Daptomycin and ceftaroline combination for the treatment of persistent methicillin-resistant Staphylococcus aureus bloodstream infections: a case series and literature review.

Methicillin-resistant Staphylococcus aureus (MRSA) is challenging to treat due to a lack of guidance for clinicians. The daptomycin and ceftaroline combination is promising for treating persistent MRSA bloodstream infections (BSIs). In this report, we present a case series of 7 patients who failed vancomycin and then were treated with daptomycin and ceftaroline for persistent MRSA BSIs. The median age (IQR) of the included patients was 59 (48-67), with 5 male and 2 female patients. Six patients (85.7%) had a clinical cure for their persistent BSIs. The median time (IQR) for sterilization of MRSA BSIs after initiation of daptomycin and ceftaroline combination was 2 days (1-3). Among the patients who had clinical cures, the median time for clinical cures (IQR) was 6 weeks (4.5-6 weeks). The combination of daptomycin and ceftaroline could be an excellent treatment option for persistent MRSA BSIs.

Novel ß-lactam-ß-lactamase inhibitors as monotherapy versus combination for the treatment of drug-resistant Pseudomonas aeruginosa infections: A multicenter cohort study.

BACKGROUND: Data comparing the clinical outcomes of novel ß-lactam-ß-lactamase inhibitors given in combination versus monotherapy for the treatment of multidrug-resistant (MDR) P. aeruginosa infections are lacking. METHOD: This retrospective cohort study included patients who received novel ß-lactam-ß-lactamase inhibitors as monotherapy or in combination for the treatment of MDR P. aeruginosa infections. The study was conducted between 2017 and 2022 in 6 tertiary care hospitals in Saudi Arabia. Overall in-hospital mortality, 30-day mortality, clinical cure, and acute kidney injury (AKI) were compared between recipients of monotherapy versus combination using multivariate logistic regression analysis. RESULT: 118 patients and 82 patients were included in monotherapy and combination therapy arms, respectively. The cohort represented an ill population with 56% in the intensive care unit and 37% in septic shock. A total of 19% of patients presented with bacteremia. Compared to monotherapy, combination therapy did not significantly differ in clinical cure (57% vs. 68%; P = 0.313; OR, 0.63; 95% CI, 0.36-1.14) in-hospital mortality (45% vs. 37%; P = 0.267; OR, 1.38; 95% CI, 0.78-2.45), or 30-day mortality (27% vs. 24%; P = 0.619; OR, 1.18; 95% CI, 0.62-1.25). However, AKI (32% vs. 12%; P = 0.0006; OR, 3.45; 95% CI, 1.67-7.13) was significantly more common in patients who received combination therapy. CONCLUSION: Novel ß-lactam-ß-lactamase inhibitors when used in combination with other antibiotics did not add clinical benefit compared to their use as monotherapy in the treatment of MDR P. aeruginosa infections. A Combination regimen was associated with an increased risk of nephrotoxicity.

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.

Epidemiology of Reportable Bacterial Infectious Diseases in Saudi Arabia.

INTRODUCTION: Bacterial infections have a significant impact on human health; they can cause severe morbidity and mortality, particularly in susceptible populations. Epidemiological surveillance is a critical tool for monitoring the population's health and facilitate the prevention and control of infectious disease outbreaks. Knowing the burden of bacterial communicable diseases is an initial core step toward public health goals. METHODS: Saudi epidemiology surveillance data were utilized to depict the changing epidemiology of bacterial infectious diseases in Saudi Arabia from 2018 to 2021. The cumulative numbers of cases, demographics, and incidence rates were analyzed and visualized. Parametric tests were used to compare the difference in the mean values between categorical variables. Regression analysis was employed to estimate trends in disease rates over time. Statistical significance was set at p value ≤ 0.05. RESULTS: The results revealed that brucellosis, tuberculosis, and salmonellosis were the most frequently reported bacterial infectious diseases in Saudi Arabia. Males were more significantly affected by brucellosis and tuberculosis infections than females. Salmonellosis infections were more significant among Saudi citizens, while pulmonary tuberculosis was more significant in non-Saudis. Interestingly, there was a decline in the incidence rates of numerous bacterial infectious diseases during the Coronavirus Disease 2019 (COVID-19) pandemic and COVID-19 restrictions. Some bacterial infectious diseases were rarely reported in Saudi Arabia, including syphilis and diphtheria. CONCLUSIONS: The future perspective of this research is to enhance disease surveillance reporting by including different variables, such as the source of infection, travel history, hospitalization, and mortality rates. The aim is to improve the sensitivity and specificity of surveillance data and focus on the mortality associated with bacterial pathogens to identify the most significant threats and set a public health priority.

