eye protection or face shields. CDC guidelines outline when PPE should be worn ( Table 109.2 ). Prior to donning PPE, all people entering a room requiring PPE should perform hand hygiene. Donning of PPE upon room entry and discarding PPE prior to exiting the patient room is recommended by the CDC to prevent environmental contamination and pathogen transfer.

TABLE 109.2

Personal Protective Equipment

Component Usage Recommendations
Gloves Contact with blood, bodily fluids, secretions, excretions, contaminated items, mucous membranes, or nonintact skin
Mask, eye protection/face shield Procedures/activities likely to generate splashes/sprays of blood, body fluids, or secretions (e.g., suctioning, endotracheal intubation)
N95 or higher respirator in addition to gloves, gown, and face/eye protection When caring for patients with suspected or proven infections transmitted by respiratory aerosols

Antimicrobial resistance and antimicrobial stewardship

Antimicrobial resistance is a major problem in healthcare, as the prevalence of resistant pathogens is increasing, yet development of new antimicrobial drugs to treat these infections has not kept pace. Pediatric patients with a history of bacterial colonization, especially with multidrug-resistant organisms, and children with chronic health issues who require invasive devices more frequently or for longer periods of time are at increased risk for infection caused by an antimicrobial-resistant organism. , In critically ill children, the associated risk of increased morbidity and mortality from sepsis leads providers to start empiric, broad-spectrum antibiotics early. Once antibiotics are initiated, it is challenging to narrow or discontinue their use absent clinical or laboratory signs of improvement. Empiric antimicrobial treatment is common in the PICU, with 40% to 72% of PICU patients receiving a course during their hospital stay. Between one-third and one-half of these antibiotic prescriptions are either unnecessary or inappropriate, the latter defined as antimicrobial overuse or misuse. Development and implementation of antimicrobial stewardship programs improves correct antimicrobial choice based on culture and drug sensitivities, along with optimal antimicrobial dosing and treatment duration based on infection site and organism. , , In pediatric studies, specific interventions include a combination of these elements: developing antimicrobial stewardship programs, implementing antibiotic restriction policies, following formal antibiotic use guidelines, instituting a mandatory antimicrobial time-out 48 to 72 hours after antimicrobial initiation, and structuring audits with feedback to providers. , Despite reductions in the use of specific antimicrobials that are heavy contributors to the development of pathogen resistance, no study in the pediatric population has shown reduction in antimicrobial resistance patterns or HAIs.

Visitation policies

Many hospitals implement hospital-wide visitation policies during peak respiratory viral season with the goal of decreasing hospital-acquired respiratory viral infections by limiting exposure to infected individuals. Others implement policies for high-risk patient populations, such as ICU and immunocompromised patients. These policies often restrict the number of nonparent/legal guardian visitors, nonsibling children, and ill visitors, and prohibit young children in patient care areas. In a study conducted at a large, freestanding children’s hospital, implementation of such policies reduced the incidence of hospital-acquired respiratory viral infections by 37% on non-ICU floors. However, this did not include a significant infection reduction in any ICU—neonatal, pediatric, or cardiac.

Specific healthcare-associated infections in the pediatric intensive care unit

Bloodstream infections

BSIs remain the most common hospital-acquired infection in the PICU population. As discussed earlier, the majority of BSIs are associated with the presence of a CVC. , , , , CLABSIs lead to considerable morbidity, mortality, increased ICU and hospital LOS, and increased healthcare costs, estimated at $33,000 to $39,000 per episode. These costs are primarily driven by increased LOS. , The CLABSI-attributable mortality is reported as ranging from 11% to 18%. Per NHSN surveillance criteria, a primary BSI is laboratory confirmed by blood culture or nonculture-based microbiological testing and not attributable to infection at another site. If the identified organism is one commonly found on skin—that is, a common commensal organism—the patient must be symptomatic (fever, chills, or hypotensive) with the same organism identified from two or more blood specimens collected on separate occasions to meet BSI criteria. A CLABSI is a primary BSI when a central catheter has been in place more than 2 calendar days. Mucosal barrier injury (MBI) BSIs are a subset of primary BSIs or CLABSIs in specific high-risk patient populations. These infections are diagnosed only in patients with neutropenia or evidence of severe gastrointestinal graft versus host disease in the setting of hematopoietic stem cell transplant. The CLABSI definition lacks specificity and likely overestimates the number of BSIs caused by CVCs. However, given the greater burden of proof required to meet catheter -related BSI (CRBSI) criteria, nearly all PICUs report and use CLABSI for quality initiatives. Table 109.3 compares the CLABSI and CRBSI criteria.

TABLE 109.3

Criteria for Central Line–Associated and Catheter-Related Bloodstream Infections

Infection Criteria
CLABSI A primary bloodstream infection confirmed by blood culture or non-culture-based microbiologic testing, and a CVC has been in place more than 2 calendar days and the infection is not attributable to another site

  • Patient has clinical signs of infection and positive peripheral blood culture and no other obvious source, and one of the following:

    • Catheter tip culture positive with >15 CFU (semiquantitative) or >10 3 CFU (quantitative) of same organism as peripheral culture

    • Simultaneous positive blood culture from the CVC with a colony count at least threefold greater than the peripheral culture

    • Differential time to positivity between CVC culture and peripheral is <120 minutes

CFU, Colony-forming units; CLABSI, central line–associated bloodstream infection; CRBSI, catheter-related bloodstream infection; CVC, central venous catheter.

