Comparison of methicillin-resistant Staphylococcus aureus (MRSA) carriage rate in the general population with the health-worker population.

Abstract

The emergence of antibiotic resistance in bacteria is becoming a widespread problem and a major health issue. Methicillin resistant Staphylococcus aureus (MRSA) is becoming increasingly frequent in hospitals. In this study we compared the carriage rate of MRSA in 100 health workers at North Shore Hospital with the carriage rate of MRSA in the general population (100 staff members and students of Auckland University of Technology) and found a prevalence of MRSA in the health workers of 4%, but none in the general population group. The implication of MRSA carriage in health workers is discussed.

Key words: Staphylococcus aureus, MRSA, methicillin, prevalence, health workers

N Z J Med Lab Sci 2008; 62: 4-6

Introduction

Staphylococcus aureus is a virulent bacterium that can cause serious infections including skin and soft tissue infections, wound infection, bacteremia, pneumonia, and endocarditis (1). It is an organism that is renowned for its potential to acquire resistance to antimicrobial agents. In 1961 there were reports from the United Kingdom of S. aureus that had acquired resistance to methicillin (methicillin-resistant S. aureus) (2). The clinical significance of oxacillin-resistant (methicillin-resistant) S. aureus is heightened by the fact that these isolates are usually resistant to other anti-staphylococcal agents such as lindamycin, erythromycin, tetracycline, and sometimes trimethoprim/sulphamethoxazole, with the exception of vancomycin (4). Although oxacillin-resistant staphylococci appear susceptible in vitro to other [beta]-lactam agents, (such as the cephalosporins) these are clinically ineffective. Therefore, all oxacillin-resistant staphylococci are reported as resistant to all [beta]-lactam agents, including cephalosporins, [beta]-lactam/ [beta]-lactamase inhibitor combinations, and imipenem (2).

Currently nearly 90% of S. aureus isolates are penicillin-resistant. Methicillin and other semi-synthetic penicillins were successful in treating penicillin-resistant S. aureus until the 1980s, when methicillin resistance emerged (3). Methicillin is no longer commercially available, and in many laboratories testing for methicillin resistance has been replaced by oxacillin and/or cefoxitin. Cefoxitin gives clearer endpoints because it is a better inducer of the mecA gene (2). The genetic basis of methicillin resistance in MRSA is the acquisition of mecA gene, that renders MRSA resistant to all [beta]-lactam antibiotics (2,3).

The methicillin resistance gene (mecA) encodes a methicillin-resistant penicillin-binding protein (PBP2a) that is not present in susceptible strains and is believed to have been acquired from a distantly related species. MecA is carried on a mobile genetic element, the staphylococcal cassette chromosome mec (SCCmec), of which four forms have been described that differ in size and genetic composition.

The origins of the major MRSA strains are still poorly understood. It has been proposed that all MRSAs were descended from a single ancestral S. aureus strain that acquired mecA, but more recent studies show that some MRSAs are very divergent, implying that mecA has been transferred between S. aureus families (2,4).

In the past three decades, MRSA has become wide spread in many hospitals (2) and S. aureus (including MRSA) is commonly found in two main carriage sites, the nose (20%) and the perineum (3%). The skin, including the hands, can be transiently contaminated (5). The major form of spread is hand borne transmission (2).

Hospital infection control staff need to limit the spread of MRSA for several reasons. There have recently been reports of strains of MRSA that have intermediate resistance to vancomycin. This is an important concern since the already limited treatment options for serious MRSA infections may become more limited due to the increase in resistance to vancomycin. Limiting the transmission of MRSA might reduce the potential for these strains to spread (6).

Another concern is the simultaneous spread of MRSA and vancomycin-resistant enterococci (VRE), possibly resulting in the transfer of the vancomycin-resistance gene from VRE to MRSA, rendering MRSA fully resistant to vancomycin. The first such isolate was detected in the United States in 2002 (7). The cost of treating an MRSA infection is another concern because vancomycin, the antibiotic most commonly used to treat MRSA infection is expensive.

