Abstract

Background: Tigecycline, the initial representative of the glycylcyclines, presents a therapy option for emerging multidrug-resistant (MDR) pathogens. India, a nation rarely monitored in global surveillance programs, appears in need of agents active against MDR isolates of Enterobacteriaceae (ESBLs), Acinetobacters (carbapenem-resistant) and Grampositive cocci (MRSA, VRE). Numerous sites were sampled using reference susceptibility methods. Methods: Eleven sites forwarded 1,714 strains to a regional monitor (WCH, Adelaide, Australia) that susceptibility tested 27 antimicrobials by CLSI methods (M7-A7, 2006). Identifications were confirmed and interpretive/screening criteria were also by CLSI guidelines (M100-S18, 2008), except for tigecycline where United States Food and Drug Administration breakpoints were applied. Major pathogens were: S. aureus (250), coagulase-negative staphylococci (CoNS; 228), enterococci (93), Enterobacter spp. (76), E. coli (217), K. pneumoniae (268), Salmonella spp. (55) and Acinetobacter spp. (108). Results: Tigecycline was active against 98-100% of indicated/ tabulated species, lowest for Acinetobacter spp. S. aureus tigecycline MIC90 values were not influenced by oxacillin susceptibility patterns (0.25 mg/L; 100% S). Increased resistance patterns noted were: tetracycline-resistant (4-100%; average 53%), AmpC, ESBLand fluoroquinolone resistance in Enterobacteriaceae (8-70, 14-78, 1-91%, respectively), VRE (1%), MRSA (36%) and Acinetobacters carbapenem-resistant (38%). S. typhi and S. paratyphi were common (tigecycline MIC90, 0.5 mg/L), and 84% were nalidixic acid-resistant. Carbapenem resistance in Enterobacteriaceae (1-7%) was consistent with harbouring metallo-s-lactamases; confirmed by PCR testing. Cum. % inhibited at MIC (mg/L): Organism (no. tested) ≤0.06 0.12 0.25 0.5 1 2 4 % S S. aureus (250) 9 58 98 100 100.0 Enterococci (93) 12 70 100 100.0 E. coli (217) 1 23 76 >99 100 100.0 Enterobacters (76) 0 1 16 79 93 100 100.0 K. pneumoniae (268) 0 0 24 74 96 99 >99 98.5 Salmonella spp. (55) 0 15 56 98 100 100.0 Acinetobacters (108) 2 21 40 75 95 98 >99 98.1 a. US-FDA and Jones et al. (2007) criteria. Conclusions: Although MDR rates across Gram-positive and -negative species (particularly among enteric bacilli and Acinetobacters) was high in India, tigecycline remained active (MIC90, 1 mg/L overall) against these MDR strains. Tigecycline exhibited promising spectrum/potency exceeding currently available agents against sampled isolates from India.

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