Correction: Nasrullah et al. Omeprazole Prevents Colistin-Induced Nephrotoxicity in Rats: Emphasis on Oxidative Stress, Inflammation, Apoptosis and Colistin Accumulation in Kidneys. Pharmaceuticals 2022, 15, 782.

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Evaluation of Appropriate Use of Proton Pump Inhibitors in Non-critically Ill Patients in Tertiary Medical Center: A Retrospective Study.

BACKGROUND: There are concerns about indiscriminate prescriptions and the inappropriate use of proton pump inhibitors (PPIs) without any clear indications, especially among noncritically hospitalized patients. OBJECTIVE: This study aimed to characterize PPI prescriptions among non-critically hospitalized patients in a tertiary care hospital in Saudi Arabia. METHODS: A retrospective cross-sectional study was conducted at the King Abdulaziz University Hospital between June and August 2021. The data of adult patients who received PPIs on hospital admission in the medical and surgical wards were collected and analyzed for appropriateness based on the current international guidelines and recommendations. RESULTS: A total of 174 patient records were included in this study. The proportion of patients with appropriate and inappropriate PPI prescriptions was 67.24% (n=117) and 32.76% (n=57), respectively. Female patients (risk=50.00%, 95% CI: 36.89-63.11, p<0.001) were more likely to receive an inappropriate PPI prescription than their male counterparts (risk=33.33%, 95% CI: 24.56-43.43, p<0.001). Intravenous omeprazole 40 mg once daily was the most frequently prescribed PPI (n=62). The hospital length of stay differed significantly between the groups of patients who received appropriate and inappropriate PPIs (24.56 ± 47.14 vs. 13.50 ± 13.84; t=2.34, 95% CI: 1.72-20.4; p=0.02). However, there was no significant difference in the total therapy duration in both the groups (3.76 ± 2.50 vs. 4.75 ± 3.32, t=-1.62, 95%CI: -1.79-0.17; p=0.11). CONCLUSION: The findings show a high trend of inappropriate PPI prescriptions. Hence, educational programs are recommended to encourage healthcare professionals to stick to the approved guidelines when prescribing PPIs.

Intermittent hemodialysis: a review of the top antimicrobial stewardship practices to be employed.

The vulnerability of patients on hemodialysis (HD) to infections is evident by their increased susceptibility to infections in general and to resistant organisms in particular. Unnecessary, inappropriate, or suboptimal antimicrobial prescribing is common in dialysis units. This underscores the need for dedicated antimicrobial stewardship (AMS) interventions that can be implemented both in the inpatient and outpatient settings. In this review, we provide a comprehensive approach for clinicians with the most updated coordinated AMS principles in HD setting in six areas: prevention, diagnosis, treatment, education and empowerment, monitoring, and research.

COVID-19 vaccine hesitancy among healthcare workers in Arab Countries: A systematic review and meta-analysis.

BACKGROUND: Vaccine hesitancy is a major obstacle to the large efforts made by governments and health organizations toward achieving successful COVID-19 vaccination programs. Healthcare worker's (HCWs) acceptance or refusal of the vaccine is an influencing factor to the attitudes of their patients and general population. This study aimed to report the acceptance rates for COVID-19 vaccines among HCWs in Arab countries and identify key factors driving the attitudes of HCWs in the Arab world toward vaccines. METHODS: This systematic review and meta-analysis followed the PRISMA guidelines. PubMed and Scopus databases were searched using pre-specified keywords. All cross-sectional studies that assessed COVID-19 vaccine hesitancy and/or acceptance among HCWs in Arab countries until July 2022, were included. The quality of the included studies and the risk of bias was assessed using the JBI critical appraisal tool. The pooled acceptance rate of the COVID-19 vaccine was assessed using a random-effects model with a 95% confidence interval. RESULTS: A total of 861 articles were identified, of which, 43 were included in the study. All the studies were cross-sectional and survey-based. The total sample size was 57,250 HCWs and the acceptance rate of the COVID-19 vaccine was 60.4% (95% CI, 53.8% to 66.6%; I2, 41.9%). In addition, the COVID-19 vaccine acceptance rate among males was 65.4% (95% CI, 55.9% to 73.9%; I2, 0%) while among females was 48.2% (95% CI, 37.8% to 58.6%; I2, 0%). The most frequently reported factors associated with COVID-19 vaccine acceptance were being male, higher risk perception of contracting COVID-19, positive attitude toward the influenza vaccine, and higher educational level. Predictors of vaccine hesitancy most frequently included concerns about COVID-19 vaccine safety, living in rural areas, low monthly income, and fewer years of practice experience. CONCLUSION: A moderate acceptance rate of COVID-19 vaccines was reported among HCWs in the Arab World. Considering potential future pandemics, regulatory bodies should raise awareness regarding vaccine safety and efficacy and tailor their efforts to target HCWs who would consequently influence the public with their attitude towards vaccines.

