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Antimicrobial
A-gents
ELSEVIER

International Journal of Antimicrobial Agents 5 (1995) 101-106

The worldwide prevalence of methicillin-resistant

Staphylococcus aureus

Andreas Vossa**, Bradley N. Doebbelingb

Utziversiry Hospitul Nijnlegen, Department of Medical Microbiology, RO. Box 9101, 6500 HB Nijmegen. The Netlrrrhncis
hThe University of Iowa College of Medicine, Department of Inlernul Medicine, IOWUCity. IA, CSA

Accepted 16 May 1994

Abstract
Literature on the occurrence of methicillin-resistant
Staphylococcus
aureus (MRSA) in hospitals and long-term-care
facilities in
various countries of America, Africa, Asia, Australia/New
Zealand, and Europe is reviewed. It is concluded that the increasing
prevalence of MRSA is a worldwide problem, affecting both affluent and poor countries, and that infection control guidelines are
needed in all regions affected.
Keywords: Staphylococcus uureus; Methicillin

resistance;

Nosocomial

1. Introduction

At a time when the majority of nosocomial staphylococcal isolates were already penicillin-resistant, the introduction of semi-synthetic beta-lactamase-resistant
penicillins was a major therapeutical breakthrough [12].
Unfortunately the first methicillin-resistant Staphylococcus aureus (MRSA) was isolated just a year later in London [26]. MRSA became a clinical and therapeutical
problem with the occurrence of multi-resistant strains
in the late 1970s [6,7]. Today MRSA is recognized as a
major nosocomial pathogen, causing nosocomial infections in community and referral hospitals, as well as
long-term-care
facilities
throughout
the
world
[3,27,38,44,61]. Differences in the virulence of methicillin-resistant and methicillin-susceptible
strains of
Staphylococcus
uureus have been debated [4,23,37,46].
However, infections with MRSA continue to challenge
clinicians, hospital epidemiologists and administrators,
since they lead to important therapeutical and infection
control problems, and significant costs [6,10].
Using phage typing in the 1960s Lidwell and colleagues demonstrated that patients admitted to the hospital gradually become colonized with staphylococci, primarily from other patients, although transfer of strains

*Corresponding

author.

0924-8579/95/$29.00 0 1995 Elsevier Science Publishers

SSDI 0924-8579(94)00036-T

B.V. All rights

infections

from health care workers (HCWs) was also important.

Recently, higher rates of MRSA carriage have been
found among patients than hospital staff [41]. Chronic
colonization or infections of tracheostomies, as well as
wound or decubitus ulcers are important hospital reservoirs of MRSA [60]. Chronic nasal carriage has been
convincingly demonstrated as the primary reservoir site
[49]. Therefore patients or HCWs that are MRSA carriers may be the source of case clusters, leading to
outbreaks of MRSA infection which are reported intermittently throughout the world. Furthermore, the environment may serve as the source of an MRSA epidemic,
as seen among inpatients with severe psoriasis or skin
ulcers who received oatmeal baths in a common bathtub
[69]. Other hospitals have had recurrent outbreaks of
MRSA, up to four in seven years [9]. MRSA outbreaks
and the occurrence of epidemic strains have been reported in Australia [5,13,74], Argentina [29], Belgium
[58], Canada [51], Denmark [25], France [29], Germany
[71], Greece [29], Hong Kong [15], Italy [29], Japan [59],
Malaysia [21], Netherlands [16,68], New Zealand [22],
Portugal [35], Saudi Arabia [19], Spain [45,64], Singapore [14], Sweden [48], Taiwan [8], United Kingdom
[36,47,50] and United States of America [3,18,42].
This review will focus on the prevalence of MRSA in
hospitals and long-term-care facilities. Since a number of
papers do not state whether special methods necessary
to reliably detect MRSA were used, the interpretation of
reserved

102

A. Voss. B. N. Doehhelit~~llrrtrn~crtionul Jo~muI of Antimicrohiul

the data reviewed herein is limited to a certain degree. No

attempt was undertaken
to summarize data on the incidence or distribution
of antibiotic resistance since these
data are not reported in most published
studies, and
presumably
vary greatly even on a national
level (e.g.
ciprofloxacin-resistance
in various German areas: < 5%
to >95%). MRSA antibiotic
resistance
in European
countries using standardized
and uniform testing methods has been recently reviewed [32,73].

