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.

Anna Giammanco,Michael J Dowzicky,Teresa Fasciana,Cinzia Calà,Patricia A Bradford

doi:10.1128/msphere.00310-16

Anna Giammanco, Michael J Dowzicky + Show 3 more

Open Access

https://doi.org/10.1128/msphere.00310-16

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Journal: mSphere	Publication Date: Jan 18, 2017
Citations: 111	License type: CC BY 4.0

Affiliation: University of Palermo, Pfizer (United States)

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 the in vitro activities of tigecycline and a panel of marketed antimicrobials against a range of clinically significant pathogens. In this study, in vitro data are presented for MDR Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, and Enterobacter cloacae isolates collected from 2004 to 2014. In total, 13% (21,967/170,759) of isolates displayed multidrug resistance globally, with the highest rates recorded among A.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% for K.oxytoca (203/8,000) to 12% for P.aeruginosa and K.pneumoniae (3,951/32,786 and 3,895/32,888, respectively), and rates among these pathogens remained stable during the study period. Against MDR E.coli, Klebsiella spp., and E.aerogenes, the lowest rates of resistance were to tigecycline (0.2%, 6%, and 12%, respectively), and the lowest MIC90 value against A.baumannii was observed for tigecycline (2mg/liter; MIC range, ≤0.008 to ≥32mg/liter). The only significant change in resistance to tigecycline during the study period was for MDR E.coli (P < 0.01), among which eight resistant isolates were identified globally from 2009 to 2013. In summary, these results show that tigecycline retained in vitro activity against the majority of MDR Gram-negative organisms presented here, but the rising rates of MDR A.baumannii highlight the need for the continued monitoring of global multidrug resistance. IMPORTANCE Multidrug 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 the in vitro antimicrobial 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, including Acinetobacter baumannii, Pseudomonas aeruginosa, and members of the Enterobacteriaceae, during this time. Our results show that tigecycline retained in vitro activity against many MDR Gram-negative pathogens over the study period, while rates of MDR A.baumannii increased globally. Using these findings, we hope to highlight the current status of multidrug resistance in medical facilities worldwide.

Highlights

Multidrug-resistant (MDR) Gram-negative organisms are a burden on the global health care system
Our results show that tigecycline retained in vitro activity against many MDR Gram-negative pathogens over the study period, while rates of MDR A. baumannii increased globally
Isolates collected during the earlier years of the study period have been included in previous Tigecycline Evaluation and Surveillance Trial (TEST) publications, including reports focused on MDR A. baumannii [10] and MDR Enterobacteriaceae [11] isolates that were collected in the United States between 2004 and 2006 and on MDR Gram-negative isolates collected globally between 2004 and 2013 [12]

Summary

Introduction

Multidrug-resistant (MDR) Gram-negative organisms are a burden on the global health care system. The only significant change in resistance to tigecycline during the study period was for MDR E. coli (P Ͻ 0.01), among which eight resistant isolates were identified globally from 2009 to 2013 These results show that tigecycline retained in vitro activity against the majority of MDR Gram-negative organisms presented here, but the rising rates of MDR A. baumannii highlight the need for the continued monitoring of global multidrug resistance. MDR Gram-negative pathogens, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and the Enterobacteriaceae, are associated with increased lengths of hospitalization, higher health care costs, and greater rates of mortality [2, 4,5,6] These organisms have been highlighted as clinically important bacteria, and some are included among the ESKAPE pathogens (an acronym for Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, A. baumanii, Pseudomonas aeruginosa, and Enterobacter spp.) [7]. Isolates collected during the earlier years of the study period have been included in previous TEST publications, including reports focused on MDR A. baumannii [10] and MDR Enterobacteriaceae [11] isolates that were collected in the United States between 2004 and 2006 and on MDR Gram-negative isolates collected globally between 2004 and 2013 [12]

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