Evaluation of Antimicrobial Stewardship Programs (ASPs) and their perceived level of success at Makkah region hospitals, Kingdom of Saudi Arabia.

Antimicrobial stewardship programs (ASPs) are collaborative efforts to optimize antimicrobial use in healthcare institutions through evidence-based quality improvement strategies. The general administration of pharmaceutical care in the Saudi ministry of health (MOH) is putting outstanding efforts in implementing antimicrobial stewardship in Saudi health care settings. Several surveys have been conducted globally and reported many types of antimicrobial stewardship strategies in health institutions and their effectiveness. This study aims to identify ASPs in Makkah region hospitals and their perceived level of success. We administered a regional survey to explore current progress and issues related to the implementation of ASPs in Makkah region hospitals at the pharmacy level (n = 25). Among responding hospitals, 19 (76%) hospitals, the most commonly reported ASP were as following: formulary restrictions (90%) for broad-spectrum antimicrobials and use of prospective feedback on antimicrobial prescribing (68%), use of clinical guidelines and pathways (100%), and use of automatic stop orders (68%) to limit inappropriate antimicrobial therapy. The study outcomes will also be of pivotal importance to devise policies and strategies for antimicrobial stewardship implementation in other non-MOH settings in the Makkah region. Based on our results, all reported institutions have at least one antimicrobial stewardship program in a process with a high success rate. A multidisciplinary ASP approach, active involvement of drug & therapeutic committee, formulary restrictions, and availability of education & training of pharmacists and physicians on ASP are the primary elements for perceived successful antimicrobial stewardship programs in the Makkah region hospitals.

Synthesis, molecular docking study and biological evaluation of new pyrrole scaffolds as potential antitubercular agents for dual targeting of enoyl ACP reductase and dihydrofolate reductase.

In this study, new series of N'-(2-(substitutedphenoxy)acetyl)-4-(1H-pyrrol-1-yl)benzohydrazides (3a-j) 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N'-(2-(substitutedphenoxy)acetyl)benzohydrazides (5a-j) were synthesized, characterized and assessed as inhibitors of enoyl ACP reductase and DHFR. Most of the compounds exhibited dual inhibition against the enzymes enoyl ACP reductase and DHFR. Several synthesized substances also demonstrated significant antibacterial and antitubercular properties. A molecular docking analysis was conducted in order to determine the potential mechanism of action of the synthesized compounds. The results indicated that there were binding interactions seen with the active sites of dihydrofolate reductase and enoyl ACP reductase. Additionally, important structural details were identified that play a critical role in sustaining the dual inhibitory activity. These findings were useful for the development of future dual inhibitors. Therefore, this study provided strong evidence that several synthesized molecules could exert their antitubercular properties at the cellular level through multi-target inhibition. By shedding light on the mechanisms through which these compounds exert their inhibitory effects, this research opens up promising avenues for the future development of dual inhibitors with enhanced antibacterial and antitubercular properties. The study's findings underscore the importance of multi-target approaches in drug design, providing a strong foundation for the design and optimization of novel compounds that can effectively target bacterial infections at the cellular level.

Threat of Antimicrobial Resistance among Pilgrims with Infectious Diseases during Hajj: Lessons Learnt from COVID-19 Pandemic.