Epidemiological studies have shown that since the mid 1990s, the incidence of MRSA has been increasing in New Zealand (6). In 2006 the incidence of MRSA amongst hospital patients and staff was approximately 0.17% (10). Amongst S. aureus isolates in N.Z, 7% were resistant to oxacillin/methicillin in 2005.

There are four main strains of MRSA, each of which has distinguishing characteristics (11). In New Zealand, different strains of MRSA can become epidemic in different geographical regions (10). EMRSA -15 is predominately isolated in hospitals, whereas WSPP is found more frequently in the community.

The aim of this study was to compare the carriage rate of MRSA in 100 health workers at North Shore Hospital with the carriage rate of MRSA in a general population of 100 staff members and students of the Auckland University of Technology.

Methods

Nasal swabs from 200 participants were collected, and inserted directly into 7% salt broth for 24 hr incubation at 37?C (12). After 24 hr the broths were sub-cultured onto mannitol salt agar (MSA, Fort Richards, USA)) and examined after a further 24 hr and 48 hr for yellow colonies. Any yellow colonies on MSA plates had a DNA test and purity plate on Columbia human blood (Fort Richards, USA). DNA positive isolates had a coagulase test performed. All presumptive S. aureus isolates (coagulase positive, DNA positive yellow colonies) were subjected to testing with MRSA screen slide latex agglutination kit (Pro-Lab Diagnostic) and sensitivities by disc diffusion on Mueller-Hinton agar. The antibiotics tested were penicillin, cefoxitin, erythromycin, tetracycline, clindamycin, ciprofloxacin, gentamycin, fucidic acid, rifampicin, mupirocin and vancomycin. Zone size for determining sensitivity or resistance is shown in Table 1. Isolates of S. aureus showing resistance to penicillin and cefoxitin were considered positive for MRSA in this study.

Previous history for MRSA was determined where available. If a new isolate demonstrated resistance to more than penicillin and cefoxitin, a slope was sent to ESR for phage typing to assist in strain identification. PCR typing was not performed. Infection control nurses were notified of isolates of MRSA.

Positive participants were treated and followed up by infection control and occupational health nurses. The Waitemata DHB protocol for MRSA positive staff is as follows:

* Nasal: apply bactroban/fucidic acid to nostrils twice a day x 5days.

* Body wash: chlorhexidine 4% washes (shower) daily x 5 days.

* Hair wash: chlorhexidine 4% hair washes x per week 3 sets of swabs to be taken 48 hr apart.

* Follow up: swabs taken monthly for 6 months, then 6 monthly for 18 months.

Due to the small number of positive tests, statistical analysis was not carried out. The study was approved by the Northern Regional Ethics Committee.

Results

The main finding of our study was that the carriage rate of MRSA in health workers was 4% compared to 0% in the control population. The cohorts were well matched for age while there were more females than males in both groups. Average age of the health workers and control population were 42 yr and 40 yr respectively while there were 85 females in the health workers group and 64 females in the control group.

All four individuals in whom MRSA was isolated were nurses with more than 2 years of clinical experience. Three of the MRSA positive nurses were strain EMRSA-15 and one WSPP1. All four subjects showed resistance to cefoxitin and penicillin, three showed additional resistance to erythromycin, two additional resistance to ciprofloxacin and one additional resistance to clindamycin. One of the four nurses had previously isolated MRSA. Three of the four nurses were treated with the standard Waitemata DHB protocol and subsequently showed negative results for MRSA (Table 2).

Discussion This study, although small in size, found that 4% of health workers in the Waitemata DHB hospital carried MRSA, compared to none of the healthy volunteers in the wider Auckland community. Our figure of 4% is higher than the national reported incidence of 0.17% amongst hospital patients and staff (10), but compares with studies conducted on patient cohorts in the United Kingdom, where MRSA incidence ranged between 1.6% and 5.3% (15). However, our study is novel, because we compared carriage rate of MRSA in New Zealand health workers with the general community. We could not find any published studies with which to directly compare our results.

