Efficacy Of Doripenem Research Articles

The Efficacy and Safety of Doripenem in the Treatment of Acute Bacterial Infections-A Systemic Review and Meta-Analysis of Randomized Controlled Trials.

This study aims to assess the efficacy and safety of doripenem on treating patients with acute bacterial infections. The Pubmed, Embase, and Cochrane databases were searched up to April 2019. Only randomized clinical trials comparing doripenem and other comparators for the treatment of acute bacterial infection were included. The primary outcome was the clinical success rate and the secondary outcomes were microbiological eradication rate and risk of adverse events. Eight randomized controlled trials (RCTs) were included. Overall, doripenem had a similar clinical success rate with comparators (odds ratio [OR], 1.15; 95% CI, 0.79–1.66, I2 = 58%). Similar clinical success rates were noted between doripenem and comparators for pneumonia (OR, 0.84; 95% CI, 0.46–1.53, I2 = 72%) and for intra-abdominal infections (OR, 1.00; 95% CI, 0.57–1.72). For complicated urinary tract infection, doripenem was associated with higher success rate than comparators (OR, 1.89, 95% CI, 1.13–3.17, I2 = 0%). The pool analysis comparing doripenem and other carbapenems showed no significant differences between each other (OR, 0.96, 95% CI, 0.59–1.58, I2 = 63%). Doripenem also had a similar microbiological eradication rate with comparators (OR, 1.08; 95% CI, 0.86–1.36, I2 = 0%). Finally, doripenem had a similar risk of treatment-emergent adverse events as comparators (OR, 0.98; 95% CI, 0.83–1.17, I2 = 33%). In conclusion, the clinical efficacy of doripenem is as high as that of the comparator drugs in the treatment of acute bacterial infection; furthermore, this antibiotic is as well tolerated as the comparators.

Comparative In Vitro Efficacy of Doripenem and Imipenem Against Multi-Drug Resistant Pseudomonas aeruginosa.

To compare the in vitro efficacy of doripenem and imipenem against multi-drug resistant (MDR) Pseudomonas aeruginosa from various clinical specimens. Descriptive cross-sectional study. Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi, from November 2012 to November 2013. MDR Pseudomonas aeruginosa isolates from various clinical samples were included in the study. Susceptibility of Pseudomonas aeruginosa against doripenem and imipenem was performed by E-test strip and agar dilution methods. The results were interpreted as recommended by Clinical Laboratory Standard Institute (CLSI) guidelines. The maximum number of Pseudomonas aeruginosa were isolated from pure pus and pus swabs. In vitro efficacy of doripenem was found to be more effective as compared to imipenem against MDR Pseudomonas aeruginosa with both E-test strip and agar dilution methods. Overall, p-values of 0.014 and 0.037 were observed when susceptibility patterns of doripenem and imipenem were evaluated with E-test strip and agar dilution methods. In vitro efficacy of doripenem was found to be better against MDR Pseudomonas aeruginosaas compared to imipenem when tested by both E-test and agar dilution methods.

PWSF1-6 - Comparison of Doripenem and Meropenem as the First-Line Mono-Therapy in Febrile Neutropenic Patients with Acute Leukemia

Background: Febrile neutropenia (FN) are often observed in hematological malignancy (HEM) such as acute leukemia (AL). Carbapenem antibiotics having a potent and broad antibacterial activity against gram-positive and gram-negative bacteria including Pseudomonas aeruginosa, are recommended to use early and sufficiently as empiric first-line therapy for FN. Several beta-lactam antibiotics including imipenem/cilastatin (IPM/CS), meropenem (MEPM), ceftazidime (CAZ) or cefepime (CFPM) have been studied as empirical therapy for FN. However, limited data are available concerning the efficacy of doripenem (DRPM) in FN patients with HEM.Methods: We conducted a randomized, cooperative group, open-label trial comparing DRPM (1.0g every 8 hours) with MEPM (1.0g every 8 hours) as first-line empirical antibacterial treatment for FN patients. 146 hospitalized FN patients with AL during or after chemotherapy were randomized to each drug group (DRPM, 73; MEPM, 73). These study drugs were administered as mono-therapy at least for 5 days without drug toxicity. The efficacy and safety were evaluated.Results: The overall response rate within seven days of DRPM and MEPM were not significantly different (DRPM: 67.3%, MEPM: 52.9%, P = 0.098). Both the resolution of fever by mono-therapy at day 3 to 5 (DRPM: 57.8%, MEPM: 47.4% (p = 0.26)), or survival at day 30 (DRPM: 98.2%, MEPM: 100% (p = 0.312)) was not significantly different in the two groups. Only grade 1-2 adverse events: liver dysfunction, renal dysfunction, diarrhea and rash were observed in some cases, and a little less often in DRPM group (DRPM: 29.8%, MEPM: 40.8% (p = 0.046)). These adverse events were clinically minimal in the two groups, and most of patients could continue the treatment by both study drugs.Conclusions: We could prove the non-inferiority of DRPM in comparison with MEPM for the initial treatment in AL patients with FN. Both drugs were well tolerated as first line therapy for FN.

