Clinical Efficacy and Safety of Reduced-Dose Prasugrel versus Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: This systematic review and meta-analysis of randomized controlled trials (RCTs) compared the clinical efficacy and safety of reduced-dose prasugrel (loading dose: 20 mg; daily maintenance dose: 3.75 mg) and clopidogrel in patients undergoing percutaneous coronary intervention (PCI). Methods: PubMed, Embase, and the Cochrane Library database were searched for relevant articles from inception to March 8, 2021. Only RCTs that compared the clinical efficacy and safety of reduced-dose prasugrel and clopidogrel treatment in adult patients undergoing PCI were included. The primary outcome was the risk of major cardiovascular events (MACEs). Results: Four RCTs involving 2464 patients were included. The overall risk of MACEs was 8.3% (102/1235) in the study group (reduced-dose prasugrel) and 9.8% (121/1229) in the control group (clopidogrel). No significant difference was observed in the risk of MACEs between the study and control groups (risk ratio: 0.84, 95% confidence interval: 0.65-1.08, I 2 = 0%). In addition, cardiovascular-related death, all-cause death, nonfatal myocardial infarction, nonfatal stroke, revascularization, and stent thrombosis did not differ significantly between the two groups. Apart from a higher risk of minor bleeding in the study group, reduced-dose prasugrel had a similar bleeding risk to clopidogrel. Conclusions: The clinical efficacy of reduced-dose prasugrel is comparable to that of clopidogrel; however, the risk of minor bleeding should be considered when prescribing this regimen for patients undergoing PCI.

Efficacy and Safety of Sitafloxacin in the Treatment of Acute Bacterial Infection: A Meta-analysis of Randomized Controlled Trials.

This meta-analysis aimed to assess the efficacy and safety of sitafloxacin in treating acute bacterial infection. PubMed, Embase, and Cochrane databases were searched up to August 13, 2019. Only randomized controlled trials (RCTs) evaluating sitafloxacin and comparators in the treatment of acute bacterial infections were included. The outcomes were clinical and microbiological responses and the risk of adverse event (AE). Five RCTs were enrolled, including 375 and 381 patients who received sitafloxacin and the comparator, respectively. Overall, the clinical response rate of sitafloxacin in the treatment of acute bacterial infections was 94.6%, which was noninferior to that of the comparator (92.5%) (odds ratio (OR), 1.01; 95% CI, 0.24-4.32; I2 = 66%). For patients with complicated urinary tract infection (cUTI)/acute pyelonephritis (APN), the clinical response rate of sitafloxacin and the comparator was 96.9% and 91.3%, respectively (OR, 2.08; 95% CI, 0.35-12.44; I2 = 54%). For patients with pneumonia, the clinical response rate of sitafloxacin was 88.6%, which was comparable to that of the comparator (OR, 0.36; 95% CI, 0.11-1.21; I2 = 0%). The microbiological response of sitafloxacin was 82.0%, which was noninferior to that of the comparator (77.8%) (OR, 1.59; 95% CI, 0.77-3.28; I2 = 47%). The risk of treatment-emergent adverse event (TEAE), drug-related TEAE, and all-cause mortality were similar between sitafloxacin and the comparators (TEAE, OR, 1.14; 95% CI, 0.64-2.01, drug-related TEAE, OR, 1.14; 95% CI, 0.48-2.69, mortality, OR, 0.93; 95% CI, 0.09-9.44). In conclusion, sitafloxacin is noninferior to other commonly used antibiotics with respect to both clinical and microbiological response rates in patients with an acute bacterial infection, including cUTI/APN and pneumonia. In addition, sitafloxacin is also as safe as the comparators.

The use of ceftolozane-tazobactam in the treatment of complicated intra-abdominal infections and complicated urinary tract infections-A meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this study was to assess the clinical efficacy and safety of ceftolozane-tazobactam in the treatment of complicated intra-abdominal infections (cIAIs) and complicated urinary tract infections (cUTIs) in adult patients through meta-analysis. METHODS: PubMed, Embase and Cochrane databases were searched up to June 2019. Only randomized controlled trials (RCTs) that evaluated ceftolozane-tazobactam and comparators for treating cIAIs and cUTIs in adult patients were included. Primary outcome was clinical cure rate; secondary outcomes were clinical failure rate, microbiological eradication rate, and risk of an adverse event (AE). RESULTS: Three RCTs were included. Overall, ceftolozane-tazobactam had a clinical cure rate similar to comparators in the microbiological intent-to-treat (mITT) population (odds ratio [OR], 0.87; 95% confidence interval [CI], 0.43-1.79; I2 = 73%) and in the clinically evaluable (CE) population (OR, 1.22; 95% CI, 0.79-1.88; I2 = 0%). Furthermore, ceftolozane-tazobactam had a similar microbiological eradication rate for pathogens (OR, 1.31; 95% CI, 0.42-4.10; I2 = 37%). There were no significant differences in the risks of treatment-emergent AEs (OR, 1.04; 95% CI, 0.87-1.23; I2 = 0%), serious AEs (OR, 1.16; 95% CI, 0.67-1.99; I2 = 37%), discontinuation of study drug due to an AE (OR, 0.77; 95% CI, 0.17-3.47) and mortality (OR, 1.62; 95% CI, 0.69-3.77, I2 = 0%) between ceftolozane-tazobactam and comparators. CONCLUSIONS: The clinical efficacy of ceftolozane-tazobactam is as high as that of comparators in the treatment of cIAIs and cUTIs in adult patients, and this antibiotic is well tolerated.

