COMPARATIVE ACTIVITY OF DORIPENEM, IMIPENEM AND MEROPENEM AGAINST GRAM NEGATIVE PATHOGENS: A PRELIMINARY STUDY (original) (raw)
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International Journal of Antimicrobial Agents, 2010
The Comparative Activity of Carbapenems Testing (COMPACT) Study was designed to determine the in vitro potency of doripenem compared with imipenem and meropenem against a large number of contemporary Gram-negative pathogens from more than 100 centres across Europe and the Asia-Pacific region and to assess the reliability of Etest methodology for doripenem minimum inhibitory concentration (MIC) determination against these pathogens. Data from eight countries within the Asia-Pacific region, which collected 1612 bacterial isolates, are presented here. Etest methodology was found to be a reliable method for MIC determination. Doripenem showed in vitro activity similar to or better than meropenem and at least four-fold better than imipenem against Enterobacteriaceae. Against Pseudomonas aeruginosa, doripenem was also the most active of the three carbapenems in vitro. However, in vitro results do not necessarily correlate with clinical outcome.
European Journal of Clinical Microbiology & Infectious Diseases, 2010
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Clinical Microbiology and Infection, 1997
Objective: To investigate and compare the in vitro pharmacodynamics of three carbapenems: imipenem, meropenem and 80-2727. Methods: The following studies were performed: (1) comparative studies of the rate of killing of the three carbapenems of reference strains of Gram-positive and Gram-negative bacteria at a concentration corresponding to the 1-h serum level following 500 mg intravenously in humans; (2) comparative studies of the rate of killing of 80-2727, meropenem and imipenem at different antibiotic concentrations of reference strains of Gram-positive and Gram-negative bacteria; (3) comparative studies of the rate of killing of BO-2727, meropenem and imipenem of bacteria which are phenotypically tolerant; (4) studies of the postantibiotic effect of BO-2727 using viable counts and optical density; (5) studies of the postantibiotic sub-MIC effect (PA SME) of 80-2727 using optical density. Results: No difference in killing rate was noted between the three carbapenems, and there was no concentrationdependent killing of the Gram-negative strains after 6 h. A pronounced paradoxical effect was seen against Sraphylococcus aureus. All three antibiotics were able to kill phenotypically tolerant bacteria. Only very short or no postantibiotic effect of 80-2727 was found against the investigated strains. Very long PA SMEs were noted for the Gram-negative strains, although there was a pronounced variation for the different strains of Pseudomonas aeruginosa. Conclusion: There was no significant difference between the studied carbapenems in their pharmacodynamic properties. All three antibiotics acted similarly to other p-lactam antibiotics.
Activity of a novel carbapenem, doripenem, against anaerobic pathogens
Diagnostic Microbiology and Infectious Disease, 2009
Doripenem, a synthetic 1-β-methyl carbapenem, has a broad-spectrum of activity against almost all species of anaerobic bacteria, including all Bacteroides fragilis group species, most with MIC 90 results at ≤1 μg/mL (with the exception of Sutterella wadsworthensis). Against Clostridium difficile strains, it has a narrow range of inhibitory concentrations (1-4 μg/mL) that "may be achievable in the colon", potentially resulting in lower disease rates. It has been shown to be active in vitro against strains isolated from a variety of clinical infections, including bacteremias, diabetic foot and other soft tissues infections and in intra-abdominal and pelvic sites. In addition, a study of a pyometrium animal model of mixed infections noted a better microbiologic response than with imipenem. Two phase 3 multinational clinical trials of complicated mixed aerobic/anaerobic intra-abdominal infections noted "noninferiority" of doripenem when compared with meropenem, but in vitro against the anaerobes, it was "more potent than meropenem, ertapenem, … and similar to imipenem". Doripenem activity against anaerobes seems comparable with the other extant carbapenems. Although resistance among anaerobic bacteria to this agent is possible, it remains relatively rare.
Activities of Doripenem (S-4661) against Drug-Resistant Clinical Pathogens
Antimicrobial Agents and Chemotherapy, 2004
Doripenem (formerly S-4661), a new 1--methyl carbapenem, was challenged with a worldwide collection of 394 drug-refractory isolates. For endemic extended-spectrum -lactamase-and stably derepressed AmpCproducing enteric bacilli, the doripenem MICs at which 90% of the isolates were inhibited (MIC 90 s) were 0.03 to 0.5 g/ml, generally lower than those of comparator carbapenems. A greater proportion of strains among carbapenem-resistant nonfermentative gram-negative bacilli were inhibited by doripenem at <4 g/ml, and doripenem was the most active carbapenem (MIC 90 , 1 to 4 g/ml) against penicillin-resistant streptococci.