Hajj pilgrimage is a large mass gathering global event that may facilitate the spread and emergence of various infectious diseases as well as antimicrobial resistance (AMR) in a local and global scenario. Planning and preparing for these public health issues is a challenging and complex process for the Kingdom of Saudi Arabia (KSA) health authorities. Despite multiple efforts for the prevention and treatment of infectious diseases through longtime funding in education and medical care, the prevalence of infectious disease is still high among Hajj pilgrims. The commonly observed infectious diseases during Hajj include respiratory tract infections (influenza and pneumonia), urinary tract infections and skin infections that may necessitate the use of antimicrobials. Beta-lactams are used as a first-line treatment for hospital acquired infections as well as community acquired infections due to their broad-spectrum activity. However, most of the bacterial isolates such as Staphylococcus spp., Pseudomonas spp. and E. coli are resistant to beta-lactams. Irrational use of antimicrobials, lack of infection prevention practices and suboptimal healthcare access further exacerbate the risk of spreading AMR among Hajj pilgrims. Enhanced collaboration between countries, sharing of best practices and international cooperation are crucial in addressing AMR threats among pilgrims. Consequently, robust surveillance systems for early detection and monitoring of AMR, collaboration with national as well as international healthcare agencies, effective infection prevention and control measures, public awareness and rational use of antimicrobials via antimicrobial stewardship programs are required to mitigate the risk of AMR and ensure the health and well-being of pilgrims during Hajj.

Dose optimization of vancomycin in obese patients: A systematic review.

Background: Dose optimization of vancomycin plays a substantial role in drug pharmacokinetics because of the increased incidence of obesity worldwide. This systematic review was aimed to highlight the current dosing strategy of vancomycin among obese patients. Methods: This systematic review was in concordance with Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The literature search was carried out on various databases such as Scopus, PubMed/MEDLINE, ScienceDirect and EMBASE using Keywords and MeSH terms related to vancomycin dosing among obese patients. Google Scholar was also searched for additional articles. The English language articles published after January, 2000 were included in this study. The quality of the study was assessed using different assessment tools for cohort, and case reports. Results: A total of 1,029 records were identified. After screening, 18 studies were included for the final review. Of total, twelve studies are retrospective and remaining six are case-control studies. A total of eight studies were conducted in pediatrics while remaining studies were conducted in adult population. Most of the studies reported the dosing interval every 6-8 h. Differences in target trough concentration exist with respect to target ranges. The administration of loading dose (20-25 mg/kg) followed by maintenance dose (15-25 mg/kg) of vancomycin is recommended in adult patients to target therapeutic outcomes. Moreover, a dose of 40-60 mg/kg/day appears appropriate for pediatric patients. Conclusion: The initial dosing of vancomycin based on TBW could be better predictor of vancomycin trough concentration. However, the clinical significance is uncertain. Therefore, more studies are needed to evaluate the dosing strategy of vancomycin in overweight or obese patients.

Trimethoprim-Sulfamethoxazole (Bactrim) Dose Optimization in Pneumocystis jirovecii Pneumonia (PCP) Management: A Systematic Review.

(1) Background: Pneumocystis jirovecii pneumonia (PCP) has a substantial impact on the morbidity and mortality of patients, especially those with autoimmune disorders, thus requiring optimal dosing strategies of Trimethoprim-Sulfamethoxazole (TMP-SMX). Therefore, to ensure the safety of TMP-SMX, there is a high demand to review current evidence in PCP patients with a focus on dose optimization strategies; (2) Methods: Various databases were searched from January 2000 to December 2021 for articles in English, focusing on the dose optimization of TMP-SMX. The data were collected in a specific form with predefined inclusion and exclusion criteria. The quality of each article was evaluated using a Newcastle-Ottawa Scale (NOS) for retrospective studies, Joanna Briggs Institute (JBI) critical checklist for case reports, and Cochrane bias tool for randomized clinical trials (RCTs); (3) Results: Thirteen studies met the inclusion criteria for final analysis. Of the 13 selected studies, nine were retrospective cohort studies, two case reports, and two randomized controlled trials (RCT). Most of the studies compared the high-dose with low-dose TMP-SMX therapy for PCP. We have found that a low dose of TMP-SMX provides satisfactory outcomes while reducing the mortality rate and PCP-associated adverse events. This strategy reduces the economic burden of illness and enhances patients' compliance to daily regimen plan; (4) Conclusions: The large-scale RCTs and cohort studies are required to improve dosing strategies to prevent initial occurrence of PCP or to prevent recurrence of PCP in immune compromised patients.