Efficacy of doripenem and ertapenem against KPC-2-producing and non-KPC-producing Klebsiella pneumoniae with similar MICs

In the clinical setting, the choice of definitive drug therapy is typically guided by the antimicrobial susceptibility profile of the infecting organism. We evaluated the activity of doripenem and ertapenem against Klebsiella pneumoniae isolates with similar MICs that exhibited KPC-based and non-KPC-based genotypes. Five doripenem-non-susceptible K. pneumoniae isolates, three producing KPC carbapenemases and two exhibiting porin modifications plus AmpC β-lactamase production, were tested in a neutropenic murine thigh infection model. The ertapenem MIC for all isolates was >32 mg/L. Regimens of 2 g of doripenem every 8 h (4 h infusion) and 1 g of ertapenem every 24 h (0.5 h infusion) simulating human concentration-time profiles were administered 2 h after inoculation. The change in bacterial density was evaluated after 24 h of therapy. Consistent with the observed MICs, treatment with ertapenem resulted in minimal activity against all isolates tested. When comparing the activity of doripenem between the KPC and non-KPC producers with doripenem MICs of 8 mg/L, significantly better activity was noted for the non-KPC producer (P<0.001). Likewise, when comparing the two KPC-producing isolates with doripenem MICs of 24 mg/L and >32 mg/L with the non-KPC producer with an MIC of 32 mg/L, significantly greater activity was noted for the non-KPC producer (P<0.001). When doripenem MICs were similar, activity was greater for non-KPC-producing isolates when compared with KPC producers. While the in vitro MIC is typically the sole method utilized to aid in drug selection, these data suggest that the genetic driver behind these MICs may also play a role in predicting in vivo activity.

Evaluation of doripenem in an experimental model of resistant Pseudomonas aeruginosa pneumonia

Sir, In a previous study we demonstrated that doripenem, the most recently approved carbapenem, exhibited antimicrobial activity similar to that of imipenem or meropenem in an experimental rabbit model of susceptible Pseudomonas aeruginosa pneumonia. Mutational inactivation of oprD is known to be the main mechanism of imipenem resistance in the absence of acquired carbapenemase. Although oprD inactivation also increases the MICs of meropenem and doripenem, clinical resistance to these drugs is thought to require additional mechanisms. In this work we compared the efficacy of doripenem versus imipenem or meropenem against a resistant oprD-inactive strain of P. aeruginosa in an experimental model. The experimental rabbit model of pneumonia has been described previously. The bacterial strain was a DoprD PAO1, which is resistant to carbapenems after inactivation of OprD porin, a carbapenem-specific transport porin. This strain was provided by courtesy of Professor P. Plesiat, Besancon, France. MICs of meropenem, doripenem and imipenem were 8, 1 and 16 mg/L, respectively. Antibiotics were delivered through a venous catheter, with changing infusion rates determined by computer-controlled electric pumps, in order to simulate the pharmacokinetics observed in human serum. Animals were randomly assigned to four groups: (i) controls (no treatment); (ii) meropenem group [computer-controlled syringe-pump infusion to simulate a human equivalent (HE) dosage of meropenem of 1 g three times daily]; (iii) doripenem group (simulating an HE dosage of doripenem of 0.5 g three times daily); and (iv) imipenem group (simulating an HE dosage of imipenem of 1 g three times daily). Evaluation of infection was performed at the end of treatment (2 days). The spleen and both lungs from each animal were weighed and homogenized in 1 mL of saline buffer and used for quantitative cultures on agar for 24 h at 378C. Viable counts after 24 h of incubation were expressed as the mean+SD log10 cfu/g of lung. Spleen culture results were expressed quantitatively (positive or negative). From each animal, plasma antibiotic concentrations were determined by a microbioassay to obtain a pharmacokinetic analysis. Selection of variants resistant in vivo to doripenem, meropenem or imipenem was evaluated by spreading undiluted homogenates on agar plates that contained the appropriate antibiotic at a concentration of 4-fold the MIC. Bacterial counts were determined after 48 h of incubation at 378C. Quantitative variables were compared using one-way analysis of variance. This analysis was completed with a post hoc Bonferroni test. Proportions (percentages) were compared using Fisher’s exact test. P,0.05 was considered statistically significant. Animals were treated in accordance with institutional policies and the guidelines stipulated by the animal welfare committee. The Committee of Animal Ethics of the University of Nantes approved all animal experimentation in this study. Mean pulmonary bacterial loads were 3.1+1.3, 2.6+0.4 and 2.8+0.7 log10 cfu/g for meropenem, doripenem and imipenem, respectively, compared with 5.9+0.8 log10 cfu/g for control animals. The results of these pulmonary bacterial counts are shown in Figure 1; they were significantly lower in the treated animals compared with the controls (P,0.05), but were similar between the different antibiotic regimens. The proportions of positive versus negative spleen cultures for controls, meropenem, doripenem and imipenem were 4/3, 3/4, 1/6 and 2/7, respectively; they were not statistically different. No resistant mutants were isolated from any of the post-treatment biological samples.

Double-blind, controlled study to evaluate safety and efficacy of doripenem and meropenem in patients with complicated urinary tract infection

Double-blind, controlled study to evaluate safety and efficacy of doripenem and meropenem in patients with complicated urinary tract infection

Study of safety and efficacy of doripenem in patients with sepsis and infective endocarditis

Study of safety and efficacy of doripenem in patients with sepsis and infective endocarditis