Mortality of continuous infusion versus intermittent bolus of meropenem: a systematic review and meta-analysis of randomized controlled trials.

Background: Meropenem belongs to the carbapenem class, which is categorized as beta-lactam antibiotics. These antibiotics are administered in intermittent bolus doses at specific time intervals. However, the continuous infusion approach ensures sustained drug exposure, maintaining the drug concentration above the minimum inhibitory concentration (MIC) throughout the entire treatment period. This study aimed to find out the association between continuous infusions of meropenem and mortality rates. Materials and methods: We conducted a search of the PubMed/Medline, EMBASE, Cochrane Central, and ClinicalTrials.gov databases up to 14 August 2023. The six randomized controlled trials (RCTs) were identified and included in our analysis. The random-effects model was implemented using Comprehensive Meta-Analysis software to examine the outcomes. Results: Our study included a total of 1,529 adult patients from six randomized controlled trials. The primary outcome indicated that continuous infusion of meropenem did not lead to reduction in the mortality rate (odds ratio = 0.844, 95% CI: 0.671-1.061, P =0.147). Secondary outcomes revealed no significant differences in ICU length of stay (LOS), ICU mortality, clinical cure, or adverse events between continuous infusion and traditional intermittent bolus strategies of meropenem. Notably, we observed significant improvements in bacterial eradication (odds ratio 19 = 2.207, 95% CI: 1.467-3.320, P < 0.001) with continuous infusion of meropenem. Our study also suggested that performing continuous infusion may lead to better bacterial eradication effects in resistant pathogens (coefficient: 2.5175, P = 0.0138*). Conclusion: Continuous infusion of meropenem did not result in the reduction of mortality rates but showed potential in improving bacterial eradication. Furthermore, this strategy may be particularly beneficial for achieving better bacterial eradication, especially in cases involving resistant pathogens.

Remdesivir-Induced Bradycardia and Mortality in SARS-CoV-2 Infection, Potential Risk Factors Assessment: A Systematic Review and Meta-Analysis.

Background: The efficacy of remdesivir in reducing disease severity among COVID-19-infected patients has been established, but concerns have emerged regarding the potential side effects of bradycardia. The aim of this study was to investigate the association between remdesivir-induced bradycardia and mortality, while also identifying the related risk factors. Materials and methods: The PubMed/Medline, Cochrane Central and ClinicalTrials.gov databases were searched. Randomized controlled trials and prospective or retrospective cohort studies were included (through 14 July 2023). The random-effects model was implemented using Comprehensive Meta-Analysis software version 3.0 to examine the outcomes. Results: A total of 12 prospective or retrospective studies involving 7674 patients were analyzed. The primary outcomes revealed a significant association between remdesivir administration and bradycardia development (Odds ratio = 2.556, 95% CI = 2.049-3.188, p < 0.001). However, no statistically significant increase in the mortality rate was observed among patients with bradycardia during remdesivir treatment (Odds ratio = 0.872, 95% CI = 0.483-1.576, p = 0.651). The secondary outcome demonstrated a significant association between chronic kidney disease (CKD) and remdesivir-induced bradycardia (OR: 1.251, 95% CI: 1.003-1.561, p = 0.047). Moreover, patients with obesity (OR = 1.347, 95% CI = 1.098-1.652, p = 0.004) were more likely to experience remdesivir-induced bradycardia. Conclusions: Although a higher risk of bradycardia occurred during remdesivir treatment, the occurrence of remdesivir-induced bradycardia did not lead to higher mortality. Our study also identified patients with obesity and CKD as high-risk subgroups for experiencing bradycardia during remdesivir treatment.

Correlation between antibiotic consumption and resistance of Pseudomonas aeruginosa in a teaching hospital implementing an antimicrobial stewardship program: A longitudinal observational study.

BACKGROUND/PURPOSE: The rapid emergence of Pseudomonas aeruginosa resistance made selecting antibiotics more challenge. Antimicrobial stewardship programs (ASPs) are urging to implant to control the P. aeruginosa resistance. The purpose of this study is to evaluate the relationship between antimicrobial consumption and P. aeruginosa resistance, the impact of ASPs implemented during the 14-year study period. METHODS: A total 14,852 P. aeruginosa isolates were included in our study. The resistant rate and antimicrobial consumption were investigated every six months. Linear regression analysis was conducted to examine the trends in antibiotics consumption and antimicrobial resistance over time. The relationship between P. aeruginosa resistance and antimicrobial consumption were using Pearson correlation coefficient to analysis. The trend of resistance before and after ASPs implanted is evaluated by segment regression analysis. RESULTS: P. aeruginosa resistance to ceftazidime, gentamicin, amikacin, ciprofloxacin and levofloxacin significantly decreased during the study period; piperacillin/tazobactam (PTZ), cefepime, imipenem/cilastatin and meropenem remained stable. The P. aeruginosa resistance to ciprofloxacin and levofloxacin increasing initial then decreased after strictly controlled the use of levofloxacin since 2007. As the first choice antibiotic to treat P. aeruginosa, the consumption and resistance to PTZ increase yearly and resistance became stable since extended-infusion therapy policy implant in 2009. CONCLUSION: Our ASP intervention strategy, which included extended infusion of PTZ and restrict use of levofloxacin, may be used to control antimicrobial resistance of P. aeruginosa in medical practice.

Development of a combination antibiogram for empirical treatments of Pseudomonas aeruginosa at a university-affiliated teaching hospital.

INTRODUCTION: The significantly higher mortality rate in the critical illness patients with Pseudomonas aeruginosa (PA) infection is linked to inappropriate selecting of empirical treatment. Traditional local antibiogram provides clinicians the resistant rate of a single antimicrobial agent to the pathogen in the specific setting. The information is valuable to the clinicians in selecting suitable empirical antibiotic therapy. However, traditional local antibiogram can only provide information for single agent empirical antibiotic not combination regimens. The combination antibiogram should be developed to facilitate the selection of appropriate antibiotics to broader the coverage rate of resistant PA. METHODS: The susceptibility to the ß-lactam antibiotics (piperacillin/tazobactam (PTZ), ceftazidime, cefepime, imipenem, or meropenem) or to those administered in combination with an aminoglycoside (gentamicin or amikacin) or fluoroquinolone (ciprofloxacin or levofloxacin) was calculated. The chi-square test was used to compare the differences of combination coverage rates between non-ICU and ICU isolates. RESULTS: 880 PA isolates were isolated during study period. The susceptibility of single agents ranged from 83.1% to 89.7%. The combination regimens containing amikacin provide the highest cover rate (98.9%-99.1%) and those containing levofloxacin provide less coverage rate (92.3%-93.9%). The susceptibility to five ß-lactam single agents in ICU isolates significantly lower than non-ICU isolates. The non-ICU isolates exhibited significantly higher susceptibility to the PTZ-gentamicin (p = 0.002) and ceftazidime-gentamicin (p = 0.025) than ICU isolates. CONCLUSION: Our results support the use of aminoglycosides instead of fluoroquinolones as additive agents in empirical combination treatments for patients with critical infections caused by PA.