Vol. 14 •Issue 21 • Page 21
Methicillin-Resistant Staphylococcus aureus: Can Infection Control Methods Be Cost-Effective?
Studies show that employing hospital-wide infection control programs may be more economical than treating single cases.
It has been estimated that 80,000 people in the United States are infected with methicillin-resistant Staphylococcus aureus (MRSA) each year, with many of these infections acquired during hospital stays.1 Such high estimates should encourage more effort from infection control personnel to curb the incidence of hospital-acquired MRSA infections. However, the emerging controversy concerning MRSA lies in the argument that once it has become endemic, efforts to contain the spread are fruitless. Such approaches to infection control not only cost the hospital more money, as some have argued, but increase the mortality of patients, thereby affecting patient care.
With the need to optimize patient care and ensure cost-effective infection control measures and treatments, infection control programs have been implemented that have decreased the incidence of MRSA infection. Though methods may differ, they have demonstrated that endemic control and prevention of MRSA is not only possible, but also cost-effective and necessary. Numerous studies have shown that employing hospital-wide infection control programs may be more economical than treating single cases of MRSA.
S. aureus is one of the most clinically important species of bacteria. It can be normal flora of the skin, mucous membranes, oropharynx, gastrointestinal tract and urogenital tract of humans and other animals. It is estimated that 15 percent of healthy adults are nasopharyngeal carriers of the bacteria.2 Important virulence factors of S. aureus include its ability to produce a protein that binds immunoglobulin (Ig) types G 1, 2 and 4 via the constant region of the antibody, thus blocking antibody function. This prevents complement activation and makes the bacteria anti-phagocytic. In addition, the bacteria can produce a number of exotoxins that cause symptoms such as fever, vomiting, diarrhea and subcutaneous infections.
Clinical syndromes of S. aureus include staphylococcus scalded skin syndrome, toxic shock syndrome, food poisoning, cutaneous infections (such as folliculitis, furuncles, carbuncles and wound infections), bacteremia, endocarditis, pneumonia, empyema, osteomyelitis and septic arthritis.
S. aureus was relatively susceptible to antibiotics until the “golden age” of antibiotics, when penicillin, the first antibiotic, was prescribed not only for treatment, but for normal everyday use because people thought it would prevent infections. The over-use of penicillin led to the emergence of antibiotic-resistant strains of bacteria, including S. aureus.
As more antimicrobial agents became available, S. aureus continued to evolve into more and more resistant strains, including resistance to methicillin. Today, all strains of S. aureus that are resistant to anti-staphylococcal beta-lactamase-stable penicillins (e.g. methicillin, oxicillin and nafcillin) are termed MRSA. Oxacillin is used for detection and susceptibility because it has a longer shelf life, and methicillin is less readily available in the United States.3
The Laboratory’s Role
The clinical microbiology laboratory plays an increasingly important role in the detection of MRSA and susceptibility testing to various antimicrobial agents. The screening test for MRSA recommended by the NCCLS uses Mueller-Hinton agar supplemented with 6µg/mL of oxacllin and 4 percent NaCl. Agar plates are available from a number of commercial manufacturers. Colonies should be suspended into broth or saline to produce turbidity equal to a McFarland 0.5 standard. A swab is used to inoculate a portion of the plate. Cultures should be incubated no higher than 35 C, in ambient air for 24 hours.4
Although broth-based and agar-based tests will detect MRSA, clinical laboratory scientists must be careful when strains of S. aureus exhibit heteroresistance, a phenomenon when highly resistant cells are present in low number, while the majority of cells exhibit low level resistance or susceptibility. Heteroresistant strains often grow slower than susceptible populations; therefore, personnel must follow the NCCLS recommendations for growth conditions for positive identification.
Another test for MRSA is the polymerase chain reaction (PCR) to detect the mecA gene. The mecA gene codes for an alternate penicillin-binding protein, PBP2a, prohibiting beta-lactam antimicrobial agents from binding to the bacterial cell.3 A latex agglutination kit to detect PBP2a (Oxoid Inc., Ogdensburg, NY) is also available.
