Managing infectious diarrhea among young children in community pharmacies in Saudi Arabia and the implications for AMR.

Introduction: Diarrhea remains a major global health issue for children under five, contributing substantially to morbidity and mortality. Community pharmacists play a pivotal role in the management of these children; however, their competence in managing childhood diarrhea in Saudi Arabia is under-researched. This is important to ensure optimal patient care. Method: Simulated patients (SPs) presenting with three pediatric diarrhea scenarios were used to evaluate pharmacists' practice in terms of their counselling, history taking, over-the-counter (OTC) prescribing, medication instructions, diet/fluid advice, and/or information provision. Pharmacists' practice was categorized into adequate, less adequate, and poor. Results: 182 community pharmacists, primarily male and non-Saudi, participated in the study, of which 60% were in chain pharmacies. Only 5% showed adequate practice in currently managing pediatric diarrhea. Of the 182 simulated patient visits, 62% received medication in all three scenarios and 20% were referred to physicians, with 16% of pharmacists failing to provide any form of intervention. The main medications recommended were kaolin (34%), pectin (34%) and metronidazole (11%). While most pharmacists (86%) asked about the patient's identity and age, 15% provided incorrect management information, 16% failed to provide guidance on the prescribed medicines, and 18% dispensed antimicrobials without a valid prescription. Conclusion: A high level of inadequate management of pediatric diarrhea in Saudi Arabia was observed. This highlights the need for extensive training to improve community pharmacists' practice in service delivery including providing counselling and advice on the appropriate management of childhood diarrhea. The latter is particularly important to reduce antimicrobial resistance.

Prevalence and antimicrobial susceptibility pattern of methicillin-resistant Staphylococcus aureus (MRSA) at a maternity and children hospital in Saudi Arabia: A cross-sectional study.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) pathogens are considered a serious global health threat, leading to increased mortality and antimicrobial resistance. Rates in Saudi Arabia remain high, necessitating continuous surveillance. This study investigates MRSA prevalence and susceptibility at a Saudi maternity and children's hospital. Method: A cross-sectional study was conducted on pediatric (<18 years) and maternal patients with S. aureus infection from Jan. 2020 to March. 2022. Bacterial strains were obtained from patient's clinical specimens and was identified by standard method. The BD Phoenix™ M50 was used for antibiotic susceptibility tests and MRSA detection. Data were analysed using descriptive and inferential statistics (Chi-square test) with SPSS software. Results: Out of 152 S. aureus cases, 114/152 (75 %) were pediatric and 38/152 (25 %) were maternal patients. The overall MRSA infection was 69/152 (45.4 %). Among pediatrics, 31/54 (57.4 %) MRSA cases were female; over 30/54 (56 %) were under 1 year old; and most MRSA infections were obtained from skin 29/54 (53.7 %) compared to other sites of infections (p = 0.024). Among maternal cases, 15/38 (39.5 %) were MRSA, primarily from wound infections 14/15 (93.3 %) compared to other sites of infections (p = 0.39). All MRSA isolates were sensitive to vancomycin and linezolid. While 51/60(85 %) were sensitive to Trimethoprim/ sulfamethoxazole. Conclusion: This investigation found a high prevalence of MRSA among pediatrics and maternal inpatients, indicating a significant burden. All MRSA isolates were susceptible to vancomycin but demonstrated variable sensitivity to other antibiotics. These findings highlight the need for ongoing surveillance, infection control strategies, and research into alternative treatment options to combat this major public health threat.

Evaluating preceptorship during advanced pharmacy practice experiences in Saudi Arabia: A Cross-Sectional Study.

