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Journal of Clinical Microbiology, November 1998, p. 3415-3416, Vol. 36, No. 11
Department of Microbiology, All India
Institute of Medical Sciences, New Delhi, India 110029
Received 2 February 1998/Returned for modification 24 March
1998/Accepted 9 July 1998
In vitro susceptibility patterns of newer Acinetobacter baumannii
is emerging as a major cause of nosocomial infections, particularly in
intensive care units, where antimicrobial use is greatest and the host
is most susceptible (3). Besides they are frequently
resistant to multiple antibiotics, including most of the To determine the quantitative difference in the susceptibility of
A. baumannii to A/S and A/C, the MICs of these agents were studied. Since ampicillin and amoxicillin are the antibacterial components of A/S and A/C, respectively, in these combinations, we
tested the MICs of ampicillin and amoxicillin for these A. baumannii strains separately as well.
A total of 100 consecutive isolates of A. baumannii from
various samples (54 from blood cultures, 38 from the respiratory tract,
and 8 from urine cultures) obtained from different patients received in
the Clinical Bacteriology Laboratory of the All India Institute of
Medical Sciences from September to December 1997 were tested. The
isolates were maintained at room temperature in nutrient agar slopes
and were subcultured two times before testing. The agar dilution method
was used to determine the MIC of A/S, A/C, ampicillin, and amoxicillin
as per National Committee for Clinical Laboratory Standards guidelines
(4). The breakpoints of resistance and susceptibility were
16/8 µg/ml for A/S and A/C and 16 µg/ml for ampicillin and
amoxicillin. Escherichia coli ATCC 25922 and A. baumannii ATCC 19606 standard strains were inoculated as quality
controls each time the tests were performed. Statistical analysis of
the results was done with McNemar's test to look for the significance
of association and comparison of resistance of A. baumannii
to A/S and A/C. The ranges of MICs and comparisons to those of A/S and
A/C by agar dilution are shown in Table
1.
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In Vitro Activities of Ampicillin-Sulbactam and
Amoxicillin-Clavulanic Acid against Acinetobacter
baumannii
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-lactamase-inhibiting
antibiotics ampicillin-sulbactam (A/S) and amoxicillin-clavulanic acid
(A/C) for 100 consecutive isolates of Acinetobacter
baumannii obtained from various clinical samples were studied.
The A/C MIC for 86% of the strains was more than 16/8 µg/ml, whereas
there was an A/S MIC of more than 16/8 µg/ml for only 38% of the
strains. This showed that A/S has significantly superior in vitro
activity compared to A/C against A. baumannii, although,
theoretically, both should have similar activities. The therapeutic
superiority of A/S over A/C needs to be studied, or else the
breakpoints for these agents in in vitro tests need to be redefined.
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Abstract
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-lactams
and aminoglycosides. Most of the resistance to
-lactams is due to
production of
-lactamase enzyme (2). The newer
-lactamase-inhibiting antibiotics, such as ampicillin-sulbactam
(A/S) and amoxicillin-clavulanic acid (A/C), are increasingly being
used in the treatment of
-lactamase-producing strains involved in
various infections in hospital patients. Theoretically they are
considered to have almost identical spectra of activity (4).
However, we noticed a lack of concordance of the antibiotic sensitivity
results between A/S and A/C when tested against multidrug-resistant A. baumannii strains. We observed that 276 isolates of
A. baumannii obtained from various samples in the Clinical
Bacteriology Laboratory of the All India Institute of Medical Sciences,
New Delhi, India, from January 1997 to August 1997 when tested against
A/C and A/S by the disc diffusion test showed a discordance in
susceptibility patterns. Sixteen percent of the isolates were
susceptible to both combinations, and 13% were resistant to both.
However, 71% of the isolates which were resistant to A/C were
susceptible to A/S.
TABLE 1.
Susceptibility of A. baumannii to A/S and A/C
based on MIC ranges by agar dilution
We observed that the A/C MIC for 86% of the strains was >16/8 µg/ml
(breakpoint, 16/8 µg/ml), whereas there was an A/S MIC of 16/8
µg/ml (breakpoint, 16/8 µg/ml) for only 38% of the strains. Ampicillin also showed an advantage over amoxicillin in in vitro tests.
A total of 93% of the strains were resistant to amoxicillin and 79%
were resistant to ampicillin (MIC of > 32 µg/ml). This showed
that A/S has a significantly superior activity against A. baumannii in in vitro tests compared to A/C (P < 0.001). It has been reported that sulbactam is superior to and is a
broader-spectrum
-lactamase inhibitor than clavulanic acid
(1). It is still debatable if this in vitro activity of
sulbactam is significant. Perhaps the difference between the
combination of ampicillin in A/S and amoxicillin in A/C gives A/S
some advantage over A/C. Recently O'Shaughnessy et al.
(5) have also reported a discordance between the results of
in vitro tests of sensitivity to A/S and A/C in Escherichia
coli strains, in which they found A/C has a better in vitro
activity than A/S.
In light of this finding, it is essential that a prospective study to determine the therapeutic superiority of A/S over A/C be done, or if in fact A/S and A/C are of equivalent clinical efficacies, then the in vitro susceptibility testing breakpoints for these agents need to be redefined.
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FOOTNOTES |
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* Corresponding author. Mailing address: Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India 110029. Phone: 91-011-619-5105. Fax: 91-011-686-2663. E-mail: akapil{at}medinst.ernet.in.
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REFERENCES |
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Chambers, H. F., and H. C. Neu.
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Other -lactam antibiotics, p. 264-272.
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Ling, J. M.,
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Susceptibilities to 23 antimicrobial agents and -lactamase production of blood culture isolates of Acinetobacter species in Hong Kong.
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| 3. | Marques, M. B., E. S. Brookings, S. A. Moser, P. B. Sonke, and K. B. Waites. 1997. Comparative in vitro antimicrobial susceptibilities of nosocomial isolates of Acinetobacter baumannii and synergistic activities of nine antimicrobial combinations. Antimicrob. Agents Chemother. 41:881-885[Abstract]. |
| 4. | National Committee for Clinical Laboratory Standards. 1993. Performance standards for antimicrobial susceptibility testing. M100-S6. National Committee for Clinical Laboratory Standards, Wayne, Pa. |
| 5. | O'Shaughnessy, E. M., G. A. Fahle, and F. G. Witebsky. 1997. Correlation of in vitro susceptibility results for amoxicillin-clavulanate and ampicillin-sulbactam tested against Escherichia coli. J. Clin. Microbiol. 35:1902-1903[Abstract]. |
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