The impact of a restricted pregabalin prescription policy on drug utilization: An observational multicenter study.

Background: The Saudi Food and Drug Authority (SFDA) classified pregabalin as a controlled substance in 2018; however, whether this policy change has affected pregabalin use is unclear. This study examined the trends in pregabalin prescriptions before and after the SFDA restriction. In addition, the co-prescription of controlled analgesics and the use of pregabalin for approved indications were also evaluated. Method: A cross-sectional study was conducted on outpatient pregabalin prescriptions from three healthcare centers in Saudi Arabia. Interrupted time series analysis was used to assess changes over time in pregabalin prescriptions and the number of patients receiving pregabalin. June 2016 to June 2017 was identified as the pre-restriction period, and July 2018 to July 2019 as the post-restriction period. Results: In this study, 77,760 pregabalin prescriptions were identified. There were 9,076 patients on pregabalin in the pre-restriction period with 16,875 prescriptions, compared with 7,123 patients and 19,484 prescriptions post-restriction. The total number of pregabalin users decreased by 21.5% post-restriction, and prescriptions increased by 15.5%. There was no significant change in the monthly trends in pregabalin prescriptions before and after the restriction. However, the of tramadol and acetaminophen/codeine prescriptions in patients who were using pregabalin increased in the post-restriction period by 21% and 16.1%, respectively. Conclusion: Pregabalin use was reduced after the SFDA-enforced prescription restriction was implemented. This was accompanied by increased narcotics use in the post-implementation phase.

Inhaled colistin for the treatment of nosocomial pneumonia due to multidrug-resistant Gram-negative bacteria: A real-life experience in tertiary care hospitals in Saudi Arabia.

BACKGROUND: Nosocomial pneumonia (NP) due to multidrug-resistant (MDR) Gram-negative pathogens, has continued to rise over the last several decades. Parenteral administration of colistin results in poor alveolar penetration and subtherapeutic concentration; therefore, direct drug deposition at site of infection may improve the effectiveness while minimizing the systemic exposure. The aim of this study is to describe the safety and effectiveness of inhaled colistin for the treatment of NP caused by MDR Gram-negative pathogens. METHOD: Patients who received inhaled colistin from May 2015 to May 2019 at 2 different tertiary care hospitals in Riyadh, Saudi Arabia were identified from pharmacy databases and their charts were retrospectively reviewed. RESULTS: 86 patients were enrolled in this study. The mean age was 56 ± 20 years. The mean Acute Physiology and Chronic Health Evaluation (APACHE II) was 17 ± 5. The responsible pathogens for NP were Pseudomonas aeruginosa (60%) Acinetobacter baumannii (28%), and Klebsiella pneumoniae (9%). Most patients (76/86) received concomitant intravenous antibiotics. Mean colistin total daily dose was 6 ± 3 million international units divided into 2-3 doses. Mean inhaled colistin duration of therapy was 11 ± 6 days. Favorable clinical outcome was achieved in 51 (59%) patients while favorable microbiological outcome occurred in 29 (34%) patients. Death due to all causes was noted in 39 (45%) cases. Renal injury occurred in 19 (22%) patients, all received concomitant intravenous colistin. CONCLUSION: Inhaled colistin can be considered as salvage therapy as adjunct to intravenous administration for treatment of patients with NP due to MDR Gram-negative pathogens.

Linezolid-Associated Thrombocytopenia: Assessment of Risk Factors in Patients without Hemato-Oncologic Diseases.