The impact of Saudi Arabia - United States clinical pharmacy post-graduate training programs agreements on clinical pharmacy faculty in Saudi universities: A retrospective descriptive study focused on history and future recommendations.

Background: There has been a growing demand for clinical pharmacy services in the Kingdom of Saudi Arabia (KSA) in the past 3 decades. The Ministry of Education has established agreements with several institutions in the United States to secure clinical pharmacy residency and research fellowship programs opportunities for Saudi scholars. The aims of this study were to describe the Saudi scholars' clinical pharmacy training pathways and their contribution to the pharmacy profession in KSA. Methods: This is a retrospective, descriptive study conducted on clinical pharmacy faculty in governmental Saudi universities who graduated from the US until 2023. The study outcomes included the post-graduate year-1 (PGY-1) residency match rate, post-graduate year-2 (PGY-2) acceptance rate, the PGY-2 specialties of Saudi scholars, and the number of clinical pharmacy programs established in KSA. Results: In total, 115 Saudi scholars have pursued clinical pharmacy pathway in the US. The PGY-1 residency match rate was 80 % (92/115). In contrast, the PGY-2 acceptance rate was 60.9 % (70/115). The most common PGY-2 specialty was in infectious diseases (N = 17; 24 %). Two pharmacy colleges had established residency programs and 1 pharmacy college had established a research fellowship. Conclusion: The Ministry of Education's efforts for clinical pharmacy program agreements were fundamental for advancing clinical pharmacy in Saudi universities. A significant number of Saudi scholars returned to KSA with clinical pharmacy degrees. There are more opportunities for further development, including expanding the clinical pharmacy program collaboration in the US and increasing the number of residency and research fellowship positions in KSA.

Assessing Galleria mellonella as a preliminary model for systemic Staphylococcus aureus infection: Evaluating the efficacy and impact of vancomycin and Nigella sativa oil on gut microbiota.

Background: Staphylococcus aureus is a Gram-positive bacterium that can cause various infections. The Galleria mellonella has been used as a preliminary test for infection model. The study aimed to evaluate the effectiveness of G. mellonella as a microbiome model and compare the efficacy of vancomycin and antimicrobial activity of Nigella sativa (NS) on the gut flora. Methods: G. mellonella larvae were subjected to metagenomic analysis. The larvae's guts were collected, homogenized in phosphate-buffered saline (PBS), and the gut contents isolated for bacterial DNA extraction. Larvae were assigned into the following groups: negative control (PBS only); positive control (MRSA only); vancomycin treated group; NS oil treated group and combination (vancomycin and NS oil) treated group. Larvae were cultured, inoculated with S. aureus, and treated with vancomycin and NS oil. Larval activity, cocoon formation, growth, melanization, and survival were monitored. The toxicity of vancomycin and NS oil was tested, and S. aureus burden and natural microbiota were determined. Hemocyte density was measured. Statistical analysis was conducted using R. Results: Enterococcus related species dominated approximately 90 % of the gastrointestinal tract of the larvae. The survival rate following treatment was 85 % with vancomycin, 64 % with NS oil, and 73 % with a combination of both. The count of Enterococcus Colony Forming Units (CFUs) was significantly lower in the vancomycin treatment group (8.14E+04) compared to those treated with NS oil (1.97E+06) and the combination treatment (8.95E+05). Furthermore, the S. aureus burden was found to be lower in the NS oil (1.04E+06) and combination treatment groups (9.02E+05) compared to the vancomycin treatment group (3.38E+06). Hemocyte densities were significantly higher in the NS oil (8.29E+06) and combination treatment groups (8.18E+06) compared to the vancomycin treatment group (4.89E+06). Conclusions: The study supported the use of G. mellonella model as a preliminary test to assess the effect of different antimicrobials against S. aureus and gut microbiota. NS oil showed more selectivity against S. aureus and protectiveness for the natural Enterococcus gut flora.

