Prevalence of Acinetobacter spp. isolates with reduced susceptibility to imipenem, as determined by a USA-wide electronicsurveillance network

J Antimicrob Chemother 1999; 43: 429– 431

Mark E. Jonesa,*, Clyde Thornsberryb, David M. Livermorec and Daniel F. Sahmb

a MRL Pharmaceutical Services, Den Brielstaat 11, 3554XD Utrecht, The Netherlands; b MRL Pharmaceutical Services, Herndon, VA, USA; c Antibiotic Reference Unit, Central Public Health Laboratory, Colindale, London,UK

Sir,

Resistance to multiple antibiotics amongst aerobic Gram-negative bacilli has led to increased useof the carbapenems. While acquired resistance to these agents is rare, several authors haverecently expressed concern about carbapenem resistance amongst Acinetobacter spp. 1 ,2 ,3 ,4 ,5 ,6 Reports of carbapenem-resistant isolates belonging to this genus have originated in SouthAmerica, 1 ,4 ,5 Europe 1 ,2 ,3 6 and the Far East and Middle East, 1 but little is known of their prevalence. The present study used routine laboratory data, collectedvia The Surveillance Network (TSN) Database–USA, to investigate the pattern ofisolation of Acinetobacter spp. with reduced susceptibility to carbapenems in the USA.

TSN Database–USA electronically collects all routine susceptibility data daily from,currently, 158 laboratory databases throughout the USA. These data are selected in such a waythat ensures that they are geographically, demographically and methodologically representativeand they are pooled and filtered through expert rules so that repeat isolates and isolates withunusual antibiograms that cannot be confirmed, are identified and excluded from analysis. Thedatabase currently comprises >13,565,000 results, collected between 1 January 1994 and 24 June 1998, for 976,927 strains from652,454 patients. All of this information is available for on-line analysis by participatinginstitutions via the TSN website (www.thetsn.com).

During the >4-year study period, imipenem susceptibility data for 10,578 isolates of Acinetobacter spp. were collected. They were identified as Acinetobacter calcoaceticus or Acinetobacter baumannii (9229 isolates), Acinetobacter lwoffii(938) and other Acinetobacter spp. (411); for the purpose of the present analysis, A. calcoaceticus and A. baumannii isolates are grouped together as the `ACB complex' because these species cannotbe reliably distinguished by routine laboratory tests. Susceptibility to meropenem was determinedfor only a few strains. All of the reporting laboratories used methods and interpretative criteriarecommended by the National Committee for Clinical Laboratory Standards, with resistance toimipenem being defined as a MIC of >8 mg/L or an inhibition zone diameter of <=13 mm with a 10 µg disc and intermediate susceptibility as a MIC of 8 mg/L or a zone diameter of >=13 mm but <=16 mm. 7

One hundred and forty-eight (1.4%) isolates were categorized as being of intermediatesusceptibility to imipenem and a further 292 (2.76%) as resistant. The percentages of ACBcomplex, A. lwoffii and Acinetobacter spp. strains that were resistant were similar, while most of the isolates that exhibitedintermediate susceptibility belonged to the ACB complex (Table). There was no significantdifference between strains that had been tested by the microbroth dilution and disc diffusionmethods in terms of rates of resistance, the implication being that resistance was not amethodological artefact.


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Table. Susceptibilities of Acinetobacterspp. isolates to imipenem as determined by the disc diffusion (DD) and microbroth dilution (MBD) methods
 
Following trends in the patterns of susceptibility to imipenem amongst ACB complexisolates for the last 3 years of the collection period revealed year-to-year increases in theincidences of strains exhibiting intermediate susceptibility, i.e. from 3.1% (79 of 2565 strains) to4.6% (174 of 3773) to 5.8% (113 of 1961) in 1996, 1997 and the first half of 1998 respectively;these differences did not reach statistical significance (0.1 > P > 0.05). Similar trends were observed when the susceptibility patterns of the resistant isolates wereconsidered. However, marked changes in the susceptibility patterns of A. lwoffii and Acinetobacter spp. isolates were not observed.

