Loading dose and efficacy of continuous or extended infusion of beta-lactams compared with intermittent administration in patients with critical illnesses: A subgroup meta-analysis and meta-regression analysis.

WHAT IS KNOWN AND OBJECTIVE: The role of continuous/extended beta-lactam infusions (CEIs) in improving clinical outcomes among critically ill patients remains controversial. Therefore, we aimed to compare the clinical efficacy of CEI versus intermittent administration (IA) of beta-lactams by performing a systematic review and meta-analysis. METHODS: PubMed, the Cochrane Library and Embase were searched from inception until December 2018 for studies comparing clinical outcomes of CEI versus IA in critically ill patients. The meta-analysis included 18 randomized controlled trials (RCTs) and 13 non-RCTs. RESULTS AND DISCUSSION: For CEI versus IA, the summary relative risk (RR) for overall mortality and clinical cure was 0.82 (95% confidence interval [CI]: 0.72-0.94) and 1.31 (95% CI: 1.15-1.49), respectively. Subgroup and meta-regression analyses of the loading dose revealed a significantly increased clinical cure rate in the loading-dose group (RR: 1.44, 95% CI: 1.22-1.69), which remained significant after adjustments for beta-lactam type, and association between clinical cure and loading dose for clinical cure (RR: 1.47, 95% CI: 1.20-1.80; p = .001). Subgroup analysis of administration type indicated that both groups had low mortality and high clinical cure rates; however, the heterogeneity analysis did not support an association across continuous infusion and extended infusion groups. Subgroup analysis of the Acute Physiology and Chronic Health Evaluation (APACHE) score was conducted; according to APACHE scores ≥ 16, overall mortality and clinical cure significantly differed between CEI and IA. WHAT IS NEW AND CONCLUSION: CEIs with loading-dose treatment may significantly improve the clinical outcomes in critically ill sepsis or septic shock patients.

Optimal Sequence and Second-Line Systemic Treatment of Patients with RAS Wild-Type Metastatic Colorectal Cancer: A Meta-Analysis.

Although several sequential therapy options are available for treating patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), the optimal sequence of these therapies is not well established. A systematic review and meta-analysis of 13 randomized controlled trials and 4 observational studies were performed, resulting from a search of the Cochrane Library, PubMed, and Embase databases. Overall survival (OS) did not differ significantly in patients with RAS-WT failure who were administered a second-line regimen of changed chemotherapy (CT) plus anti-epidermal growth factor receptor (EGFR) versus only changed CT, changed CT plus bevacizumab versus changed CT plus anti-EGFR, or changed CT versus maintaining CT plus anti-EGFR after first-line therapy with CT, plus bevacizumab. However, OS was significantly different with a second-line regimen that included changed CT plus bevacizumab, versus only changing CT. Analysis of first-line therapy with CT plus anti-EGFR for treatment of RAS-WT mCRC indicated that second-line therapy of changed CT plus an anti-EGFR agent resulted in better outcomes than changing CT without targeted agents. The pooled data study demonstrated that the optimal choice of second-line treatment for improved OS was an altered CT regimen with retention of bevacizumab after first-line bevacizumab failure. The best sequence for first-to-second-line therapy of patients with RAS-WT mCRC was cetuximab-based therapy, followed by a bevacizumab-based regimen.

Ertapenem in the treatment of bacteremia caused by extended-spectrum beta-lactamase-producing Escherichia coli: a propensity score analysis.

OBJECTIVE: This study assessed the impact of ertapenem and other carbapenems on mortality in patients with monomicrobial extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) bacteremia. METHODS: This non-concurrent prospective study included adult patients with ESBL-EC bacteremia during a 2.5-year period at a 2200-bed teaching hospital. We used a multivariate logistic regression model and Cox's proportional hazards model including propensity score analysis to assess variables associated with 30-day mortality. RESULTS: Of 71 patients who met the study criteria, nine died within 3 days. Among the 62 remaining patients who received definitive antimicrobial therapy, 13 died within 30 days. Male gender, ICU stay, solid tumor, and primary bacteremia were independent predictors of 30-day mortality, whereas definitive antimicrobial therapy using either ertapenem or imipenem/meropenem was protective (p<0.001 and p=0.002, respectively). Adjustment by propensity score found that ertapenem appeared to exhibit more favorable outcomes, but the difference fell short of statistical significance (hazard ratio 0.02, p=0.06). Inappropriate initial therapy was not a significant predictor of mortality. CONCLUSIONS: ICU stay, but not initial choice of empirical antimicrobial therapy, was a major predictor of mortality. Using a carbapenem as definitive therapy was a protective factor for 30-day mortality. The choice of ertapenem is reasonable for less severely-ill patients who are at risk of ESBL-EC bacteremia and unlikely to have infection due to Pseudomonas aeruginosa.

Risk factors for bloodstream infections due to extended-spectrum beta-lactamase-producing Escherichia coli.

BACKGROUND/PURPOSE: The risk factors for production of extended-spectrum beta-lactamases (ESBLs) have rarely been studied for bloodstream infections of Escherichia coli alone. A case-control study was undertaken to identify the risk factors associated with bloodstream infections caused by ESBL producing E. coli. METHODS: From January 1, 2005 to June 30, 2007, all patients with a confirmed diagnosis of bloodstream infection caused by ESBL-producing E. coli were reviewed. Each patient was matched with one control subject who experienced ESBL-negative E. coli bacteremia during the same study period. RESULTS: Of the 97 patients diagnosed with ESBL-producing E. coli bacteremia, six were excluded owing to incomplete follow-up and missing data. Comparisons were made between 91 patients and their controls. Multivariate analysis identified urinary catheterization [odds ratio (OR) = 6.21, 95% confidence interval (CI) = 1.91-20.25; p = 0.003], prior exposure to antibiotics (OR = 2.93, 95% CI = 1.18-7.30; p = 0.021) and previous treatment with oxyimino-cephalosporins (OR = 5.16, 95% CI = 1.03-25.79; p = 0.046) as independent predictors for bloodstream infection by ESBL-producing E. coli. Conversely, patients classified as having a community-acquired infection were less likely to acquire bacteremia caused by ESBL-producing E. coli than those caused by non-ESBL-producing E. coli (OR = 0.22, 95% CI = 0.09-0.57; p = 0.002). CONCLUSION: More judicious use of antimicrobial agents, especially oxyimino-cephalosporins, and avoidance of urinary catheterization may decrease the possibility of ESBL-producing E. coli bacteremia in hospitalized patients.