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Drugs of Today (Barcelona, Spain : 1998) Jun 2006Doripenem is a new member of the carbapenem class of beta-lactam antibiotics with broad-spectrum coverage of Gram-positive, Gram-negative and anaerobic pathogens similar... (Review)
Review
Doripenem is a new member of the carbapenem class of beta-lactam antibiotics with broad-spectrum coverage of Gram-positive, Gram-negative and anaerobic pathogens similar to imipenem and, especially, meropenem. This parenteral antibiotic may offer slightly more activity than meropenem against selected pathogens, including coverage of some strains of Pseudomonas aeruginosa strains not susceptible to the other antipseudomonal carbapenems. Empiric therapy with doripenem, as with other antipseudomonal carbapenems, may be useful in hospital and intensive care unit settings where multidrug resistance has emerged, especially in Gram-negative enteric pathogens. When P. aeruginosa or multidrug-resistant Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci are involved, doripenem must be used in combination. Doripenem has a broad spectrum of activity against many common hospital pathogens, including P. aeruginosa and Burkholderia cepacia, which is similar to meropenem.
Topics: Bacteria, Anaerobic; Bacterial Infections; Carbapenems; Clinical Trials, Phase III as Topic; Doripenem; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Randomized Controlled Trials as Topic
PubMed: 16845443
DOI: 10.1358/dot.2006.42.6.985634 -
Journal of Clinical Medicine Jul 2022Clinically, doripenem therapy for nosocomial pneumonia remains a serious concern. The purpose of this meta-analysis was to explore the efficacy and the safety of... (Review)
Review
INTRODUCTION
Clinically, doripenem therapy for nosocomial pneumonia remains a serious concern. The purpose of this meta-analysis was to explore the efficacy and the safety of doripenem therapy for nosocomial pneumonia in comparison with other antimicrobial agents.
METHODS
Studies were eligible for inclusion only if they directly compared the clinical effectiveness of doripenem and other antimicrobial agent therapies for nosocomial pneumonia in adult patients between 1 January 2000 and 30 April 2022. All studies were included if they reported one or more of the following outcomes: clinical cure rate, microbiological cure rate, all-cause mortality, and adverse events.
RESULTS
Six randomized controlled trials and three retrospective studies were included in the meta-analysis. There were 952 patients in the doripenem group and 1183 patients in the comparator group. The comparator antimicrobial agents included imipenem/cilastatin, meropenem, and piperacillin/tazobactam. Seven studies had a high risk of bias. Doripenem therapy for nosocomial pneumonia had a microbiological cure rate, a clinical cure rate, an all-cause mortality, and adverse events similar to those of comparators.
CONCLUSIONS
The efficacy and the safety of doripenem therapy for nosocomial pneumonia were comparable with those of comparators. Randomized controlled trials are needed to confirm the role of doripenem in nosocomial pneumonia therapy.
PubMed: 35887777
DOI: 10.3390/jcm11144014 -
Clinical Infectious Diseases : An... Jul 2009Carbapenems play a significant role in the current antibiotic armamentarium. Doripenem is the newest carbapenem to be commercially released. Its antimicrobial spectrum... (Review)
Review
Carbapenems play a significant role in the current antibiotic armamentarium. Doripenem is the newest carbapenem to be commercially released. Its antimicrobial spectrum more closely resembles those of meropenem and imipenem than that of ertapenem. Thus, it has significant in vitro activity against streptococci, methicillin-susceptible staphylococci, Enterobacteriaceae (including extended-spectrum beta-lactamase-producing strains), Pseudomonas aeruginosa, Acinetobacter species, and Bacteroides fragilis. Doripenem does not have clinically useful activity against methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and the majority of gram-negative bacilli that are resistant to meropenem or imipenem. In vitro, resistant P. aeruginosa mutants appear to be harder to select with doripenem than with other carbapenems. Doripenem has been approved for use in treatment of complicated intra-abdominal infection and complicated urinary tract infection. Studies of hospital-acquired pneumonia have also been completed, including one that used a 4-h infusion to enhance the pharmacodynamic profile. In vitro, doripenem lacks the propensity to cause seizures, and a low risk of seizures has been demonstrated in clinical studies. Currently unanswered questions regarding doripenem include the utility and dosing in neonatal, pediatric, and cystic fibrosis populations and specific dosage recommendations for patients receiving hemodialysis, peritoneal dialysis, or continuous renal replacement therapies. The longevity of doripenem will depend on our ability to curtail the spread of carbapenem-resistant organisms, which are already a significant problem at some institutions.