2. America
United States
Overall, 97% of U.S. hospitals reported having patients with MRSA between 1987 and 1989. The proportion of hospitals with large numbers
of MRSA cases
(> 50 per year) increased
significantly
from 18% to
32% during the same period [3]. Approximately
11% of
the S. aureus isolates from U.S. hospitals in the National
Nosocomial
Infections
Surveillance
(NNIS)
System
from 1975 through 1991 tested for susceptibility
to methicillin, oxacillin, or nafcillin were resistant [44]. The proportion of MRSA among all U.S. hospitals rose from
2.4% in 1975 to 29% in 1991, although the rate of increase varied significantly
among different sized hospitals [44]. In 1991. hospitals with less than 200 beds had
15% of S. uUreU.s isolates that were MRSA, increasing
with hospital size to 38% of isolates in hospitals with 500
or more beds. MRSA has also been reported to measurably add to the overall burden of nosocomial
infections
]571.
MRSA colonization
of patients is common in longterm-care facilities. Thurn et al. recently reported that
approximately
12% of nursing homes in Minnesota
had
residents known to be colonized with MRSA and 69%
of those facilities had sought outside help with control
[62]. In contrast, 81% of facilities in western New York
h?d identified patients with MRSA in the previous year
[40]. Culturing
of residents occurred infrequently
and
many facilities did not have written policies for colonized
or infected residents. Policies regarding care of colonized
or infected patients in nursing homes were not uniform
[62]. Only bed size was an independent
predictor of the
number of residents with MRSA [40]. In prospective
studies, the carrier state appears to be little affected by
a roommates carrier status [4,24]. However, MRSA carriage in long-term-care
facilities is infrequently
associated with prior hospitalization.
Although high levels of endemic MRSA colonization
were present in a Veterans Affairs facility, only 10% of
newly admitted
patients
acquired
MRSA during one
year of follow-up and MRSA infections were rare [4]. In
contrast,
Muder and colleagues reported that MRSAcolonized patients in a similar facility had a nearly four
times greater risk of staphylococcal
infection than those

Agents 5

(1995) 101-106

colonized with methicillin-susceptible

strains [37]. However, severe underlying
comorbidity
was also strongly
associated
with MRSA colonization
in the study; the
results observed may have been due to such confounders
which were not adequately controlled.
Independent
predictors of colonization
at admission include prior positive MRSA culture, male gender, urinary incontinence,
and pressure sores [39]. Careful handwashing
and use of
gloves may limit spread within nursing homes [39]. Colonized patients may be identified with targeted surveillance cultures of the most debilitated patients at admission, and those with a history of prior carriage [39].
South America
Data from continent-wide
or even nation-wide
prevalence studies were not available. However, interhospital
spread of MRSA - a known problem [20,28] ~ was reported by Sader et al. from Sao Paulo. Brazil [54]. The
authors highlighted
a particularly
interesting
aspect of
the problem, namely the influence of the socioeconomic
situation
on the prevalence
of certain MRSA strains.
Based on their molecular
epidemiology
study, the authors suggested the dissemination
of a unique oxacillinand quinolone-resistant
strain of S. aweus in several
hospitals of Sao Paulo. They concluded that this spread
is due to the disproportionate
distribution
of hospitals,
an extremely low health care worker-to-patient
ratio,
and employment
of poorly paid HCWs in two or more
hospitals. These observations
may apply to other heavily
populated and poor areas of the world, thus potentially
explaining
an increased prevalence
of certain MRSA
strains.

3. Africa
Nigeria
MRSA in Nigerian hospitals has been reported only
recently [1,53]. At the university hospital in Lagos, the
proportion
of methicillin-resistant
isolates among S. aurem rose from less than 2% in 1985 to 50% in 1987
[53,67]. Molecular typing indicated that the isolates from
the two periods were unrelated and showed no similarity
to epidemic MRSA strains of Australia or the UK [67].

4. Asia
Japan
Among all countries of the world, Japan appears to be
one of those mostly impacted with the occurrence
of
MRSA. The proportion
of methicillin-resistant
strains
among S. aureus isolates from 43 university
hospitals
was as high as 60% in 1991 [27]. An even higher prevalence of MRSA was reported in the surgery department
of another university
hospital [57]. During a two-year

A. Voss, B.N. DoebbelinglInternational

Journal

study period the average rate of clinical MRSA isolates

was 83%. Similarly, the proportion of MRSA among all
S. aureus strains causing skin infections at the Medical
University of Osaka was 41.5% in 199 1, indicating a high
proportion even among strains only causing infections
1391.
China
No national surveys were available to determine

the
prevalence of MRSA in China and data on regional
occurrence varied markedly. The Tian Tan Hospital in
Peking reported 15.6% of S. aureus isolates to be methicillin-resistant, a rate reportedly lower than in other
districts of the area [56]. Among strains of S. aureus
randomly collected from a university hospital in Wuhan,
MRSA accounted for 79.6% of all isolates, responsible
for over 90% of S. aureus isolates in some departments.
Hands of HCWs were swabbed and 68.9% were found
to be MRSA-carriers [I I].