Antimicrobial utilization in Hajj 2022: An evaluation of quality indicators.

BACKGROUND: The mass gathering in Hajj (Islamic pilgrimage) makes the spread of infectious diseases inevitable. Antibiotics are frequently prescribed during this season. We aimed to measure antimicrobial utilization during the 2022 Hajj and evaluate the practice using quality indicators. METHODS: Antimicrobial utilization by Hajj medical facilities (77 primary clinics and 7 hospitals) was measured using the anatomic therapeutic classification defined daily dose (DDD) and DDD/1,000-inhabitant/day (DID), where inhabitants were the Hajj 2022 pilgrims (n = 899,353). Quality indicators included percentages of consumption of different antibiotic classes of the total consumption of antibacterials for systemic use in DID. RESULTS: During Hajj, there was 87,173 outpatient visits and 740 hospitalizations (215 critically ill). Amoxicillin was the most prescribed antibiotic (DID=11.708) followed by azithromycin (DID=7.395). Penicillins fell in the second quartile (i.e., highly prescribed) with a quality indicator value (J01_CE%) of 48.149. The consumption of other antibacterials, including fluoroquinolones, fell in the first quartile (<25%). The overall ratio of broad- to narrow-spectrum antibiotic prescribing (J01_B/N) was 1.49. CONCLUSION: Although the prescribing of ß-lactams over fluoroquinolones indicates a good practice, clinicians should be reminded that most infections spreading in mass gatherings are viral; hence, do not require antibiotics. Implementation of antimicrobial stewardship is recommended to improve antimicrobial utilization.

Impact of a multidisciplinary antimicrobial stewardship program on antibiotic utilization and clinical outcomes at a tertiary hospital in Saudi Arabia: a quasi-experimental study.

BACKGROUND: This study aims to assess the impact of a multidisciplinary antimicrobial stewardship program (ASP) intervention on various metrics. METHODS: A quasi-experimental study was performed on non-ICU patients for whom a restricted antibiotic was ordered. In September 2020, a prospective audit and feedback was implemented involving infectious disease clinical pharmacists, utilization of electronic resources, and improved documentation. Outcomes included defined daily dose and days of therapy per 100-patient days (DDD/100PD and DOT/100PD) and patient clinical outcomes. RESULTS: 402 episodes were evaluated for 167 and 190 unique patients in the pre- and post-intervention phases, respectively. DDD/100PD and DOT/100PD were lower in the post-phase than in the pre-phase (1.75 vs. 2.54 and 16.13 vs. 44.93). Antibiotic de-escalation and clinical cure rates were significantly higher in the post-phase than in the pre-phase (62% vs. 40.6% and 83.5% vs. 65.8%; P < 0.001 for both comparisons). Hospital and ICU stays were significantly shorter in the post-phase (14 vs. 22 and 3 vs. 9, respectively; P < 0.001 for both comparisons). In-hospital mortality and 30-day readmission rates were lower in the post-phase (13% vs. 20.8%; P = 0.037 and 20.5% vs. 33.8%; P = 0.003, respectively). CONCLUSION: The implemented multidisciplinary ASP intervention was associated with a significant improvement in antibiotic utilization and patient clinical outcomes.

Evaluation of Weight-Based Co-trimoxazole Dosing in a Saudi Tertiary Hospital.