Dose optimization of ß-lactams antibiotics in pediatrics and adults: A systematic review.

Background: ß-lactams remain the cornerstone of the empirical therapy to treat various bacterial infections. This systematic review aimed to analyze the data describing the dosing regimen of ß-lactams. Methods: Systematic scientific and grey literature was performed in accordance with Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The studies were retrieved and screened on the basis of pre-defined exclusion and inclusion criteria. The cohort studies, randomized controlled trials (RCT) and case reports that reported the dosing schedule of ß-lactams are included in this study. Results: A total of 52 studies met the inclusion criteria, of which 40 were cohort studies, 2 were case reports and 10 were RCTs. The majority of the studies (34/52) studied the pharmacokinetic (PK) parameters of a drug. A total of 20 studies proposed dosing schedule in pediatrics while 32 studies proposed dosing regimen among adults. Piperacillin (12/52) and Meropenem (11/52) were the most commonly used ß-lactams used in hospitalized patients. As per available evidence, continuous infusion is considered as the most appropriate mode of administration to optimize the safety and efficacy of the treatment and improve the clinical outcomes. Conclusion: Appropriate antibiotic therapy is challenging due to pathophysiological changes among different age groups. The optimization of pharmacokinetic/pharmacodynamic parameters is useful to support alternative dosing regimens such as an increase in dosing interval, continuous infusion, and increased bolus doses.

A Systematic Review on Clinical Safety and Efficacy of Vancomycin Loading Dose in Critically Ill Patients.

BACKGROUND: The clinical significance of utilizing a vancomycin loading dose in critically ill patients remains unclear. OBJECTIVE: The main aim of this systematic review is to evaluate the clinical safety and efficacy of the vancomycin loading dose in critically ill patients. METHODS: We performed a systematic review using PRISMA guidelines. PubMed, the Web of Science, MEDLINE, Scopus, Google Scholar, the Saudi Digital Library and other databases were searched. Studies that reported clinical outcomes among patients receiving the vancomycin LD were considered eligible. Data for this study were collected using PubMed, the Web of Science, MEDLINE, Scopus, Google Scholar and the Saudi Digital Library using the following terms: "vancomycin", "safety", "efficacy" and "loading dose" combined with the Boolean operator "AND" or "OR". RESULTS: A total of 17 articles, including 2 RCTs, 11 retrospective cohorts and 4 other studies, met the inclusion/exclusion criteria out of a total 1189 studies. Patients had different clinical characteristics representing a heterogenous group, including patients in critical condition, with renal impairment, sepsis, MRSA infection and hospitalized patients for hemodialysis or in the emergency department. CONCLUSIONS: The study shows that the target therapeutic level is achieved more easily among patients receiving a weight-based LD as compared to patients received the usual dose without an increased risk of new-onset adverse drug reactions.

Dose Optimization of Colistin: A Systematic Review.

Colistin is considered a last treatment option for multi-drug and extensively resistant Gram-negative infections. We aimed to assess the available data on the dosing strategy of colistin. A systematic review was performed to identify all published studies on the dose optimization of colistin. Grey literature and electronic databases were searched. Data were collected in a specified form and the quality of the included articles was then assessed using the Newcastle-Ottawa scale for cohort studies, the Cochrane bias tool for randomized clinical trials (RCT), and the Joanna Briggs Institute (JBI) critical checklist for case reports. A total of 19 studies were included, of which 16 were cohort studies, one was a RCT, and two were case reports. A total of 18 studies proposed a dosing regimen for adults, while only one study proposed a dosing schedule for pediatric populations. As per the available evidence, a loading dose of 9 million international units (MIU) of colistin followed by a maintenance dose of 4.5 MIU every 12 h was considered the most appropriate dosing strategy to optimize the safety and efficacy of treatment and improve clinical outcomes. This review supports the administration of a loading dose followed by a maintenance dose of colistin in severe and life-threatening multi-drug Gram-negative bacterial infections.