Home infusion services in Saudi Arabia: Where are we standing?

Diseases management has reached the highest level of complexity and cost in history, worldwide, and in Saudi Arabia in particular, which led to prolonged, unnecessary hospital stays. There have been many recent innovative measures to reduce these issues. One is to provide home infusion services. Hence, this narrative review emphasizes the expected benefits and challenges of such services and the applicability of their implementation in Saudi Arabia. A literature search was conducted via PubMed database, involving all published studies from inception until March 24th, 2023. Many studies showed positive impacts of home infusion on reducing the length of hospital stays, increasing cost-saving, and leading to high patient satisfaction.

Correlation of CRISPR/Cas and Antimicrobial Resistance in Klebsiella pneumoniae Clinical Isolates Recovered from Patients in Egypt Compared to Global Strains.

The CRISPR/Cas system has been long known to interfere with the acquisition of foreign genetic elements and was recommended as a tool for fighting antimicrobial resistance. The current study aimed to explore the prevalence of the CRISPR/Cas system in Klebsiella pneumoniae isolates recovered from patients in Egypt in comparison to global strains and correlate the CRISPR/Cas to susceptibility to antimicrobial agents. A total of 181 clinical isolates were PCR-screened for cas and selected antimicrobial resistance genes (ARGs). In parallel, 888 complete genome sequences were retrieved from the NCBI database for in silico analysis. CRISPR/Cas was found in 46 (25.4%) isolates, comprising 18.8% type I-E and 6.6% type I-E*. Multidrug resistance (MDR) and extensive drug resistance (XDR) were found in 73.5% and 25.4% of the isolates, respectively. More than 95% of the CRISPR/Cas-bearing isolates were MDR (65.2%) or XDR (32.6%). No significant difference was found in the susceptibility to the tested antimicrobial agents among the CRISPR/Cas-positive and -negative isolates. The same finding was obtained for the majority of the screened ARGs. Among the published genomes, 23.2% carried CRISPR/Cas, with a higher share of I-E* (12.8%). They were confined to specific sequence types (STs), most commonly ST147, ST23, ST15, and ST14. More plasmids and ARGs were carried by the CRISPR/Cas-negative group than others, but their distribution in the two groups was not significantly different. The prevalence of some ARGs, such as blaKPC, blaTEM, and rmtB, was significantly higher among the genomes of the CRISPR/Cas-negative strains. A weak, nonsignificant positive correlation was found between the number of spacers and the number of resistance plasmids and ARGs. In conclusion, the correlation between CRISPR/Cas and susceptibility to antimicrobial agents or bearing resistance plasmids and ARGs was found to be nonsignificant. Plasmid-targeting spacers might not be naturally captured by CRISPR/Cas. Spacer match analysis is recommended to provide a clearer image of the exact behavior of CRISPR/Cas towards resistance plasmids.

Effectiveness of antibiotic-loaded bone cement in total joint arthroplasty at a tertiary medical center: A retrospective cohort study.

