G.A. Ortolano, Ph.D., J.H. Angelbeck, Ph.D., J.S. Cervia, M.D., and F.P. Canonica, Ph.D.

Introduction

Infectious disease physicians, infection control practitioners, facilities managers and healthcare providers responsible for the care of patients at risk for healthcare-associated infections (HAIs) should appreciate that:

• The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has increased its commitment to focus on nosocomial or healthcare-associated infections
• Pseudomonas aeruginosa is particularly virulent and a significant cause of HAI morbidity and mortality
• Studies in the scientific literature have linked HAIs to drug-resistant P. aeruginosa in the hospital water supply
•  Recent data suggest that P. aeruginosa found in hospital water is a significant source of HAIs, and that exposure to this pathogen can be prevented with point-of-use bacterial retention filters at faucets and showerheads as an adjunct to existing water disinfection regimens.

This clinical update brochure reviews the evidence in support of concerns for waterborne P. aeruginosa as a source of infection in healthcare environments. Furthermore, it introduces the concept of point-of-use water filtration as either an alternative or adjunct to traditional disinfection strategies for institutional potable water. A more expansive review of waterborne infections is available that is not limited to P. aeruginosa.¹

HAIs and JCAHO 

• HAIs are defined as infections that develop greater than 48 hours following admission to a hospital or other healthcare institution.
• In the U.S. alone, the combination of HAIs and medical errors total greater than 2 million per year and are the proximate cause of an estimated 44,000-98,000 annual fatalities.^2,3,4
• HAIs represent a significant increase in the cost of healthcare both nationally, at an estimated cost of 4.5 to 5.7 billion dollars per year,^5,6 and at a per patient cost ranging from $5,000-$50,000 per episode.^7,8,9,10
• Although HAIs have long been a target of cost control for hospitals, recent concerns regarding an increase in HAIs and the continual emergence of antibiotic resistance has prompted JCAHO to mandate a “culture of safety” initiative effective January, 2005. The spirit of this policy prompts heightened awareness of practices and procedures required to assess HAI etiology, treatment, and the development of prevention strategies.
• On its website, JCAHO infection control standards address the surveillance, prevention, and control of infection.
• In November 2003, JCAHO approved revised infection control standards to be implemented in January 2005.

The new standards retain many of the concepts embodied in existing standards, but sharpen and raise expectations of organization leadership and of the infection control program itself.

For 2004, JCAHO added infection control as National Patient Safety Goal (NPSG) No. 7.11 Critical access hospitals are encouraged to maintain surveillance, prioritize infectious complications, implement strategies to prevent further incidences, and be responsive to the results of continuous surveillance by repeatedly prioritizing and implementing solutions in a process of continuous improvement.

Consistent with JCAHO infection control goals and healthcare cost containment strategies is the recognition that infectious complications deserve high priority and focused attention. The directive specifies, among other things, that institutions will “Manage as sentinel events all identified cases of unanticipated death or major permanent loss of function associated with a healthcare-associated infection.”¹²

The Relative Importance of Pseudomonas aeruginosa in HAIs

The National Nosocomial Infection Surveillance (NNIS) system report compiles data from nearly 300 participating hospitals, encompassing a cross section of size and facility types in order to reflect the U.S. national experience. Figure 1 depicts data from 205 medical and surgical intensive care units collected over a seven-year period comprising 500,000 patients with 29,000 nosocomial infections. The data provided valuable information concerning the body sites and microorganisms responsible for HAIs.¹³

The fact that it ranks among the top five most frequently encountered organisms contributing to all types of HAIs underscores the obvious concern that exists to control sources of infection related to P. aeruginosa. In fact, one large study describes P. aeruginosa as the most frequently occurring pathogen (24.4%) responsible for ventilator-associated pneumonia.¹⁴

P. aeruginosa is ubiquitous in water, soil and on vegetables. It can be carried by touch contamination.¹⁵ As an opportunistic microorganism, it rarely causes harm to the immune competent individual. However, P. aeruginosa is commonly recognized as one of the more virulent microorganisms among immunocompromised patients both in and out of the hospital setting. It has been shown to be responsible for fatality rates approximating 30% among those with pneumonia and septicemia,¹⁶ and when the causative agent of ventilator-associated pneumonia, mortality may be as high as 38%.¹⁷ Among AIDS patients, P. aeruginosa can effect 50% death rates¹⁸ and is lethal in 60% of the highly susceptible burn patient population. Cystic fibrosis patients are particularly susceptible, with virulence and antibiotic resistance having been well studied.¹⁹

Figure 1. NNIS System Report: P. aeruginosa ranks among the top five most frequently encountered organisms responsible for healthcare-associated infections.