Introduction: Doctor of Pharmacy (PharmD) programs offer students' academic coursework and Advanced Pharmacy Practice Experiences (APPEs). APPEs are crucial for students, providing hands-on training in practice settings and enhancing clinical skills and decision-making abilities. Nevertheless, successful APPEs relies mainly on preceptorship. Hence, this study aims to evaluate preceptorship during APPEs in one of the non-major cities in Saudi Arabia. Method: A Cross-Sectional survey study was conducted among 40 PharmD students at Taibah University's College of Pharmacy which involved two telephone interviews conducted seven months apart. The survey instrument consisted of 46 questions divided into eight sections which covered various aspects such as demographics, clarity of rotation objectives, clinical and communication skills, assessment of the training and learning opportunities, preceptors' feedback and evaluation, interaction with patients, healthcare providers, and preceptors. Descriptive statistics and Cronbach's alpha coefficient were utilized to analyze the collected data and to assess the internal consistency of the multi-item Likert questions. Results: Preceptors were predominantly male, aged 26-35, with extensive experience in pharmacy practice and mentorship, yet they lacked specialized post-graduate training or education certification. Almost 50% of the preceptors exhibited competence in pharmacotherapy-related science, demonstrated a willingness to teach students and acknowledged the students' knowledge and skills. Furthermore, most of the students reported understanding of the APPEs objectives as the internship progressed. However, only 15% of late rotation participants strongly agreed on the safety of the learning environment, adequate time and regular contact with their preceptors. Starkly, only 3.0% of early rotation students and 6.1% of late rotation students strongly agreed with the improvement of their written and verbal communications. Conclusion: This study reported a noted decline in perceived learning support and environment safety as the APPEs' year progressed. Feedback and communication skills development were areas of concern, with limited satisfaction reported. The study highlights regional disparities in training quality, emphasizing the need for structured learning experiences and re-evaluation of preceptorship. Future research should aim to better understand the challenges associated with APPEs in non-major cities and rural areas, thereby making significant contributions to the enhancement of the pharmacy profession.

Assessment of Knowledge and Practice of Healthcare Providers in Saudi Arabia Regarding Clostridioides difficile Infection Diagnosis and Management: A Cross-Sectional Questionnaire-Based Study.

Introduction: Diagnosis of Clostridioides difficile infection (CDI) depends on clinical presentation and laboratory testing. Stool diagnostic tests are essential for effective detection of toxigenic C. difficile strains. No study to date has evaluated the readability of microbiology labs in Saudi Arabia to test for CDI and evaluated the knowledge and practice of healthcare providers regarding CDI management. Therefore, this study aimed to assess the knowledge and practice of healthcare providers in Saudi Arabia regarding CDI diagnosis and treatment. Methods: A cross-sectional, descriptive, questionnaire-based study was conducted on healthcare providers in Saudi Arabia, primarily physicians and clinical pharmacists. The questionnaire was developed based on a literature review and input from infectious diseases experts. The questionnaire was administered online. Data were analyzed using descriptive and inferential statistics. Results: Of 183 respondents, 27.9% had adequate knowledge on CDI diagnosis and management. The majority were internal medicine specialists (37.7%) working in governmental or semi-governmental hospitals (80.9%) in central (46.6%) or southern (30.1%) regions of Saudi Arabia. Most participants assessed laxative use (86.3%) and reported positive C. difficile specimens to infection control (67.2%). However, knowledge varied, with 57.4% supporting unnecessary retesting and 53% assuming positive PCR test indicates moderate CDI probability. Factors such as specialization, hospital accreditation status, and bed capacity influenced knowledge levels (p<0.01 for all factors). Conclusion: The study revealed a significant knowledge gap among Saudi healthcare providers regarding CDI diagnosis, management, and severity classification, highlighting the need for improved education and adherence to guidelines to improve patient outcomes and reduce recurrence risks.

Assessment of Public Knowledge about Chronic Kidney Disease and Factors Influencing Knowledge Levels: A Cross-Sectional Study.