Background: Data regarding the effectiveness of antibiotic-loaded bone cement (ALBC) in preventing prosthetic joint infections (PJI) after total joint arthroplasty (TJA) is inconsistent. The objective of this study was to evaluate if the routine use of ALBC influenced the risk of revision surgery due to PJI. Methods: This is a retrospective cohort study performed between January 2018 and September 2020. Adult patients aged ≥ 18 years who underwent TJA (knee or hip) and received either ALBC or plain cement (PC) were included. The outcome of this study was the rate of revision due to PJI. Multivariate analysis using logistic regression was used to identify factors that may be associated with increased risk of PJI, using STATA 15.1 (StataCorp LP, College Station, Texas, USA). Results: A total of 844 patients were screened and 319 patients were included. There were 247 patients in ALBC group and 72 patients in the PC group. Only vancomycin powder was used in all ALBC cases, with a 2 g dose in 50% of the cases (dose ranged between 1 g and 8 g). The status of the prosthetic joint was assessed and recorded up to 2 years of the TJA. Overall, the difference in the rates of PJI between the two groups after primary arthroplasty was not statistically significant (5.6% vs 1.4%; p = 0.173; OR, 4.2; 95% CI, 0.5-33). Conclusion: ALBC was not associated with a reduction in PJI rates after primary TJA. More research is needed to further evaluate the effectiveness of ALBC in preventing PJI.

Heart transplantation and human immunodeficiency virus-navigating drug-drug interactions: a case report.

BACKGROUND: Antiretroviral therapy (ART) has led to a decline in human immunodeficiency virus (HIV)-related mortality, but comorbidities, including organ dysfunction, are increasingly the focus of care. Heart transplant (HT) is a very effective therapeutic strategy for end-stage heart failure (HF); however, clinicians may be hesitant due to concerns of complex drug-drug interactions (DDIs) between ART and HT immunosuppressive regimens and the potential impact of ART on long-term HT outcomes. In this report, we describe long-term (76-month) follow-up of a patient with HIV-positive status who underwent orthotopic HT with special emphasis on complex drug interactions. CASE PRESENTATION: A 58-year-old man with HIV-1 developed ischemic cardiomyopathy, progressed to end-stage HF and underwent orthotopic HT. To avoid DDIs with planned immunosuppressive therapies, the ART regimen was modified to consist of lamivudine, tenofovir disoproxil fumarate, rilpivirine, and raltegravir. Following HT, the patient's immunosuppression consisted of tacrolimus and mycophenolate mofetil. He has had normal cardiac function and no opportunistic infections and was subsequently switched to tenofovir alafenamide, emtricitabine, and bictegravir in combination for convenience. Serial HIV-1 RNA blood levels were constantly below the limit of quantification, and his CD4 count remained above 200 cells/mm3 (30-35%). Several DDIs were identified and addressed; however, his long-term post-HT complications included one episode of asymptomatic acute cellular rejection, adenocarcinoma of the prostate, basal cell carcinoma, cardiac allograft vasculopathy, and peripheral neuropathy. CONCLUSION: The clinical outcome of this case supports the conclusion of previously published reports, summarized here within, demonstrating that HIV-1 positive status should not preclude HT in carefully selected individuals. Both addressing potential DDIs prior to HT and long-term monitoring for routine post-transplant complications and secondary and incidental malignancies are imperative.

Adherence to evidence-based guidelines for the management of pneumonia in a tertiary teaching hospital in Riyadh.

Background: Adherence to therapeutic guidelines is crucial when treating pneumonia, as it reduces mortality rate, length of hospital stay and duration of antibiotic therapy. However, the high non-adherence rate to treatment guidelines, in general, and to the Infectious Disease Society of America (IDSA) guidelines, are still reported globally. According to our knowledge, no existing data is available regarding the rate of physicians' adherence to the IDSA guidelines for managing pneumonia in Saudi Arabia. Therefore, we aim to assess the adherence rate and the clinical outcomes among patients treated according to the IDSA guidelines, in a tertiary care center in Riyadh. Methods: A single-centered, retrospective, cross-sectional, observational study was conducted at King Khalid University Hospital, Riyadh, Saudi Arabia. All data were extracted from the hospital's electronic information system, known as Esihi. Adult patients (≥18 years old) diagnosed and treated in the hospital for community-acquired pneumonia, hospital-acquired pneumonia, or ventilator-associated pneumonia from Nov 2019 to Nov 2021 were included. Results: A total of 148 patients were included in this study, and the management of 50% of them (74 patients) adhered to the guidelines' recommendations. Even though the patients who received guidelines-adhered management were older (70 ± 16 vs 59 ± 22; p = 0.001), and had a higher CURB-65 score for pneumonia severity (1.86 ± 1.03 vs 1.39 ± 1.26; p = 0.026) and an average calculated Charlson comorbidity index (4.62 ± 2.19 vs 3.28 ± 2.80; p = 0.001) than patients who were treated irrespectively of the guidelines, yet they had a better cure rate (95% vs 84%; adjusted OR, 3.9; 95% CI, 0.82-18.58), lower mortality (5% vs 14%; adjusted OR, 0.38; 95% CI, 0.04-4.05) and shorter length of hospital stay (LOS) (6.5 vs 8 days; p = 0.082); compared to patients who were treated irrespectively of the guidelines. Conclusions: Comparable to previous literature, non-adherence to evidence-based guidelines has been observed in 50% of patients treated for pneumonia. Despite being nonsignificant, higher clinical cure rates, shorter LOS, and lower mortality rates have been observed in patients who were treated based on evidence-based guidelines. Further measures to improve guidelines compliance in pneumonia treatment are needed.

