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Doripenem European surveillance: antimicrobial activity against 6480 contemporary pathogens (2004)

Abstract number: p1623

Fritsche  T., Sader  H., Jones  R.

Objective: 

To characterize the spectrum of activity and potency of DOR (formerly S-4661) and comparator agents against contemporary wild-type bacterial isolates from medical centres in Europe and the Middle East in 2004. DOR is a novel parenteral 1-B-methyl carbapenem in late stage clinical development whose molecular structure confers stability to B-lactamases and resistance (R) to renal dehydropeptidases.

Methods: 

The collection included 6480 non-duplicate, consecutive clinical isolates from patients in 24 medical centres in Europe (21), Turkey (2) and Israel (1) that were submitted to the DOR surveillance program (2004) for identification confirmation and susceptibility (S) testing. MIC values for >30 antimicrobials were determined using NCCLS broth microdilution methods (2003). A tentative DOR susceptible (S) breakpoint of <=4 mg/L (<=0.25 mg/L for S. pneumoniae) was used for comparative purposes; CLSI (2005) criteria were used for other tested agents.

Results: 

Antimicrobial activities of DOR and other carbapenems vs. selected isolates. DOR consistently displayed activity against staphylococci and streptococci (MIC90, 0.06 and 0.5 mg/L) most similar to that of imipenem, and against E. coli and Klebsiella spp. (MIC90, 0.06 and 0.5 mg/L, respectively, including 8.7 and 26.9% of strains that met ESBL screening criteria), most similar to that of meropenem. Enterobacter spp. isolates, including 35.8% that were ceftazidime-R (indicative of AmpC production), were also highly S to DOR and other carbapenems (0.5 to 1.4% R). DOR also provided slightly enhanced coverage against P. aeruginosa (82.7% S) and Acinetobacter spp. (54.4% S) compared to other carbapenems. Carbapenem R among these latter strains is, however, a particularly worrisome development.

Conclusions: 

DOR is a new carbapenem with a competitive profile that incorporates both potent Gram-negative and Gram-positive activity, with enhanced activity against the commonly occurring non-fermentative Gram-negative bacilli. Carbapenems are assuming a greater therapeutic role in many nations as multi-drug resistance (including emergence of Ambler class A, C and D B-lactamases) spreads, necessitating their accelerated development.

Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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