title: Global Assessment of the Activity of Tigecycline against Multidrug-Resistant Gram-Negative Pathogens between 2004 and 2014 as Part of the Tigecycline Evaluation and Surveillance Trial.
abstract: Multidrug-resistant (MDR) Gram-negative organisms are a burden on the global health care system. The Tigecycline Evaluation and Surveillance Trial (TEST) is an ongoing global study designed to monitor thein vitroactivities of tigecycline and a panel of marketed antimicrobials against a range of clinically significant pathogens. In this study,in vitrodata are presented for MDRAcinetobacter baumannii,Pseudomonas aeruginosa,Escherichia coli,Klebsiella pneumoniae,Klebsiella oxytoca,Enterobacter aerogenes, andEnterobacter cloacaeisolates collected from 2004 to 2014. In total, 13% (21,967/170,759) of isolates displayed multidrug resistance globally, with the highest rates recorded amongA. baumannii(overall rate, 44% [8,294/18,741], increasing from 23% [309/1,323] in 2004 to 63% [447/712] in 2014). Other multidrug resistance rates ranged from 2.5% forK. oxytoca(203/8,000) to 12% forP. aeruginosaandK. pneumoniae(3,951/32,786 and 3,895/32,888, respectively), and rates among these pathogens remained stable during the study period. Against MDRE. coli,Klebsiellaspp., andE. aerogenes, the lowest rates of resistance were to tigecycline (0.2%, 6%, and 12%, respectively), and the lowest MIC90value againstA. baumanniiwas observed for tigecycline (2 mg/liter; MIC range, ≤0.008 to ≥32 mg/liter). The only significant change in resistance to tigecycline during the study period was for MDRE. coli(P< 0.01), among which eight resistant isolates were identified globally from 2009 to 2013. In summary, these results show that tigecycline retainedin vitroactivity against the majority of MDR Gram-negative organisms presented here, but the rising rates of MDRA. baumanniihighlight the need for the continued monitoring of global multidrug resistance.IMPORTANCEMultidrug resistance among bacterial pathogens is an ongoing global problem and renders antimicrobial agents ineffective at treating bacterial infections. In the health care setting, infections caused by multidrug-resistant (MDR) Gram-negative bacteria can cause increased mortality, longer hospital stays, and higher treatments costs. The aim of the Tigecycline Evaluation and Surveillance Trial (TEST) is to assess thein vitroantimicrobial activities of tigecycline and other contemporary agents against clinically relevant pathogens. This paper presents antimicrobial activity data from the TEST study between 2004 and 2014 and examines global rates of MDR Gram-negative isolates, includingAcinetobacter baumannii,Pseudomonas aeruginosa, and members of theEnterobacteriaceae, during this time. Our results show that tigecycline retainedin vitroactivity against many MDR Gram-negative pathogens over the study period, while rates of MDRA. baumanniiincreased globally. Using these findings, we hope to highlight the current status of multidrug resistance in medical facilities worldwide.
authors.affiliation: Department of Sciences for Health Promotion and Mother and Child Care "G. D'Alessandro," University of Palermo, Palermo, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Giammanco
authors.affiliation: Department of Sciences for Health Promotion and Mother and Child Care "G. D'Alessandro," University of Palermo, Palermo, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Calà
authors.affiliation: Department of Sciences for Health Promotion and Mother and Child Care "G. D'Alessandro," University of Palermo, Palermo, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Fasciana
authors.affiliation: Pfizer Inc., Collegeville, Pennsylvania, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Dowzicky
keywords: Gram-negative bacteria; multidrug resistance; surveillance studies; tigecycline