Biofilms are organized communities of both viable and nonviable microorganisms that exist within a sticky matrix of extracellular polysaccharides (or EPS), absorbed nutrients, and entrained particles adhered to an inert or living surface. They form when a surface is first preconditioned through continual exposure to water, inorganics such as calcium, and organics such as proteins and lipids. Waterborne bacteria are then transported to the preconditioned surface by a combination of Brownian motion, frictional drag, electrostatic attraction, gravitational forces, and turbulent water currents. The bacteria that initially contact the preconditioned surface adhere reversibly and, through a communication phenomenon known as quorum sensing, release signals called autoinducers into the surrounding environment. Autoinducers attract other bacteria to the surface and stimulate the replication of already adsorbed cells. Cell replication is accompanied by the production of EPS, which leads to irreversible cell adhesion and the formation of a biofilm. The biofilm continues to grow until it matures to a self-sustaining critical mass.

Once established at a particular location, a mature biofilm can seed the formation of additional biofilms at other locations. Through the processes of streaming, detaching, rolling, and rippling, all or part of the biofilm relocates. In addition, biofilms continually shed individual bacteria that migrate downstream and potentially contribute to the establishment of new biofilm communities. Biofilms contribute to morbidity and mortality in a healthcare facility setting. The routes of waterborne pathogen transmission to at-risk patients and hospital staff are varied and numerous:

• Direct contact with water used for routine hand washing, preoperative surgical scrubbing, and medical device reprocessing
• Ingestion of water and ice
• Inhalation of aerosolized water droplets

P. aeruginosa is a common constituent of biofilms. As is the case for all microbial pathogens, its ability to cause infection and disease is governed by three factors: the number of microorganisms present, their virulence, and the immune competency of the host.²⁰

A principal factor in the establishment and maintenance of virulence in P. aeruginosa is its resistance to antibiotics. When protected within the biofilm matrix, the proximity of P. aeruginosa to other bacteria may facilitate the transfer of antimicrobial resistance genes. Also contributing to virulence are a collection of bacteria-derived toxins which serve to degrade elastin, a structural protein that holds cells together and allow for penetration across natural barriers to the passage of microorganisms. Finally, P. aeruginosa can exhibit a mucoid phenotype that confers resistance to the immune response of the host.²¹ Virulence is an innate property of this microorganism that cannot easily be overcome.

NNIS data show the rapidly growing antibiotic resistance of P. aeruginosa.²² Comparing data from the period 1998-2002 with more recent observations made in 2003, there has been an increase in resistance to imipenem, quinolones, and third generation cephalosporins by 15%, 9%, and 20%, respectively. In addition, the cost of care to treat an infection caused by an antibiotic-resistant organism generally exceeds that of managing an infection caused by organisms that are more susceptible to standard antimicrobial therapies.²³ The problem of antimicrobial resistance may be greater in high-risk groups such as burn patients.²⁴

Confounding efforts to prevent P. aeruginosa infection is the formation of biofilm in the pipes and plumbing fixtures of the water supply within the healthcare institution. Biofilm protects bacteria from disinfectants and antibiotics when residing in plumbing lumens or implanted medical devices.^25,26 This makes traditional disinfection strategies in water less than totally effective, particularly if the treatment is episodic or the concentration of disinfectant varies within the plumbing system over time.

P. aeruginosa in Hospital Drinking Water

P. aeruginosa is a relatively virulent and ubiquitous Gram-negative bacterium frequently responsible for HAIs. It is found in water, on inanimate surfaces, on skin, and in body fluids contiguous with skin surfaces such as the lining of the nose and mouth.

Table 1 summarizes a number of studies, discussed in greater detail elsewhere, that illustrate the presence of P. aeruginosa strains, some of which were drug-resistant, in hospital tap water that coincided with strains recovered from infected patients.²⁷ Interestingly, recent data show that “Faucets served as the source of infection for patients in 35% of cases, and on the other hand, retrograde contamination of faucets by patients was observed in 15% of cases.”²⁸

Site of Infection	Molecular methods used to link patient and water strain	Reference
Lungs, wound infection	RAPD	Trautmann et al, 200429
BSI, lungs, peritoneum, trachea, urine	AP-PCR	Trautmann et al, 200130
Lung, sinuses, urine	DNA macrorestriction analysis	Bert et al, 199831
CVC-BSI, skin, urine	PFGE	Buttery et al, 199832
Urine	PFGE	Ferroni et al, 199833
BSI	ERIC-PCR, RAPD	Ezpeleta et al, 199834
Not reported	DNA fingerprinting	Burucoa et al, 199535
BSI, lung, wound	DNA typing, serotyping	Richard et al, 199436
BSI	Phage typing, serotyping	Kolmos et al, 199337
BSI, CSF, trachea	Genotyping, serotyping	Grundmann et al, 199338
Urine	ExoA DNA probe	Worlitzsch et al, 198939

Table 1. Studies demonstrating hospital water as the source of P. aeruginosa infection.