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.

Impact of COVID-19 on the Health-Related Quality of Life of Patients during Infection and after Recovery in Saudi Arabia.

This study evaluated the impact of COVID-19 and other factors on the health-related quality of life (HRQoL) of Saudi patients during infection and after recovery using the EQ-5D-5L and EQ-VAS instruments. An observational prospective study was conducted in November 2022, during which 389 COVID-19 patients were surveyed during their visit to a medical center. Two weeks after their recovery, they were contacted again to re-evaluate their HRQoL (192 patients either refused to participate or withdrew). The mean of the EQ-5D-5L index and EQ-VAS scores significantly increased from (0.69 ± 0.29 and 63.16 ± 24.9) during infection to (0.92 ± 0.14 and 86.96 ± 15.3) after recovery. Specifically, COVID-19 patients experienced improvement of several HRQoL dimensions post recovery, such as better mobility, enhanced self-care, returning to usual activities, less pain/discomfort, and alleviated anxiety/depression. Multiple linear regression analyses showed that having a normal weight, being employed, not being anemic, and previously taking the BCG vaccine were positively associated with a greater change in the HRQoL. An interaction between being asthmatic and taking the influenza vaccine positively predicted a lower change in the HRQoL. Having a normal weight positively predicted a greater change in the perceived health state after recovery. Increasing the consumption of natural supplements (honey and curcuma) did not improve the HRQoL or the perceived health state. Based on these findings, COVID-19 mildly impacted the HRQoL of Saudis with varying effects depending on some socio-demographic/clinical characteristics of the patients.

Echinocandin exposures in obese patients: A scoping review and clinical perspectives.

PURPOSE: Echinocandins are favored drugs for the treatment of fungal infections. There is growing evidence that obese patients treated with echinocandins have lower exposures due to pharmacokinetic (PK) alterations. We conducted a scoping review to characterize, evaluate, and summarize the available evidence on echinocandins exposures in obese patients. SUMMARY: A comprehensive search of PubMed, Embase, and Cochrane Library for studies on echinocandins published from database inception to October 28, 2022, was conducted using PRISMA-ScR methodology. A total of 25 studies comprising more than 3,174 subjects (8 micafungin studies, 7 caspofungin studies, 9 anidulafungin studies, and 1 rezafungin study) were included in this review. Seventeen studies reported lower echinocandins exposures in overweight and obese individuals compared with normal-weight individuals; the authors of these studies recommended dose adjustments. Conversely, 8 studies did not find significant differences in echinocandin exposure among subjects in varying body weight categories. Clinicians may consider dose adjustments of echinocandins in obese patients; however, there is limited evidence on the ideal dose adjustment strategy to overcome the low echinocandins exposures in obese patients. CONCLUSION: This scoping review shed light on a growing body of evidence indicating that obese patients have lower echinocandin exposures relative to targeted PK indices, which may lead to negative therapeutic implications. Currently, a lack of high-quality evidence impedes reaching consensus on recommendations for echinocandin dosing adjustment in obese patients. Future research evaluating the optimal echinocandin dosing strategy for obese patients is needed.