Background and Objectives: Chronic kidney disease (CKD) poses a significant risk for end-stage renal disease (ESRD), cardiovascular diseases, and premature death. The study aims to assess CKD knowledge and predictive variables among the general public. Materials and Methods: A cross-sectional study was conducted among the general public in Al Medina Al-Munawara, Saudi Arabia, utilizing a 21-item questionnaire-based approach over a 4-month period from January 2023 to April 2023. The developed questionnaire was validated for readability by experts and refined in light of the feedback received from the experts and the final version was prepared. The reliability of the questionnaire was 0.71, which shows an acceptable level of internal consistency. The data analysis was performed using IBM SPSS software (version 25). Results: A total of 777 complete surveys were received after applying the exclusion criteria. The study results revealed that the majority of the respondents had poor knowledge 505 (65%), 203 (26.1) had moderate knowledge, and 69 (8.9%) had good knowledge. Gender (p = 0.004), age (<0.001), education level (p = 0.039), marital status (p = 0.003), and occupation (p = 0.002) play significant roles in shaping participants' knowledge levels regarding CKD. Lower odds of good knowledge were associated with females with an OR (95% CI) of 0.448 (0.263-0.764) and intermediate or higher secondary school level of education displayed an OR (95% CI) of 0.39 (0.18-0.89). Higher odds of good knowledge levels were associated with the age group of 18-27 with an OR (95% CI) of 5.077 (1.21-21.38) and being employed with an OR of 3.555 (1.04-12.21). Conclusions: A significant proportion of respondents had poor knowledge about CKD. Several demographic factors were associated with CKD knowledge. Further research is needed to explore these knowledge disparities and develop targeted interventions to improve CKD knowledge among the general public.

Acute kidney injury associated with piperacillin-tazobactam versus other antibiotics combined with vancomycin in critically ill patients: A retrospective cohort study.

Introduction: Evidence of acute kidney injury (AKI) induced by piperacillin-tazobactam (Piptazo) versus other broad-spectrum antibiotics (BSA) combined with vancomycin has been established in the literature. However, there is limited evidence regarding these combinations among critically ill patients. This study assessed the risk of nephrotoxicity of Piptazo versus other BSA as an add-on to vancomycin among patients admitted to an intensive care unit (ICU). Methods: We have reviewed patients' charts retrospectively to investigate AKI incidence among ICU patients receiving Piptazo versus other BSA as an add-on to vancomycin. Furthermore, we have assessed the duration of AKI and ICU stay, as well as the association between patients' criteria and risk of AKI using logistic regression analyses. Results: A total of 79 patients were included, 50 patients received the Piptazo combination while 29 patients received other BSA combinations. Almost 52 % of the patients in the Piptazo group developed AKI while only 37.9 % of those in the BSA group did, yet the difference was not statistically significant (p = 0.22). On the other hand, the risk of AKI was highly associated with vancomycin trough concentration above 20 mcg/mL, nephrotoxic medications, and African descent (OR 7.1, 95 %CI 1.96-25.84, OR 3.94, 95 %CI 1.27-12.2, OR 3.53, 95 %CI 1.1-11.27, respectively). Conclusion: Although the difference in AKI risk was not statistically significant between Piptazo versus BSA groups, the elevated trough concentration of vancomycin and the concomitant use of nephrotoxic medications, were found to increase the risk of AKI, independently of the combined antibiotics used.

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.

The Significance of Bayesian Pharmacokinetics in Dosing for Critically Ill Patients: A Primer for Clinicians Using Vancomycin as an Example.

Antibiotic use is becoming increasingly challenging with the emergence of multidrug-resistant organisms. Pharmacokinetic (PK) alterations result from complex pathophysiologic changes in some patient populations, particularly those with critical illness. Therefore, antibiotic dose individualization in such populations is warranted. Recently, there have been advances in dose optimization strategies to improve the utilization of existing antibiotics. Bayesian-based dosing is one of the novel approaches that could help clinicians achieve target concentrations in a greater percentage of their patients earlier during therapy. This review summarizes the advantages and disadvantages of current approaches to antibiotic dosing, with a focus on critically ill patients, and discusses the use of Bayesian methods to optimize vancomycin dosing. The Bayesian method of antibiotic dosing was developed to provide more precise predictions of drug concentrations and target achievement early in therapy. It has benefits such as the incorporation of personalized PK/PD parameters, improved predictive abilities, and improved patient outcomes. Recent vancomycin dosing guidelines emphasize the importance of using the Bayesian method. The Bayesian method is able to achieve appropriate antibiotic dosing prior to the patient reaching the steady state, allowing the patient to receive the right drug at the right dose earlier in therapy.

Defining and supporting a professional role for pharmacists associated with traditional and complementary medicines: a cross-country survey of pharmacists.

