Control of methicillin-resistant Staphylococcus aureus in Canadian paediatric institutions is still a worthwhile goal

In both Europe and the United States, the presence of methicillin-resistant Staphylococcus aureus (MRSA) in hospitalized patients is no longer a sporadic occurrence, and MRSA has become an endemic problem in many institutions (1). Fortunately, in most health care facilities in Canada, the presence of MRSA is still sporadic. However, MRSA outbreaks in health care facilities and the presence of MRSA in the community indicate that Canadian hospitals are at risk of having MRSA introduced into their facilities (2,3). A recent cross-Canada MRSA surveillance study of 21 hospitals noted an increase in the proportion of isolates that are methicillin-resistant (1.2% in 1995 compared with 2.3% in 1996), with most isolates originating in Ontario and Quebec (4). The proportion of methicillin-resistant isolates continues to increase; from 1995 to 1998, MRSA accounted for 3.4% of the S aureus isolates collected from across Canada. Given that the overall numbers remain relatively low, prevention of MRSA infection in patients hospitalized in Canada should be an achievable goal, if appropriate measures are taken. The purpose of this statement is to provide an approach to control MRSA.

MRSA is a good example of the phenomenon of natural selection. It has been seen repeatedly that soon after a new antibiotic comes into use, S aureus develops resistance to the antibiotic while maintaining its pathogenic characteristics. Table 1 demonstrates the chronology of the antimicrobial resistance of S aureus.

TABLE 1:

Historical progression of antibiotic resistance of Staphylococcus aureus

Antibiotic	Year introduced	Reports of resistance
Penicillin	1941	1940s
Streptomycin	1944	mid-1940s
Tetracycline	1948	1950s
Erythromycin	1952	1950s
Methicillin	1959	late 1960s
Gentamicin	1964	mid-1970s
Ciprofloxacin	1988	late 1980s
Vancomycin	1958	1997

IDENTIFICATION OF MRSA

The National Committee for Clinical Laboratory Standards, Villanova, Pennsylvania (NCCLS), developed protocols to standardize the detection and reporting of MRSA (5). Although the disk diffusion technique used in accordance with NCCLS guidelines gives reliable results for most antimicrobials, the use of an oxacillin screen plate is more accurate for MRSA testing (6). The latter test is performed by inoculating the isolate onto Mueller-Hinton agar supplemented with 4% sodium chloride and 6 μg/mL of oxacillin. The screen plate and a control plate with no antibiotics are inoculated as a spot or a streak using a cotton swab dipped into a 0.5 McFarland direct-colony suspension of the isolate. The plates are incubated at 35°C for 24 h and then examined for any growth. Growth on the screen plate indicates resistance. Results from the oxacillin screen plate correlate almost 100% with the results of tests that detect the presence of the gene responsible for methicillin resistance, mecA (7). An epidemic strain of MRSA emerged in Ontario (8). This strain exhibits phage type 95 and has unusual phenotypic properties, including a negative rapid-slide coagulase test, a negative or weak tube coagulase reaction at 4 h but positive at 24 h, and a negative or weak DNAase reaction (9).

Typing of MRSA isolates can be used to identify the potential sources of MRSA and to differentiate between endemic and epidemic strains. The antimicrobial profile for typing is readily available in clinical laboratories but provides limited information for strain differentiation because typical strains of MRSA are multiply antibiotic resistant. Molecular typing techniques may be indicated in an epidemiological investigation (10).

TRANSMISSION

MRSA is most commonly introduced into an institution by an infected or colonized patient who serves as a reservoir and less commonly by a health care worker who disseminates the organism directly (11). The principal mode of transmission is from patient to patient on the hands of hospital personnel. Airborne and environmental contamination are uncommon, except in certain circumstances. For example, environmental MRSA contamination may be an important route of transmission in a burn unit or an intensive care unit, and airborne transmission may occur during the care of a tracheostomized patient with MRSA pneumonia.

EPIDEMIOLOGY

S aureus may colonize the external nares and skin, and, less commonly, the perineal area. MRSA phage type 95 has a propensity to colonize patients at extra nasal sites. Most children and 40% of adults are nasal carriers of S aureus. Examples of populations with an increased frequency of S aureus carriage are newborns, hospital workers, hemodialysis patients and those with skin disorders such as eczema. Additional factors associated with MRSA colonization are prolonged hospitalization, burns, surgery necessitating intensive care and the use of multiple antibiotics, especially during a prolonged course of treatment. MRSA may be carried for an extremely long period; a study of known carriers indicated a half-life of carriage of about 40 months (12). There are conflicting data on the virulence of MRSA but the morbidity and mortality attributable to S aureus appear to be similar for methicillin-susceptible and MRSA (13).