Topics: Carbapenems; Doripenem; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Peritonitis; Pneumonia, Bacterial; Seizures; Urinary Tract Infections
PubMed: 19527173
DOI: 10.1086/600036 -
Drugs in R&D 2003Doripenem [S 4661] is a new parenteral carbapenem antibacterial undergoing clinical trials in Japan and North America. It is characterised by a 1beta-methyl group and a... (Review)
Review
Doripenem [S 4661] is a new parenteral carbapenem antibacterial undergoing clinical trials in Japan and North America. It is characterised by a 1beta-methyl group and a sulfamoylaminomethyl substituted pyrrolidylthio group at the C2 position. The compound has good activity against both Gram-positive and Gram-negative bacteria and superior activity to meropenem and imipenem against Pseudomonas aeruginosa. It possesses higher stability than imipenem or meropenem against animal dehydropeptidase I. The compound is stable to most beta-lactamases produced by Gram-negative bacteria. Shionogi has stated that doripenem is expected to be effective at low doses. In May 2003, Shionogi and Peninsula Pharmaceuticals (USA) entered a licensing agreement for doripenem under which Peninsula obtained exclusive rights (including sublicense rights) to market and develop the product in North America. Shionogi will manufacture doripenem for worldwide distribution. Doripenem is currently undergoing phase III trials in Japan for pneumonia, chronic respiratory tract infections (RTIs) and urinary tract infections (UTIs). In its November 2002 pipeline, Shionogi stated that it plans to file a NDA in Q4 of 2003. Doripenem is also in phase II studies in hospitalised patients with complicated urinary tract infections including pyelonephritis. In September 2003, Peninsula announced it had completed enrolment in this trial, and results are expected later in the year. Doripenem has also completed two phase I studies in healthy volunteers with a number of different dosing regimens.
Topics: Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Clinical Trials as Topic; Doripenem; Drug Stability; Humans
PubMed: 14584966
DOI: 10.2165/00126839-200304060-00006 -
Clinical Infectious Diseases : An... Sep 2016The global emergence of carbapenem-resistant Enterobacteriaceae highlights the urgent need to reduce carbapenem dependence. The phase 3 RECAPTURE program compared the... (Randomized Controlled Trial)
Randomized Controlled Trial
Ceftazidime-avibactam Versus Doripenem for the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis: RECAPTURE, a Phase 3 Randomized Trial Program.
BACKGROUND
The global emergence of carbapenem-resistant Enterobacteriaceae highlights the urgent need to reduce carbapenem dependence. The phase 3 RECAPTURE program compared the efficacy and safety of ceftazidime-avibactam and doripenem in patients with complicated urinary tract infection (cUTI), including acute pyelonephritis.
METHODS
Hospitalized adults with suspected or microbiologically confirmed cUTI/acute pyelonephritis were randomized 1:1 to ceftazidime-avibactam 2000 mg/500 mg every 8 hours or doripenem 500 mg every 8 hours (doses adjusted for renal function), with possible oral antibiotic switch after ≥5 days (total treatment duration up to 10 days or 14 days for patients with bacteremia).