Introduction: An estimated 80% of the world's population use traditional and complementary medicine (T&CM) products as part of their healthcare, with many accessed through pharmacy. This cross-cultural study posed a set of professional practice responsibilities and actions to pharmacists related to T&CM products, with a view toward developing consensus, safeguarding, and promoting the health of the public. Methods: Data were collected from 2,810 pharmacists across nine countries during 2022 via a cross-sectional online survey reported in accordance with the guidelines of STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) and the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). Results: Of the 2,810 participants from nine countries, 2,341 completed all sections of the survey. Of these, most agreed (69%) that T&CM product use was common in the community they served, but most did not have adequate training to support consumer needs. Over 75% acknowledged that there were known and unknown safety risks associated with T&CM use. Of 18 professional responsibilities posed, 92% agreed that pharmacists should be able to inform consumers about potential risks, including T&CM side effects and drug-herb interactions. The provision of accurate scientific information on the effectiveness of T&CM products, skills to guide consumers in making informed decisions, and communication with other healthcare professionals to support appropriate and safe T&CM product use were all ranked with high levels of agreement. In order to effectively fulfill these responsibilities, pharmacists agreed that regulatory reforms, development of T&CM education and training, and access to quality products supported by high-quality evidence were needed. Conclusion: General agreement from across nine countries on eighteen professional responsibilities and several stakeholder actions serve as a foundation for the discussion and development of international T&CM guidelines for pharmacists.

An Overview of Antimicrobial Resistance in Saudi Arabia (2013-2023) and the Need for National Surveillance.

Antimicrobial resistance (AMR) is a well-recognized global threat. The World Health Organization (WHO) issued a report ranking the critical types of bacterial resistance that need to be monitored. Several studies from individual institutions in Saudi Arabia have reported rates of antimicrobial resistance using automated methods. However, no national surveillance study has been conducted to date using gold standard methods for antimicrobial susceptibility testing. This review summarizes AMR rates for major bacterial pathogens in Saudi Arabia and provides a justification for the need for a national surveillance project. In Saudi Arabia, AMR rates for both Gram-positive and Gram-negative bacteria are on the rise. Surveillance studies help identify AMR trends and emergence of outbreaks. The WHO has started a program, the Global Antimicrobial Resistance Surveillance System (GLASS), encouraging its member states, including Saudi Arabia, to conduct antimicrobial surveillance studies to estimate AMR rates worldwide. Of the microbiological methods used to test antimicrobial susceptibility, only broth microdilution (BMD) is considered the "gold standard." As AMR studies in Saudi Arabia are sparse, mostly limited to single centers and were conducted using automated methods, a national AMR surveillance project is needed to evaluate the current status and to inform stewardship decisions.

Uptake, Safety and Attitudes Towards COVID-19 Vaccination: A Cross-Sectional Study on First and Second Doses Among the General Public.

Objective: To investigate public uptake, attitudes and the safety of the first and second doses of COVID-19 vaccination. Methods: This was a cross-sectional web-based survey study. A self-administered questionnaire was prepared from a literature search and information about COVID-19 available at various resources. The developed questionnaire was validated for readability by experts and refined in light of the feedback received from the experts and the final version was prepared. The reliability of the questionnaire was 0.7 which shows an acceptable level of scale internal consistency. The data analysis was performed using IBM SPSS software (version 25). Results: A total of 513 participants completed the survey, including 311 (60.6%) women and 202 (39.4%) men. The mean age was (31.5±12.8) years. It was found that 493 (96.1%) took the first and second doses of COVID-19 and 376 (73.3%) suffered from side effects, of these 14% (56/376) reported the side effects to the health authorities. The most common side effects were fatigue (51.5%), fever (42.3%), headache (39.5%), and injection site pain (37.6%). Half of the participants (50.5%) had a positive attitude towards COVID-19 preventive measures. Females had higher odds of experiencing side effects than males OR (95% CI); 2.002 (1.312-3.056). Individuals living in urban areas had lower odds of experiencing side effects than those living in rural areas OR (95% CI); 0.364 (0.142-0.933). Conclusion: Vaccine uptake was massive and side effects due to the COVID-19 vaccine were common but minor. The majority of the participants had positive attitudes towards recommended COVID-19 preventive measures. Being female and living in rural areas were associated with experiencing side effects.

Clinical characteristics, microbiology and outcomes of a cohort of patients treated with ceftolozane/tazobactam in acute care inpatient facilities, Houston, Texas, USA.