5. Australia/New

Zealand

Australiu

Turnidge et al. performed a national survey involving

14 teaching hospitals in major Australian cities [66]. The
study was conducted over three separate periods during
19861987. The national prevalence of MRSA was
found to be 14.4%, with a wide variation among the
different states: 25.2% in Queensland, 23.5% in Victoria,
12.6% in New South Wales, 11.3% in South Australia
and 0.4% in Western Australia [66]. This study, as sporadic reports of epidemic spread, e.g. among Victorian
hospitals with a prevalence of 2040% [43], shows that
MRSA is a major nosocomial pathogen especially in
large hospitals in Eastern Australia. The increase in the
isolation of MRSA in Eastern Australia was not only
suspected to be associated with the spread of a particular
epidemic MRSA strain, such as those seen in London
hospitals, but was also shown to be indistinguishable
from the London epidemic isolates by restriction endonuclease analysis of plasmid DNA [63]. Interestingly, the
differences between Western and Eastern Australia resemble those between Northern and Southern Europe,
and furthermore led to similar prevention strategies.
After an outbreak at the Royal Perth Hospital due to a
patient who was transferred from outside the state, a
screening of all patients and health care workers who had
been in hospitals outside Western Australia was implemented. During the first two years of this screening program 4.3% of the patients were found to harbour MRSA,
and no further serious outbreaks were observed [31].
New) Z&and
According to a recent study, MRSA is isolated only
infrequently in New Zealand and has not become en-

of Antimicrobial

Agents 5 (1995)

101-106

103

demic in hospitals. From 1988 to 1990 only 235 patients

were infected or colonized with MRSA. These were
included in the three outbreaks
involving more
than 20 patients each that were reported to the New
Zealand Communicable Disease Center. Interestingly,
30-50% of the MRSA strains originated from overseas, mainly from Australia and the Pacific Islands
[22,34].

6. Europe
Western Europe

Data on the frequency of MRSA in Europe have

so far been based on the numerous reports of recent
MRSA outbreaks
in various European
countries
[2,15,17.36,45,58,68,71], and on the reports of epidemic
strains that were recognized to spread in certain areas,
such as the EMRSA-1 in the North Thames or EMRSA3 in the South-east Thames regions in England [30,33].
Only a few European countries have performed surveillance or national surveys [30,52,55,68,71]. A recently
conducted systematic survey in 43 laboratories from ten
European countries documented a marked difference in
the prevalence of MRSA in different parts of Europe
[73]. Of the more than 7000 S. uureus isolates screened
by a uniform method, 12.8% were shown to be methicillin-resistant. The proportion of MRSA in the surveyed European countries ranged from 0.1% and 0.3%
in Denmark and Sweden respectively, to > 30% in Spain,
France and Italy. MRSA was most frequently isolated
from patients in the surgical and internal medicine services, with a higher prevalence among patients in intensive
care units. This was especially evident in Italy and Austria, where more than 50% of all staphylococcal isolates
from ICUs were MRSA. Approximately 87% of the
MRSA strains (using the international set of phages up
to 1000x RTD) could be typed, with up to 93% typed
with the use of experimental phages. Strains of group III
and especially those typeable with phage 77 were predominant, a result observed by other investigators. Vinde1 et al. in Spain reported that MRSA strains classified
as phage group III (and a second non-typeable group)
are increasingly involved in hospital infections since
1989. and are creating epidemics in different regions of
Spain today [70]. For each region phage typing detected
one or a few dominant (epidemic) types, although 46%
of the strains were unique. The European MRSA population therefore seems to be a mixture of epidemic and
non-epidemic strains.
CentraNEustern

Europe

Recently a prospective study on the prevalence of

MRSA in the Alpe-Adria region (including Hungary,
Poland. Czech/Slovakian Republics and the former Yugoslavia) was conducted [72]. More than 1400 S. wreus

104

A. Voss, B.N. Doebbelingllnternational

Journal of Antimicrobial Agents 5 (I995)

strains were screened using standard methods and overall 218 (15.6%) MRSA strains were found. The proportion of MRSA among S, aureu~ isolates from universityaffiliated hospitals was lowest in the CzechlSlovakian
Republics (4.3%) and Hungary (8.6%). Similar proportions were reported in national surveys in the Czech
Republic (7%) and Hungarian (6%) university hospitals
(Urbascova P, Hatala M and Ban E, Konkoly-Thege:
Abstracts, Gram-positive infection in Central Europe,
Prague, 13 November 1993). In Poland and Yugoslavia,
19.7% and 30.9%, respectively, of the strains were methicillin-resistant [72]. Although the distribution of the isolates by medical specialty in these Eastern European
countries was similar to those in Western Europe, Eastern European patients colonized or infected with MRSA
were typically younger (mean age 35 years) and less frequently hospitalized in intensive care units (mean
28.7%). In a local survey, MRSA accounted for 13.7%
of all S. aureus isolates tested at a Warsaw institute
during 1992 [65]. In a national survey on the antibiotic
resistance of S. aureu~ in Poland a year later, the same
authors found 27% of the strains to be methicillin-resistant (Hryniewicz W. Trzcinski K: Abstract, Gram-positive infection in Central Europe, Prague, 13 November
1993). Outbreaks and endemic MRSA continue to occur
as well. Currently, the proportion of MRSA in neonatal
units in Warsaw is as high as 65% (personal communication) .

The reports reviewed herein demonstrate that the increasing prevalence of MRSA is a worldwide problem.
Despite certain national epidemiological problems, both
aftluent and poor countries are affected by the occurrence of MRSA and equally in need of infection control
guidelines and antibiotic restriction policies to potentially limit the spread of MRSA, locally, nationally and
internationally.

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