BACKGROUND: Infections caused by Stenotrophomonas maltophilia (S. maltophilia) and Pneumocystis jirovecii (Pneumocystis jirovecii pneumonia (PJP)) require weight-based dosing for co-trimoxazole. The aim of this study is to assess the appropriateness of co-trimoxazole dosing in adult inpatients for the treatment of these infections. METHODOLOGY: This is a single-center, cross-sectional study that included adult inpatients treated with co-trimoxazole for a weight-based dose indication (S. maltophilia and PJP). The primary outcome was the appropriateness of co-trimoxazole dosing for these infections. RESULTS: Forty-three patients were included in the study. Of the 43 patients, 29 (67.4%) were using co-trimoxazole for PJP treatment, and 14 (32.6%) were using it for S. maltophilia treatment. The co-trimoxazole dose was appropriate in 22 (51.2%) patients, 21 (72.4%) in the PJP treatment group, and one (7.1%) in the S. maltophilia treatment group. Underdosing was observed in 21 (48.8%) patients, of whom eight (27.6%) were in the PJP treatment group and 13 (92.9%) were in the S. maltophilia treatment group. CONCLUSIONS: This study found a relatively high rate of underdosing of co-trimoxazole based on weight in hospitalized adults with PJP and S. maltophilia infections.

Addressing Consumer Misconceptions on Antibiotic Use and Resistance in the Context of Sore Throat: Learnings from Social Media Listening.

A misunderstanding of the mechanism of action and bacterial targets of antibiotics by consumers may drive inappropriate antibiotic use and antimicrobial resistance (AMR). Tackling AMR requires an in-depth understanding of consumer beliefs and misconceptions. We explored consumer conversations on a number of social media platforms on antibiotic use and AMR in the context of sore throat and how coronavirus disease 2019 (COVID-19) affected online conversations between 1 January 2018 and 25 November 2021 across eight countries. Five distinct consumer groups were identified (antibiotic-preserving peer educators, antibiotic-cautious consumers, medication-resistant antibiotic opponents, believers in the strength of antibiotics, determined pro-antibiotic consumers) with a wide spectrum of beliefs around antibiotics in sore throat. Many opinions were based upon misconceptions, the most prominent of which was that antibiotics are strong medications that can treat all types of sore throat. COVID-19 had a multifaceted effect on the sore throat and AMR conversation. Sore throat triggered anxiety as consumers feared it may be a COVID-19 symptom while engagement in conversations around antibiotics for COVID-19 increased. Finally, consumers sought multiple routes to access antibiotics, such as directly from the pharmacy or by attempting to persuade physicians to prescribe. Knowledge obtained from this study could be used to develop focused approaches to dispel consumer misconceptions and mitigate AMR.

Long-term gastrointestinal adverse effects of doxycycline.

INTRODUCTION: Doxycycline is an antibiotic with known gastrointestinal (GI) adverse effects. Esophagitis is the most pronounced among these effects, and might be associated with a prolonged duration of therapy. The aim of this study is to evaluate the incidence of esophagitis and other GI side effects in adults who received doxycycline for at least a month. METHODOLOGY: This retrospective descriptive study included adults who received oral doxycycline for at least one month between 2016 and 2018. The primary outcome was the frequency of esophagitis. The secondary outcomes were frequency of and discontinuation due to GI adverse effects. RESULTS: A total of 189 subjects were included with a median age of 32 years. The median duration of doxycycline use was 44 days (interquartile range 30-60). Twelve patients (6.3%) reported having GI adverse effects resulting in doxycycline discontinuation in five of them (2.6%), and three patients (1.6%) had esophagitis. The incidence of GI adverse effects was significantly higher in patients who were ≥ 50 years than < 50 years old (8/50 vs. 4/139; p = 0.003) and in those who received a daily dose of 200 mg than 100 mg (12/93 vs. 0/96; p < 0.001). CONCLUSIONS: GI adverse events, including esophagitis, are not rare with long-term use of oral doxycycline, particularly in older age and a higher dose of 200 mg/day. Future large and randomized studies are needed to compare the efficacy and safety of different doxycycline doses.

