The Impact of Midodrine Tapering Versus Nontapering Regimens on the Clinical Outcomes of Critically Ill Patients: A Retrospective Cohort Study.

BACKGROUND: Midodrine has been used in the intensive care unit (ICU) setting to reduce the time to vasopressor discontinuation. The limited data supporting midodrine use have led to variability in the pattern of initiation and discontinuation of midodrine. OBJECTIVES: To compare the effectiveness and safety of 2 midodrine discontinuation regimens during weaning vasopressors in critically ill patients. METHODS: A retrospective cohort study was conducted at King Abdulaziz Medical City. Included patients were adults admitted to ICU who received midodrine after being unable to be weaned from intravenous vasopressors for more than 24 hours. Patients were categorized into two subgroups depending on the pattern of midodrine discontinuation (tapered dosing regimen vs. nontapered regimen). The primary endpoint was the incidence of inotropes and vasopressors re-initiation after midodrine discontinuation. RESULTS: The incidence of inotropes or vasopressors' re-initiation after discontinuation of midodrine was lower in the tapering group (15.4%) compared with the non-tapering group (40.7%) in the crude analysis as well as regression analysis (odd ratio [OR] = 0.15; 95% CI = 0.03, 0.73, P = 0.02). The time required for the antihypertensive medication(s) initiation after midodrine discontinuation was longer in patients who had dose tapering (beta coefficient (95% CI): 3.11 (0.95, 5.28), P = 0.005). Moreover, inotrope or vasopressor requirement was lower 24 hours post midodrine initiation. In contrast, the two groups had no statistically significant differences in 30-day mortality, in-hospital mortality, or ICU length of stay. CONCLUSION AND RELEVANCE: These real-life data showed that tapering midodrine dosage before discontinuation in critically ill patients during weaning from vasopressor aids in reducing the frequency of inotrope or vasopressor re-initiation. Application of such a strategy might be a reasonable approach among ICU patients unless contraindicated.

Ceftolozane-Tazobactam Versus Ceftazidime-Avibactam for the Treatment of Infections Caused by Multidrug-Resistant Pseudomonas aeruginosa: a Multicenter Cohort Study.

Ceftolozane-tazobactam (C-T) and ceftazidime-avibactam (CAZ-AVI) are two novel antimicrobials that retain activity against resistant Pseudomonas aeruginosa. The comparative effectiveness and safety of C-T versus CAZ-AVI remain unknown. A retrospective, multicenter cohort study was performed in six tertiary centers in Saudi Arabia and included patients who received either C-T or CAZ-AVI for infections due to multidrug-resistant (MDR) P. aeruginosa. Overall in-hospital mortality, 30-day mortality, and clinical cure were the main study outcomes. Safety outcomes were also evaluated. A multivariate analysis using logistic regression was used to determine the independent impact of treatment on the main outcomes of interest. We enrolled 200 patients in the study (100 in each treatment arm). A total of 56% were in the intensive care unit, 48% were mechanically ventilated, and 37% were in septic shock. Approximately 19% of patients had bacteremia. Combination therapy was administered to 41% of the patients. The differences between the C-T and CAZ-AVI groups did not reach statistical significance in the overall in-hospital mortality (44% versus 37%; P = 0.314; OR, 1.34; 95% CI, 0.76 to 2.36), 30-day mortality (27% versus 23%; P = 0.514; OR, 1.24; 95% CI, 0.65 to 2.35), clinical cure (61% versus 66%; P = 0.463; OR, 0.81; 95% CI, 0.43 to 1.49), or acute kidney injury (23% versus 17%; P = 0.289; OR, 1.46; 95% CI, 0.69 to 3.14), even after adjusting for differences between the two groups. C-T and CAZ-AVI did not significantly differ in terms of safety and effectiveness, and they serve as potential options for the treatment of infections caused by MDR P. aeruginosa.

Infectious diseases pharmacy practice, education, and research in Saudi Arabia: A review and future perspectives by the Infectious Diseases Pharmacy Specialty Network at the Saudi Society of Clinical Pharmacy.

