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Frontiers in Pharmacology 2020Continuous Renal Replacement Therapy (CRRT) is more and more widely used in patients for various indications recent years. It is still intricate for clinicians to decide... (Review)
Review
Continuous Renal Replacement Therapy (CRRT) is more and more widely used in patients for various indications recent years. It is still intricate for clinicians to decide a suitable empiric antimicrobial dosing for patients receiving CRRT. Inappropriate doses of antimicrobial agents may lead to treatment failure or drug resistance of pathogens. CRRT factors, patient individual conditions and drug pharmacokinetics/pharmacodynamics are the main elements effecting the antimicrobial dosing adjustment. With the development of CRRT techniques, some antimicrobial dosing recommendations in earlier studies were no longer appropriate for clinical use now. Here, we reviewed the literatures involving in new progresses of antimicrobial dosages, and complied the updated empirical dosing strategies based on CRRT modalities and effluent flow rates. The following antimicrobial agents were included for review: flucloxacillin, piperacillin/tazobactam, ceftriaxone, ceftazidime/avibactam, cefepime, ceftolozane/tazobactam, sulbactam, meropenem, imipenem, panipenem, biapenem, ertapenem, doripenem, amikacin, ciprofloxacin, levofloxacin, moxifloxacin, clindamycin, azithromycin, tigecycline, polymyxin B, colistin, vancomycin, teicoplanin, linezolid, daptomycin, sulfamethoxazole/trimethoprim, fluconazole, voriconazole, posaconzole, caspofungin, micafungin, amphotericin B, acyclovir, ganciclovir, oseltamivir, and peramivir.
PubMed: 32547394
DOI: 10.3389/fphar.2020.00786 -
Antimicrobial Agents and Chemotherapy Nov 2011In this review, we summarize the current "state of the art" of carbapenem antibiotics and their role in our antimicrobial armamentarium. Among the β-lactams currently... (Review)
Review
In this review, we summarize the current "state of the art" of carbapenem antibiotics and their role in our antimicrobial armamentarium. Among the β-lactams currently available, carbapenems are unique because they are relatively resistant to hydrolysis by most β-lactamases, in some cases act as "slow substrates" or inhibitors of β-lactamases, and still target penicillin binding proteins. This "value-added feature" of inhibiting β-lactamases serves as a major rationale for expansion of this class of β-lactams. We describe the initial discovery and development of the carbapenem family of β-lactams. Of the early carbapenems evaluated, thienamycin demonstrated the greatest antimicrobial activity and became the parent compound for all subsequent carbapenems. To date, more than 80 compounds with mostly improved antimicrobial properties, compared to those of thienamycin, are described in the literature. We also highlight important features of the carbapenems that are presently in clinical use: imipenem-cilastatin, meropenem, ertapenem, doripenem, panipenem-betamipron, and biapenem. In closing, we emphasize some major challenges and urge the medicinal chemist to continue development of these versatile and potent compounds, as they have served us well for more than 3 decades.
Topics: Anti-Bacterial Agents; Carbapenems; Cilastatin; Cilastatin, Imipenem Drug Combination; Doripenem; Drug Combinations; Ertapenem; Humans; Imipenem; Thienamycins; beta-Alanine; beta-Lactams
PubMed: 21859938
DOI: 10.1128/AAC.00296-11 -
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 -
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 -
Pharmacy (Basel, Switzerland) Aug 2019Understanding antibiotic allergies and the risk of cross-sensitivity between and within antibiotic classes can have a substantial impact on patient care. The purpose of... (Review)
Review
Understanding antibiotic allergies and the risk of cross-sensitivity between and within antibiotic classes can have a substantial impact on patient care. The purpose of this review article is to provide insight into carbapenem allergies, describing the overall incidence, risk factors, and in-class cross-sensitivity. A PubMed search was conducted using the following search terms: carbapenem, allergy, cross-sensitivity, incidence, imipenem/cilastatin, meropenem, ertapenem, and doripenem. Article bibliographies and relevant drug monographs were also reviewed. The overall reported incidence of carbapenem allergy is 0.3%-3.7%. Risk of cross-sensitivity between penicillins and carbapenems is less than 1% in patients with a positive penicillin skin test. Data on cross-sensitivity between cephalosporins and carbapenems are limited; however, the risk appears to also be low. No clinical studies have described cross-sensitivity between the carbapenem agents thus far. The limited data available from case reports demonstrates a lack of cross-sensitivity between the individual carbapenems, suggesting that an alternative carbapenem may cautiously be used in patients with a reported carbapenem allergy.
