Background To systematically review the literature about the association between systemic corticosteroid therapy (CST) and outcomes of COVID-19 patients. Methods We searched Medline, Embase, EBM Reviews, Scopus, Web of Science, and preprints up to July 20, 2020. We included observational studies and randomized controlled trials (RCT) that assessed COVID-19 patients treated with CST. We pooled adjusted effect estimates of mortality and other outcomes using a random effect model, among studies at low or moderate risk for bias. We assessed the certainty of evidence for each outcome using the GRADE approach. Results Out of 1067 citations screened for eligibility, one RCT and 19 cohort studies were included (16,977 hospitalized patients). Ten studies (1 RCT and 9 cohorts) with 10,278 patients examined the effect of CST on short term mortality. The pooled adjusted RR was 0.92 (95% CI 0.69–1.22, I 2 = 81.94%). This effect was observed across all stages of disease severity. Four cohort studies examined the effect of CST on composite outcome of death, ICU admission and mechanical ventilation need. The pooled adjusted RR was 0.41(0.23−0.73, I 2 = 78.69%). Six cohort studies examined the effect of CST on delayed viral clearance. The pooled adjusted RR was 1.47(95% CI 1.11–1.93, I 2 = 43.38%). Conclusion In this systematic review, as of July 2020, heterogeneous and low certainty cumulative evidence based on observational studies and one RCT suggests that CST was not associated with reduction in short-term mortality but possibly with a delay in viral clearance in patients hospitalized with COVID-19 of different severities. However, the discordant results between the single RCT and observational studies as well as the heterogeneity observed across observational studies, call for caution in using observational data and suggests the need for more RCTs to identify the clinical and biochemical characteristics of patients’ population that could benefit from CST.

Background Drug-resistant gram-negative bacteria (GNB) are a global public health threat, especially in intensive care units (ICU). This study explored the prevalence of drug-resistant Enterobacteriaceae infections in an ICU in Saudi Arabia. The appropriateness of the antibiotic therapies used and their ability to improve the clinical outcomes were also assessed. Methods A retrospective study was conducted from 2015 to 2018 in the different ICUs of a tertiary-care hospital in Saudi Arabia. Positive cultures for multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) Enterobacteriaceae, including Klebsiella pneumoniae, Escherichia coli , and Enterobacter sp., were included. The primary outcomes involved microbiological cure and 30 days in-hospital mortality rate, while the secondary outcome included the length of hospital stay (LOS). Regression models were used to assess the relationship between appropriateness of the antibiotic therapy and clinical outcomes. Results Of the 227 Enterobacteriaceae cultures included in this study, 60% were either MDR (n= 130) or XDR (n= 8) infections; no PDR Enterobacteriaceae cultures were identified. Majority of the patients were female (54%), and the average age was 60.1 ± 17.7 years. MDR/XDR cultures primarily comprised E. coli (51.4%), followed by K. pneumoniae (33%) and Enterobacter sp. (16%). Most commonly used antibiotics were piperacillin/tazobactam (53%), carbapenems (47%), and cephalosporins (21.3%). Antibiotic therapy was considered appropriate in only 85 of 138 (61.59%) patients. Microbiological cure rate was achieved in 40% of the cases, and in-hospital death rate was 84%. The average LOS was 27 days. Appropriateness of the antibiotic therapy prescribed could not predict any of the study outcomes. Conclusion The study revealed a high prevalence of drug-resistant Enterobacteriaceae infections, which were associated with a high mortality rate. Therefore, it is essential to assess the effectiveness of antimicrobial stewardship program and infection prevention and control practices, particularly in critically ill patients.

