Tigecycline disk diffusion breakpoints of Acinetobacter spp.: a clinical point of view.

In the January 2007 issue of the Journal of Clinical Microbiology, Jones et al. reported a multicenter study of the tigecycline disk diffusion breakpoints of Acinetobacter spp., including multidrug-resistant (MDR) strains. The authors concluded that a breakpoint zone diameter of 16/ 12 mm to define susceptibility/resistance, respectively, instead of those proposed by the U.S. Food and Drug Administration (FDA) for Enterobacteriaceae family organisms ( 19/ 14 mm, respectively), reduces the intermethod minor errors to an acceptable level (only 9.7% instead of 23.3%, with the FDA breakpoints proposed) (1). We believe that this microbiological conclusion has major clinical relevance. 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 the drug’s launch, 61% of the tigecycline prescriptions were “off label,” especially for patients with ventilator-associated pneumonia (VAP) due to MDR Acinetobacter sp. infection (D. Curcio, unpublished data). The high concentration of tigecycline in alveolar cells (77.5-fold higher than that in serum) (4), the increase of carbapenemresistant Acinetobacter spp. in Argentina (54%) (5), the lack of medical evidence for the use of colistin in pulmonary infections (2), and the association between inappropriate initial antibiotic therapy and mortality in patients with VAP (defined as the susceptibility of cultured organisms to the antibiotics used) (3) seem to be the main reasons for using tigecycline in this indication. We analyzed data from the Tigecycline Resistance Surveillance Program (Fulfillment) and found that a low proportion of infections due to Acinetobacter spp. were associated with the appropriate initial antibiotic empirical treatments compared with the proportion of infections due to microorganisms other than Acinetobacter spp. (27 versus 65%, respectively; P 0.00001). Besides, using FDA-proposed breakpoints, the Acinetobacter species resistance rate to tigecycline was 26%. The same resistance rate using a 16-mm breakpoint was 3%. In Argentina, over 90% of the clinical microbiology laboratories perform the antibiotic susceptibility test only through the disk diffusion method (unpublished data). That is why this is the only tool physicians have to prescribe antibiotics with microbiological documentation. Regarding this point, Argentinean attending physicians are still expecting the definitive tigecycline breakpoints of Acinetobacter spp. and also the results of the phase 3 clinical trial about the clinical efficacy of tigecycline in nosocomial pneumonia (http://www.clinicaltrial.gov).