Background: Infectious diseases (ID) pharmacy is one of the rapidly evolving clinical pharmacy specialties in the Kingdom of Saudi Arabia (KSA). There are gaps in the literature on ID pharmacy status in KSA. This review aimed to provide an update on the current status of several areas related to ID pharmacy in KSA, including practice, education, and research, and make pertinent recommendations for future development to achieve the KSA Vision, 2030, KSA Vision, 2030. Methods: This review was developed by a group of ID pharmacists working in different sectors under the umbrella of the ID Pharmacy Specialty Network (PSN) of the Saudi Society of Clinical Pharmacy (SSCP). The authors evaluated domains related to ID pharmacy in KSA and searched the literature for relevant articles. Based on the experts' assessment of the current gaps and challenges, recommendations were made for future improvement. Results: Several aspects of ID pharmacy in KSA were evaluated, including history and development, antimicrobial resistance (AMR), antimicrobial stewardship programs (ASP), roles of ID pharmacists, ID pharmacy education, and research. The biggest challenges include AMR, the varying levels of ASP implementation, and the low number of ID-trained pharmacists, especially in non-major cities. Several recommendations for improvement were discussed. Conclusion: Infectious diseases pharmacy has sustained remarkable progress in KSA in several areas. However, more efforts are needed to increase ASP implementation, increase the number of ID-trained pharmacists, and encourage ID pharmacists in publishing and participating in practice guidelines, which will eventually help achieve the KSA Vision, 2030, KSA Vision, 2030.

Implementation of Pharmacy Executive Quality and Safety Walkrounds at a Tertiary Academic Medical Center.

Background: Executive Quality and Safety WalkRounds (EWRs) is a tool that engages department leadership in discussion with the front-line employees to solicit feedback to improve quality and safety. The purpose of this study was to evaluate the impact of the implementation of pharmacy department specific EWRs on quality and safety at a tertiary academic medical center. Method: This was a single-center, retrospective analysis conducted at Brigham and Women's Hospital between November 2016 and November 2019. This study aimed to analyze the implementation of EWRs conducted every other month throughout various service areas and satellites of the pharmacy department. Data evaluated included the number of EWRs conducted, the specific areas visited, the total number of action items recommended by the staff, along with the total number of action items that were completed or remained in process. Results: During the study period, 17 visits were completed in 12 different BWH pharmacy sub-departments. A total of 98 operational, technological, and environmental action items were recommended by staff to improve quality and safety. Of the 98 action items documented, 95 (96.9%) were completed by time of our analysis. Conclusion: Pharmacy department EWRs are an important and systematic process of communication between the pharmacy leadership and frontline staff. Pharmacy department EWRs have resulted in safety and quality improvements at different levels in the pharmacy department. The EWRs program at the pharmacy department was effective in identifying and completing safety initiatives to improve the safety culture of the department.

Trimethoprim-sulfamethoxazole versus levofloxacin for the treatment of Stenotrophomonas maltophilia infections: A multicentre cohort study.

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) has long been considered the treatment of choice for infections caused by Stenotrophomonas maltophilia. Levofloxacin has emerged as a potential option for treating these infections. This study aimed to evaluate the clinical outcomes in patients who received TMP-SMX versus levofloxacin for treating S. maltophilia infections. METHODS: A retrospective, cohort study was conducted in 4 tertiary centres and included patients who were treated with either TMP-SMX or levofloxacin for infections caused by S. maltophilia. The main study outcomes were overall in-hospital mortality, 30-d mortality, and clinical cure. Safety outcomes were also evaluated. Multivariate analysis using logistic regression was used to control for the effect of the covariables. RESULTS: We included 371 patients in this study, 316 received TMP-SMX and 55 patients received levofloxacin. A total of 70% were in the intensive care unit and 21% presented with bacteraemia. No statistically significant differences were observed in overall in-hospital mortality (52% vs. 40%; P = 0.113; odd ratio [OR], 1.59; 95% confidence interval [CI], 0.89-2.86), 30-d mortality (28% vs. 25%; P = 0.712; OR, 1.13; 95% CI, 0.59-2.18), or clinical cure (55% vs. 64%; P = 0.237; OR, 0.70; 95% CI, 0.37-1.31). Rates of acute kidney injury were comparable between the two groups (11% vs. 7%; P = 0.413). CONCLUSION: Patients receiving levofloxacin for the treatment of infections caused by S. maltophilia demonstrated clinical outcomes similar to those receiving TMP-SMX. Our study suggests that levofloxacin can be a reasonable alternative to TMP-SMX to treat these infections.

Monotherapy versus combination for the treatment of Stenotrophomonas maltophilia: a multicenter cohort study.