Antimicrobial Resistance Awareness, Antibiotics Prescription Errors and Dispensing Patterns by Community Pharmacists in Saudi Arabia.

BACKGROUND: Antibiotic overuse and misuse have greatly facilitated the development of antimicrobial resistance (AMR). The Kingdom of Saudi Arabia is one of the countries that took a strategic approach, beginning with the prohibition of over-the-counter antibiotic dispensing, followed by the implementation of antimicrobial stewardship programs and various educational and awareness governmental activities and plans. However, the status of antibiotic prescriptions and dispensing in Saudi community pharmacies is still unclear. As a result, this study investigates community pharmacists' antibiotic dispensing practices and their knowledge of their role in fighting AMR, in addition to the status of antibiotic prescribing errors by physicians. METHOD: This is an online-based survey study of 671 participants distributed among community pharmacists of large pharmacy chains throughout the Saudi Arabia. RESULT: A number of 671 community pharmacists were participated in total, with a response rate of 96.57% (648 responses). The majority of community pharmacists (67%) had a long experience (>5 years) in this field. An antibiotic prescribing error was prevalent, with a mean of 3.32 per month in each pharmacy. Dentists (36.7%) and general practitioners (28.7%) were the most prescribers associated with antibiotic prescription errors. Most community pharmacists had a generally good practice of dispensing antibiotics, accounting for 71.5% of daily antibiotic dispensing. However, more than one-third of those pharmacists (35.2%) agreed on dispensing topical antibiotics without a prescription, based on their evaluation of the case presented in the pharmacy, as the majority of community pharmacists demonstrated a significant understanding of AMR. CONCLUSION: The current study demonstrated that there is a good antibiotic dispensing practice in the community pharmacies in Saudi Arabia, in addition to a substantial understanding of the community pharmacist's vital role in fighting AMR. This study could inform decision-makers on antibiotic usage in Saudi community pharmacies to improve the current inappropriate antibiotic use and dispensing situation and, thus, control AMR spread in Saudi Arabia.

Evaluation of the Clinical Outcome and Cost Analysis of Antibiotics in the Treatment of Acute Respiratory Tract Infections in the Emergency Department in Saudi Arabia.

This study aims to assess the prevalence and antibiotic-treatment patterns of respiratory tract infections (RTIs), prevalence and types of antibiotic-prescribing errors, and the cost of inappropriate antibiotic use among emergency department (ED) patients. A cross-sectional study was conducted at the ED in King Abdulaziz Medical City, Riyadh, Saudi Arabia. Patient characteristics (age, sex, weight, allergies, diagnostic tests (CX-Ray), cultures, microorganism types, and prescription characteristics) were studied. During the study, 3185 cases were diagnosed with RTIs: adults (>15 years) 55% and pediatrics (<15 years) 44%. The overall prevalence of RTIs was 21%, differentiated by upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI) (URTI 13.4%; LRTI 8.4%), of total visits. Three main antibiotics (ATB) categories were prescribed in both age groups: penicillin (pediatrics 43%; adults 26%), cephalosporin (pediatrics 29%; adults 19%), and macrolide (pediatrics 26%; adults 38%). The prevalence of inappropriate ATB prescriptions was 53% (pediatrics 35%; adults 67%). Errors in ATB included selection (3.3%), dosage (22%), frequency (3%), and duration (32%). There is a compelling need to create antimicrobial stewardship (AMS) programs to improve antibiotic use due to the high number of prescriptions in the ED deemed as inappropriate. This will help to prevent unwanted consequences on the patients and the community associated with antibiotic use.

Efficacy and safety of delafloxacin, ceftaroline, ceftobiprole, and tigecycline for the empiric treatment of acute bacterial skin and skin structure infections: A network meta-analysis of randomized controlled trials.

