Early Versus Late Antipseudomonal ß-Lactam Antibiotic Dose Adjustment in Critically Ill Sepsis Patients With Acute Kidney Injury: A Prospective Observational Cohort Study.

Background: Acute kidney injury (AKI) is a common complication of sepsis, contributing to an increased mortality rate. However, some studies have demonstrated that renal function improves in sepsis patients with AKI within 48 hours, raising questions about the necessity for early antibiotic adjustment. This study evaluates the association between the timing of antipseudomonal ß-lactam dose adjustment and the outcomes of critically ill sepsis patients with AKI. Methods: A prospective, multicenter observational study of critically ill patients aged ≥18 years admitted to the intensive care unit with sepsis and AKI and started on antipseudomonal ß-lactam therapy. After the initial dose, eligible patients were grouped as early ß-lactam antibiotic (E-BLA) or late ß-lactam antibiotic (L-BLA) dose adjustments based on the administration of subsequent renally adjusted doses within 24 hours and after 24 hours of sepsis recognition, respectively. The main outcome of interest was in-hospital mortality. Results: Among 1185 patients screened, 224 (mean age, 62.7 ± 16.8 years; 62% were male) met inclusion criteria. Eighty-four and 140 patients were included in the E-BLA and L-BLA groups, respectively. Approximately half of the cohort presented with AKI stage II, and piperacillin-tazobactam was prescribed as initial empirical therapy in more than 50% of the cohort. In the multivariable Cox proportional hazards model, L-BLA was associated with a significant reduction in in-hospital mortality compared to E-BLA (hazard ratio, 0.588 [95% confidence interval, .355-.974]). Conclusions: In sepsis patients with AKI, L-BLA was associated with in-hospital mortality benefits.

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.

Ceftolozane-tazobactam vs. colistin for the treatment of infections due to multidrug-resistant Pseudomonas aeruginosa: a multicentre cohort study.

OBJECTIVES: The aim of this study was to compare the safety and effectiveness of ceftolozane-tazobactam (C-T) to colistin-based regimen for treating infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa. METHODS: This was a retrospective, multicentre, observational cohort study of inpatients who received either C-T or intravenous colistin for treating infections caused by MDR P. aeruginosa. The study was conducted in five tertiary care hospitals in Saudi Arabia. The main study outcomes included clinical cure at end of treatment, in-hospital mortality, and acute kidney injury (AKI). Univariate analysis and multivariate logistic regression model were conducted to evaluate the independent effect of C-T on the clinical outcome. RESULTS: A total of 184 patients were included in the study: 82 patients received C-T, and 102 patients received colistin-based regimen. Clinical cure (77% vs. 57%; P = 0.005; OR, 2.52; 95% CI, 1.32-4.79) was significantly more common in patients who received C-T. After adjusting the difference between the two groups, treatment with C-T is independently associated with clinical cure (adjusted OR, 2.47; 95% CI, 1.16-5.27). In-hospital mortality (39% vs. 49%; P = 0.175; OR, 0.67; 95% CI, 0.37-1.20) was lower in patients who received C-T, but the difference was not significant. AKI (15% vs. 41%; P < 0.001; OR, 0.25; 95% CI, 0.12-0.51) was significantly less common in patients who received C-T. CONCLUSION: C-T is associated with a higher rate of clinical cure and lower rate of AKI compared to colistin. Our findings support the preferential use of C-T over colistin-based regimen for treating these infections.

Evaluation of the Potential of National Sharing of a Unified Progress Test Among Colleges of Pharmacy in the Kingdom of Saudi Arabia.