ERADICATION OF THE CARRIER STATE

Eradicating MRSA in a carrier is very difficult, and is usually only considered for the health care worker who has been epidemiologically linked to an outbreak and for patients in long term care facilities. Therapies to clear nasal carriage of MRSA have met with some success, but relapse can occur within months of the completion of therapy. Although many agents are active in vitro, few agents reach sufficient concentrations in nasal secretions to be clinically useful. Topical agents can deliver higher concentrations to the colonized site, especially the nares where oral agents appear in lower concentrations. Treatment with any antibiotic may lead to the emergence of resistance. Most reports about the efficacy of antimicrobial therapy for the eradication of MRSA are based on uncontrolled studies with short follow-up periods.

Topical agents that have been used to treat MRSA include bacitracin, mupirocin, vancomycin and povidone-iodine. Initial clearance of MRSA with each topical agent is 90% to 100%, although recolonization does occur. In one study with mupirocin, 50% of patients were recolonized at two months (14). Resistance has been documented with long term and intermittent use of topical agents (15). Oral therapies that have been tried include trimethoprim/sulfamethoxazole (TMP/SMX), novobiocin, ciprofloxacin and minocycline, usually used in combination with rifampin. The clearance of carriage with oral agents has not been very successful, rarely achieving 50% clearance, and resistance frequently occurs. Ciprofloxacin, which appeared in vitro to be a promising oral agent for use in the eradication of MRSA, has been disappointing because of the rapid emergence of resistance even when combined with rifampin (16). The use of topical and oral therapy together has been evaluated in uncontrolled studies using oral TMP/SMX, oral rifampin and topical bacitracin. Clearance of nasal carriage was successful (80% to 100%), and failures were due to the development of resistance to rifampin.

Until more conclusive studies are performed, it is reasonable to use a combination of topical and oral therapy for the eradication of nasal carriage in specific situations, such as the management of an outbreak. A combination, such as mupirocin 2% ointment and TMP/SMX (maximum dose 160/800 mg bid), may be successful in clearing nasal carriage in the short term.

CONTROL MEASURES

The Infectious Diseases and Immunization Committee of the Canadian Paediatric Society recommends the following measures to control MRSA colonization of patients and to prevent MRSA from becoming endemic in paediatric health-care facilities (summarized in Table 2).

TABLE 2:

Summary of recommendations to control methicillin-resistant Staphylococcus aureus (MRSA) colonization and prevent MRSA from becoming endemic in paediatric health care facilities

1. Identification of cases
Selective screening of patients	• Hospitalized outside of Canada within the past year
	• From a centre with an outbreak or endemic MRSA
	• With a colonized or infected family member
Sporadic cases	• Identified by laboratory, reported to the infection control practitioner and attending physician
Previously known cases	• Identified by a flagging system
2. Patient placement
Inpatients	• In single rooms
Outpatients	• Separated from other patients during clinic visits
New admissions screened and awaiting results	• In single rooms
3. Barrier precautions
Health care workers	• Wear gloves, gowns, masks
	• Wear goggles or face shields for direct contact with patient secretions
4. Washing
Health care workers	• Wash hands with antimicrobial soap
	• Wash hands after gloves removed
	• Use hand lotion to prevent dry or cracked skin
Patient	• Use antimicrobial skin cleanser for all patient bathing
5. Eradication of MRSA
Considered in selective situations only	• Use a combination of topical and oral therapy, eg, mupirocin 2% ointment to both nares four times a day for 10 days, trimethoprim/sulfamethoxazole (TMP/SMX) by mouth 8 mg TMP/SMX/kg/day ÷ bid (maximum dose 160/800 mg bid), plus rifampin 20 mg/kg or 600 mg once daily for 10 days
6. Duration of isolation
At identification	• Continue over the entire length of hospitalization
If rescreened	• Discontinue isolation after three consecutive cultures negative for MRSA when the patient is not receiving antibiotic therapy
7. Management of contacts
If one case	• Screen immediate patient contacts
If one nosocomial case	• Further screening may be warranted to identify the potential source
If an outbreak	• Seek the advice of an expert
8. Education
Health care workers	• For all staff
	• Repetitive education programs
9. Transfer to another facility	• Inform the facility in advance

