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Antimicrobial Agents and Chemotherapy, April 2009, p. 1567-1573, Vol. 53, No. 4
0066-4804/09/$08.00+0     doi:10.1128/AAC.01133-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Urinary Bactericidal Activity of Doripenem versus That of Levofloxacin in Patients with Complicated Urinary Tract Infections or Pyelonephritis{triangledown}

Florian M. E. Wagenlehner,1* Christine Wagenlehner,2 Rebecca Redman,3 Wolfgang Weidner,1 and Kurt G. Naber4

Clinic for Urology and Pediatric Urology, Justus-Liebig-University, Giessen, Germany,1 Evangelisches Krankenhaus, Giessen, Germany,2 Johnson & Johnson Pharmaceutical Research & Development, LLC, Raritan, New Jersey,3 Technical University Munich, Munich, Germany4

Received 23 August 2008/ Returned for modification 8 November 2008/ Accepted 19 January 2009

The aim of this study was to investigate the urinary bactericidal titers (UBTs) and 24-h area under the UBT-versus-time curve (AUBT) of intravenous doripenem (500 mg every 8 h [q8h]), a new carbapenem, versus those of intravenous levofloxacin (250 mg q24h) in patients with complicated urinary tract infections (cUTIs) or pyelonephritis. UBTs and AUBTs are pharmacokinetic/pharmacodynamic parameters able to reflect the activity of an antimicrobial substance in the urine. Doripenem and levofloxacin show comparable urinary excretion of approximately 80% and are therefore registered for the treatment of UTIs. In order to assess and compare the urinary antimicrobial activities of the two substances, UBTs were investigated for 24 patients (10 treated with doripenem and 14 with levofloxacin) for 31 uropathogens and one control strain. Eight strains were tested for all patients and 27 only in the urine of the corresponding patient. Median UBTs (AUBTs) of doripenem for the uropathogens tested ranged between 1.5 and 65,536 (224 and 909,312) and were significantly higher than median UBTs (AUBTs) of levofloxacin, ranging between 0 and 128 (0 and 2,208). Eight microbiological failures were observed, three after doripenem treatment and five after levofloxacin treatment. For levofloxacin, microbiological failures correlated well with low UBTs and AUBTs, whereas for doripenem there was no correlation. From this study, a calculated target attainment rate for levofloxacin predicting therapeutic success in patients with UTIs approximated mean UBTs of 100 over 24 h or AUBTs of 2,240. Doripenem demonstrated excellent urinary bactericidal activity with the dose administered and appears to be a good alternative in the empirical treatment of cUTI.

* Corresponding author. Mailing address: Clinic for Urology and Pediatric Urology, Justus-Liebig-University Giessen, Rudolf-Buchheim-Str. 7, D-35385 Giessen, Germany. Phone: 49-641-9944518. Fax: 49-641-9944509. E-mail: Wagenlehner{at}aol.com

{triangledown} Published ahead of print on 2 February 2009.

Antimicrobial Agents and Chemotherapy, April 2009, p. 1567-1573, Vol. 53, No. 4
0066-4804/09/$08.00+0     doi:10.1128/AAC.01133-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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