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.

Comparison of high-dose, short-course levofloxacin treatment vs conventional regimen against acute bacterial infection: meta-analysis of randomized controlled trials.

Objects: This meta-analysis aims to assess the efficacy and safety of high-dose, short-dose levofloxacin in comparison with conventional therapy on treating acute bacterial infection. Methods: PubMed, Embase and Cochrane database were searched up to September 2018. Only randomized controlled trials (RCTs) evaluating high-dose, short-course levofloxacin and conventional regimen in the treatment of acute bacterial infection were included. The primary outcomes were clinical responses, microbiologic eradication and adverse effects. Results: Seven RCTs of 3,731 patients (1,835 in the high-dose, short-course levofloxacin regimen group and 1,896 in the conventional regimen group) were included. Overall, no significant difference between the high-dose, short-course levofloxacin regimen group and the conventional regimen was found in terms of clinical response (risk ratio, RR: 1.01; 95%CI: 0.98-1.04, I 2=10%). In addition, the high-dose, short-course levofloxacin regimen had a similar microbiological eradication rate to conventional regimen (RR: 1.02; 95%CI: 0.98-1.06, I 2=0%). Moreover, the high-dose, short-course levofloxacin regimen had a similar incidence of treatment-emergent adverse events to conventional regimen (RR: 1.07; 95%CI: 0.99-1.17, I 2=0%). This trend was not affected by the different types of infections-community-acquired pneumonia, complicated urinary tract infection/acute pyelonephritis or acute sinusitis, different conventional regimen-levofloxacin (500 mg daily for 7-14 days) or ciprofloxacin (400 mg IV or 500 mg oral, twice daily for 10 days). Conclusion: High-dose, short-course levofloxacin exhibits similar clinical success and microbiologic eradication rates with conventional regimen in the treatment of acute bacterial infection. Moreover, the high-dose, short-course levofloxacin regimen was well tolerated and had comparable safety profiles with the conventional regimen.

Echinocandins vs. amphotericin B against invasive candidiasis in children and neonates: A meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this meta-analysis was to assess the efficacy and safety of treatment with echinocandins compared with amphotericin B in paediatric patients with invasive candidiasis. METHODS: PubMed, Embase and Cochrane databases were searched up to August 2018. Only randomized controlled trials (RCTs) evaluating echinocandins and amphotericin B in the treatment of paediatric patients with invasive candidiasis were included. The outcomes were clinical responses and adverse effects. RESULTS: Five RCTs of 354 patients (191 patients in the echinocandins group and 163 patients in the amphotericin B group) were included in this study. Overall, no significant differences in clinical response were found between echinocandins and amphotericin B (odds ratio [OR], 1.38; 95% confidence interval [CI], 0.68-2.80; I2 = 39%). Similar results were also observed in the high-risk group (OR, 3.10; 95% CI, 0.10-97.23; I2 = 76%), the low-risk group (OR, 1.29; 95% CI, 0.36-4.62; I2 = 21%) and the neutropenia group (OR, 1.56; 95% CI, 0.75-3.26; I2 = 0%). The risk of discontinuing treatment because of adverse effects was significantly lower in the echinocandins group than in the amphotericin B group (OR, 0.30, 95% CI, 0.12-0.76; I2 = 0%). CONCLUSIONS: There were no differences in efficacy between the echinocandins group and the amphotericin B group in the treatment of invasive candidiasis in paediatric patients. However, the echinocandins group had a significantly lower risk of discontinuing treatment than the amphotericin B group.

Intravenous Colistin Monotherapy versus Combination Therapy against Carbapenem-Resistant Gram-Negative Bacteria Infections: Meta-Analysis of Randomized Controlled Trials.

This meta-analysis aims to compare intravenous colistin monotherapy and colistin-based combination therapy against carbapenem-resistant gram-negative bacteria (GNB) infections. PubMed, Embase, and Cochrane databases were searched up to July 2018. Only randomized controlled trials (RCTs) evaluating colistin alone and colistin-based combination therapy in the treatment of carbapenem-resistant GNB infections were included. The primary outcome was all-cause mortality. Five RCTs including 791 patients were included. Overall, colistin monotherapy was associated with a risk ratio (RR) of 1.03 (95% confidence interval (CI), 0.89⁻1.20, I² = 0%) for all-cause mortality compared with colistin-based combination therapy. The non-significant difference was also detected in infection-related mortality (RR, 1.23, 95% CI, 0.91⁻1.67, I² = 0%) and microbiologic response (RR, 0.86, 95% CI, 0.72⁻1.04, I² = 62%). In addition, no significant difference was observed in the subgroup analysis-high or low dose, with or without a loading dose, carbapenem-resistant Acinetobacter baumannii infections, and in combination with rifampicin. Finally, colistin monotherapy was not associated with lower nephrotoxicity than colistin combination therapy (RR, 0.98; 95% CI, 0.84⁻1.21, I² = 0%). Based on the analysis of the five RCTs, no differences were found between colistin monotherapy and colistin-based combination therapy against carbapenem-resistant GNB infections, especially for A. baumannii infections.