JAC Advance Access originally published online on January 9, 2007
Journal of Antimicrobial Chemotherapy 2007 59(3):583-585; doi:10.1093/jac/dkl496
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Correspondence |
In vitro activity of tigecycline against clinical isolates of Acinetobacter baumannii and Stenotrophomonas maltophilia
Servicio de Microbiología y Enfermedades Infecciosas, Hospital General Universitario ‘Gregorio Marañón’, Universidad Complutense, Madrid, Spain
* Corresponding author. Tel: +34-91-5868459; Fax: +34-91-5044906; E-mail: ecercenado{at}teleline.es
Keywords: A. baumannii , S. maltophilia , glycylcyclines
Acinetobacter baumannii and Stenotrophomonas maltophilia have emerged as increasingly important nosocomial pathogens. Treatment of infections caused by these organisms is difficult since both are intrinsically resistant to multiple antimicrobial agents, and can also acquire new mechanisms of resistance that may compromise the activity of all available antimicrobial agents.
Tigecycline is a glycylcycline that overcomes all known resistance mechanisms that affect tetracyclines (ribosomal protection and active drug efflux) and is active in vitro against many Gram-positive and Gram-negative microorganisms including multiresistant strains. However, there are few data to support the activity of tigecycline against A. baumannii and S. maltophilia, since only a few series have been published and these involved relatively limited numbers of isolates.1,2 In fact, the EUCAST database (www.eucast.org) only includes 190 clinical isolates of A. baumannii and 240 of S. maltophilia.
In this study we determined the in vitro activity of tigecycline against a large series of non-related clinical isolates of these pathogens including imipenem-resistant A. baumannii and trimethoprim/sulfamethoxazole-resistant S. maltophilia.
A total of 142 isolates of A. baumannii and 120 isolates of S. maltophilia collected from January 2003 to July 2006 at our microbiology laboratory were studied. The origins of the A. baumannii/S. maltophilia isolates were, respectively: respiratory tract (61/46), skin and soft tissue (34/17), blood (14/33), urine (14/7), catheter (6/5), other sterile fluids (3/5), and a miscellany of other samples (10/7). Isolates were identified by the MicroScan system (Dade Behring, Sacramento, USA) and susceptibility testing was performed by the broth microdilution method using the MicroScan Combo Gram negative 1S panels, following the manufacturer's instructions. Fifty-four per cent of the A. baumannii isolates were resistant to ß-lactams (including carbapenems and ampicillin/sulbactam), aminoglycosides, fluoroquinolones and trimethoprim/sulfamethoxazole, and were only susceptible to colistin. Four S. maltophilia isolates were resistant to trimethoprim/sulfamethoxazole.
MICs of tigecycline were determined by the Etest method (AB Biodisk, Solna, Sweden) in Mueller–Hinton agar. We also determined the susceptibility to tetracycline, doxycycline and minocycline by the disc diffusion method in Mueller–Hinton agar, following the CLSI criteria.3 Since EUCAST considers that to date there is insufficient evidence to establish tigecycline breakpoints for Acinetobacter, provisional MIC breakpoints used for tigecycline were 
2, 4 and 
8 mg/L for susceptible, intermediate and resistant strains, respectively, as published in previous studies.1 Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 were used as control strains.
Results of the activity of tigecycline are shown in Table 1. Tigecycline was shown to have good activity against both species. Tigecycline was more active against S. maltophilia (MIC90 1.5 mg/L) than against A. baumannii (MIC90 3 mg/L). This correlates with the greater activity of the tetracyclines against S. maltophilia isolates than against A. baumannii isolates: 42% versus 39% susceptible to tetracycline, 93% versus 50% susceptible to doxycycline and 100% versus 79% susceptible to minocycline, respectively. Eighty per cent of the multiresistant A. baumannii isolates were inhibited by 2 mg/L of tigecycline, and 63% were inhibited by 1 mg/L. Tigecycline was more active against isolates without any mechanism of resistance to tetracyclines (susceptible to tetracycline, doxycycline and minocycline), or against minocycline-susceptible isolates than it was against other strains tested (Table 1). In Escherichia coli it has been postulated that this may be caused by the presence in high concentrations of the Tet efflux transporter, the actions of chromosomally mediated multidrug transporter genes,4 or changes in the interdomain region of the efflux pump.5 The distribution of tigecycline MICs for our S. maltophilia isolates was similar to that described in the EUCAST database; however, our distribution of tigecycline MICs for A. baumannii was higher than that reported by EUCAST (www.eucast.org).
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The finding of increased tigecycline MIC values (8 mg/L) for two A. baumannii isolates in our study is a cause of concern. It has been described that mutations of tet(A) selected in vitro enable efflux of glycylcyclines5 and that the up-regulation of chromosomally-mediated efflux pumps can lead to the resistance of A. baumannii to tigecycline.6
Trimethoprim/sulfamethoxazole is considered the best option for the treatment of infections caused by S. maltophilia. In our study, four isolates of S. maltophilia were resistant to trimethoprim/sulfamethoxazole and tigecycline MICs for these strains were <1 mg/L (MICs of 0.094, 0.38, 0.5 and 0.75 mg/L). We cannot extrapolate our results to all trimethoprim/sulfamethoxazole-resistant S. maltophilia strains, since the number of isolates studied is very small, but the data are encouraging.
Treatment options for infections due to multidrug-resistant organisms are very limited, and tigecycline is likely to find a role in the treatment of severe infections caused by A. baumannii and S. maltophilia.
In conclusion, this study proves that tigecycline exhibits good in vitro activity against clinical isolates of A. baumannii and S. maltophilia, including imipenem-resistant A. baumannii isolates, and trimethoprim/sulfamethoxazole-resistant S. maltophilia, and it may be considered as a promising therapeutic option for the treatment of nosocomial infections due to these pathogens.
None of the authors of this paper has a conflict of interest with any pharmaceutical company or organization.
Acknowledgements
This study was presented in part at the ‘XII Congreso de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC)’, Spain, 2006 (abstract 645). This study was supported in part by ‘Red Española de Investigación en Patología Infecciosa’ (REIPI-ISCIII C03/14).
References
1
Pachon-Ibanez ME, Jimenez-Mejias ME, Pichardo C, et al. (2004) Activity of tigecycline (GAR-936) against Acinetobacter baumannii strains, including those resistant to imipenem. Antimicrob Agents Chemother 48:4479–81.
2
Henwood CJ, Gatward T, Warner M, et al. (2002) Antibiotic resistance among clinical isolates of Acinetobacter in the UK, and in vitro evaluation of tigecycline (GAR-936). J Antimicrob Chemother 49:479–87.
3 Clinical and Laboratory Standards Institute. (2006) Performance Standards for Antimicrobial Susceptibility Testing—16th Informational Supplement: Approved Standard M100-S16(NCCLS, Wayne, PA, USA).
4
Hirata T, Saito A, Nishino K, et al. (2004) Effects of efflux transporter genes on susceptibility of Escherichia coli to tigecycline (GAR-936). Antimicrob Agents Chemother 48:2179–84.
5 Tuckman M, Petersen PJ, Projan SJ. (2000) Mutations in the interdomain loop region of the tetA(A) tetracycline resistance gene increase efflux of minocycline and glycylcyclines. Microb Drug Resist 6:277–82.[Web of Science][Medline]
6
Livermore DM. (2005) Tigecycline: what is it, and where should it be used? J Antimicrob Chemother 56:611–14.
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