Background:

As resistances (R) among Gram-negative bacilli (GNBs) expand, few antimicrobial agents have been developed to address this clinical problem. Tigecycline (TIG), a novel glycylcycline, has an expanded spectrum of activity and potency, tigecycline covers many routine Gram-negative resistant strains and additionally possesses activity versus some uncommonly isolated non-fermentative GNBs. This study compares TIG with contemporary broad-spectrum agents using recent clinical isolates from Europe and other continents.

Methods:

All strains (2420) were centrally processed by reference, broth microdilution methods against more than 20 antimicrobials. All concurrent QC results were within NCCLS published ranges, with identifications performed by traditional methods and/or the Vitek System. Over 2400 isolates were tested from the Enterobacteriaceae (ENT) and non-fermentative GNBs categories. Susceptibility (S) for TIG was defined as <=4 mg/L, that breakpoint used for all tetracyclines by the NCCLS.

Results:

The ENT were divided into three groups for analysis: ESBL-producing isolates (154 strains), Proteae group (131 strains; includes P. mirabilis and indole-positive species) and all enteric bacilli. TIG was very active against all ESBL-producing isolates (MIC90, 0.25–2 mg/L; highest among TC-R subsets), and all ENT (MIC50/90, 0.25/1 mg/L). Proteae had a MIC90 at 4 mg/L and all but one of TIG-R or intermediate strains (MICs, 8 and 16 mg/L) were M. morganii or P. mirabilis. P. aeruginosa was marginally inhibited by TIG (MIC90, 32 mg/L). In contrast, Acinetobacter spp. (MIC90, 2 mg/L; 96.1% S) and S. maltophilia (MIC90, 2 mg/L; 100.0% S) were readily inhibited by TIG. Among all ENT studied, 31.0% were TC-R, but only one strain (P. mirabilis) was TIG-R (MIC at 16 mg/L).

Conclusions:

Remarkable potency and breadth of spectrum was observed for TIG against ENT (99.4% at <=4 mg/L vs. 66.8% for TC), S. maltophilia and Acinetobacter spp. Limited activity was noted versus P. aeruginosa (16.0% at <=4 mg/L) and some Proteae (MIC90, 4 mg/L). TIG should be of value for the treatment of infections caused by several commonly R GNB groups.