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.

Comparison of laboratory results between central venous access devices and venipuncture: A systematic review and meta-analysis.

OBJECTIVES: To compare the hematologic, blood chemistry, and coagulation test results between two blood sampling methods via central venous access devices (CVADs) and venipuncture. METHOD: The authors searched PubMed, Embase, Cochrane, Web of Science, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) for controlled studies that compared the differences in hematologic, blood chemistry, and coagulation test results between venipuncture and CVADs from the date of database establishment to July 2022. Two researchers independently performed the literature screening, data extraction, and quality assessment. The standardized mean difference was used as the effect size for continuous variables and a 95% confidence interval was provided. The random-effects model was used for an I2 > 50%, otherwise the fixed-effects model was used. Sources of heterogeneity were determined by subgroup analysis or sensitivity analysis, as indicated. RESULTS: This review ultimately identified 17 studies for systematic review, of which 12 were selected for meta-analysis. A total of 541 adult participants were included in the meta-analysis. With the exception of the activated partial thromboplastin time, there were no significant differences in hematologic, blood chemistry, and coagulation test results between blood sampling via venipuncture and CVADs. CONCLUSIONS: The results of this study provide substantial evidence that blood sampling via venipuncture and CVADs had equal reliability in most laboratory tests. Serial blood sampling via CVADs will reduce the risk of bleeding episodes and pain at the blood collection site, and safety for healthcare professionals.

A case of G6PD Utrecht associated with ß-thalassemia responding to splenectomy.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disease caused by a pathogenic G6PD mutation. An 8-year-old Chinese male child was investigated because of chronic nonspherocytic hemolytic anemia (CNSHA) associated with hepatosplenomegaly. Genetic analysis unraveled co-inheritance of a hemizygous mutation c.1225C>T (p.Pro409Ser) in G6PD (G6PD Utrecht, previously reported only in The Netherlands) and heterozygote HBB mutation c.316-197C>T (IVS-Ⅱ-654 C>T). Because IVS-Ⅱ-654 C>T on its own does not cause CNSHA, we believe that the clinical manifestations in this patient are essentially due to the G6PD c.1225C>T mutation. The boy gained transfusion independence after splenectomy.

Disproportionality analysis of quinolone safety in children using data from the FDA adverse event reporting system (FAERS).

Background: Quinolones are widely prescribed for the treatment or prevention of infectious diseases in children. To gain further insight into quinolone-associated adverse event (AE) in children and better protect pediatric patients, continued surveillance of safety data is essential. The purpose of this study was to characterize the safety profiles of quinolone-associated AEs in children by mining the FDA adverse event reporting system (FAERS). Methods: FAERS reports from quarter 1 of 2004 to quarter 1 of 2022 were included in the study. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify adverse events. Reporting odds ratios (ROR) corresponding 95% confidence intervals (CIs) and information component (IC) along with 95% CIs were calculated to detect drug-AE pairs with higher-than-expected reporting rates within the FAERS from System Organ Classes (SOCs) to Preferred Terms (PTs). Reports were considered as signals if the 95% confidence interval did not contain the null value. Results: After inclusion criteria were applied, a total of 4,704 reports associated with quinolones were considered. Most FAERS reports associated with ciprofloxacin (N = 2,706) followed by levofloxacin (N = 1,191), moxifloxacin (N = 375), oflaxacin (N = 245) and ozenoxacin (N = 187). The most common age group was 12-18 years. The median weight was 39.0 kilogram. The adverse effects of quinolones emerging for SOCs primarily included Infections and infestations, gastrointestinal symptoms, blood and lymphatic system disorders, cardiac disorders, nervous system disorders, musculoskeletal and connective tissue disorders and psychiatric disorders. The most frequently AE signals at the PT level were pyrexia (N = 236), febrile neutropenia (N = 120), off label use (N = 48), drug resistance (N = 18) and cardiac arrest (N = 22) following the use of ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, and ozenoxacin, respectively. Serious oznoxacin-associated AE signals were found and have not been documented in the package insert. They included cardiac arrest (N = 22; ROR = 19.83; IC = 3.68), overdose (N = 21; ROR = 4.98; IC = 2.07), seizure (N = 16; ROR = 6.01; IC = 2.29), small for dates baby (N = 9; ROR = 14.7; IC = 3.05), completed suicide (N = 15, ROR = 18.87; IC = 3.51), asthma (N = 9; ROR = 6.69; IC = 2.24;) and hypotension (N = 9; ROR = 3.83; IC = 1.68). Conclusion: This study provided additional evidence with respect to quinolones-related AEs for children. Generally, the findings of this study are compatible with AEs recorded in package inserts. The unexpected signals of ozenoxacin justify active vigilance by clinicians and timely monitoring by pharmacovigilance experts.