Infection Control Methods
Several European studies have been conducted to determine if infection control .programs could change the rate of infection for endemic MRSA and be cost-effective. Harbarth et al. conducted a study on the effects of delayed infection control, such as a delay in placing patients in isolation, or a lack of systematic surveillance cultures of new patients upon admission.5 A hospital outbreak of MRSA started in 1989, when the incidence of MRSA increased from 0.05 per 100 admissions to 0.57 in 1992. The overall prevalence of MRSA increased from 0.07 percent in 1989 to 0.84 percent in 1992.
A new infection control program begun in January 1993 initiated the isolation of all new MRSA-infected or -colonized patients as well as known MRSA-infected or -colonized patients. Clinical microbiology laboratory results were monitored daily. Roommates of MRSA patients were placed on surveillance cultures; systematic surveillance cultures at the time of admission were implemented later in the study. Finally, a hospital-wide program was instituted to improve compliance with hand hygiene and the use of alcohol-based hand cleaners.
Harbarth et al. reported 1,771 MRSA-infected or Ðcolonized cases in 506,012 patients between 1989 and 1997. Initially, the prevalence of MRSA patients increased from 0.93 percent in 1993 to 1.42 percent in 1994. Then, from 1994 to 1997 the prevalence decreased from 1.42 percent to 0.59 percent, with the number of new cases of MRSA decreasing from 0.60 per 100 admissions to 0.24 new cases per 100 admissions. In the end, the control program was able to reduce the relative risk of MRSA acquisition from 9.8 percent to 4.4 percent.
MRSA was more frequently isolated from surgical sites and soft tissue infections than any other site. In addition, the number of patients with MRSA bacteremia strongly correlated with the prevalence of MRSA patients (r = 0.77) and the number of new MRSA patients (r = 0.98). Harbarth et al. felt that the control program probably was not cost-effective for the hospital but was a benefit to patient care. The authors thought that MRSA control might be achieved with fewer resources.
Another study investigated the effect improved cleaning had on MRSA transmission. Rampling et al. designed a domestic cleaning program of the male and adjacent female ward that increased cleaning time by 57 hours per week.6 The study also included an enhanced surveillance of male surgical patients, screening of staff, routine infection control and infection measures, and enhanced environmental surveillance methods. The authors tried to estimate the minimum financial savings following the intervention through model estimate costs of infection during inpatient episodes.
Rampling et al. concluded that there was a sharp decrease in the acquisition rate of outbreaks following the infection control intervention. They had observed during the 27-month study that the acquisition of MRSA strains occurred at low levels (three patients) during outbreak control intervention in the male ward, while the female ward only experienced isolation of MRSA from six patients.
A study by Chaix et al. investigated the costs and benefits of an MRSA control program in an endemic setting in a French university hospital.7 The control program included screening for MRSA upon admission to the intensive care unit (ICU). The data included patients at risk of harboring MRSA, patients in the ICU for seven days or more, and isolating all patients infected or colonized with MRSA until documented eradication of MRSA colonization. Hospital staff responded to patients with confirmed or suspected MRSA infection by wearing disposable gowns or aprons, gloves, facemasks and by using antiseptic hand wash. A cost comparison was made between the treatment of 27 MRSA-infected patients to the 27 patients not colonized or infected with MRSA but who still underwent surveillance.
Of the 27 who had MRSA, compared to 27 without MRSA, it was calculated that treatment of MRSA patients cost an average of $9,275 more per patient than the cost of treating patients without MRSA. The costs of the control program ranged from $340 to $1,480 per patient. It was also reported that the control program reduced the incidence of MRSA by 14 percent.
These three studies addressed the concern of the cost benefit of MRSA surveillance and control and came to the same conclusion–implementation of cost-effective MRSA control is possible. Chaix et al. reported financial savings when comparing MRSA prevention to treatment, prevention costing as little as $340 while treatment costs averaged $9,275 per patient.7 Such figures are significant enough to show that infection control is more economic than MRSA treatments.
Their study, however, compared practices of not screening or using standard precautions. Even if hospitals did not institute a specific infection control program, certain degrees of standard precautions are taken in most developed countries. Also, while the 27 control patients did not have MRSA infections, some had other nosocomial infections. The goal of improving patient safety and satisfaction is not reached if only MRSA is prevented but other infections are allowed to occur.
The Rampling et al. study reported that the importance of good hospital hygiene can greatly affect the rate of infection.6 The control methods, such as extensive cleaning of patient rooms to remove dust, created higher than normal standards that led to better MRSA control. Rampling stressed that cost-cutting on cleaning services would not be cost-effective and only make infection control more difficult.