BACKGROUND: The aim of this study was to compare the safety and effectiveness of monotherapy versus combination therapy for the treatment of infections caused by S. maltophilia. METHODS: This retrospective, multicenter, cohort study included patients treated with either monotherapy or combination therapy for infections caused by S. maltophilia. Primary outcomes included overall in-hospital mortality, 30-day mortality, and clinical cure. Safety outcomes were also evaluated. Multivariable logistic regression was used as a control for confounding variables. RESULTS: A total of 407 patients were included, 330 patients received monotherapy and 77 patients received combination therapy. A total of 21% presented with concomitant bacteremia. After adjusting the differences between the two groups, there were no statistically significant differences between patients who received monotherapy versus combination therapy in clinical cure (55% vs 65%; OR, 0.72; 95% CI, 0.40-1.31) and overall in-hospital mortality (52% vs 49%; OR, 0.84; 95% CI, 0.45-1.57). However, patients who received monotherapy had a lower rate of 30-day mortality (28% vs 32%; OR, 0.45; 95% CI, 0.22-0.90) and acute kidney injury (9% vs 18%; OR, 0.35; 95% CI, 0.16-0.78). CONCLUSION: Clinical outcomes did not significantly differ in patients who received combination therapy versus monotherapy. More data are needed to validate these findings.

Incidence and potential risk factors for remdesivir-associated bradycardia in hospitalized patients with COVID-19: A retrospective cohort study.

Background: Remdesivir is widely used for the management of COVID-19 and several studies have reported bradycardia as a potential side effect associated with this agent. The aim of the present study was to evaluate the incidence rate, severity, and potential risk factors of remdesivir-associated bradycardia. Methods: We performed a retrospective cohort study among hospitalized adult patients with COVID-19 who were treated with remdesivir from March 2020 to October 2021. Our primary outcome of interest was the incidence rate and severity of bradycardia after remdesivir administration. We defined mild bradycardia as a heart rate of 51-59 beats per minute, moderate bradycardia as a heart rate of 41-50 beats per minute, and severe bradycardia as a heart rate of ≤40 beats per minute. We also performed univariable and multivariable regression analyses to determine potential bradycardia risk factors. Baseline characteristics were reported as means with standard deviations or medians with interquartile ranges (IQRs). All the statistical tests are shown as odds ratios (ORs) with 95% confidence intervals (CIs). Results: In total, 1,635 patients were included in this study. The median age with IQR was 68 (57-79) years and 51.7% of the patients were male. In total, 606 (37.1%) patients developed bradycardia. Among them, 437 patients (26.7%) developed mild bradycardia, 158 patients (9.7%) moderate bradycardia, while 11 patients (0.7%) experienced severe bradycardia. In our adjusted multivariate logistic regression, the odds of bradycardia development after remdesivir administration were higher among patients with age ≥65 years (OR 1.76, 95% CI: 1.04-2.99, p = 0.04), those with hypertension (OR 1.37, 95% CI: 1.07-1.75, p = 0.01), and obesity (OR 1.32, 95% CI: 1.02-1.68, p = 0.03). Conclusion: More than 1 out of 3 patients (37%) who received remdesivir for COVID-19 developed bradycardia with the majority of these patients developing mild or moderate bradycardia that is usually a benign manifestation not needing treatment in most cases. Age ≥65 years, hypertension, and obesity were potential risk factors for remdesivir-associated bradycardia among hospitalized COVID-19 patients. Clinicians should be aware of this adverse event and consider close clinical monitoring for patients at high risk for this adverse event.

Effectiveness and Safety of Ceftriaxone Compared to Standard of Care for Treatment of Bloodstream Infections Due to Methicillin-Susceptible Staphylococcus aureus: A Systematic Review and Meta-Analysis.

(1) Background: Ceftriaxone is a potential alternative for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSIs) in acute care and outpatient parenteral antimicrobial therapy (OPAT) settings. We evaluated the effectiveness and safety of ceftriaxone for the treatment of MSSA BSIs. (2) Method: We searched PubMed, Embase, and Cochrane Library from their inception to October 30th 2021. Our outcomes included clinical cure, microbiological cure, 30- and 90-day mortality, 90-day hospital readmission, and adverse drug reactions (ADRs). We compared ceftriaxone against standard of care (SOC) therapy. We used the random-effects model for the meta-analysis, and our estimated effects were reported as odds ratios (ORs) with 95% confidence intervals (CI). (3) Results: Twelve retrospective cohort studies were included, comprising 1037 patients in the ceftriaxone arms and 2088 patients in the SOC arms. The clinical cure rate of the ceftriaxone regimen was not statistically different from SOC: OR 0.65 (95% CI: 0.29-1.45). Ceftriaxone was also not statistically different from SOC in microbiological cure: OR 1.48 (95% CI: 0.29-7.51); 30-day mortality: OR 0.79 (95% CI: 0.14-4.65); 90-day mortality: OR 0.82 (95% CI: 0.38-1.80); 90-day hospital readmission: OR 1.20 (95% CI: 0.92-1.56); and ADRs: OR 0.92 (95% CI: 0.39-2.18). (4) Conclusion: Ceftriaxone could provide an alternative for the treatment of MSSA BSIs in acute care and OPAT settings (except in patients whose BSIs were due to infective endocarditis).