Abbreviations: CVC-BSI = central venous catheter blood stream infection; RAPD = random amplified polymorphic DNA; AP = arbitrarily primed; -PCR = polymerase chain reaction; PFGE = pulse field gel electrophoresis; ERIC = enterobacterial repetitive intergenic consensus sequencing; ExoA = exotoxin A.

The contribution of biofilm to enhanced microbial virulence and increased antibiotic resistance, as well as its ability to serve as a repository for the continuous shedding of microbes into the healthcare facility water system reinforces the need for greater protection than systemic water treatment technologies such as chlorine dioxide, hot water flushes, and copper-silver ionization can provide. Point-of-use filters establish and maintain a physical barrier to the passage of bacteria from the water supply to healthcare workers and patients.

Experience with Point-of-Use Hospital Water Filtration

Early experience with point-of-use hospital water filtration was applied to the control of Legionella. Preliminary data suggest that outbreak control was perceived by clinicians to be cost-permissive.⁴⁰ At the 9th European Congress of Clinical Microbiology and Infectious Diseases (Berlin, Germany - March, 1999), Hummel et al.⁴¹ presented the implementation of point-of-use water filters because Legionella was refractory to conventional water sanitation treatments. The incidence of Legionella infection dropped from 23 to 15% after filter installation. Vonberg et al.⁴² of the Medical School Hannover (Hannover, Germany) evaluated the performance of point-of-use tap water filters in three intensive care units. Without filtration, it was shown that over 90% of 32 samples collected were positive for Legionella at concentrations ranging from 1—106 cfu/ml. In contrast, 250 out of 251 samples recovered from taps fitted with filters for 7 days failed to recover any Legionella. In the single positive sample, the residual Legionella concentration was only 1 cfu/ml.

At the University of Bonn in Germany, point-of-use hospital water filters appear to have been effective in reducing the incidence of P. aeruginosa HAIs. Identified sources of P. aeruginosa included surface cleaning equipment, taps, wash basin drains and showers in an outbreak of P. aeruginosa infections in an adult hematology/oncology unit.⁴³ After implementation of a strategy that included point-of-use water filters, the HRI rate reportedly reverted to pre-outbreak levels. Perhaps the most convincing report to date emerged from Trautmann et al., who detailed the incidence of waterborne  P. aeruginosa before and after hospital-wide implementation of point-of-use filters.²⁹ The monthly incidence of P. aeruginosa infections for periods before and after hospital-wide implementation of point-of-use filters was tabulated and analyzed, revealing a significant reduction from 2.5 to 0.9 infections per month (Figure 2). These data suggest that point-of-use hospital water filters may serve as an adjunct to routine systemic water disinfection treatment regimens for the reduction of exposure to pathogens implicated in waterborne HAIs.

Figure 2. Monthly rate of P. aeruginosa infection before and after hospital-wide implementation of point-of-use water filters

Data from Trautmann et al.²⁹ were tabulated as infections per month and t-test for unpaired data applied.

Summary

1. JCAHO’s 2005 NPSGs reflect the fact that a significant percentage of patients who unexpectedly die or suffer major permanent loss of function have healthcare-associated infections. These deaths and injuries meet the definition of a sentinel event. They are therefore required to be subjected to root cause analyses, including attention to identifying potential improvements that would reduce further risk of infection.
2. “Reduce the risk of healthcare-associated infections” is a 2005 JCAHO NPSG.
3. P. aeruginosa ranks among the top five most frequently encountered bacteria responsible for healthcare-associated infections.
4. Biofilms that form in healthcare facility water plumbing systems are a persistent source of potentially pathogenic waterborne microorganisms.
5. P. aeruginosa can be a drug-resistant constituent of biofilms found in healthcare facility water systems.
6. Point-of-use filters can serve as an adjunct to routine systemic water disinfection treatment regimens for the reduction of exposure to pathogens implicated in waterborne HAIs.

References