Antimicrobial Usage and Resistance in Makkah Region Hospitals: A Regional Point Prevalence Survey of Public Hospitals.

(1) Background: Inappropriate use of antimicrobials and subsequently rise of antimicrobial resistance (AMR) remains a major public health priority. Over-prescribing of broad-spectrum antibiotics is one of the main contributing factors for the emergence of AMR. We sought to describe antimicrobial prescribing trends among patients in public hospitals in Makkah hospitals. (2) Method: We undertook a point prevalence survey (PPS) in six hospitals in Makkah, Saudi Arabia, from January 2019 to July 2019. The survey included all the inpatients receiving antimicrobials on the day of PPS. Data was collected using the Global point prevalence survey (PPS) tool developed by the University of Antwerp, Belgium. (3) Results: Of 710 hospitalized patients, 447 patients (61.9%) were treated with one or more antimicrobials during the study period. The average bed occupancy among six hospitals was 74.4%. The majority of patients received antimicrobials parenterally (90.3%). Of the total prescribed antimicrobials, 415 (53.7%) antimicrobials were used in medical departments, 183 (23.7%) in surgical departments, and 175 (22.6%) in ICUs. Pneumonia (17.3%), skin and soft tissue infections (10.9%), and sepsis (6.6.%) were three common clinical indications. Ceftriaxones were the most commonly used antibiotics that were prescribed in 116 (15%) of patients, followed by piperacillin, with an enzyme inhibitor in 84 (10.9%). (4) Conclusion: There was a high prevalence of antibiotic use in the hospitals of Makkah, which could be a potential risk factor for the incidence of resistant strains, particularly MRSA infection. Public health decision-makers should take these findings into consideration to update national policies for antibiotic use in order to reduce the risks of further increases of AMR.

Evaluation of a Multidisciplinary Antimicrobial Stewardship Program in a Saudi Critical Care Unit: A Quasi-Experimental Study.

Background: Antimicrobial stewardship programs (ASPs) are collaborative efforts to optimize antimicrobial use in healthcare institutions through evidence-based quality improvement strategies. With regard to critically ill patients, appropriate antimicrobial usage is of significance, and any delay in therapy increases their risk of mortality. Therefore, the implementation of structured multidisciplinary ASPs in critical care settings is of the utmost importance to promote the judicious use of antimicrobials. Methods: This quasi-experimental study evaluating a multidisciplinary ASP in a 20-bed critical care setting was conducted from January 1, 2016 to July 31, 2017. Outcomes were compared nine months before and after ASP implementation. The national antimicrobial stewardship toolkit by Ministry of health was reviewed and the hospital antibiotic prescribing policy was accordingly modified. The antimicrobial stewardship algorithm (Start Smart and Then Focus) and an ASP toolkit were distributed to all intensive care unit staff. Prospective audit and feedback, in addition to prescribing forms for common infectious diseases and education, were the primary antimicrobial strategies. Results: We found that the mean total monthly antimicrobial consumption measured as defined daily dose per 100 bed days was reduced by 25% (742.86 vs. 555.33; p = 0.110) compared to 7% in the control condition (tracer medications) (35.35 vs. 38.10; p = 0.735). Interestingly, there was a negative impact on cost in the post-intervention phase. Interestingly, the use of intravenous ceftriaxone measured as defined daily dose per 100 bed days was decreased by 82% (94.32 vs. 16.68; p = 0.008), whereas oral levofloxacin use was increased by 84% (26.75 vs. 172.29; p = 0.008) in the intensive care unit. Conclusion: Overall, involvement of higher administration in multidisciplinary ASP committees, daily audit and feedback by clinical pharmacists and physicians with infectious disease training, continuous educational activities about antimicrobial use and resistance, use of local antimicrobial prescribing guidelines based on up-to-date antibiogram, and support from the intensive care team can optimize antibiotic use in Saudi healthcare institutions.