Comparative Remission Rates and Tolerability of Drugs for Generalised Anxiety Disorder: A Systematic Review and Network Meta-analysis of Double-Blind Randomized Controlled Trials.

Background: Generalized anxiety disorder (GAD) is one of the most common psychiatric disorders associated with substantial dysfunction and socioeconomic burden. Pharmacotherapy is the first choice for GAD. Remission [Hamilton Anxiety Scale (HAM-A) score ≤7] is regarded as a crucial treatment goal for patients with GAD. There is no up-to-date evidence to compare remission rate and tolerability of all available drugs by using network meta-analysis. Therefore, the goal of our study is to update evidence and determine the best advantageous drugs for GAD in remission rate and tolerability profiles. Method: We performed a systematic review and network meta-analysis of double-blind randomized controlled trials (RCTs). We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, wanfang data, China Biology Medicine and ClinicalTrials.gov from their inception to March 2020 to identify eligible double-blind, RCTs reporting the outcome of remission in adult patients who received any pharmacological treatment for GAD. Two reviewers independently assessed quality of included studies utilizing the Cochrane Collaboration's risk of bias tool as described in Cochrane Collaboration Handbook and extracted data from all manuscripts. Our outcomes were remission rate (proportion of participants with a final score of seven or less on HAM-A) and tolerability (treatments discontinuations due to adverse events). We calculated summary odds ratios (ORs) and 95% confidence intervals (CIs) of each outcome via pairwise and network meta-analysis with random effects. Results: Overall, 30 studies were included, comprising 32 double-blind RCTs, involving 13,338 participants diagnosed as GAD by DSM-IV criteria. Twenty-eight trials were rated as moderate risk of bias, four trials as low. For remission rate, agomelatine (OR 2.70, 95% CI 1.74-4.19), duloxetine (OR 1.88, 95% CI 1.47-2.40), escitalopram (OR 2.03, 95% CI 1.48-2.78), paroxetine (OR 1.74, 95% CI 1.25-2.42), quetiapine (OR 1.88, 95% CI 1.39-2.55), and venlafaxine (OR 2.28, 95% CI 1.69-3.07) were superior to placebo. For tolerability, sertraline, agomelatine, vortioxetine, and pregabalin were found to be comparable to placebo. However, the others were worse than placebo in terms of tolerability, with ORs ranging between 1.86 (95% CI 1.25-2.75) for tiagabine and 5.98 (95% CI 2.41-14.87) for lorazepam. In head-to-head comparisons, agomelatine, duloxetine, escitalopram, quetiapine, and venlafaxine were more efficacious than tiagabine in terms of remission rate, ORs from 1.66 (95% CI 1.04-2.65) for duloxetine to 2.38 (95% CI 1.32-4.31) for agomelatine. We also found that agomelatine (OR 2.08, 95% CI 1.15-3.75) and venlafaxine (OR 1.76, 95% CI 1.08-2.86) were superior to vortioxetine. Lorazepam and quetiapine were poorly tolerated when compared with other drugs. Conclusions: Of these interventions, only agomelatine manifested better remission with relatively good tolerability but these results were limited by small sample sizes. Duloxetine, escitalopram, venlafaxine, paroxetine, and quetiapine showed better remission but were poorly tolerated.

[A systematic review of anti-interleukin-17 antibody in the treatment of plaque psoriasis].

OBJECTIVE: To evaluate the efficacy and safety of anti-interleukin-17 antibody in the treatment of plaque psoriasis. METHDOS: Randomized controlled trials (RCT) of anti-interleukin-17 antibody (Secukinumab, Brodalumab, and Ixekizumab) in the treatment of plaque psoriasis published between January, 2000 and March, 2017 were searched from PubMed, Cochrane Library, EBSCO, EMbase, CBM, CNKI, VIPdetabase, and Wangfang database. The quality of the retrieved trials was evaluated and the results of studies were analyzed using RevMan 5.0 software. RESULTS: Thirteen RCTs were included involving a total of 11 203 patients. Meta-analysis showed a significant differences between anti-interleukin-17 antibody and placebo (or positive drug) in terms of PASI75 and sPGA (P<0.05). The total incidence of adverse events differed significantly between anti- interleukin-17 antibody and placebo, but no significant differences were found between them in the incidence of serious adverse events and discontinuation rate due to adverse events (P>0.05). CONCLUSION: Anti-interleukin-17 antibody is safe and effective for treatment of plaque psoriasis.