Background The aim of this study was to compare the safety and effectiveness of ceftazidime-avibactam (CAZ-AVI) to colistin-based regimen in the treatment of infections caused by carbapenem-resistant Enterobacterales (CRE). Methods This was a retrospective, multicenter, observational cohort study of inpatients who received either CAZ-AVI or intravenous colistin for treatment of infections due to CRE. The study was conducted in 5 tertiary care hospitals in Saudi Arabia. Main study outcomes included in-hospital mortality, clinical cure at end of treatment, and acute kidney injury (AKI). Univariate analysis and multivariate logistic regression model were conducted to assess the independent impact of CAZ-AVI on the clinical outcome. Results A total of 230 patients were included in this study: 149 patients received CAZ-AVI and 81 patients received colistin-based regimen. Clinical cure (71% vs 52%; P = 0.004; OR, 2.29; 95% CI, 1.31–4.01) was significantly more common in patients who received CAZ-AVI. After adjusting the difference between the two groups, treatment with CAZ-AVI is independently associated with clinical cure (adjusted OR, 2.75; 95% CI, 1.28–5.91). In-hospital mortality (35% vs 44%; P = 0.156; OR, 0.67; 95% CI, 0.39–1.16) was lower in patients who received CAZ-AVI but the difference was not significant. AKI (15% vs 33%; P = 0.002; OR, 0.37; 95% CI, 0.19–0.69) was significantly less common in patients who received CAZ-AVI. Conclusion CAZ-AVI is associated with higher rate of clinical cure and lower rate of AKI compared to colistin. Our findings support the preferential use of CAZ-AVI over colistin-based regimen for treating these infections.

To compare the effectiveness and safety of aerosolized (AER) plus intravenous (IV) colistin with IV colistin alone in patients with nosocomial pneumonia (NP) due to multidrug-resistant (MDR) Gramnegative bacteria. Methods: This was a retrospective cohort study of adults with NP who received IV colistin alone or in combination with AER colistin. The primary endpoint was clinical cure at end of therapy. Secondary endpoints included microbiological eradication, in-hospital mortality and nephrotoxicity. Results: In total, 135 patients were included in this study: 65 patients received AER plus IV colistin and 70 patients received IV colistin alone. Baseline characteristics were similar between the two groups. Clinical cure was achieved in 42 (65%) patients who received AER plus IV colistin and 26 (37%) patients who received IV colistin alone (P = 0.01). Among a total of 88 patients who were microbiologically evaluable, 27 (42%) patients who received AER plus IV colistin and 12 (17%) patients who received IV colistin alone attained favourable microbiological outcomes (P = 0.022). In-hospital mortality (43% vs 59%, P = 0.072) was higher in patients who received IV colistin alone, but the difference was not significant. Renal injury occurred in 31% of patients who received AER plus IV colistin and in 41% of patients who received IV colistin alone (P = 0.198). Conclusion: AER colistin can be considered as salvage therapy as an adjunct to IV administration for the treatment of patients with NP due to MDR Gram-negative pathogens.

Background. Highly resistant gram-negative bacteria (GNB) is a global public health threat, especially in intensive care units (ICU). The purpose of this study is to explore the prevalence of drug resistant Enterobacteriaceae infections at an Intensive Care Unit (ICU) in Saudi Arabia. It also aims to assess the appropriateness of therapies used and whether these therapies improved clinical outcomes. Methods. A retrospective study was conducted from 2015 to 2018 in a tertiary hospital ICUs in Saudi Arabia. Positive cultures for multidrug-resistant (MDR), extensive drug resistant (XDR), and pan drug-resistant (PDR) Enterobacteriaceae: Klebsiella pneumoniae (K. pneumonia), Escherichia coli (E. coli), and Enterobacter species were included. Primary outcome was microbiological cure and 30 days in hospital mortality rates; while secondary outcome was length of hospital stay (LOS). Regression models were used to assess the relationship between appropriateness of therapy and outcomes. Results. This study included 227 Enterobacteriaceae cultures in which 60% were either MDR (n=130) or XDR (n=8) infections; no PDR Enterobacteriaceae cultures were identified. The average subjects’ age was 60.1±17.7 years and 54% were females. Half of the MDR/XDR cultures were E. coli, followed by 33% K. pneumoniae, and 16% Enterobacter infection. The most common antibiotics used were piperacillin/tazobactam (53%), followed by carbapenems (47%) and cephalosporins (21.3%). Antibiotic therapy was considered appropriate in 85 out of 138 (61.59%) subjects only. In-hospital death was 84%, microbiological cure rate was achieved in 40% of cases, and the average LOS was 27 days. Appropriateness of antibiotic therapy prescribed was not a predictor of any of the study clinical outcomes. Conclusion. In this study, there was a high prevalence of resistant Enterobacteriaceae infections, which were associated with a high mortality rate. This warrants the need to assess the effectiveness of antimicrobial stewardship program and infection prevention and control practices particularly in critically ill patients.