ACB complex strains isolated from the lower respiratory tract were more often ofintermediate susceptibility or resistant to imipenem than those from the upper respiratory tract,cerebrospinal fluid, skin and soft tissues or urinary tract, but these differences were notstatistically significant (P > 0.1). Similarly, there were no differences in terms of susceptibility to imipenem between ACBcomplex strains isolated from intensive care unit patients (five of 988 (0.5%) strains exhibitingintermediate susceptibility and 24 of 988 (2.5%) that were resistant) and those isolated frompatients on other wards (16 of 4247 (0.4%) strains exhibiting intermediate susceptibility and 78of 4247 (1.8%) that were resistant). On the other hand, the rates of reduced susceptibilityamongst ACB complex isolates recovered from patients in hospitals with >500 beds (113 of 5693 (2%) strains exhibiting intermediate susceptibility and 161 of 5693 (2.8%)that were resistant) were higher than those amongst isolates recovered from patients in smallerinstitutions (24 of 3296 (0.7%) strains exhibiting intermediate susceptibility and 55 of 3296(1.7%) that were resistant), although the differences only approached statistical significance (0.1 > P > 0.05).

MICs for 741 of the 9229 ACB complex isolates were determined with a full range oftwo-fold dilutions and values of 1, 2, 4, 8 and >8 mg/L were recorded in respect of 69 (9.3%), 25 (3.4%), seven (1%), five (0.7%) and 16 (2.1%)strains respectively, compared with MICs of 0.12– 0.5 mg/L for susceptible Acinetobacter spp. isolates. 1 Borderline MICs (i.e. those between 4 and 8 mg/L) are difficult to interpret, low-level ß-lactamase-mediated resistance in other species having been associated with clinical failures,although no such correlation has been observed with Acinetobacter spp. and carbapenems. Extrapolating the percentages of isolates with MICs of 2 and 4 mg/L,which closely approximate the MIC susceptibility breakpoint, to the entire population of ACBcomplex strains studied suggests that the number of isolates for which potentially misleadingin-vitro susceptibility test results are obtained is large.

We conclude that the incidence of reduced susceptibility to imipenem amongst ACBcomplex strains in the USA is increasing. This increase may reflect clonal spread or plasmiddissemination and resistance may or may not be attributable to carbapenemases. Molecularstudies will be necessary to resolve these issues, but the vast collection of phenotypic dataavailable through electronic surveillance programmes, such as TSN, can be used to rapidly assessthe prevalence of emerging resistance profiles of public health importance reported by researchand reference laboratories. Only with such systems can we monitor and respond to the problemof emerging drug resistance.

Notes

* Tel: +31-30-265-1794; Fax: +31-30-265-1784. (Email: mjones{at}thetsn.com) Back

References

1 . Afzal-Shah, M. & Livermore, D. M. (1998). Worldwide emergence of carbapenem-reistantAcinetobacter spp. Journal of Antimicrobial Chemotherapy 41, 576–7.[Free Full Text]

2 . Weinbren, M. J., Johnson, A. P., Kaufmann, M. E. & Livermore, D. M. (1998). Acinetobacter spp. isolates with reduced susceptibilities to carbapenems in a UK burns unit.Journal of Antimicrobial Chemotherapy 41, 574–6.[Free Full Text]

3 . Paton, R., Miles, R. S., Hood, J. & Amyes, S. G. B. (1993). ARI-1: ß -lactamase-mediated imipenem resistance in Acinetobacter baumannii. International Journal of Antimicrobial Agents 2, 81–8.

4 . Brown, S., Bantar, C., Young, H. K. & Amyes, S. G. B. (1997). Limitation of Acinetobacter baumannii treatment by plasmid- mediated carbapenemase ARI-2. Lancet 351, 186–7.[ISI]

5 . Brown, S., Bantar, C., Young, H. K. & Amyes, S. G. B. (1996). An outbreak of imipenemresistance in Acinetobacter strains from Buenos Aires, Argentina. In Program and Abstracts of the Thirty-Sixth Interscience Conference on Antimicrobial Agents andChemotherapy, New Orleans, LA, 1996. Abstract C123, p. 56. American Society for Microbiology, Washington,DC.

6 . Tankovic, J., Legrand, P., De Gatines, G., Chemineau, V., Brun-Buisson, C. & Duval, J.(1994). Characterization of a hospital outbreak of imipenem-resistant Acinetobacter baumannii by phenotypic and genotypic typing methods. Journal of Clinical Microbiology 32, 2677–81.[Abstract]

7 . National Committee for Clinical Laboratory Standards. (1998). Performance Standards for Antimicrobial Susceptibility Testing—Eighth InformationalSupplement: Approved Standard M100-S8. NCCLS, Wayne, PA.