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Antimicrobial Agents and Chemotherapy, December 2001, p. 3623-3624, Vol. 45, No. 12
Clinical Microbiology Laboratory, Duke
University Medical Center, Durham, North Carolina 27710
Received 1 June 2001/Returned for modification 3 July
2001/Accepted 5 September 2001
Antimicrobial susceptibility testing of 192 group B streptococcal
isolates from patients with invasive disease demonstrated that 31 (16%) were resistant to erythromycin and 17 (9%) were resistant to
clindamycin. One isolate demonstrated high-level resistance to
streptomycin, but none was highly resistant to gentamicin. Erythromycin
and clindamycin are no longer reliable empirical alternatives to
penicillin for the treatment and prevention of group B streptococcal infections.
The group B streptococcus (GBS) is
an important cause of neonatal sepsis and meningitis, infections in
pregnant women, and invasive disease in nonpregnant adults, especially
among those with diabetes mellitus, malignancy, liver disease, and
other forms of immune impairment (2). Although GBS is
regarded as uniformly susceptible to penicillin, recent reports have
highlighted the emergence of strains resistant to erythromycin and
clindamycin (3, 5, 6, 8-11). The presence of these
resistant strains raises concerns about the use of erythromycin and
clindamycin for the prophylaxis or treatment of GBS infections in
patients allergic to For serious GBS infections, an aminoglycoside is often administered in
combination with penicillin or ampicillin to provide bactericidal
synergism. Although rarely tested for, high-level aminoglycoside
resistance, which indicates that the isolate will not be affected
synergistically by a combination of a penicillin plus an
aminoglycoside, has been documented in GBS isolates (1).
Therefore, we tested all strains of GBS isolated from patients with
invasive disease at Duke University Medical Center over a 10-year
period to determine the patterns of antimicrobial resistance, including
high-level aminoglycoside resistance.
A total of 192 clinical isolates of GBS were studied. All isolates were
obtained from the blood or cerebrospinal fluid of patients admitted to
Duke University Medical Center between July 1990 and June 2000. The
patients were 20 neonates with early-onset disease, 14 neonates with
late-onset disease, 10 children, 2 pregnant women, and 146 nonpregnant
adults. Identification of GBS was made by standard methods and latex
agglutination (Streptex; Murex Biotech, Dartford, United Kingdom).
Susceptibility testing was performed by the broth microdilution method
with cation-adjusted Mueller-Hinton broth supplemented with 2 to 5%
lysed horse blood as recommended by the National Committee for Clinical
Laboratory Standards (NCCLS) (7). The MICs of penicillin,
ampicillin, ceftriaxone, clindamycin, erythromycin, vancomycin,
levofloxacin, and chloramphenicol were determined as outlined by NCCLS;
and the MIC of meropenem, which is used for the therapy of meningitis
with penicillin-resistant Streptococcus pneumoniae, was
determined as described previously (4). In addition, wells
containing gentamicin and streptomycin at concentrations of 500, 1,000, and 2,000 µg/ml were used to detect the presence or absence of
high-level aminoglycoside resistance. Preprepared microdilution trays,
based on the MicroScan MICroSTREP panel, were manufactured and provided
by Dade Behring Inc. (West Sacramento, Calif.).
Frozen isolates of GBS were thawed, inoculated onto 5% sheep blood
agar, and incubated at 35°C in an atmosphere containing 5%
CO2 for 18 to 24 h. Each isolate was
subcultured onto fresh 5% sheep blood agar and incubated for an
additional 18 to 24 h. Five to 10 colonies were then emulsified
into 3 ml of deionized water to a turbidity equivalent to that of a 0.5 McFarland standard. The suspension in each well was then diluted
to a final concentration of approximately 5 × 105 CFU/ml. The microdilution trays were
incubated in ambient air at 35°C for 20 to 24 h. S. pneumoniae ATCC 49619, Enterococcus faecalis ATCC
51299, and E. faecalis ATCC 29212 were used as controls. The
MIC was defined as the lowest concentration of antibiotic that
inhibited bacterial growth.
The susceptibilities of the 192 isolates to all antibiotics tested
except gentamicin and streptomycin are summarized in Table 1. Thirty-one isolates were resistant to
erythromycin (MICs,
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.12.3623-3624.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Antimicrobial Susceptibilities of Group B
Streptococci Isolated from Patients with Invasive Disease:
10-Year Perspective
ABSTRACT
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-lactams.
1 µg/ml), 17 were resistant to clindamycin
(MICs, 1 µg/ml), and 2 were resistant to chloramphenicol (MICs,
16 µg/ml). All but one of the clindamycin-resistant isolates were
also resistant to erythromycin. The rates of resistance to both
erythromycin and clindamycin increased over the 10-year study period.
For the period from July 1990 to June 1995, 12% of isolates were
resistant to erythromycin and 4% were resistant to clindamycin; from
July 1995 to June 2000, the rates of erythromycin and clindamycin
resistance had risen to 20 and 10%, respectively.
TABLE 1.
Susceptibilities of 192 GBS isolates
High-level resistance to gentamicin was not detected in any of the isolates, but for one isolate the streptomycin MIC was 1,000 µg/ml. The latter isolate was also notable for its reduced susceptibility to erythromycin (MIC, >64 µg/ml) and chloramphenicol (MIC, 16 µg/ml).
Our findings confirm those reported by other investigators. GBS strains
isolated from patients with invasive disease remain uniformly
susceptible to -lactams, but resistance to erythromycin and
clindamycin has emerged to a clinically significant level. Other recent
reports from North America have documented rates of erythromycin
resistance of 6.7 to 21% and rates of clindamycin resistance of 3.4 to
15% (3, 5, 6, 8-10). Resistance rates are even higher in
Taiwan, where 29.7% of GBS strains are resistant to erythromycin and
26.6% are resistant to clindamycin (11).
To our knowledge, this study is the first to systematically test for high-level aminoglycoside resistance in GBS isolates from North America. Only one isolate exhibited high-level resistance to streptomycin. This is in contrast to France, where more than 10% of GBS isolates were found to be highly resistant to streptomycin (1). None of our GBS isolates were highly resistant to gentamicin. To date, this type of resistance has been documented in only one GBS strain, which was isolated in Paris in 1987 (1).
Penicillins remain the preferred antibiotics for prophylaxis and
treatment of GBS infections. Routine testing for susceptibilities to
-lactams and for high-level aminoglycoside resistance is
unnecessary. However, erythromycin and clindamycin can no longer be
considered reliable alternatives to -lactams, and susceptibilities
to these agents should be determined in the setting of penicillin intolerance.
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ACKNOWLEDGMENTS |
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We thank Dade Behring Inc. for providing the microdilution panels.
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FOOTNOTES |
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* Corresponding author. Present address: Microbiology Unit, Canterbury Health Laboratories, P.O. Box 151, Christchurch, New Zealand. Phone: 64 3 364 0347. Fax: 64 3 364 0238. E-mail: david.murdoch{at}cdhb.govt.nz.
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Antimicrobial Agents and Chemotherapy, December 2001, p. 3623-3624, Vol. 45, No. 12
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.12.3623-3624.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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