RESULTS
Of 1033 randomized patients, 393 and 417 treated with ceftazidime-avibactam and doripenem, respectively, were eligible for the primary efficacy analyses; 19.6% had ceftazidime-nonsusceptible baseline pathogens. Noninferiority of ceftazidime-avibactam vs doripenem was demonstrated for the US Food and Drug Administration co-primary endpoints of (1) patient-reported symptomatic resolution at day 5: 276 of 393 (70.2%) vs 276 of 417 (66.2%) patients (difference, 4.0% [95% confidence interval {CI}, -2.39% to 10.42%]); and (2) combined symptomatic resolution/microbiological eradication at test of cure (TOC): 280 of 393 (71.2%) vs 269 of 417 (64.5%) patients (difference, 6.7% [95% CI, .30% to 13.12%]). Microbiological eradication at TOC (European Medicines Agency primary endpoint) occurred in 304 of 393 (77.4%) ceftazidime-avibactam vs 296 of 417 (71.0%) doripenem patients (difference, 6.4% [95% CI, .33% to 12.36%]), demonstrating superiority at the 5% significance level. Both treatments showed similar efficacy against ceftazidime-nonsusceptible pathogens. Ceftazidime-avibactam had a safety profile consistent with that of ceftazidime alone.
CONCLUSIONS
Ceftazidime-avibactam was highly effective for the empiric treatment of cUTI (including acute pyelonephritis), and may offer an alternative to carbapenems in this setting.
CLINICAL TRIALS REGISTRATION
NCT01595438; NCT01599806.
Topics: Adult; Aged; Anti-Bacterial Agents; Azabicyclo Compounds; Carbapenems; Ceftazidime; Doripenem; Drug Combinations; Female; Humans; Male; Middle Aged; Pyelonephritis; Urinary Tract Infections
PubMed: 27313268
DOI: 10.1093/cid/ciw378 -
Drugs 2007The carbapenems are beta-lactam antimicrobial agents with an exceptionally broad spectrum of activity. Older carbapenems, such as imipenem, were often susceptible to... (Comparative Study)
Comparative Study Review
The carbapenems are beta-lactam antimicrobial agents with an exceptionally broad spectrum of activity. Older carbapenems, such as imipenem, were often susceptible to degradation by the enzyme dehydropeptidase-1 (DHP-1) located in renal tubules and required co-administration with a DHP-1 inhibitor such as cilastatin. Later additions to the class such as meropenem, ertapenem and doripenem demonstrated increased stability to DHP-1 and are administered without a DHP-1 inhibitor. Like all beta-lactam antimicrobial agents, carbapenems act by inhibiting bacterial cell wall synthesis by binding to and inactivating penicillin-binding proteins (PBPs). Carbapenems are stable to most beta-lactamases including AmpC beta-lactamases and extended-spectrum beta-lactamases. Resistance to carbapenems develops when bacteria acquire or develop structural changes within their PBPs, when they acquire metallo-beta-lactamases that are capable of rapidly degrading carbapenems, or when changes in membrane permeability arise as a result of loss of specific outer membrane porins. Carbapenems (imipenem, meropenem, doripenem) possess broad-spectrum in vitro activity, which includes activity against many Gram-positive, Gram-negative and anaerobic bacteria; carbapenems lack activity against Enterococcus faecium, methicillin-resistant Staphylococcus aureus and Stenotrophomonas maltophilia. Compared with imipenem, meropenem and doripenem, the spectrum of activity of ertapenem is more limited primarily because it lacks activity against Pseudomonas aeruginosa and Enterococcus spp. Imipenem, meropenem and doripenem have in vivo half lives of approximately 1 hour, while ertapenem has a half-life of approximately 4 hours making it suitable for once-daily administration. As with other beta-lactam antimicrobial agents, the most important pharmacodynamic parameter predicting in vivo efficacy is the time that the plasma drug concentration is maintained above the minimum inhibitory concentration (T>MIC). Imipenem/cilastatin and meropenem have been studied in comparative clinical trials establishing their efficacy in the treatment of a variety of infections including complicated intra-abdominal infections, skin and skin structure infections, community-acquired pneumonia, nosocomial pneumonia, complicated urinary tract infections, meningitis (meropenem only) and febrile neutropenia. The current role for imipenem/cilastatin and meropenem in therapy remains for use in moderate to severe nosocomial and polymicrobial infections. The unique antimicrobial spectrum and pharmacokinetic properties of ertapenem make it more suited to treatment of community-acquired infections and outpatient intravenous antimicrobial therapy than for the treatment of nosocomial infections. Doripenem is a promising new carbapenem with similar properties to those of meropenem, although it appears to have more potent in vitro activity against P. aeruginosa than meropenem. Clinical trials are required to establish the efficacy and safety of doripenem in moderate to severe infections, including nosocomial infections.