1. Identification of cases

   • The selective screening of patients admitted to hospital has been a strategy adopted by many centres. Patients hospitalized outside of Canada within the past year should be screened for MRSA. Similarly, patients being transferred from any centre with an outbreak or endemic problem due to MRSA, or patients with a colonized or infected family member should be screened. Culture of both anterior nares with one swab, as well as a wound culture or sputum, if present, should be taken to detect the carrier. Experience with MRSA phage type 95 suggests that it may be prudent to add a perineal or rectal swab for screening (8). An umbilical swab should be done in neonates. In long term carriers, the nasal swab has been found to be the most useful site with a sensitivity of 93%: negative predictive value 95% (12).
   • Sporadic cases of MRSA in hospitalized patients may be identified by detecting MRSA on a clinical specimen. The laboratory must promptly inform the infection control practitioner and attending physician so that appropriate measures can be carried out.
   • A flagging system should be required to identify patients who were previously identified as MRSA cases, so that upon readmission they are recognized promptly and isolated appropriately.
2. Patient placement

   • Inpatients with MRSA should be placed in single rooms.
   • Outpatients with MRSA should be separated from other patients during clinic visits. For example, clinic visits should be scheduled at the end of the day.
   • New admissions who have been screened and are awaiting results of the MRSA screen should be placed in a single room.
3. Barrier precautions

   • Precautions are required in inpatient and outpatient settings.
   • Gloves and gowns should be put on before entering a patient’s room and removed immediately before leaving.
   • Masks should be worn by health care workers to reduce the risk of nasal colonization by preventing contact with contaminated hands during patient care activities.
   • Goggles or face shields should be worn for direct contact with patient secretions (eg, suctioning) or when working within one metre of a coughing patient.
4. Washing

   • Hands should be washed with a hospital-approved antimicrobial soap before and after patient contact, after touching contaminated equipment or surfaces, and when leaving the isolation room.
   • Hands should be washed after gloves have been removed.
   • An approved antimicrobial skin cleanser should be used for all patient bathing (eg, chlorohexidine gluconate, triclosan).
   • Hand lotion to prevent dry or cracked skin should be used as necessary by the health care worker.
5. Eradication of MRSA colonization

   • Eradication is not routinely done for sporadic cases, but may be considered for outbreak control or for patients who are to be transferred to a facility where isolation is not feasible.
   • If antimicrobial therapy is given, a combination of topical and oral agents should be used, such as mupirocin 2% ointment to both nares four times a day for 10 days, and TMP/SMX by mouth 8 mg TMP/kg/day ÷ bid (maximum dose 160/800 mg bid), plus rifampin 20 mg/kg or 600 mg once daily for 10 days. The antimicrobial susceptibilities of the organism should be considered when selecting an agent for oral use.
6. Duration of isolation

   • The patient should generally be isolated for the entire length of hospitalization.
   • Repeat swabs are generally not indicated during that admission.
   • Patients should be isolated and rescreened on subsequent admissions or rescreened in follow-up clinic visits.
   • Isolation can be discontinued after three consecutive cultures, taken a minimum of one week apart, are negative for MRSA when the patient is not receiving antibiotic therapy. A single negative swab does not indicate that the patient may be taken out of isolation. Rescreening consists of nasal and wound swabs, as well as any other sites that were positive on previous assessment.
7. Management of contacts

   • If one patient with MRSA is identified, then screen immediate patient contacts as described above.
   • If the acquisition of MRSA is considered nosocomial, further screening may be warranted to identify the potential source.
   • An outbreak is defined as an increase in the incidence or prevalence of MRSA over background rates. In a place with no previous MRSA, this would mean two cases documented concurrently or in close proximity. For centres with endemic MRSA, it is important to know background rates to determine whether an outbreak has occurred. Seek the advice of an expert for outbreak management.
8. Education

   • Education of all staff is crucial for staff compliance with infection control guidelines.
   • Education efforts must be repetitive because of staff turnover and also to reinforce good habits, especially hand washing.
9. Transfer to another facility

   • Inform the facility of the patient’s MRSA colonization in advance.