JAC Advance Access originally published online on June 7, 2007
Journal of Antimicrobial Chemotherapy 2007 60(2):449-450; doi:10.1093/jac/dkm202
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Correspondence |
Acinetobacter spp. susceptibility to tigecycline: a worldwide perspective
Sanatorio San José, Infectología Institucional SRL, Sanchez de Bustamante 1674(1425), Capital Federal, Argentina
* Corresponding author. Tel: +54-11-4567-4426; Fax: +54-11-4822-2748; E-mail: djcurcio{at}gmail.com or infectologia.institucional{at}gmail.net.ar
Keywords: Acinetobacter baumannii , glycylcyclines , resistance
In the April 2007 issue of the Journal of Antimicrobial Chemotherapy, Navon-Venezia et al.1 reported high resistance rates to tigecycline in multiple clones of multidrug-resistant (MDR) Acinetobacter baumannii (n = 82). The authors found that 66% (54/82) were resistant to tigecycline (MIC 
8 mg/L), 12% (10/82) were intermediate (MIC 4–6 mg/L) and 22% (18/82) were susceptible (MIC 
2 mg/L). They used Etest to determine MICs and all the values correlated 100% with inhibition zone diameters using the disc diffusion method with tigecycline discs.1
We agree with the authors that MDR in Acinetobacter spp. represents a global challenge to physicians; for this reason we will try to offer a wider point of view.
The Tigecycline Evaluation and Surveillance Trial (TEST) is a worldwide programme that includes, at the moment, 4247 isolates of Acinetobacter spp. of which only 2% have a tigecycline MIC 2 mg/L.2
Based on this data, we compare the results of Navon-Venezia et al.1 with those of TEST, using the global data and the Argentinean sub-set data. We selected from the TEST database the isolates of MDR A. baumannii with the same resistance profile as those analysed by Navon-Venezia et al.1 (i.e. A. baumannii resistant to aminoglycosides, cephalosporins and fluoroquinolones) (Table 1).
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In contrast with the 78% published by Navon-Venezia et al.,1 only 5.3% of the global isolates and 2% of the Argentinean sub-set isolates of MDR A. baumannii in TEST had tigecycline MICs
2 mg/L. We asked ourselves what would be the probability of encountering such a difference if all the isolates belong to the same population. We performed a proportion test to do so. The probability was very low (P << 0.0001). Regarding the MDR A. baumannii isolates as previously defined, and additionally resistant or intermediate to imipenem, the resistance ratio to tigecycline showed important differences (95%, 5.6% and 0% for Navon-Venezia et al.,1 TEST global2 and Argentinean sub-set,2 respectively).
Tigecycline has been approved for the treatment of complicated intra-abdominal infections and complicated skin and skin structure infections. However, in Argentina, in the first month after launch, 61% of the tigecycline prescriptions were 'off label', especially for patients with ventilator-associated pneumonia (VAP) due to MDR Acinetobacter spp. (D. Curcio, F. Fernández and F. Duret, unpublished data). The high concentration in alveolar cells (77.5-fold higher than serum),3 the increase in carbapenem-resistant Acinetobacter spp. in Argentina (54%),4 the lack of medical evidence to use colistin in pulmonary infections and the association between inappropriate initial antibiotic therapy with mortality in patients with VAP (defined as the susceptibility of cultured organisms to the antibiotics used)5 seem to be the main reasons for using tigecycline in this indication.
Concerning tigecycline and Acinetobacter spp. several points should be taken into account: (i) definitive breakpoints of susceptibility are not available; (ii) results for Phase 3 clinical trials regarding clinical efficacy of tigecycline in nosocomial pneumonia and other infections produced by MDR microorganisms are not available; and (iii) we know that the overexpression of the intrinsic multidrug efflux pump (AdeABC) may decrease the susceptibility to tigecycline in Acinetobacter spp.6
However, at least in Argentina, some physicians consider this new antibiotic as a possibility to treat microbiologically documented severe infections caused by MDR A. baumannii, in order to improve the patient outcome when the therapeutic options are limited (i.e. isolates only susceptible to colistin).
Moreover, from a clinical point of view, until data on tigecycline clinical efficacy in severe Acinetobacter spp. infections become available, before treating a patient, physicians must consider the pharmacological and microbiological profile of tigecycline for each specific patient condition and carefully assess local susceptibility data to support its use.
Finally, we agree with the authors, that the high MICs for A. baumannii found by them is a worrisome local phenomenon and requires further investigation.
D. C. is a speaker for Wyeth SA (Argentina) for Tygacil®. F. F. does not have any conflict of interest.
References
1 Navon-Venezia S, Leavitt A, Carmeli Y. High tigecycline resistance in multidrug-resistant. Acinetobacter baumannii. J Antimicrob Chemother (2007) 59:772–4.
2 Tigecycline Evaluation and Surveillance Trial (TEST). 19 April 2007, date last accessed. http://www.testsurveillance.com/home.php.
3
Pankey GA. Tigecycline. J Antimicrob Chemother (2005) 56:470–80.
4
Pasterán F, Rapoport M, Petroni A, et al. Emergence of PER-2 and VEB-1a in Acinetobacter baumannii strains in the Americas. Antimicrob Agents Chemother (2006) 50:3222–4.
5
Luna CM, Aruj P, Niederman MS, et al. Appropriateness and delay to initiate therapy in ventilator-associated pneumonia. Eur Respir J (2006) 27:158–64.
6
Ruzin A, Keeney D, Bradford PA. AdeABC multidrug efflux pump is associated with decreased susceptibility to tigecycline in Acinetobacter calcoaceticus-Acinetobacter baumannii complex. J Antimicrob Chemother (2007) 59:1001–4.
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