In vitro activity of tigecycline against multidrug-resistant Gram-negative blood culture isolates from critically ill patients

Sir, With increasing resistance to currently available antibiotics and decreasing numbers of newer antimicrobial agents, tigecycline represents a new therapeutic alternative. Tigecycline (a 9-t-butylglycylamide derivative of minocycline) is a glycylcycline antimicrobial agent having potent in vitro activity against most of the multidrug-resistant (MDR) Gram-positive and Gram-negative bacteria, except for Pseudomonas aeruginosa and Proteae.1,2 Moreover, tigecycline is not affected by the mechanisms of resistance to tetracycline (efflux and ribosomal protection).3 As in other tertiary care hospitals in India, drug resistance in bacteria has been an obstacle to treatment in intensive care units. Carbapenems have been the last resort in treating MDR Gram-negative infections. An increase in carbapenem resistance in Gram-negative organisms has also been noted recently.3 This study was conducted to evaluate the in vitro activity of tigecycline against extended-spectrum β-lactamase (ESBL)-producing and/or MDR Gram-negative bacteria isolated from the blood of critically ill patients. From May 2010 to February 2011, blood culture was performed using the automated BacT/Alert blood culture system (bioMérieux, Marcy l'Étoile, France) from 827 critically ill patients admitted to the intensive care unit of St John's Medical College and Hospital, Bangalore, India. Only one isolate per patient was included. Non-repetitive Gram-negative bacilli (n = 69; 8.34%) were isolated from 827 patients. The isolates were identified as Escherichia coli (n = 20), Klebsiella pneumoniae (n = 9), Enterobacter cloacae (n = 2), Proteus mirabilis (n = 2), Serratia marcescens (n = 1), Citrobacter koseri (n = 1), Acinetobacter baumannii (n = 18), Acinetobacter lwoffii (n = 1), Pseudomonas aeruginosa (n = 11), Pseudomonas putida (n = 1), Achromobacter xylosoxidans (n = 2) and Chromobacterium indologenes (n = 1), using routine phenotypic microbiological methods and an automated identification system (VITEK 2, bioMérieux). MICs of antibiotics were determined using an automated system (VITEK 2), following the manufacturer's guidelines. For analysis of in vitro activity of tigecycline, ESBL-producing strains of Enterobacteriaceae [85% of the E. coli (n = 17) and 77.8% of the K. pneumoniae (n = 7)] and MDR (resistant to at least three classes of commonly used antimicrobials) strains of non-fermenting Gram-negative bacteria [84.2% of the Acinetobacter spp. (n = 16) and 100% of the Pseudomonas spp. (n = 12)] were included. ESBL production for Enterobacteriaceae was determined by the VITEK 2 ESBL confirmation test (AST-GN25 card; bioMérieux) and/or double disc synergy test using cefotaxime and cefotaxime/clavulanic acid discs. For tigecycline a susceptibility breakpoint of ≤2 mg/L was applied for all the Gram-negative isolates, according to CLSI guidelines. The study was approved by the institutional ethics review board of St John's Medical College and Hospital, Bangalore, India. Tigecycline showed good potency, inhibiting 100% of the ESBL-producing E. coli, 85.7% of the ESBL-producing K. pneumoniae and 93.7% of the MDR A. baumannii at a concentration of ≤2 mg/L (Table 1). A tigecycline MIC90 of 2 mg/L was noted for A. baumannii, a result similar to those of other studies.4,5 As expected, 100% of the P. aeruginosa (MIC50 and MIC90 of 16 mg/L) and Proteus mirabilis showed resistance to tigecycline, irrespective of being MDR or not. However, a single strain of MDR P. putida isolated was susceptible to tigecycline (MIC 2 mg/L). It should be noted that the MIC90 for K. pneumoniae was higher compared with the other Enterobacteriaceae tested, as also observed by Souli et al.6 Carbapenem resistance was observed in 28.6% of ESBL-producing K. pneumoniae, 100% of MDR Acinetobacter spp. and 66.7% of MDR Pseudomonas spp. The results of our study support the previous studies showing good in vitro activity of tigecycline against MDR organisms,1,5,6 with a few exceptions.3 MIC (mg/L) distribution for tigecycline and meropenem against multidrug-resistant Gram-negative bacteria isolated from blood MIC (mg/L) distribution for tigecycline and meropenem against multidrug-resistant Gram-negative bacteria isolated from blood Good in vitro potency of tigecycline was observed against ESBL-producing E. coli, K. pneumoniae and MDR Acinetobacter spp. Tigecycline can play a key role in tackling MDR organisms in the critical care units of tertiary care hospitals. This work was supported by ‘Council of Scientific and Industrial Research’ (CSIR), India. None to declare. We thank the staff of the intensive care unit for their help and support.