Background: Linezolid is used for Gram-positive bacterial infections. Thrombocytopenia is one of its main adverse effects resulting from myelosuppression. Several studies have assessed risk factors that may increase the risk of this adverse effect. However, most studies included patients with hemato-oncologic diseases, which may confound such assessments. This study aimed to investigate risk factors for linezolid-associated thrombocytopenia in patients without hemato-oncologic diseases. Methods: This was a multicenter retrospective case-control study of adult patients treated with linezolid twice daily for ≥3 days. Patients with hemato-oncologic diseases, active dengue fever, active COVID-19, baseline platelet count <100 × 103/mm3, concurrent therapy with trimethoprim/sulfamethoxazole or valproic acid, and a recent platelet transfusion within 7 days were excluded. Thrombocytopenia was defined as a drop in platelet count below 100 × 103/mm3. Results: Out of 158 evaluated patients, 33 developed thrombocytopenia, indicating an incidence rate of 20.9%. Of all the risk factors assessed, creatinine clearance of <60 mL/min and bacteremia/infective endocarditis were significantly associated with linezolid-associated thrombocytopenia (adjusted odds ratios, 3.25 and 5.95; 95% CI 1.12-9.45 and 1.23-28.66; p = 0.031 and 0.026, respectively). End of therapy platelet counts were significantly lower in the cases than in the controls (79 vs. 243 × 103/mm3; p < 0.001). Similarly, the percentage of platelet count change was significantly different (-55.1% vs. -10.2%; p < 0.001). Conclusions: In our study, the incidence rate of linezolid-associated thrombocytopenia was 20.9%, and we found that patients with renal impairment and bacteremia may need close monitoring of platelet counts. Prospective studies are warranted to evaluate the potential need for renal dose adjustment.

Impact of Nurse Leaders Behaviors on Nursing Staff Performance: A Systematic Review of Literature.

Nursing leadership is critical in facilitating and improving nurse performance, which is essential for providing quality care and ensuring patient safety. The aim of this study is to explore the relationship between nursing leadership and nurse performance by understanding the leadership behaviors and factors that motivate nurses to perform well. To study the factors that nurses believe motivate them to perform better, a systematic review was undertaken, correlating these factors to leadership behaviors/styles. The PRISMA guidelines were followed to identify relevant articles. After applying the selection criteria, 11 articles were included in the final analysis. Overall, 51 elements that influence nurses' motivation to perform better were found and categorized into 6 categories, including autonomy, competencies, relatedness, individual nursing characteristics, relationships and support, and leadership styles/practices. It has been discovered that both direct and indirect nursing leadership behaviors affect nurses' performance. A better understanding of the factors that motivate nurses to perform well and facilitating them in the work environment through leadership behaviors/styles can improve nurses' performance. There is a need to increase research on nurse leadership and nurses' performance in the current innovative and technologically integrated work environment to identify new factors of influence.

Ceftazidime-Avibactam versus Colistin for the Treatment of Infections Due to Carbapenem-Resistant Enterobacterales: A Multicenter Cohort Study.

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.

Aerosolized plus intravenous colistin vs intravenous colistin alone for the treatment of nosocomial pneumonia due to multidrug-resistant Gram-negative bacteria: A retrospective cohort study.

OBJECTIVE: 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) Gram-negative 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.

Insights into the ancestry evolution of the Mycobacterium tuberculosis complex from analysis of Mycobacterium riyadhense.

Current evolutionary scenarios posit the emergence of Mycobacterium tuberculosis from an environmental saprophyte through a cumulative process of genome adaptation. Mycobacterium riyadhense, a related bacillus, is being increasingly isolated from human clinical cases with tuberculosis-like symptoms in various parts of the world. To elucidate the evolutionary relationship between M. riyadhense and other mycobacterial species, including members of the M. tuberculosis complex (MTBC), eight clinical isolates of M. riyadhense were sequenced and analyzed. We show, among other features, that M. riyadhense shares a large number of conserved orthologs with M. tuberculosis and shows the expansion of toxin/antitoxin pairs, PE/PPE family proteins compared with other non-tuberculous mycobacteria. We observed M. riyadhense lacks wecE gene which may result in the absence of lipooligosaccharides (LOS) IV. Comparative transcriptomic analysis of infected macrophages reveals genes encoding inducers of Type I IFN responses, such as cytosolic DNA sensors, were relatively less expressed by macrophages infected with M. riyadhense or M. kansasii, compared to BCG or M. tuberculosis. Overall, our work sheds new light on the evolution of M. riyadhense, its relationship to the MTBC, and its potential as a system for the study of mycobacterial virulence and pathogenesis.

Association of corticosteroids use and outcomes in COVID-19 patients: A systematic review and meta-analysis.

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, I2 = 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, I2 = 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, I2 = 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.

Multidrug-Resistant and Extensively Drug-Resistant Enterobacteriaceae: Prevalence, Treatments, and Outcomes - A Retrospective Cohort Study.

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.