Vancomycin Area under the Concentration-Time Curve Estimation Using Bayesian Modeling versus First-Order Pharmacokinetic Equations: A Quasi-Experimental Study.

AIM: To evaluate the efficiency of Bayesian modeling software and first-order pharmacokinetic (PK) equations to calculate vancomycin area under the concentration-time curve (AUC) estimations. METHODS: Unblinded, crossover, quasi-experimental study at a tertiary care hospital for patients receiving intravenous vancomycin. Vancomycin AUC monitoring was compared using Bayesian modeling software or first-order PK equations. The primary endpoint was the time taken to estimate the AUC and determine regimen adjustments. Secondary endpoints included the percentage of vancomycin concentrations usable for AUC calculations and acute kidney injury (AKI). RESULTS: Of the 124 patients screened, 34 patients had usable vancomycin concentrations that led to 44 AUC estimations. Without electronic health record (EHR) integration, the time from assessment to intervention in the Bayesian modeling platform was a median of 9.3 min (quartiles Q1-Q3 7.8-12.4) compared to 6.8 min (Q1-Q3 4.8-8.0) in the PK equations group (p = 0.004). With simulated Bayesian software integration into the EHR, however, the median time was 3.8 min (Q1-Q3 2.3-6.9, p = 0.019). Vancomycin concentrations were usable in 88.2% in the Bayesian group compared to 48.3% in the PK equation group and there were no cases of AKI. CONCLUSION: Without EHR integration, Bayesian software was more time-consuming to assess vancomycin dosing than PK equations. With simulated integration, however, Bayesian software was more time efficient. In addition, vancomycin concentrations were more likely to be usable for calculations in the Bayesian group.

Early oral switch to combined cefixime therapy for management of osteoarticular infections in pediatric sickle cell disease patients: A descriptive analysis.

BACKGROUND: The treatment of osteoarticular infections in pediatric patients with sickle cell disease (SCD) is a challenging task for the practitioner. The aim of this study is to evaluate cefixime for the treatment of osteoarticular infections in pediatric SCD patients by retrospective design. METHODS: This study was done in the pediatric hospital of King Saud Medical City, Riyadh, Saudi Arabia. The data was obtained from medical records of patients aged 1-16 years admitted between January 2019 to December 2020, diagnosed with SCD and received cefixime for the treatment of OI. A descriptive study for pediatric patients admitted between January 2019 to December 2020 diagnosed with sickle cell disease and diagnosed with osteoarticular infection. All patients were treated with cefixime. Medians and interquartile ranges (IQRs) were used for the descriptive analysis. RESULTS: A total of 260 patients were screened, and 51 cases [osteomyelitis (OM), n = 43, and septic arthritis (SA), n = 8] met the inclusion criteria. The median age of OM patients was 7 years, with males making up 67.4% of the cohort. The median length of IV antibiotics and hospital stays were 10 days and 11 days, respectively. The median total duration of antibiotic use was 37 and 25 days for OM and SA, respectively. The treatment success rate was 88% in OM cases and 100% in SA patients. Readmission was noted in 39.5% of the OM patients, while only 25% of the SA patients were recorded for reinfection. CONCLUSION: The study's findings revealed that Cefixime is a viable oral alternative for treating osteoarticular infection in pediatric SCD patients. Nonetheless, a prospective investigation is required to corroborate the findings of this study.

Sensorineural hearing loss with macrolide antibiotics exposure: a meta-analysis of the association.

OBJECTIVE: Macrolide antibiotics are among the most commonly used antibiotics; the association of macrolide antibiotics exposure with sensorineural hearing loss (SNHL) has been hypothesized. A systematic search was conducted in PubMed, EMBASE and Cochrane Library from inception to 15 July 2019 to identify studies used macrolide antibiotics for any indication. The results were reported as odds ratio (OR) with 95% confidence interval (CI) using random-effects model to derive the association of macrolide antibiotics exposure with SNHL. The objective of this meta-analysis was to estimate the association of macrolide antibiotics exposure and SNHL from up-to-date evidence. KEY FINDINGS: Nine studies met the inclusion criteria. There was no statistically significant association between macrolide antibiotics exposure and SNHL; the OR was 1.20 (95% CI: 0.96 to 1.49). No significant association was found with any of the subgroup meta-analyses. SUMMARY: Whilst the frequency of SNHL was higher with macrolide antibiotics exposure compared with controls, overall, no association was found between macrolide antibiotics and SNHL.