Efficacy, safety, and tolerability of antimicrobial agents for complicated intra-abdominal infection: a systematic review and network meta-analysis.

BACKGROUND: Which antimicrobial agents provide the optimal efficacy, safety, and tolerability for the empirical treatment of complicated intra-abdominal infection (cIAI) remains unclear but is paramount in the context of evolving antimicrobial resistance. Therefore, updated meta-analyses on this issue are warranted. METHODS: We systematically searched four major electronic databases from their inception through October 2022. Randomized controlled trials examining antimicrobial agents for cIAI treatment were included. Two reviewers independently assessed the quality of included studies utilizing the Cochrane Collaboration's risk of bias tool as described in the updated version 1 of the Cochrane Collaboration Handbook and extracted data from all manuscripts according to a predetermined list of topics. All meta-analyses were conducted using R software. The primary outcome was clinical success rate in patients with cIAIs. RESULTS: Forty-five active-controlled trials with low to medium methodological quality and involving 14,267 adults with cIAIs were included in the network meta-analyses. The vast majority of patients with an acute physiology and chronic health evaluation II score < 10 had low risk of treatment failure or death. Twenty-one regimens were investigated. In the network meta-analyses, cefepime plus metronidazole was more effective than tigecycline and ceftolozane/tazobactam plus metronidazole (odds ratio [OR] = 1.96, 95% credibility interval [CrI] 1.05 ~ 3.79; OR = 3.09, 95% CrI 1.02 ~ 9.79, respectively). No statistically significant differences were found among antimicrobial agents regarding microbiological success rates. Cefepime plus metronidazole had lower risk of all-cause mortality than tigecycline (OR = 0.22, 95% CrI 0.05 ~ 0.85). Statistically significant trends were observed favoring cefotaxime plus metronidazole, which exhibited fewer discontinuations because of adverse events (AEs) when compared with eravacycline, meropenem and ceftolozane/tazobactam plus metronidazole (OR = 0.0, 95% CrI 0.0 ~ 0.8; OR = 0.0, 95% CrI 0.0 ~ 0.7; OR = 0.0, 95% CrI 0.0 ~ 0.64, respectively). Compared with tigecycline, eravacycline was associated with fewer discontinuations because of AEs (OR = 0.17, 95% CrI 0.03 ~ 0.81). Compared with meropenem, ceftazidime/avibactam plus metronidazole had a higher rate of discontinuation due to AEs (OR = 2.09, 95% CrI 1.0 ~ 4.41). In pairwise meta-analyses, compared with ceftriaxone plus metronidazole, ertapenem and moxifloxacin (one trial, OR = 1.93, 95% CI 1.06 ~ 3.50; one trial, OR = 4.24, 95% CI 1.18 ~ 15.28, respectively) were associated with significantly increased risks of serious AEs. Compared with imipenem/cilastatin, tigecycline (four trials, OR = 1.57, 95%CI 1.07 ~ 2.32) was associated with a significantly increased risk of serious AEs. According to the surface under the cumulative ranking curve, Cefepime plus metronidazole was more likely to be optimal among all treatments in terms of efficacy and safety, tigecycline was more likely to be worst regimen in terms of tolerability, and eravacycline was more likely to be best tolerated. CONCLUSION: This study suggests that cefepime plus metronidazole is optimal for empirical treatment of patients with cIAIs and that tigecycline should be prescribed cautiously considering the safety and tolerability concerns. However, it should be noted that data currently available on the effectiveness, safety, and tolerability of antimicrobial agents pertain mostly to lower-risk patients with cIAIs.

Cost-effectiveness analysis of ceftazidime-avibactam as definitive treatment for treatment of carbapenem-resistant Klebsiella pneumoniae bloodstream infection.

Background: Ceftazidime-avibactam (CAZ-AVI) is a novel antibiotic that has been confirmed in the United States and China for use in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection (BSI). However, the cost-effectiveness of CAZ-AVI is unknown in China. This study aimed to evaluate the cost-effectiveness of CAZ-AVI compared to polymyxin B (PMB) monotherapy or PMB-based therapy for the treatment of CRKP BSI from the Chinese healthcare perspective. Methods: A hybrid decision tree and Markov model were constructed for a hypothetical cohort of patients with CRKP BSI. The time horizon of the Markov model was 5 years with an annual discount rate of 5% used in both costs and quality-adjusted life-years (QALYs). The model data was derived from published literature and publicly available database. Regimens with an incremental cost-effectiveness ratio (ICER) lower than the willingness-to-pay (WTP) threshold of $ 11,600 per QALY were considered cost-effective. Deterministic and probabilistic sensitivity analyses were performed to examine the robustness of model analysis. Results: In the base-analysis, CAZ-AVI provided an additional 60 QALYs and reduced the cost by $ 2,218,300, yielding an ICER of $ -36,730.9/QALY, well below the WTP threshold of $ 11,600 per QALY when compared with PMB-based therapy. CAZ-AVI provided an additional 350 QALYs and increased the cost of $ 208,400, producing an ICER of $ 591.7/QALY that was below the WTP threshold compared to PMB monotherapy. At a $ 11,600/QALY threshold, results were sensitive to the cost of PMB-based strategy, the cost of CAZ-AVI strategy, the probability of cure with CAZ-AVI, and the probability of cure with PMB or PMB-based therapy. CAZ-AVI was an optimal regimen in 76.9% and 80.8% of 10,000 Monte Carlo simulations at $ 11,600/QALY and $ 34,800/QALY, respectively. Meanwhile, CAZ-AVI was cost-effective at the WTP thresholds of all 31 Chinese provinces in 61.4% (Gansu) to 83.1% (Beijing) of simulations. Conclusions: Ceftazidime-avibactam is expected to be a cost-effective treatment compared with PMB monotherapy or PMB-based therapy for CRKP BSI from the Chinese healthcare perspective.