Two longitudinal studies of US PICUs examined CLABSI trends from units reporting data to the NHSN and demonstrated significant decline over time. , The utilization ratio or central line days per patient day for the study period was 0.44 and the pooled mean CLABSI rate decreased each year, from 5.8 per 1000 line days in 2006 to 1.4 in 2012. More recent data from a large multicenter cohort of US cardiac ICU patients reported an aggregate CLABSI rate of 1.1 per 1000 line days. Staphylococcal species—specifically, coagulase-negative staphylococci and Staphylococcus aureus —accounted for the greatest proportion of CLABSIs, supporting the hypothesis that skin flora contamination is the main route of infection. Gram-negative rods such as Escherichia coli , Klebsiella spp., and Pseudomonas aeruginosa cause approximately 20% of infections, with Enterococcus species (mainly E. faecalis and E. faecium ) and Candida species (mainly C. albicans and C. glabrata ) accounting for additional significant proportions. Each organism has reported trends of increasing antibiotic resistance over time. ,

As briefly mentioned previously, a variety of factors contribute to a patient’s risk for developing a CLABSI. While some are intrinsic to the patient and not easily modified—such as critical and/or chronic illness, immune function, or impaired skin integrity, for example, burns—others are directly related to the catheter. These may include colonization or contamination of the CVC along its subcutaneous tract with organisms from the skin or possibly from healthcare providers or other caregivers. This may occur upon insertion or as a result of any manipulation of the line, such as during dressing changes. Similarly, catheter hub and intraluminal contamination can lead to colonization and then BSI. , Less commonly, the CVC may be colonized by hematogenous seeding from another site of infection.

The key components of prevention efforts have focused on the aforementioned catheter-related factors, namely, preventing contamination and colonization. , These practices have been incorporated into CLABSI prevention bundles, often separated into two: an insertion bundle and a maintenance bundle. Implementation of central-line bundles have been effective in decreasing and preventing CLABSIs across ICU settings, including PICUs, and the improvements have been sustained over time. Successful improvement and prevention initiatives have the support of opinion leaders, are led by those with expertise and authority, and have empowered multidisciplinary teams who maintain vigilance regarding bundle compliance and work to eliminate barriers to adherence. ,

Components of traditional insertion and maintenance bundles are included in Table 109.4 . , , , Unlike improvement efforts in critically ill adults that had success mainly via maximizing compliance with insertion bundle components, PICU CLABSI prevention is driven by focusing as much energy on the maintenance bundle. Other important elements include empowering staff to stop the procedure if a break in aseptic technique is noted, avoiding routine exchange of CVCs as an infection prevention strategy, and, if infection rates do not decline despite strict adherence to core bundle elements, use of antibiotic-impregnated catheters and a chlorhexidine gluconate (CHG) impregnated disc at the insertion site. , Passive disinfection devices contain an antiseptic agent, either alcohol or CHG, and protect the access port via continuous contact with the needleless connector, serving as a barrier against contamination while simultaneously disinfecting the connector. Their use is associated with lower rates of CLABSIs. The type of CVC, particularly those planned for short-term use, may be an important consideration for some patients in regard to infection risk. Although all CVCs have an associated infection risk, a recent single-center cohort study compared the complication rates between peripherally inserted central catheters (PICCs) and nontunneled percutaneous CVCs and found a significantly greater rate of CLABSI in PICCs. Further, lower-extremity PICCs were twice as likely as upper-extremity PICCs to develop a CLABSI. While guidelines for pediatric patients do not recommend one insertion site over another for central catheterization, this same study found that the lowest CLABSI rate was in patients with internal jugular vein CVCs.

TABLE 109.4

Prevention Bundle Elements

Infection Insertion Bundle Elements Maintenance Bundle Elements

  • Attention to hand hygiene

  • Choice of optimal site

  • Skin disinfection with CHG

  • Prepackaged insertion kit

  • Insertion checklist

  • Maximum barrier precautions

  • Maintain aseptic technique

  • Daily discussion of line necessity; remove when no longer needed

  • Attention to hand hygiene

  • Standardized, aseptic procedures for hub and needleless connector entry, to include friction scrub

  • Standardized line care procedures

  • Daily CHG bathing treatments

VAP Not applicable

  • Elevate head of bed to 30–45 degrees

  • Maintain closed circuit

  • Change circuit if grossly contaminated

  • Twice daily oral hygiene


  • Only use an indwelling catheter when clinically indicated

  • Attention to hand hygiene

  • Maintain aseptic technique

  • Prepackaged insertion kit

  • Maintain a closed drainage system

  • Maintain unobstructed flow of urine with collection bag below level of bladder

  • Perineal hygiene at least daily

  • Review catheter necessity daily; remove as soon as no longer clinically indicated


  • CHG bath the night before or morning of surgery

  • No razors for hair removal

  • CHG or povidone iodine skin antisepsis

  • Prophylactic antibiotics 0–60 minutes before the procedure

  • Strict adherence to timing of postoperative antibiotic prophylaxis

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May 20, 2021 | Posted by in RHEUMATOLOGY | Comments Off on Healthcare-associated infections

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