BACKGROUND: With the expansion in pharmacy education in Saudi Arabia, there is a pressing need to maintain quality assurance in pharmacy programs using several tools. The progress test is a formative assessment tool that can serve to provide information to all stakeholders. This study evaluated the results of a unified progress test that was shared among 15 colleges of pharmacy. METHODS: The progress test was composed of 100 MCQs where 30% of which cover basic pharmaceutical sciences and 70% cover pharmacy practice. The questions were collected from all the 15 colleges of pharmacy participated in the test. The test was administered online to all undergraduate students in the professional programs of these colleges. RESULTS: The overall attendance rate was 80% from the total number of students enrolled in the participating colleges. Mean scores of students in basic pharmaceutical sciences were relatively higher than in pharmacy practice. The assessment results of the students in the unified program learning outcomes among colleges were higher in the domains of knowledge and skills compared to competence domain. There was a significant increment in the mean scores of the students as they progress through the years of the professional program. No correlation was found between the mean scores in the test and the cumulative grade point average (cGPA) of all students regardless of their level. CONCLUSION: The results indicated growth and maintenance of the gained knowledge and skills by the students as they progress through the years of the professional program with consistency in the results among the participating colleges. Sharing a unified test was effective as a valuable tool for the colleges of pharmacy for the purposes of benchmarking and improving the curricula. In addition, it could serve to evaluate learning of students and harmonize knowledge and skills gained by students at different institutions.

Adherence to the guidelines for surgical antimicrobial prophylaxis in a Saudi tertiary care hospital.

OBJECTIVE: The study evaluated the adherence to the guidelines for surgical antimicrobial prophylaxis in a Saudi tertiary care hospital. METHODS: The medical records of 707 patients from the surgical units over a selected 3-month period were selected. The data were reviewed and statistically analysed. RESULTS: Of the 707 respondents, 51.2% were women and most were older than 50 years. The most common surgical procedures involved orthopaedics (28.3%), followed by vascular surgery (15.1%). One hundred and thirty-eight (19.5%) patients received antibiotics according to the guidelines for surgical prophylaxis. More than half of the patients (399/56.4%) received antibiotics for more than 24 h and 129 (18.2%) received antibiotics for less than 24 h. Single dose antibiotic therapy was used in 179 (25.3%) patients. Two hundred and ninety-seven (42%) patients underwent clean surgery, 284 (40%) clean-contaminated and 128 (18%) contaminated surgery. A significant difference was evident between the antibiotics administered according to the recommended guidelines and the duration of antibiotic therapy (p = 0.001), duration (p = 0.001) and the type of surgical procedure (p = 0.00). CONCLUSION: The findings of this study suggest that healthcare professionals do not strictly adhere to the guidelines for surgical antibiotic prophylaxis. Physicians are therefore encouraged to follow the recommendations appropriately and to regularly implement surgical antimicrobial prophylaxis for patient safety.

Optimizing Vancomycin Monitoring in Pediatric Patients.

BACKGROUND: Several studies have reported that trough levels may not be optimal for monitoring vancomycin therapy, because of overexposure and nephrotoxicity risks. Therefore, we developed a population pharmacokinetic model to optimize vancomycin dosing and monitoring in pediatrics. METHODS: Data were retrospectively collected on 76 pediatric patients 1-12 years of age, admitted to general pediatric wards or intensive care units at King Saud University Medical City, Riyadh, Saudi Arabia. The predictability of 3 methods for calculating the area under the curve (AUC) at steady state was assessed for optimum vancomycin therapy monitoring. The 3 methods were simple linear regression, Bayesian approach and the 2-sample pharmacokinetic equation method. We also used Monet Carlo simulations to evaluate the dosing of vancomycin. RESULTS: A 1-compartment model adequately described the data. A strong correlation occurred between the observed and predicted AUC from 0 to 24 hours (AUC0-24h) calculated using the Bayesian approach with a trough sample only or pharmacokinetic equations based on 2 measured samples (R = 0.93 and 0.92, respectively). For the simple linear regression method with a trough sample only, the predicted AUC0-24h at steady state with vancomycin trough levels of 10, 15 and 20 µg/mL were 413, 548 and 714 µg·hour/mL, respectively. The target AUC0-24h above 400 was achieved in 46% and 95% of individuals with trough values of 7-11 and 11-15 µg/mL, respectively. Monte Carlo simulations showed that 60-80 mg/kg/d doses are needed to optimize vancomycin therapy. CONCLUSIONS: In conclusion, targeting vancomycin trough levels above 15 µg/mL in pediatrics would overshoot the target AUC0-24h above 400 and expose them to unnecessary adverse events.