Evaluation of Early Tocilizumab Effect on Multiorgan Dysfunction in Critically Ill Patients With COVID-19: A Propensity Score-Matched Study.

Background: Tocilizumab (TCZ) has been proposed as potential rescue therapy for severe COVID-19. No previous study has primarily assessed the role of TCZ in preventing severe COVID-19-related multiorgan dysfunction. Hence, this multicenter cohort study aimed to evaluate the effectiveness of TCZ early use versus standard of care in preventing severe COVID-19-related multiorgan dysfunction in COVID-19 critically ill patients during intensive care unit (ICU) stay. Methods: A multicenter, retrospective cohort study includes critically ill adult patients with COVID-19 admitted to the ICUs. Patients were categorized into two groups, the treatment group includes patients who received early TCZ therapy within 24 hours of ICU admission and the control group includes patients who received standard of care. The primary outcome was the multiorgan dysfunction on day three of the ICU admission. The secondary outcomes were 30-day, and in-hospital mortality, ventilator-free days, hospital length of stay (LOS), ICU LOS, and ICU-related complications. Results: After propensity score matching, 300 patients were included in the analysis based on predefined criteria with a ratio of 1:2. Patients who received TCZ had lower multiorgan dysfunction score on day three of ICU admission compared to the control group (beta coefficient: -0.13, 95% CI: -0.26, -0.01, P-value = 0.04). Moreover, respiratory failure requiring MV was statistically significantly lower in patients who received early TCZ compared to the control group (OR 0.52; 95% CI 0.31, 0.91, P-value = 0.02). The 30-day and in-hospital mortality were significantly lower in patients who received TCZ than those who did not (HR 0.56; 95% CI 0.37, 0.85, P-value = 0 .006 and HR 0.54; 95% CI 0.36, 0.82, P-value = 0.003, respectively). Conclusion: In addition to the mortality benefits associated with early TCZ use within 24 hours of ICU admission, the use of TCZ was associated with a significantly lower multiorgan dysfunction score on day three of ICU admission in critically ill patients with COVID-19.

Psychogenetic, genetic and epigenetic mechanisms in Candida auris: Role in drug resistance.

In recent years, we are facing the challenge of drug resistance emergence in fungi. The availability of limited antifungals and development of multi-drug resistance in fungal pathogens has become a serious concern in the past years in the health sector. Although several cellular, molecular, and genetic mechanisms have been proposed to explain the drug resistance mechanism in fungi, but a complete understanding of the molecular and genetic mechanisms is still lacking. Besides the genetic mechanism, epigenetic mechanisms are pivotal in the fungal lifecycle and disease biology. However, very little is understood about the role of epigenetic mechanisms in the emergence of multi-drug resistance in fungi, especially in Candida auris (C. auris). The current narrative review summaries the clinical characteristics, genomic organization, and molecular/genetic/epigenetic mechanisms underlying the emergence of drug resistance in C. auris. A very few studies have attempted to evaluate the role of epigenetic mechanisms in C. auris. Furthermore, advanced genetic tools such as the CRISP-Cas9 system can be utilized to elucidate the epigenetic mechanisms and their role in the emergence of multi-drug resistance in C. auris.

Effectiveness of antimicrobial stewardship interventions on early switch from intravenous-to-oral antimicrobials in hospitalized adults: A systematic review.

BACKGROUND: This review aimed to summarize the available evidence on the effectiveness and safety of antimicrobial stewardship interventions to improve the practice of IV-to-PO antimicrobial switch therapy in hospitalized adults. METHODS: Following the PRISMA guidelines, we searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE/PubMed, and Scopus from inception to September 1, 2020, for original articles investigating any interventions aimed to improve the practice of IV-to-PO antimicrobial switch therapy in hospitalized adults with infectious diseases. We included randomized controlled trials (RCTs) and quasi-experimental studies. Studies were excluded if they evaluated drugs other than antimicrobials, head-to-head comparison of interventions, included pediatrics or oncology patients. RESULTS: Of 506 unique citations identified, 36 studies met the inclusion criteria. The 36 included studies reported 92 interventions as a single (n = 10) or a bundle of interventions (n = 26). The most common interventions used were guideline/protocol/pathway (n = 25), audit and feedback (n = 20), and education (n = 17). CONCLUSIONS: This review provides health care providers with a comprehensive summary on the interventions to promote IV-to-PO antimicrobial switch. While no one intervention could be identified as the safest and most effective as most of the included studies used a bundle of interventions, all interventions resulted in optimizing antibiotic use and reducing health care expenditures without compromising the clinical outcomes. As such, each hospital should design and utilize interventions that are applicable based on available resources and expertise.