Background: This review aimed to conduct an indirect comparison using a Bayesian network meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of delafloxacin versus other single antibiotic regimens for the empiric treatment of Acute Bacterial Skin and Skin Structure Infections. Method: A systematic search with no start date restrictions was conducted. The Cochrane Risk of Bias tool was used to assess the quality of included RCTs. Results: Of the 577 studies initially identified, nine RCTs were included in the review. The network meta-analysis showed that ceftaroline, ceftobiprole, delafloxacin and tigecycline had similar efficacy in the indirect comparisons [Ceftaroline Odds Ratio (OR) = 1.2, 95% Crl = 0.46-3.6), ceftobiprole (OR = 1.3, 95% Crl = 0.34-3.0) and tigecycline (OR = 0.96, 95% Crl = 0.30-2.9)]. However, the ranking plot for the intention to treat (ITT) population showed that delafloxacin had a probability of 80.8% to be ranked first followed by ceftobiprole (13.1%). The analysis of the overall adverse events showed that ceftaroline (OR = 0.88, 95% Crl = 0.65-1.2), ceftobiprole (OR = 1.1, 95% Crl = 0.69-2.0), delafloxacin (OR = 0.88, 95% Crl = 0.57-1.3) and tigecycline (OR = 1.4, 95% Crl = 0.88-2.2) had similar safety profiles. Conclusion: Delafloxacin did not show any statistically significant differences when compared to ceftaroline, ceftobiprole, and tigecycline in terms of efficacy and safety. However, the surface under the cumulative ranking curve (SUCRA) probability ranked delafloxacin as the first option for the ITT population.

Assessment of Caspofungin use at a Tertiary Teaching Hospital and compliance with IDSA guidelines and FDA labelings.

Objective: The aim of this study is to evaluate the utilization pattern of Caspofungin in an academic tertiary care hospital in Riyadh, Saudi Arabia. Methods: This is a retrospective study, conducted at King Saud University Medical City, Riyadh, Saudi Arabia. Adult patients who received Caspofungin from January 2015 to December 2018 were included. The appropriate use of Caspofungin was evaluated according to the international guidelines and approved recommendations. Caspofungin doses were assessed according to the FDA-approved loading and maintenance doses as well as dose-adjustment per hepatic function for cirrhotic patients and drug-drug interactions. Cultures and laboratory tests were used to evaluate the appropriate duration of Caspofungin therapy. Results: 388 patients were included. Caspofungin was inappropriately used in 253 (64%) patients. This included 78 (20%) due to inappropriate indication, 165 (42%) due to wrong dosage, and 10 (2%) patients who had a wrong duration of therapy. Conclusion: The rate of inappropriate use of Caspofungin was high. Hence, developing antifungal stewardship and drug restriction program is highly recommended.

Association Between Obesity and COVID-19 Disease Severity in Saudi Population.

Background: The persistent coronavirus disease 2019 (COVID-19) outbreak has placed a significant burden on the scientific and medical professions. The study examined the association between body mass index (BMI), stratified by category, and severe form of COVID-19, and to explore the influence of demographic characteristics and other known risk factors. Methods: This was a retrospective analysis based on COVID-19 data from the Saudi Arabian Ministry of Health. Data were collected for all patients admitted to three main hospitals in Riyadh region between March 1st and July 30, 2020. The effects of BMI, demographic characteristics, clinical presentation, and comorbidities on infection severity were investigated. Results: A total of 950 patients were included in the study (70% male, 85% aged younger than 60 years old). A total of 55 (5.8%) patients were underweight, 263 (27.7%) were normal weight, 351 (37%) were overweight, 161 (17%) were obese class I, 76 (8%) were obese class II, and 44 (4.6%) were obese class III. Cough, fever, and shortness of breath were the most common symptoms among overweight patients. According to the findings of a bivariate logistic regression study, class III obesity was significantly associated with a more severe form of COVID-19 (odds ratio, 2.874; 95% confidence interval, 1.344-6.149). Conclusion: This study revealed that patients with a BMI ≥40 kg/m2 had a higher risk of severe COVID-19 than those with normal weight. This suggests that obesity is a risk factor for severe COVID-19 and influences disease presentation.

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).