Longitudinal Analysis of Tigecycline Activity against US isolates of Enterobacteriaceae and Acinetobacter spp. Based on Patient Location and Specimen Source

Abstract

Background: In 2005, tigecycline (TIG) a novel glycylcycline was approved in the US for treatment of complicated skin and skin structure infections (cSSSI) and complicated intra-abdominal infections (cIAI). As such, it is important to continue to monitor TIG activity against target pathogens for these indications. This study reports the in vitro activity of TIG against Enterobacteriaceae (EN) and Acinetobacter spp. (AC) as observed during development (‘01–‘04), and during the years following its approval for use (‘05, ‘06 and ‘07). The results were further stratified to determine whether any potential variability in TIG activity against EN and AC exists according to patient location (PL) and specimen source (SS). Methods: EN and AC isolates were collected from multiple locations across all nine US Bureau of Census regions during the following years (Y): ‘01–‘04 (EN: 1330, AC: 224), ‘05 (EN: 1151, AC: 77), ‘06 (EN: 958, AC: 255), and ‘07 (EN: 599, AC: 114). Isolates were centrally tested using broth microdilution according to current CLSI standards. TIG activity was analyzed by patient location (PL; outpatient [OP], intensive-care unit [ICU], and inpatient non-ICU [IP]) and by specimen source (SS; blood [BL], respiratory [RP], urine [UR: EN only], and skin and skin structure [SST]). EN FDA breakpoints (BPs) were used to interpret all TIG MIC results (as BPs for TIG against AC do not currently exist). Results: Against EN overall, TIG had an MIC90 of 1 mg/L in each study period (‘01–‘04, ‘05, ‘06, and ‘07), and EN isolates were ≥99% susceptible (S) to TIG throughout. The activity of TIG for each study period was consistent by MIC90, regardless of PL (MIC90 = 1 mg/L against OP, ICU, and IP) or SS (MIC90 = 1 mg/L against BL, RP, and SST, 0.5–1 mg/L for UR isolates). In the most recent period evaluated (‘07), EN isolates were ≥99% S to TIG for all PL and SS evaluated. Against AC overall, TIG had an MIC90 of 2 mg/L in ‘01–‘04 and ‘07 and 1 mg/L in ‘05 and ‘06. The % S of AC went from 97% in ‘01–‘04 to ≥99.5% in ‘05, ‘06 and ‘07. For each study period, little variation in TIG MIC90 was observed either by PL or SS (1–2 mg/L). In ‘07, 100% of tested acinetobacter were susceptible to TIG (EN BPs were utilized for AC). Conclusion: Little to no alteration in the in vitro activity of TIG against EN and AC was apparent by MIC90 over the years of study which span its introduction to use in 2005. The activity by MIC90 was also consistent in each study period, regardless of the PL and SS of the tested isolates. Continued surveillance is warranted both to support the further clinical development of TIG and to detect any emerging resistance among target pathogens for indications which TIG is currently approved (cSSSI and cIAI).