Doxycycline vs. macrolides in combination with a ß-lactam antibiotic for the treatment of community-acquired pneumonia in inpatients.

BACKGROUND: Hospitalized patients with non-severe community-acquired pneumonia (CAP) are treated with a ß-lactam plus either a macrolide or doxycycline. Limited data exist on the effectiveness of the latter combination. Therefore, we aimed to compare the combination of doxycycline vs. macrolide when either is combined with a ß-lactam from effectiveness and safety perspectives. METHODS: This was a retrospective cohort study in CAP inpatients between December 2013 and November 2020. Patients were divided into BL-D (ß-lactam plus doxycycline) and BL-M (ß-lactam plus a macrolide [azithromycin or clarithromycin]) groups. The primary endpoint was time to clinical stability. Secondary endpoints included length of stay (LOS) and in-hospital mortality. RESULTS: Of 197 patients included, 57 were in the BL-D arm and 140 were in the BL-M arm. Patients were similar at baseline, except for the presence of leukocytosis, risk factors for drug resistance, and duration of therapy (P < 0.05 for all comparisons). No difference in clinical cure rate was observed (94.7% vs. 91.4%; P = 0.43). Time to clinical stability and LOS were similar in both groups at 4 (P = 0.82) and 7 days (P = 0.62), respectively. While only three patients died, only one (from the BL-M group) was due to sepsis. Liver enzymes elevation was more prominent in the BL-M group (21.4% vs. 5.3%; P = 0.01). A subgroup analysis showed shorter time to clinical stability with clarithromycin but higher cure rates with azithromycin. CONCLUSIONS: Data on doxycycline use with a ß-lactam are scarce. Our study showed that such regimen was comparable in effectiveness to regimens involving macrolides with a better safety profile.

An Overview on Phenotypic and Genotypic Characterisation of Carbapenem-Resistant Enterobacterales.

Improper use of antimicrobials has resulted in the emergence of antimicrobial resistance (AMR), including multi-drug resistance (MDR) among bacteria. Recently, a sudden increase in Carbapenem-resistant Enterobacterales (CRE) has been observed. This presents a substantial challenge in the treatment of CRE-infected individuals. Bacterial plasmids include the genes for carbapenem resistance, which can also spread to other bacteria to make them resistant. The incidence of CRE is rising significantly despite the efforts of health authorities, clinicians, and scientists. Many genotypic and phenotypic techniques are available to identify CRE. However, effective identification requires the integration of two or more methods. Whole genome sequencing (WGS), an advanced molecular approach, helps identify new strains of CRE and screening of the patient population; however, WGS is challenging to apply in clinical settings due to the complexity and high expense involved with this technique. The current review highlights the molecular mechanism of development of Carbapenem resistance, the epidemiology of CRE infections, spread of CRE, treatment options, and the phenotypic/genotypic characterisation of CRE. The potential of microorganisms to acquire resistance against Carbapenems remains high, which can lead to even more susceptible drugs such as colistin and polymyxins. Hence, the current study recommends running the antibiotic stewardship programs at an institutional level to control the use of antibiotics and to reduce the spread of CRE worldwide.

Ten ways to make the most of World Antimicrobial Awareness Week.

One fundamental strategy to address the public health threat of antimicrobial resistance (AMR) is improved awareness among the public, prescribers, and policy makers with the aim of engaging these groups to act. World Antimicrobial Awareness Week is an opportunity for concerted and consistent communication regarding practical strategies to prevent and mitigate AMR. We highlight 10 ways for antimicrobial stewards to make the most of World Antimicrobial Awareness Week.