Background: Ceftolozane/tazobactam is a ß-lactam/ß-lactamase inhibitor combination with activity against a variety of Gram-negative bacteria, including MDR Pseudomonas aeruginosa. This agent is approved for hospital-acquired and ventilator-associated bacterial pneumonia. However, most real-world outcome data come from small observational cohorts. Thus, we sought to evaluate the utilization of ceftolozane/tazobactam at multiple tertiary hospitals in Houston, TX, USA. Methods: We conducted a multicentre retrospective study of patients receiving at least 48 h of ceftolozane/tazobactam therapy from January 2016 through to September 2019 at two hospital systems in Houston. Demographic, clinical and microbiological data were collected, including the infecting bacterial isolate, when available. The primary outcome was composite clinical success at hospital discharge. Secondary outcomes included in-hospital mortality and clinical disposition at 14 and 30 days post ceftolozane/tazobactam initiation. Multivariable logistic regression analysis was used to identify predictors of the primary outcome and mortality. Recovered isolates were tested for susceptibility to ceftolozane/tazobactam and underwent WGS. Results: A total of 263 patients were enrolled, and composite clinical success was achieved in 185 patients (70.3%). Severity of illness was the most consistent predictor of clinical success. Combination therapy with ceftolozane/tazobactam and another Gram-negative-active agent was associated with reduced odds of clinical success (OR 0.32, 95% CI 0.16-0.63). Resistance to ceftolozane/tazobactam was noted in 15.4% of isolates available for WGS; mutations in ampC and ftsI were common but did not cluster with a particular ST. Conclusions: Clinical success rate among this patient cohort treated with ceftolozane/tazobactam was similar compared with previous experiences. Ceftolozane/tazobactam remains an alternative agent for treatment of susceptible isolates of P. aeruginosa.

Significant Publications on Infectious Diseases Pharmacotherapy in 2020.

Purpose. To summarize the most highly esteemed, peer-reviewed, infectious diseases (ID) pharmacotherapy articles published in 2020. Summary. Members of the Houston Infectious Diseases Network (HIDN) nominated articles that were deemed to have noteworthy contributions to ID pharmacotherapy in 2020, including those on coronavirus disease 2019 (COVID-19) and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). To select the most significant articles of 2020, a survey was created and distributed to members of the Society of Infectious Diseases Pharmacists (SIDP) to vote on their top 10 articles of general ID and COVID-19 pharmacotherapy and one noteworthy HIV/AIDS publication. A total of 40 articles were nominated by HIDN: 35 articles pertaining to general ID/COVID-19 pharmacotherapy and 5 articles with HIV/AIDS involvement. Of the 247 SIDP members who responded to the survey, 205 and 42 members voted for general ID/COVID-19 pharmacotherapy articles and HIV/AIDS related articles, respectively. The top publications are summarized. Conclusion. In a taxing year of a global pandemic, the abundant and rapid distribution of ID literature has made it challenging for clinicians to stay informed of significant publications across the ID spectrum. This review summarizes significant ID-related publications in 2020 with the goal of aiding clinicians in staying up to date on the most relevant publications in ID pharmacotherapy.

Development of the invasive candidiasis discharge [I Can discharge] model: a mixed methods analysis.

Patients with invasive candidiasis (IC) have complex medical and infectious disease problems that often require continued care after discharge. This study aimed to assess echinocandin use at hospital discharge and develop a transition of care (TOC) model to facilitate discharge for patients with IC. This was a mixed method study design that used epidemiologic assessment to better understand echinocandin use at hospital discharge TOC. Using grounded theory methodology focused on patients given echinocandins during their last day of hospitalization, a TOC model for patients with IC, the invasive candidiasis [I Can] discharge model was developed to better understand discharge barriers. A total of 33% (1405/4211) echinocandin courses were continued until the last day of hospitalization. Of 536 patients chosen for in-depth review, 220 (41%) were discharged home, 109 (20%) were transferred, and 207 (39%) died prior to discharge. Almost half (46%, 151/329) of patients discharged alive received outpatient echinocandin therapy. Independent predictors for outpatient echinocandin use were osteomyelitis (OR, 4.1; 95% CI, 1.1-15.7; p = 0.04), other deep-seated infection (OR, 4.4; 95% CI, 1.7-12.0; p = 0.003), and non-home discharge location (OR, 3.9, 95% CI, 2.0-7.7; p < 0.001). The I Can discharge model was developed encompassing four distinct themes which was used to identify potential barriers to discharge. Significant echinocadin use occurs at hospital discharge TOC. The I Can discharge model may help clinical, policy, and research decision-making processes to facilitate smoother and earlier hospital discharges.