Resistance rates amongst Gram-negative pathogens are increasing in the Asia-Pacific region. The Comparative Activity of Carbapenem Testing (COMPACT) II study surveyed the carbapenem susceptibility and minimum inhibitory concentrations (MICs) of doripenem, imipenem and meropenem against 1260 major Gram-negative pathogens isolated from hospitalised patients at 20 centres in five Asia-Pacific countries (New Zealand, the Philippines, Singapore, Thailand and Vietnam) during 2010. Pseudomonas aeruginosa (n = 625), Enterobacteriaceae (n = 500), and other Gram-negative pathogens including Acinetobacter baumannii (n = 135) were collected from patients with bloodstream infection (32.2%), nosocomial pneumonia including ventilator-associated pneumonia (58.1%), and complicated intra-abdominal infection (9.7%), with 36.7% being isolated from patients in an Intensive Care Unit. As high as 29.8% of P. aeruginosa and 73.0% of A. baumannii isolates were not susceptible to at least a carbapenem, whereas the majority of Enterobacteriaceae (97.2%) were susceptible to all carbapenems. Respective MIC 50 /MIC 90 values (MICs for 50% and 90% of the organisms, respectively) of doripenem, imipenem and meropenem were: 0.38/8, 1.5/32 and 0.38/16 mg/L for P. aeruginosa; 0.023/0.094, 0.25/0.5 and 0.032/0.094 mg/L for Enterobacteriaceae; and 32/64, 32/128 and 32/64 mg/L for A. baumannii. Doripenem and meropenem had comparable activity against P. aeruginosa, both being more active than imipenem. All carbapenems were highly potent against Enterobacteriaceae, although imipenem demonstrated higher MIC values than doripenem and meropenem. The three carbapenems showed less activity against A. baumannii. The high prevalence of carbapenem resistance amongst important nosocomial pathogens (P. aeruginosa and A. baumannii) warrants rigorous infection control measures and appropriate antimicrobial use in the Asia-Pacific region.
Research Journal of Infectious Diseases, 2015
Background: Increasing prevalence of carbapenem resistance in Gram negative bacteria due to excessive and indiscriminate use of carbapenems has forced the medical fraternity to find out ways to spare carbapenems. This retrospective study was aimed to explore a new fixed dose combination (FDC) of ceftriaxone+sulbactam with adjuvant disodium edetate as a carbapenem sparing drug in the management of moderate to severe bacterial infections of lower respiratory tract infections (LRTIs), urinary tract infections (UTIs) and intra-abdominal infections (IAIs). Methods: A retrospective analysis involves those patients in whom FDC or meropenem was used empirically for the management of these infections caused by multidrug resistant pathogens. Results: The average age of evaluated patients was 58.17±13.98 years. Out of 107 patients, 95 patients selected for the evaluations in which LRTIs, UTIs and IAIs were diagnosed in 43 (45.26%), 32 (33.68%) and 20 (21.05%) patients, respectively. The most common pathogen was Escherichia coli (38.94%), followed by Klebsiella species (26.31%), Pseudomonas species (18.94%) and Acinetobacter species (15.78%). According to the susceptibility results, FDC appeared as the most active antibacterial agent against E. coli (94.54%) followed by Acinetobacter species (93.33%), Pseudomonas species (88.88%) and Klebsiella species (84%). On the other hand, meropenem susceptibility to E. coli was 86.47% followed by Acinetobacter species (78.57%), Pseudomonas species (66.66%) and Klebsiella species (64%). Further our results revealed that FDC has >75% clinical success compared to meropenem (~61% clinical success). Conclusion: These results depict non-inferiority of new FDC in the treatment of moderate to severe Gram negative bacterial infections caused by carbapenem resistant organisms and therefore, it should be considered as an alternative to carbapenem for treating LRTIs, UTIs and IAIs.
Antimicrobial activity of doripenem against Gram-negative pathogens: results from
2011
In vitro activity of doripenem and comparator antimicrobial agents was evaluated against Gram-negative bacilli recently isolated from Brazilian private hospitals that were enrolled in the INVITA-A-DORI Brazilian Study. A total of 805 unique Gram-negative bacilli were collected from patients hospitalized at 18 medical centers between May/08 and March/09. Each hospital was asked to submit 50 single Gram-negative bacilli isolated from blood, lower respiratory tract or intraabdominal secretions. Bacterial identification was confirmed and antimicrobial susceptibility testing was performed using Clinical Laboratory Standards Institute (CLSI) microdilution method at a central laboratory. CLSI M100-S21 (2011) or US-FDA package insert criteria (tigecycline) was used for interpretation of the antimicrobial susceptibility results. Doripenem was as active as meropenem and more active than imipenem against E. coli and K. pneumoniae isolates. A total of 50.0% of Enterobacter spp. isolates were re...
Diagnostic Microbiology and Infectious Disease, 2013
Carbapenems are increasingly needed to treat infections caused by drug-resistant gram-negative bacilli (GNB), but carbapenem resistance is increasing. We evaluated the activity of doripenem by broth microdilution against 96 extensively drug-resistant (XDR) Acinetobacter baumannii and Klebsiella pneumoniae isolates from patients with hospital-associated infections. All isolates were non-susceptible to doripenem, but ≥1 doripenem combination demonstrated synergy (fractional inhibitory concentration index: ≤0.5 for 2 agents, ≤0.75 for 3 agents) against 7 (15%) A. baumannii and 23 (48%) K. pneumoniae isolates; doripenem with rifampin and/or polymyxin B were most active. As doripenem has unique potential for use in prolonged infusions, suggested pharmacodynamic (PD) breakpoints range from 2-8 μg/mL; synergistic activity was found for higher proportions of XDR-GNB at higher PD breakpoints with doripenem with amikacin or with rifampin. The clinical utility of these observations requires further study, as treatment options for XDR-GNB infections are limited.