Controlling of Bacterial Virulence: Evaluation of Anti-Virulence Activities of Prazosin against Salmonella enterica.

Salmonella enterica is a Gram-negative orofecal transmitted pathogen that causes a wide diversity of local and systemic illnesses. Salmonella enterica utilizes several interplayed systems to regulate its invasion and pathogenesis: namely, quorum sensing (QS) and type three secretion system (T3SS). In addition, S. enterica could sense the adrenergic hormones in the surroundings that enhance its virulence. The current study aimed to evaluate the ability of α-adrenoreceptor antagonist prazosin to mitigate the virulence of S. enterica serovar Typhimurium. The prazosin effect on biofilm formation and the expression of sdiA, qseC, qseE, and T3SS-type II encoding genes was evaluated. Furthermore, the prazosin intracellular replication inside macrophage and anti-virulence activity was evaluated in vivo against S. typhimurium. The current finding showed a marked prazosin ability to compete on SdiA and QseC and downregulate their encoding genes. Prazosin significantly downregulated the virulence factors encoding genes and diminished the biofilm formation, intracellular replication inside macrophages, and in vivo protected mice. To sum up, prazosin showed significant inhibitory activities against QS, T3SS, and bacterial espionage, which documents its considered anti-virulence activities.

Silencing of Salmonella typhimurium Pathogenesis: Atenolol Acquires Efficient Anti-Virulence Activities.

The targeting of bacterial virulence is proposed as a promising approach to overcoming the bacterial resistance development to antibiotics. Salmonella enterica is one of the most important gut pathogens that cause a wide diversity of local and systemic illnesses. The Salmonella virulence is controlled by interplayed systems namely Quorum sensing (QS) and type three secretion system (T3SS). Furthermore, the Salmonella spy on the host cell via sensing the adrenergic hormones enhancing its virulence. The current study explores the possible anti-virulence activities of ß-adrenoreceptor blocker atenolol against S. enterica serovar Typhimurium in vitro, in silico, and in vivo. The present findings revealed a significant atenolol ability to diminish the S. typhimurium biofilm formation, invasion into HeLa cells, and intracellular replication inside macrophages. Atenolol significantly downregulated the encoding genes of the T3SS-type II, QS receptor Lux analogs sdiA, and norepinephrine membranal sensors qseC and qseE. Moreover, atenolol significantly protected mice against S. typhimurium. For testing the possible mechanisms for atenolol anti-virulence activities, an in silico molecular docking study was conducted to assess the atenolol binding ability to QS receptor SdiA and norepinephrine membranal sensors QseC. Atenolol showed the ability to compete on the S. typhimurium targets. In conclusion, atenolol is a promising anti-virulence candidate to alleviate the S. typhimurium pathogenesis by targeting its QS and T3SS systems besides diminishing the eavesdropping on the host cells.

Muting Bacterial Communication: Evaluation of Prazosin Anti-Quorum Sensing Activities against Gram-Negative Bacteria Pseudomonas aeruginosa, Proteus mirabilis, and Serratia marcescens.

Quorum sensing (QS) controls the production of several bacterial virulence factors. There is accumulative evidence to support that targeting QS can ensure a significant diminishing of bacterial virulence. Lessening bacterial virulence has been approved as an efficient strategy to overcome the development of antimicrobial resistance. The current study aimed to assess the anti-QS and anti-virulence activities of α-adrenoreceptor prazosin against three virulent Gram-negative bacteria Pseudomonades aeruginosa, Proteus mirabilis, and Serratia marcescens. The evaluation of anti-QS was carried out on a series of in vitro experiments, while the anti-virulence activities of prazosin were tested in an in vivo animal model. The prazosin anti-QS activity was assessed on the production of QS-controlled Chromobacterium violaceum pigment violacein and the expression of QS-encoding genes in P. aeruginosa. In vitro tests were performed to evaluate the prazosin effects on biofilm formation and production of extracellular enzymes by P. aeruginosa, P. mirabilis, and S. marcescens. A protective assay was conducted to evaluate the in vivo anti-virulence activity of prazosin against P. aeruginosa, P. mirabilis, and S. marcescens. Moreover, precise in silico molecular docking was performed to test the prazosin affinity to different QS receptors. The results revealed that prazosin significantly decreased the production of violacein and the virulent enzymes, protease and hemolysins, in the tested strains. Prazosin significantly diminished biofilm formation in vitro and bacterial virulence in vivo. The prazosin anti-QS activity was proven by its downregulation of QS-encoding genes and its obvious binding affinity to QS receptors. In conclusion, prazosin could be considered an efficient anti-virulence agent to be used as an adjuvant to antibiotics, however, it requires further pharmacological evaluations prior to clinical application.