Topics: Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Doripenem; Ertapenem; Humans; Imipenem; Meropenem; Thienamycins; beta-Lactams
PubMed: 17488146
DOI: 10.2165/00003495-200767070-00006 -
Expert Review of Anti-infective Therapy Jun 2009Doripenem is a novel carbapenem with a broad spectrum of activity against Gram-positive pathogens, anerobes and Gram-negative bacteria, including Pseudomonas aeruginosa.... (Review)
Review
Doripenem is a novel carbapenem with a broad spectrum of activity against Gram-positive pathogens, anerobes and Gram-negative bacteria, including Pseudomonas aeruginosa. Doripenem exhibits rapid bactericidal activity with two- to fourfold lower MIC values for Gram-negative bacteria, compared with other carbapenems such as imipenem. Doripenem is approved for the treatment of complicated intra-abdominal infection and urinary tract infections. It has been successfully used in the treatment of nosocomial and ventilator-associated pneumonia. It has a potential to be the drug of choice for these conditions. This evaluation focuses on the general review of the drug, including mechanisms of resistance, clinical efficacy and the position of doripenem in clinical practice. Stability against numerous beta-lactamases, low adverse-event potential and more potent in vitro and possibly in vivo activity against P. aeruginosa and Acinetobacter baumanni compared with existing carbapenems are attractive features.
Topics: Anti-Bacterial Agents; Bacteria, Anaerobic; Bacterial Infections; Carbapenems; Cross Infection; Doripenem; Drug Interactions; Drug Resistance, Bacterial; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Pseudomonas Infections
PubMed: 19485791
DOI: 10.1586/eri.09.37 -
Drugs 2008Doripenem, a parenteral, broad-spectrum antibacterial agent of the carbapenem family, is indicated as empirical therapy in serious bacterial infections in adults.... (Review)
Review
Doripenem, a parenteral, broad-spectrum antibacterial agent of the carbapenem family, is indicated as empirical therapy in serious bacterial infections in adults. Doripenem is indicated in Japan for use as a single agent in intra-abdominal infections (IAIs), lower respiratory tract infections (including nosocomial pneumonia), complicated urinary tract infections (cUTIs) and a variety of other bacterial infections, such as complicated skin and skin structure infections (cSSSIs), obstetric and gynaecological infections, serious ear, nose and throat infections, sepsis and endocarditis, dental and oral surgical infection, and ophthalmic infection caused by various susceptible strains of Gram-negative, Gram-positive or anaerobic bacteria. Doripenem is indicated in the US for the treatment of complicated IAIs (cIAIs) or cUTIs, including pyelonephritis, caused by susceptible strains of designated pathogens, and in the EU for the treatment of nosocomial pneumonia (including ventilator-associated pneumonia [VAP]), cIAIs or cUTIs.Doripenem has a broad spectrum of in vitro activity against Gram-positive and Gram-negative bacteria, including extended-spectrum beta-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae, and anaerobic pathogens. The drug also has a low propensity to select for resistance and is suitable for the prolonged infusions that may be required to achieve pharmacodynamic/pharmacokinetic targets for bactericidal activity (and therefore efficacy) against pathogens with increased MICs (minimum concentrations required to inhibit the pathogens). Doripenem is no less effective than other antibacterial agents, including meropenem, imipenem/cilastin, piperacillin/tazobactam or levofloxacin in a wide range of serious bacterial infections, such as complicated lower respiratory infections, nosocomial pneumonia (including VAP), cIAIs and cUTIs, and is well tolerated. Thus, doripenem is a valuable addition to the options available for the empirical treatment of serious bacterial infections in hospitalized patients.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Carbapenems; Doripenem; Drug Interactions; Drug Resistance, Bacterial; Humans; Kidney Diseases; Tissue Distribution
PubMed: 18778123
DOI: 10.2165/00003495-200868140-00007