Comparative efficacy and acceptability of antidepressants and benzodiazepines for the treatment of panic disorder: A systematic review and network meta-analysis.

OBJECTIVE: This systematic review aims to assess the efficacy and acceptability of the different types of antidepressants and benzodiazepines for the treatment of panic disorder (PD) in adult patients. METHODS: PubMed, Web of Science, EMBASE, MEDLINE, the Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) published between 1995 and 2020 on the use of antidepressants and benzodiazepines for the treatment of PD. A systematic review and network meta-analysis were performed. RESULTS: 42 RCTs were included in the network meta-analysis, with a comparison of 11 interventions.Escitalopram (odds ratios OR 1.52, 95 % credible interval CI 1.09-2.10), venlafaxine (OR 1.33, 95 % CI 1.16-1.51) and benzodiazepines (OR 1.50, 95 % CI 1.29-1.75) had greater efficacy and acceptability than the placebo. Imipramine(OR 1.43, 95 % CI 1.15-1.79) was also demonstrated to be efficacious and tolerated but the results were restricted to small sample size. Moreover, paroxetine, sertraline, fluoxetine, citalopram and clomipramine (OR 1.37, 1.36, 1.45, 1.33 and 1.36, respectively) were more efficacious, although the acceptability of paroxetine and sertraline were significantly less tolerated than benzodiazepines. Notably, the efficacy of reboxetine and fluvoxamine were merely as equal as that of the placebo. OUTCOMES: This is the first systematic review of antidepressants and benzodiazepines for the treatment of PD to use a network analysis. Escitalopram and venlafaxine as well as benzodiazepines may be effective choices as treatments for PD with relatively good acceptability, which still needs to be confirmed byhigh-quality RCTs.

Calcitonin gene-related peptide receptor antagonist ubrogepant for the treatment of acute migraine: A meta-analysis.

BACKGROUND: The objective of this study is to systematically evaluate the efficacy and safety of the calcitonin gene-related peptide (CGRP) receptor antagonist ubrogepant for the treatment of acute migraine. METHODS: Randomized controlled trials (RCTs) of ubrogepant for treatment of acute migraine were identified in PubMed, MEDLINE, EMBASE, and the Cochrane Library from database establishment to June 2020; we also searched ClinicalTrials.gov manually during the same period. Then, RevMan 5.3 software was used to perform a meta-analysis on each outcome measure. RESULTS: A total of 5 RCTs involving 4903 patients were included; there were 3358 cases in the ubrogepant group and 1545 cases in the placebo group. The meta-analysis showed the following results: at 2 hours postdose, the percentages of participants reporting pain relief and the absence of photophobia, nausea, and phonophobia were significantly higher in the ubrogepant group than in the placebo group (odds ratio [OR] = 1.71, 95%CI: 1.48-1.97, P < .00001; OR = 1.33, 95%CI: 1.22-1.45, P < .00001; OR = 1.07, 95%CI: 1.03-1.11, P = .0006; OR = 1.21, 95%CI: 1.14-1.28, P < .00001). The incidence of common adverse events was similar between the 2 groups (P > .05). CONCLUSION: Ubrogepant is effective and safe for the treatment of acute migraine. REGISTRATION NUMBER: PROSPERO CRD42019145286.

Comparative efficacy and safety of combination therapy with high-dose sulbactam or colistin with additional antibacterial agents for multiple drug-resistant and extensively drug-resistant Acinetobacter baumannii infections: A systematic review and network meta-analysis.

OBJECTIVES: This study aimed to compare the efficacy and safety of combination therapy with high-dose sulbactam or colistin with additional antibacterial agents for treating multidrug-resistant or extensively drug-resistant Acinetobacter baumannii (MDR-AB or XDR-AB) infections. METHODS: We systematically searched PubMed, Embase, Cochrane, and Web of Science (through March 30, 2020) for studies that examined high-dose sulbactam or colistin with additional antibacterial agents as therapy for patients with infections with MDR-AB and XDR-AB. Through a network meta-analysis (NMA), using both direct and indirect evidence, we determined risk ratios and 95% confidence intervals. Primary outcomes included clinical improvement, clinical cure, microbiological eradication, and mortality from any cause. Secondary outcomes included nephrotoxicity. RESULTS: The NMA included 18 studies and 1835 patients. We found that high-dose sulbactam (≥6 g per day), combined with another single antibacterial agent (levofloxacin or tigecycline), which were the highest ranking in clinical improvement and clinical cure. Still colistin-based combination in drug-resistant Acinetobacter baumannii therapy occupied the main position (the number of studies and patients) in most studies. Colistin combined with additional antibacterial agents was associated with a higher risk of nephrotoxicity. CONCLUSIONS: Therapeutic regimens including high-dose sulbactam in combination with additional antibacterial agents (including colistin) might be one of the promising options for the treatment of MDR-AB or XDR-AB infections and high-quality study will be needed to confirm clinical efficacy.