Surveillance cultures for detection of MRSA are also important. Harbarth et al. reported that active surveillance, screening and intensive control measures can decrease the prevalence and rate of infection of MRSA in hospital settings.5
The three studies offer strong support for cost-effective methods to control MRSA; however, all three experiments were conducted in Europe. MRSA control may not be cost-effective in all situations, since health care systems and hospital staff payments differ greatly.
The use of antimicrobial agents also differs between European and American medical practices. In some European countries, they are administered more freely. An increased use of antimicrobial agents may increase the prevalence of MRSA, which in turn would increase community and hospital relative risks of infections. There may be differences in the epidemiology of antimicrobial-resistant strains of S. aureus between Europe and America. It is unknown how the control methods used in these studies would apply to hospitals in other areas with different prevalence of MRSA.
Effective MRSA control throughout an institution has not been proven effective without first controlling higher-risk areas (such as units containing immunocompromised patients). A study conducted in the United States in 1996 tested the effectiveness of MRSA endemic control through contact isolation.8 Weekly surveillance for MRSA was conducted on all patients by PCR. Any patient testing positive was placed in contact isolation. It was concluded that the rate of infection in a neonatal ICU was reduced by 16 times when infected patients were placed in contact isolation.
These studies focused on areas with patients considered to be at high risk for contracting infections. More studies on the effects that control measures have on patient morbidity and mortality and the cost-effectiveness of such control measures are needed. Also, studies in which control variables are implemented one at a time are needed to assess the importance and cost-effectiveness of each individual control measure. This would identify extraneous and costly measures.
The continual evolution of bacteria is a continuing concern for health care facilities because antimicrobial treatments are losing their effectiveness. In 1996, a strain of MRSA was reported to have reduced susceptibility to vancomycin, the primary antimicrobial agent used to treat MRSA infections.9 In June 2002, eight infections caused by vancomycin-intermediate S. aureus (VISA) and one case of vancomycin-resistant S. aureus (VRSA) were confirmed.9
The emergence of new drug resistance requires future studies to determine the long-term effectiveness of hospital-wide infection control programs. The clinical microbiology laboratory will play an important role in screening and testing for susceptibility, aiding hospital studies in infection control programs and upholding strict standards in control practices. Health care systems cannot simply focus on financial benefits.
1. CDC. MRSA–Methicillin-resistant Staphylococcus aureus [online], 2002. Accessed Aug. 20, 2002 at http://www.cdc.gov/ncidod/hip/Aresist/mrsafaq.htm.
2. Murray, P.R., et al. Staphylococcus and related organisms. In Medical Microbiology, 3rd ed. 1998. Mosby, MO.
3. CDC. Laboratory detection of oxacillin/methicillin-resistant Staphylococcus aureus (MRSA), 1999. Accessed Aug. 20, 2002 at http://www.cdc.gov/ncidod/hip/Lab/FactSheet/mrsa.htm.
4. NCCLS. Performance standards for antimicrobial susceptibility testing; 12th Information Supplement. NCCLS approved standard M100-S12. NCCLS, 2002. Wayne, PA.
5. Harbarth, S., et al. Effect of delayed infection control measures on a hospital outbreak of methicillin-resistant Staphylococcus aureus. J Hospital Infect 2000;46:43-49.
6. Rampling, A., et al. Evidence that hospital hygiene is important in the control of methicillin-resistant Staphylococcus aureus. J Hospital Infect 2001;49:109-116.
7. Chaix, C., Durand-Zaleski, I., Alberti, C., and Brun-Buisson, C. Control of endemic methicillin-resistant Staphylococcus aureus: A cost-benefit analysis in an intensive care unit. J American Med Assoc 1999;282:1745.
8. Kernigan, J.A., et al. Effectiveness of contact isolation during a hospital outbreak of methicillin-resistant Staphylococcus aureus. Am J Epidemiol 1996;143(10):1079.
9. CDC. Staphylococcus aureus resistant to vancomycin–United States, 2002. MMWR 2002;51: 565-567.
David Young is a senior student and Don Lehman ([email protected]) is an assistant professor in the Department of Medical Technology at the University of Delaware, Newark.