Abstract
The in vitro activity of doripenem was evaluated against a recent collection of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and Pseudomonas aeruginosa isolates (201 ESBL-producing Enterobacteriaceae [153 Escherichia coli and 48 Klebsiella pneumoniae] and 201 P. aeruginosa). Comparator agents included amikacin, tobramycin, ciprofloxacin, cefepime, cefotaxime, ceftazidime piperacillin-tazobactam, imipenem, and meropenem. Both doripenem and meropenem inhibited 100% of the ESBL-producing Enterobacteriaceae at ≤0.5 µg/mL. For these isolates, the MIC90 of doripenem (0.12 µg/mL) was 4-fold lower than that of imipenem (0.5 µg/mL). Against P. aeruginosa, the MIC90 of doripenem and meropenem was 2 µg/mL, 4-fold lower than that of imipenem (8 µg/mL). At an MIC of ≤2 µg/mL, doripenem, meropenem, and imipenem inhibited 90.5%, 89.6%, and 82.1% of P. aeruginosa isolates, respectively. Doripenem maintained activity against imipenem-nonsusceptible isolates of P. aeruginosa; at an MIC of ≤4 µg/mL, it inhibited 15 of the 25 isolates with MICs for imipenem of >4 µg/mL. Doripenem is active against ESBL-producing Enterobacteriaceae and P. aeruginosa isolates. Its activity is similar to that of meropenem and slightly better than that of imipenem. The results of this study suggest that doripenem could be an alternative therapeutic agent for infections caused by these organisms.
References
Pitout JD, Nordmann P, Laupland KB, Poirel L (2005) Emergence of Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) in the community. J Antimicrob Chemother 56:52–59
Livermore DM (2002) Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: our worst nightmare? Clin Infect Dis 34:634–640
Quinn JP (1998) Clinical problems posed by multiresistant nonfermenting gram-negative pathogens. Clin Infect Dis 27(Suppl 1):S117–S124
Castanheira M, Jones RN, Livermore DM (2009) Antimicrobial activities of doripenem and other carbapenems against Pseudomonas aeruginosa, other nonfermentative bacilli, and Aeromonas spp. Diagn Microbiol Infect Dis 63:426–433
Ge Y, Wikler MA, Sahm DF, Blosser-Middleton RS, Karlowsky JA (2004) In vitro antimicrobial activity of doripenem, a new carbapenem. Antimicrob Agents Chemother 48:1384–1496
Mendes RE, Rhomberg PR, Bell JM, Turnidge JD, Sader HS (2009) Doripenem activity tested against a global collection of Enterobacteriaceae, including isolates resistant to other extended-spectrum agents. Diagn Microbiol Infect Dis 63:415–425
Pillar CM, Torres MK, Brown NP, Shah D, Sahm DF (2008) In vitro activity of doripenem, a carbapenem for the treatment of challenging infections caused by gram-negative bacteria, against recent clinical isolates from the United States. Antimicrob Agents Chemother 52:4388–4399
Wexler HM, Engel AE, Glass D, Li C (2005) In vitro activities of doripenem and comparator agents against 364 anaerobic clinical isolates. Antimicrob Agents Chemother 49:4413–4417
Clinical and Laboratory Standards Institute (CLSI) (2009) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard, 8th edition. M7-A8, vol. 29, no. 2. CLSI, Wayne, PA
Clinical and Laboratory Standards Institute (CLSI) (2009) Performance standards for antimicrobial susceptibility testing. 19th informational supplement. M100-S19, vol. 29, no. 3. CLSI, Wayne, PA
European Committee on Antimicrobial Susceptibility Testing (EUCAST) (2010) Breakpoint tables for interpretation of MICs and zone diameters. European Society for Clinical Microbiology and Infectious Diseases. Available online at: http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Disk_test_documents/EUCAST_breakpoints_v1.1.pdf. April 2010
Doribax product package insert (2009) Ortho-McNeil-Janssen Pharmaceuticals, Inc., Raritan, NJ. Available online at: http://www.doribax.com/doribax/shared/pi/doribax.pdf#zoom=100. Revised 11/2009
Horiuchi M, Kimura M, Tokumura M, Hasebe N, Arai T, Abe K (2006) Absence of convulsive liability of doripenem, a new carbapenem antibiotic, in comparison with beta-lactam antibiotics. Toxicology 222:114–124
Lucasti C, Jasovich A, Umeh O, Jiang J, Kaniga K, Friedland I (2008) Efficacy and tolerability of IV doripenem versus meropenem in adults with complicated intra-abdominal infection: a phase III, prospective, multicenter, randomized, double-blind, noninferiority study. Clin Ther 30:868–883
Mushtaq S, Ge Y, Livermore DM (2004) Doripenem versus Pseudomonas aeruginosa in vitro: activity against characterized isolates, mutants, and transconjugants and resistance selection potential. Antimicrob Agents Chemother 48:3086–3092
Sakyo S, Tomita H, Tanimoto K, Fujimoto S, Ike Y (2006) Potency of carbapenems for the prevention of carbapenem-resistant mutants of Pseudomonas aeruginosa: the high potency of a new carbapenem doripenem. J Antibiot (Tokyo) 59:220–228
Fujimura T, Anan N, Sugimori G, Watanabe T, Jinushi Y, Yoshida I, Yamano Y (2009) Susceptibility of Pseudomonas aeruginosa clinical isolates in Japan to doripenem and other antipseudomonal agents. Int J Antimicrob Agents 34:523–528
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Betriu, C., Gómez, M., López-Fabal, F. et al. Activity of doripenem against extended-spectrum β-lactamase-producing Enterobacteriaceae and Pseudomonas aeruginosa isolates. Eur J Clin Microbiol Infect Dis 29, 1179–1181 (2010). https://doi.org/10.1007/s10096-010-0974-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10096-010-0974-3