Detecting or identifying a MRSA can be done in several ways. Detecting the presence of mecA gene using PCR is the gold standard for identification and confirmation of MRSA isolates (13). Detection of the altered protein PBP2a using commercially available MRSA screen slide latex agglutination kits is a highly specific and sensitive method. In this test, latex particles sensitized with a monoclonal antibody against cell wall PBP2a specifically react with methicillin-resistant staphylococci to cause agglutination. In this study, the latex agglutination, together with antibiotic sensitivity by disc diffusion was used. Several studies (5,11,14) have shown that cefoxitin is superior to oxacillin in the detection of MRSA, and cefoxitin was used in our study.

It is interesting to note that the first MRSA positive health worker

was sensitive to ciprofloxacin as EMRSA-15 strains are often resistant to ciprofloxacin (11). The concern is that these health workers could transmit MRSA to vulnerable patients. Patients are at higher than normal risk of acquiring S. aureus infection particularly as the in-patient population tends to be older, sicker and weaker, making them more vulnerable to infection.

Various strategies exist for controlling the spread of MRSA within healthcare settings. Preventative measures include laboratory surveillance and screening for MRSA (5), promoting careful hand washing with soap and water rather than the antibacterial gels in common use, gowning and gloving by staff and eradication of MRSA from colonized people (decolonization therapy). Most institutions use a combination of these strategies. Potential side effects associated with the use of eradication therapy include the development of further antibiotic resistance or the possibility of adverse reaction to the antibiotic. Although clinical trials of eradication therapy in colonized healthcare workers (healthy adults) exist, in practice healthcare workers are not always systematically screened for MRSA and offered eradication therapy (3). In contrast, many hospital patients are routinely screened and offered antibiotics or drugs if they are found to be colonized (5,9). Currently at WDHB all staff members have a pre-employment nasal swab to detect MRSA but no further screening if the staff member tests negative. Patients admitted to the hospital will be screened if they are perceived to be at higher risk of MRSA carriage.

The results from this study suggest a small, but significant MRSA carriage in health workers that could be transmitted to vulnerable patients. This does raise the question whether all health workers should be screened at regular intervals for MRSA, as well as the usual pre employment screen .

Acknowledgments:

We would like to acknowledge the following: Colin Swager, Team Leader Microbiology, North Shore Hospital; Joanne Morgan and all staff members of Microbiology, North Shore Hospital; Dr. Roger Whiting, Acting Head of School, AUT ; Dr. Paul Henriques and Jim Clark, AUT; Dr. Jocelyn Peach, Director of Nursing & Midwifery, WDHB; Rachel Haggerty, Peter Pike and Andrea McLoid, previous managers, WDHB; Jane Sherard, Maori Advisor, WDHB; Pat Chainey and Dr. Tim Dare, Northern Regional Ethics Committee; Lorraine Neave and Dr. Wayne Miles, Knowledge Centre; Infectious control and occupational health nurses, WDHB; the Editor and two anonymous referees, NZ Journal of Medical Laboratory Science; and all the participants in AUT and WDHB.

References

(1.) Mahon CR, Manuselis G. Textbook of Diagnostic Microbiology, 2nd Ed., WB Saunders Co., Philadelphia, 2000.

(2.) Upton A, Roberts SA, Milsom P, Morris AJ. Staphylococcal post-sternotomy mediastinitis: five year audit. ANZ J Surg 2005; 75: 198-203.

(3.) Loeb M, Main C, Walker-Dilks C, Eady A. Antimicrobial drugs for treating methicillin-resistant staphylococcus aureus colonization (review). Wiley, 2005

(4.) Deplano A, Mendonca R, De Ryck R, Struelens M. External quality assessment of molecular typing of Staphylococcus aureus isolates by a network of laboratories. J Clin Microbiol 2006; 44: 3236-44.

(5.) Centers for Disease Control and Prevention. Information about MRSA for healthcare personnel (updated October 10, 2007). www.cdc.gov/ncidod/dhqp/ar_mrsa_healthcareFS.html

(6.) Wenzel RP. Prevention and Control of Nosocomial Infections, 2nd Ed., Lippincot Williams & Wilkins, Philadelphia, 1993.

(7.) Centers for Disease Control and Prevention. Staphylococcus aureus resistant to vancomycin - United States, 2002. MMWR Morb Mortal Wkly Rep 2002; 51: 565-7.

