In vitro activities of ampicillin, sulbactam and a combination of ampicillin and sulbactam against isolates of Acinetobacter calcoaceticusAcinetobacter baumannii complex isolated in Chile between 1990 and 1998

Helia Belloa,*, Mariana Domíngueza, Gerardo Gonzáleza, Raúl Zemelmana,b, Sergio Mellaa,c, Hilary-Kay Youngd and Sebastian G. B. Amyese

a Departamento de Microbiologia, Facultad de Ciencias Biológicas, Universidad de Concepción; b Facultad de Medicina, Universidad San Sebastián, c Departamento de Medicina Interna, Facultad de Medicina, Universidad de Concepción, Concepción, Chile; d Department of Biological Sciences, University of Dundee, Dundee DD1 4HN; e Department of Medical Microbiology, School of Medicine, University of Edinburgh, Edinburgh EH8 9AG, UK

Sir,

Isolates belonging to the Acinetobacter calcoaceticus Acinetobacter baumannii (Acb) complex are being isolated increasingly from hospitalized patients with serious infections.1 These organisms tend to exhibit resistance to multiple antibiotics, including ß-lactams, aminoglycosides and quinolones.2 However, a considerable percentage of isolates remain susceptible to the combination of ampicillin and sulbactam.3 Recently, Corbella et al.4 evaluated the efficacy of sulbactam alone as treatment for patients with non-life-threatening infections caused by isolates of A. baumannii and concluded that this compound accounted for the in vitro activity of the combination. They also warned that extensive use of sulbactam in this setting would lead to an increase in the incidence of resistance to it. The aim of the present study was to determine the susceptibilities of 280 isolates belonging to the Acb complex obtained from patients in Chilean hospitals during four time periods between 1990 and 1998.

The organisms studied were 280 non-replicate clinical isolates recovered from patients in hospitals in Chile during the periods 1990–1992 (group A; n = 75), 1993–1994 (group B; n = 59), 1995–1996 (group C; n = 72) and 1997–1998 (group D; n = 74). The isolates were identified as described previously5 and maintained in glycerol trypticase broth at –70°C. MICs were determined by an agar dilution method recommended by the NCCLS;6 the ratio of ampicillin and sulbactam in the formulation was 2:1.

The susceptibilities of the 280 isolates are summarized in the TableGo. Ampicillin exhibited either negligible or no activity against the isolates, with percentages of resistant isolates during the four time periods ranging from 95.6 to 100%. Although the activity of sulbactam was greater than that of ampicillin, it declined during the study periods, the MIC90s increasing four-fold from 16 to 64 mg/L and the percentage of resistant isolates increasing from 30.8 to 54.7%. The activity of the ampicillin/sulbactam combination was greater than that of sulbactam alone, at least during the earlier time periods. Indeed, all of the isolates isolated during 1990–1992 were susceptible to the formulation. However, both the MIC90s and percentage of resistant isolates increased thereafter, to the extent that the figures for 1997–1998 were comparable to those for sulbactam alone during the same time period. For isolates belonging to groups A, B and C, the percentages of isolates resistant to the combination were lower than the corresponding percentages of isolates resistant to either of the constituents. The implication of this finding is that ampicillin and sulbactam were acting synergically. In contrast, analysis of the MICs of ampicillin alone, sulbactam alone and the ampicillin/sulbactam formulation for individual isolates revealed that, in approximately one-third of cases, inhibition was attributable to the intrinsic activity of sulbactam (data not shown), an observation that has also been made by Corbella et al.4


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Table. In vitro activities of ampicillin, sulbactam and the ampicillin/sulbactam combination against 280 Acb clinical isolates
 
The results of this study are in accord with earlier concerns that excessive use of the ampicllin/sulbactam combination to treat patients with infections caused by isolates belonging to the Acb complex will be associated with further increases in the incidence of resistance to the formulation among these organisms and suggest the need to monitor in vitro susceptibilities to this antibiotic combination.

Acknowledgments

This work was supported by Grant 1970848 from the Fondo Nacional de Investigación Cientifica y Tecnológica (FONDECYT), Chile.

Notes

J Antimicrobial Chemother 2000; 45: 709–710

* Corresponding author. Tel: +56-41-203237; Fax: +56-41-24975; E-mail: hbello{at}udec.cl Back

References

1 . Bergogne Bèrèzin, E. & Towner, K. J. (1996). Acinetobacter spp. as nosocomial pathogens: microbiological, clinical, and epidemiological features. Clinical Microbiology Reviews 9, 148–65.[Free Full Text]

2 . Bello, H., González, G., Domínguez, M., Zemelman, R., García, A. & Mella, S. (1997). Activity of selected ß-lactams, ciprofloxacin, and amikacin against different Acinetobacter baumannii biotypes from Chilean hospitals. Diagnostic Microbiology and Infectious Disease 28, 183–6.[ISI][Medline]

3 . Aubert, G., Guichard, D. & Vedel, G. (1996). In-vitro activity of cephalosporins alone and combined with sulbactam against various strains of Acinetobacter baumannii with different antibiotic resistance profiles. Journal of Antimicrobial Chemotherapy 37, 155–60.[Abstract]

4 . Corbella, X., Ariza, J., Ardanuy, C., Vuelta, M., Tubau, F., Sora, M. et al. (1998). Efficacy of sulbactam alone and in combination with ampicillin in nosocomial infections caused by multiresistant Acinetobacter baumannii. Journal of Antimicrobial Chemotherapy 42, 793–802.[Abstract]

5 . Gerner-Smidt, P., Tjernberg, I. & Ursing, J. (1991). Reliability of phenotypic tests for identification of Acinetobacter species. Journal of Clinical Microbiology 29, 277–82.[ISI][Medline]

6 . National Committee for Clinical Laboratory Standards. (1997). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically—Fourth Edition: Approved Standard M7-A4. NCCLS, Wayne, PA.