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Dispatch
Co-trimoxazole–Sensitive,
Methicillin-Resistant Staphylococcus aureus, Israel, 1988–1997
Jihad Bishara,* Silvio Pitlik,* Zmira Samra,* Itzhak Levy,† Mical
Paul,* and Leonard Leibovici*
*Rabin Medical Center, Beilinson Campus, Petach-Tikvah, Israel; and †Schneider
Children’s Medical Center of Israel, Petach-Tikvah, Israel
Suggested citation
for this article:
Bishara J, Pitlik S, Samra Z, Levy I, Paul M, Leibovici L. Co-trimoxazole–sensitive,
methicillin-resistant Staphylococcus aureus, Israel, 1988–1997.
Emerg Infect Dis [serial online] 2003 Sep [date cited]. Available
from: URL: http://www.cdc.gov/ncidod/EID/vol9no9/02-0366.htm
Among bloodstream
methicillin-resistant Staphylococcus aureus (MRSA) isolates from
adult patients in a single hospital, susceptibility to co-trimoxazole
increased progressively from 31% in 1988 to 92% in 1997 (p<0.0001).
If also observed in other institutions, these findings should encourage
the performance of a clinical trial of sufficient size to compare co-trimoxazole
to vancomycin in treating MRSA infections.
Methicillin-resistant Staphylococcus aureus (MRSA) is a growing
medical concern. During the last 2 decades, the rates of infections caused
by MRSA increased among hospitalized patients in most developed countries
(1). The aim of this study was to examine trends in antibiotic
resistance of hospital-acquired bloodstream MRSA isolates from 1988 to
1997 in our institution.
The Study
Included in the analysis were all patients >18 years of age who had
hospital-acquired bacteremia caused by S. aureus. The study took
place at Rabin Medical Center, Beilinson Campus, Petach-Tikva, Israel,
a 900-bed university hospital. Our center serves an urban population of
approximately 1 million persons as both a first-line and tertiary facility.
A prospective surveillance of all bacteremic episodes occurring at our
medical center is performed continuously and, since 1988, has been incorporated
into a computerized database for bacteremia. Episodes of bacteremia are
detected by daily surveillance of the microbiology laboratory records,
with an annual range of 700 to 900 episodes.
Antibiotic susceptibility was tested by using the disk diffusion technique
on Mueller-Hinton agar, according to the procedures established by the
National Committee for Clinical Laboratory Standards (NCCLS) (2).
Plates were incubated at 30ºC for 18 h and 40 h for methicillin (5
µg/disk) and at 37°C for 18 h for other antibiotics. Bacteremia
was considered to be hospital-acquired if it appeared 48 h after admission.
During the study period, a total of 944 episodes of S. aureus
bacteremia were documented. We found 598 (63%) hospital-acquired episodes,
with an annual number of episodes ranging from 35 to 121. Among the hospital-acquired
episodes, 270 (45%) were due to MRSA strains. During the recent decade,
rates of resistance to methicillin were high but stable among the hospital-acquired
isolates, ranging from 25% to 57%. Rates of susceptibility to co-trimoxazole
among patients with hospital-acquired MRSA increased significantly from
31% in 1988 to 92% in 1997 (p=0.0001) (Figure).
The hospital-acquired MRSA isolates were persistently highly resistant
to chloramphenicol (69% in 1988 and 100% in 1997; p=NS), gentamicin (89%
in 1988 to 94% in 1997; p=NS), and ciprofloxacin (87% in 1988 to 96% in
1997; p=NS). The resistance to clindamycin (62% in 1988 to 92% in 1997;
p=0.04), fusidic acid (6% in 1988 to 14% in 1997; p=0.03), and rifampicin
(21% in 1988 to 76% in 1997; p=0.02) increased significantly. All isolates
were sensitive to vancomycin.
Conclusions
Our study shows that 92% of nosocomial MRSA strains were sensitive to
co-trimoxazole in 1997 as compared with 31% in 1988. Several factors may
have influenced the emergence of co-trimoxazole–sensitive MRSA, including
the reduced usage of this drug in our institution. According to the pharmacy
records, usage of co-trimoxazole in our institution decreased progressively
from 28 daily doses per 1,000 hospital days in 1990 to 17 daily doses
per 1,000 hospital days in 1997 (3). A recent multicenter
report from several Belgian hospitals showed an increase in co-trimoxazole
susceptibility among MRSA isolates (4). These findings
are in contrast with trends of increasing resistance of S. aureus
to a variety of anti-staphylococcal drugs other than co-trimoxazole, since
the beginning of the antibiotic era. These trends had culminated recently
with the appearance of glycopeptide resistance in hospitals and methicillin
resistance in the community (5). Whether our findings
reflect an increase of co-trimoxazole–sensitive MRSA clone/s in our institution
needs further exploration. In settings where co-trimoxazole is extensively
used, a substantial increase of MRSA resistance to co-trimoxazole has
been observed. For example, Martin et al. described a serial cross-sectional
study of resistance to co-trimoxazole among all clinical isolates of S.
aureus and other Enterobacteriaceae during a 16-year period
at San Francisco General Hospital (6). In this study,
resistance to co-trimoxazole increased from 0% to 48% in S. aureus
isolates obtained from HIV-infected patients. The authors explained this
increase of resistance to co-trimoxazole by the extensive use of this
drug as prophylaxis against Pneumocystis carinii pneumonia.
Eventually, our data may favor the use of co-trimoxazole as a potentially
cost-effective antimicrobial drug for treating MRSA infections. Co-trimoxazole
has been shown to be effective against MRSA both in vitro and in vivo
in mice (7), as well as in clinical reports on meningitis,
septicemia, and endocarditis (8–9). A controlled comparative
trial of intravenous co-trimoxazole versus intravenous vancomycin in 101
cases of severe S. aureus infections in intravenous drug users
was conducted by Markowitz et al. (10) in 1992. The authors
reported 100% cure rates for either drug in MRSA infections, including
bacteremia. More recently, Stein et al. showed varying degrees of success
in treating with co-trimoxazole orthopedic implant infections caused by
S. aureus (11). Unfortunately, this study did
not distinguish MRSA from methicillin-sensitive S. aureus strains.
Recent in vitro data have shown good activity of co-trimoxazole against
clinical isolates of vancomycin-intermediate S. aureus (12–13)
and vancomycin-resistant S. aureus (14). In some
of these cases, co-trimoxazole in combination with surgical debridement
and other anti-staphylococcal drugs has been used successfully (12,14).
In clinical practice, cyclical usage of co-trimoxazole and vancomycin
and possible other newer anti-MRSA drugs such as oxazolidinones and streptogramins
may prove of value in slowing down rates of development of antibiotic
resistance in MRSA. The in vitro–presented results, if confirmed in other
institutions, in conjunction with anecdotal clinical data, should encourage
the performance of a clinical trial of sufficient size to compare co-trimoxazole
to vancomycin in treating MRSA infections.
Dr. Bishara is a
specialist in internal medicine and infectious diseases, and he serves
as a senior physician and infectious disease consultant at the Rabin
Medical Center, Israel. His major research interests are infective endocarditis
and cardiovascular and nosocomial infections.
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