PubMed: 31398843
DOI: 10.3390/pharmacy7030110 -
Antibiotics (Basel, Switzerland) Jul 2022The aim of this study was to investigate the pharmacokinetics (PK) of doripenem in healthy Chinese subjects and evaluate the optimal dosage regimens of doripenem. A...
The aim of this study was to investigate the pharmacokinetics (PK) of doripenem in healthy Chinese subjects and evaluate the optimal dosage regimens of doripenem. A randomized, single-dose, three-period, self-crossover controlled extended-infusion clinical trial was conducted with 12 healthy Chinese subjects. Plasma and urine samples were collected to determine doripenem concentrations. Non-compartmental and population PK analysis were performed to characterize the PK of doripenem. The Monte Carlo simulation was employed to optimize dosing regimens based on the probability of target attainment of doripenem against pathogens with different minimum inhibitory concentrations (MIC). All 12 healthy Chinese subjects completed the study, and the doripenem was well tolerated. The study showed linearity relationships in the peak plasma concentration and the area under the concentration-time curve after intravenous infusion of doripenem from 0.25 g to 1.0 g. The cumulative urinary recovery rate of doripenem was 68.1-72.0% within 24 h. PPK modeling showed a two-compartmental model, with first-order elimination presenting the best fit for doripenem PK. Monte Carlo simulation results showed that 1.0 g q12h or 0.5 g q8h was an optimal regimen for pathogens susceptible to doripenem (MIC ≤ 1 mg/L); while high dose and extended infusion (1 g, q8h, 4 h infusion) was proposed for unsusceptible pathogens (2 ≤ MIC ≤ 8 mg/L). In the dose range of 0.25 to 1.0 g, doripenem showed linear pharmacokinetics. Doripenem at 1.0 g with a prolonged infusion time of 4 h was predicted to be effective against pathogens with MICs as high as 8 mg/L.
PubMed: 35884212
DOI: 10.3390/antibiotics11070958 -
Antibiotics (Basel, Switzerland) Aug 2022The aim of this study was to determine whether fingolimod could synergize the antibacterial activity of doripenem against carbapenem-resistant (CREC) and its potential...
The aim of this study was to determine whether fingolimod could synergize the antibacterial activity of doripenem against carbapenem-resistant (CREC) and its potential as an antibiotic adjuvant for doripenem. The used in this study had the gene and became resistant to many classes of antibiotics, particularly carbapenems. The minimum inhibitory concentrations (MICs) of fingolimod and doripenem were determined. To investigate the synergistic action between fingolimod and doripenem, synergy checkerboard, growth curve, and time-kill analyses were performed. A motility test was also performed using a semi-solid medium to determine whether fingolimod could inhibit the motility of , one of its virulence mechanisms. The expression levels of carbapenemase-, motility-, and efflux pump-related genes suppressed by fingolimod were analyzed by quantitative polymerase chain reaction (qPCR). Our study demonstrated that the combination of fingolimod and doripenem inhibited carbapenemase, biological activity and other CREC virulence factors. This study findings suggest the potential of fingolimod as an adjuvant to prevent antibiotic resistance in CREC.
PubMed: 36009912
DOI: 10.3390/antibiotics11081043