Antimicrobial resistance among Gram-negative organisms continues to be a major concern, especially considering the potential for the rapid spread of resistance mechanisms and the limited treatment options that result. In this study, we examined the activity of β-lactam, aminoglycoside, and fluoroquinolone antimicrobials against Enterobacteriaceae and A. baumannii isolates collected from nine regions within the USA. We also examined the susceptibility of each isolate to tigecycline, a glycylcycline licensed to treat infections caused by a broad spectrum of microorganisms, many of which have acquired resistance to treatment with traditional antimicrobials. In addition, Halstead et al.  published a comprehensive report of antimicrobial susceptibilities of Gram-negative isolates collected from the USA during 2004 and 2005  and we extend the study by determining the antimicrobial susceptibilities of a more diverse group of isolates that highlights ongoing nationwide changes in resistance patterns. It should be noted, however, that we failed to test each appropriate Gram-negative isolate for susceptibility to imepenem and meropenem, which forced us to incorporate our findings into the broader category of carbapenem resistance. However, we are confident this shortcoming did not prevent valid comparison of our results with previous findings.
Several other recent studies also determined the susceptibilities of Gram-negative organisms to multiple antimicrobial agents [2, 12, 13], with results similar to this study. For example, we detected similarly high prevalence of sensitivity of K. oxytoca and non-ESBL producing E. coli to levofloxacin, piperacillin-tazobactam, and ceftriaxone. In addition, Enterobacter spp., K. oxytoca, and S. marcescens were highly susceptible to the carbapenems, while the non-ESBL-producing E. coli and K. pneumoniae isolates were almost universally susceptible to the carbapenems. However, small numbers of carbapenem-resistant organisms were recovered from each genus, which also supports previous findings that highlight the necessity for continued monitoring for carbapenem resistance. In addition, A. baumannii isolates that were highly resistant to multiple other antimicrobial agents were also highly resistant to the carbapenems (imipenem/meropenem), a result which has been previously reported . This is especially disconcerting since the only option for effective treatment of these highly resistant organisms, especially MDR A. baumannii infections, may be dependent on salvage agents such as colistin which introduce a host of additional complications [14, 15].
Comparing the susceptibility patterns to previous findings  also revealed several important trends. Most notably, the prevalence of resistant organisms remained essentially unchanged in the East South Central, Middle Atlantic, and Pacific regions; the prevalence of organisms that were resistant to levofloxacin also decreased significantly (p < 0.01). Significant (p < 0.01) increases in susceptibility were identified in 8 region/organism/antimicrobial agent combinations between 2004–2005 and 2005–2011, 4 of these occurring in the Middle Atlantic region. Significant decreases in susceptibility were noted in 26 cases over the same time interval; 12 of these occurred in East North Central while 8 were noted in South Atlantic. Notably, in South Atlantic, K. pneumoniae susceptibility to levofloxacin, amikacin, amoxicillin-clavulanate, cefepime, minocycline and piperacillin-tazobactam decreased significantly. In East North Central, A. baumannii susceptibility to amikacin, ceftriaxone, levofloxacin, minocycline and piperacillin-tazobactam reduced significantly while E. coli susceptibility to amoxicillin-clavulanate, cefepime, levofloxacin and minocycline decreased significantly. These findings highlight the importance of local efforts to monitor changing antimicrobial susceptibility patterns for accurately guiding appropriate treatment regimens. In addition, evaluating the infection control practices in regions where the prevalence of antibiotic resistant organisms has not increased significantly may provide important insight into effective methods for curbing emerging resistance in other regions.
Finally, despite the lack of established efficacy standards for predicting the success of treatment with tigecycline, our findings confirmed and extended previous observations of high in vitro activity against Enterobacteriaceae (E. coli, 100% susceptible; Enterobacter, 98.4% susceptible; ESBL-positive K. pneumoniae, 97.9%) and also A. baumannii (94.4% susceptible at ≤ 2 mg/L) . Therefore, additional studies to determine the efficacy of tigecycline in vivo, especially for treating infections with MDR organisms, are warranted.