(8.) Utah department of health, Staphylococcus aureus with VISA/ VRSA. http://health.utah.gov/epi/newsletter/archives/aug97/ Default.htm.

(9.) Waitemata Health. MRSA Information Sheet for Staff / Occupational Health, 2006.

(10.) Heffernan H, Wheeler L. Annual survey of methicillin resistant staphylococcus aureus (MRSA). ESR Annual Report, 2005. www.surv.esr.cri.nz

(11.) Heffernan H, Blackmore T, Wheeler L, Davies H. Surveillance of MRSA in New Zealand: www.esr.cri.nz poster.pdf

(12.) Swager, C. Laboratory Manual, Waitemata District Health Board Laboratory, 21 March, 2006.

(13.) Heffernan, H, Wheeler, L. Phage typing methicillin resistant S. aureus (MRSA). Feb 2007. www.esr.cri.nz

(14.) CDC DHQP Guidelines. Laboratory detection of oxacillin methicillin resistant staphylococcus aureus, 2005. http://www. cdc.gov/ncidod/dhqp/ar_lab_mrsa.html

(15.) Anwar R, Botchu R, Viegas M, Animashawun Y, Shashidhara S, Slater GJ. Preoperative methicillin-resistant staphylococcus aureus (MRSA) screening: an effective method to control MRSA infections on elective orthopedics wards. Surg Pract 2006; 10: 135-7.

Zena H Fadheel (1), BSc, BMLS; Laboratory Technician

Holly E Perry (2), MApplSc (Hons); Programme Leader Bachelor of Medical Laboratory Science

Ross A Henderson (1), FRACP, FRCPA, PHD; Clinical Director Laboratory and Consultant Haematologist 

(1) North Shore Hospital, Waitemata District Health Board; (2) Auckland University of Technology, Auckland

Table 1. Interpretation of antibiotic sensitivities

                mcg               Resistant           Intermediate

Pencillin       10[union]   28mm [pounds sterling]
Cefoxitin       30            19 [pounds sterling]
Erythromycin    15            13 [pounds sterling]        14-22
Cotrimoxizole   25            10 [pounds sterling]        11-15
Tetracycline    30            14 [pounds sterling]        15-18
Clindamycin     2             14 [pounds sterling]        15-20
Ciprofloxacin   5             15 [pounds sterling]        16-20
Gentamycin      10            12 [pounds sterling]        13-14
Fucidic acid    10            18 [pounds sterling]        19-20
Rifampicin      5             16 [pounds sterling]        17-19
Mupirocin       5             13 [pounds sterling]
Vancomycin      30

                Sensitive

Pencillin       [greater than or equal to]29mm
Cefoxitin       [greater than or equal to]20
Erythromycin    [greater than or equal to]23
Cotrimoxizole   [greater than or equal to]16
Tetracycline    [greater than or equal to]19
Clindamycin     [greater than or equal to]21
Ciprofloxacin   [greater than or equal to]21
Gentamycin      [greater than or equal to]15
Fucidic acid    [greater than or equal to]21
Rifampicin      [greater than or equal to]20
Mupirocin       [greater than or equal to]14
Vancomycin      [greater than or equal to]15

Table 2. Characteristics of the MRSA positive nurses

Age              44                 30

Length of        4 years            2 years
service in
the hospital

Strain           EMRSA-15           EMRSA-15

Antibiotic       cefoxitin,         cefoxitin,
resistance       penicillin and     penicillin
                 erythromycin-      ciprofloxacin
                                    and
                                    erythromycin

Results after    Neg results        Neg results for
treatment for    for 3 swabs        1st & 2nd swab
5 days           following          and positive for
                 treatment          3rd swab

Age              56                 59

Length of        7 years            15 years
service in
the hospital

Strain           EMRSA-15           WSPP1

Antibiotic       cefoxitin          cefoxitin and
resistance       penicillin,        penicillin
                 ciprofloxacin,
                 erythromycin
                 and clindamycin

Results after    Neg results for    Not treated
treatment for    3 swabs
5 days           following
                 treatment