Validation of the General Medication Adherence Scale in Saudi Patients With Chronic Diseases.

Objective: The aim was to validate the General Medication Adherence Scale (GMAS) (English version) in Saudi patients with chronic disease. Methods: A month-long study was conducted in the out-patient department of tertiary care hospitals in three cities of Saudi Arabia that collected data from a randomized sample of Saudi patients with chronic disease. The study aimed to achieve an item-to-subject ratio greater than 1:10. Factor analyses were conducted and fit indices calculated. Convergent, discriminant, known group, and concurrent validities were analysed. Internal consistency was determined using test-retest reliability using Cronbach's alpha (α), McDonald's coefficient omega (ω t ), and Pearson's correlation coefficient (ρ). Sensitivity analysis was conducted. Data were analysed through Statistical Package for Social Sciences (SPSS) version 23. The study was ethically approved (i.e., IRB-129-26/6/1439). Results: The survey gathered responses from 171 patients with a response rate of 85.5%. An item-to-subject ratio of 1:15 was achieved. Factor analysis revealed a three-factor structure with acceptable fit indices (i.e., normed fit index (NFI) = 0.93, Tucker-Lewis index (TLI) = 0.99, and comparative fit index (CFI) = 0.99), i.e., greater than 0.9. The value of root mean square error of approximation (RMSEA) was 0.01, i.e., less than 0.08. The tool established construct validity, i.e., convergent and discriminant validities. Known group and concurrent validities were also established. An α value of 0.74 and ω t value of 0.92 were reported. Test-retest reliability ρ = 0.82, p < 0.001. The tool had high sensitivity (>75%) and specificity (>80%). Conclusion: The GMAS-English was successfully validated in Saudi patients with chronic disease.

Antimicrobial resistance among pilgrims: a retrospective study from two hospitals in Makkah, Saudi Arabia.

OBJECTIVE: To identify commonly reported community-acquired organisms and antimicrobial resistance patterns exhibited by Gram-positive and Gram-negative pathogens among pilgrims visiting emergency care departments in Makkah. METHOD: The study was designed as a retrospective audit of all patients (pilgrims) admitted to two hospitals and residing in the city of Makkah, Saudi Arabia. RESULTS: Among 374 isolates, Gram-negative pathogens accounted for 280 (75%), while the remaining 94 (25%) were Gram-positive organisms. Among all isolated pathogens, the highest resistance was observed for amoxicillin-clavulanic acid. Klebsiella pneumoniae had the highest resistance to amoxicillin-clavulanic acid and ampicillin. Most of the organisms were sensitive to tobramycin except Acinetobacter baumannii (n=3, 50%), Escherichia coli (n=4, 57%), and K. pneumoniae (n=6, 46%). CONCLUSION: Overall, a high resistance was observed for beta-lactam antibiotics. In addition, a high resistance was noted for ceftazidime with A. baumannii species (n=16, 77%). However, for quinolones, the highest resistance to ciprofloxacin was observed for E. coli, A. baumannii, methicillin-resistant Staphylococcus aureus, and K. pneumoniae.

A Point Prevalence Survey of Antimicrobial Usage for Surgical Site Infections- A Pilot Perspective from Holy Makkah, Saudi Arabia

Introduction:This study aimed to assess the incidence, microbiological features and management of surgical site infections (SSIs). Methodology:All patients in the surgical ward were followed from admissions until discharge during the study period. Only hospitalized patients with certain SSIs within 30 days of surgeries were included in the study. Results:A total of 457 patients were followed during the study period. Interestingly, only 9 (1.9 %) of the patients developed SSIs. Most of the patients were males 6 (66.7%) and Saudi nationals 7 (77.8 %). The most common surgical procedures were laparoscopic and orthopedic surgeries with a similar rate of 3 (3.3 %).Conclusion:This study revealed that the incidence of SSIswas quite lower atthe hospital where the study was conducted and different types of antibiotics were used and recommended for prophylaxis