Efficacy of empiric macrolides versus fluoroquinolones in community-acquired pneumonia associated with atypical bacteria: A meta-analysis.

INTRODUCTION: It is unclear if one empiric regimen for community-acquired pneumonia (CAP) associated with atypical bacteria is superior to another. The objective of this meta-analysis was to compare fluoroquinolones to macrolides in the rates of clinical failure in CAP associated with atypical pathogens. METHODS: We searched PubMed and EMBASE databases for randomized controlled trials (RCTs) comparing the clinical efficacy of fluoroquinolones with macrolides for CAP associated with atypical bacteria. We estimated risk differences (RRs) with 95% confidence intervals (CIs) using random-effects models and assessed for heterogeneity (I2). RESULTS: Five RCTs met the inclusion criteria. No significant differences between macrolides and fluoroquinolones and were identified in rates of clinical failure in CAP associated with any atypical bacteria (RR = 1.57 [95% CI 0.73 to 3.38]; p = 0.251; I2 = 0%), Chlamydia pneumoniae (RR = 2.12 [95% CI 0.63 to 7.14]; p = 0.223; I2 = 0%), Mycoplasma pneumoniae (RR = 1.28 [95% CI 0.57 to 2.92]; p = 0.550; I2 = 0%), or Legionella pneumophila (RR = 0.24 [95% CI 0.02 to 2.86]; p = 0.256; I2 = 0%). CONCLUSIONS: This meta-analysis of RCTs found no significant differences between macrolides and fluoroquinolones in rates of clinical failure in CAP associated with atypical bacteria.

Restriction on antimicrobial dispensing without prescription on a national level: Impact on the overall antimicrobial utilization in the community pharmacies in Saudi Arabia.

BACKGROUND: High rates of non-prescription dispensing of antimicrobials have led to a significant increase in the antimicrobial overuse and misuse in Saudi Arabia (SA). The objective of this study was to evaluate the antimicrobial utilization following the enforcement of a new prescription-only antimicrobial dispensing policy in the community pharmacy setting in SA. METHODS: Data were extracted from the IQVIA database between May 2017 and May 2019. The antimicrobial utilization rates, based on sales, defined daily dose in grams (DDD), DDD/1000 inhabitants/day (DID), and antimicrobial-claims for the pre-policy (May 2017 to April 2018) and post-policy (June 2018 to May 2019) periods were assessed. RESULTS: Overall antimicrobial utilization declined slightly (~9-10%) in the post-policy versus pre-policy period (sales, 31,334 versus 34,492 thousand units; DDD, 183,134 versus 202,936), with higher claims (~16%) after policy implementation. There was a sudden drop in the utilization rate immediately after policy enforcement; however, the values increased subsequently, closely matching the pre-policy values. Utilization patterns were similar in both periods; penicillin was the most used antimicrobial (sales: 11,648-14,700-thousand units; DDD: 71,038-91,227; DID: 2.88-3.78). For both periods, the highest dip in utilization was observed in July (sales: 1,027-1,559 thousand units; DDD: 6,194-9,399), while the highest spike was in March/October (sales: 3,346-3,884 thousand units; DDD: 22,329-19,453). CONCLUSION: Non-prescription antimicrobial utilization reduced minimally following policy implementation in the community pharmacies across SA. Effective implementation of prescription-only regulations is necessary.