Corticosteroids Do Not Increase the Likelihood of Primary Clostridioides difficile Infection in the Setting of Broad-Spectrum Antibiotic Use.

BACKGROUND: The pathogenesis of Clostridioides difficile infection (CDI) involves a significant host immune response. Generally, corticosteroids act by suppressing the host inflammatory response, and their anti-inflammatory effects are used to treat gastrointestinal disorders. Although previous investigations have demonstrated mixed results regarding the effect of corticosteroids on CDI, we hypothesized that the anti-inflammatory effect of corticosteroids would decrease the risk of CDI in hospitalized patients. METHODS: This was a case-control study of hospitalized adults. The case population included patients diagnosed with primary CDI who received at least 1 dose of a high-risk antibiotic (cefepime, meropenem, or piperacillin-tazobactam) in the 90 days before CDI diagnosis. The control population included patients who received at least 1 dose of the same high-risk antibiotic but did not develop CDI in the 90 days following their first dose of antibiotic. The primary study outcome was the development of CDI based on receipt of corticosteroids. RESULTS: The final study cohort consisted of 104 cases and 153 controls. Those who received corticosteroids had a lower odds of CDI after adjusting for age, proton pump inhibitor use, and antibiotic days of therapy (odds ratio, 0.54; 95% CI, 0.30-0.97; P = .04). We did not observe an association between corticosteroid dose or duration and CDI. CONCLUSIONS: We demonstrated a 46% relative reduction in the odds of developing CDI in patients who received corticosteroids in the past 90 days. We believe that our results provide the best clinical evidence to further support mechanistic studies underlying this phenomenon.

Comparative clinical outcomes evaluation of hospitalized patients infected with Clostridioides difficile ribotype 106 vs. other toxigenic strains.

BACKGROUND: Although Clostridioides difficile surveillance often identifies emerging strains, clinical outcome evaluations are rarely performed. Ribotype (RT) 106 is a commonly isolated C. difficile strain worldwide; however, studies investigating RT 106 clinical outcomes are limited. The purpose of this study was to investigate clinical outcomes of RT 106 infections compared with two other endemic strains of varying virulence. METHODS: This multicenter study evaluated adults hospitalized with C. difficile infection (CDI). C. difficile samples underwent PCR ribotyping and patients infected with RT 106 were compared to patients infected with a known hypervirulent strain (RT 027) and a strain associated with less virulence (RT 014-020). Electronic medical records were reviewed by blinded investigators to assess the primary outcome of poor clinical outcome (composite of initial clinical failure, discharge to a higher level of care, 90-day CDI recurrence, and CDI-contributable mortality). RESULTS: A total of 396 patients with CDI were identified (RT 106, 32.3%; RT 027, 29.3%; RT 014-020, 38.3%). Patients infected with RT 014-020 less often experienced a poor clinical outcome (40%) compared with RT 106 (56%) and RT 027 (65%) infection (P < 0.0001). After controlling for covariates and using RT 014-020 as a comparator, patients infected with RT 106 (OR, 2.25; 95% CI, 1.36-3.73) or RT 027 (OR, 2.56; 95% CI, 1.52-4.31) had higher odds of poor clinical outcome. Using RT 027 as the comparator, only RT 014-020 was associated with lower odds of poor clinical outcome (OR, 0.42; 95% CI, 0.27-0.65). CONCLUSION: This study demonstrated that the emergent C. difficile RT 106 was associated with increased rates of poor clinical outcomes compared to RT 014-020 and comparable poor clinical outcomes to RT 027. These findings can help to better understand the clinical significance of this and future emerging ribotypes.

Efficacy of clotrimazole for the management of oral candidiasis: A meta-analysis of randomized clinical trials.

PURPOSE: To assess the efficacy and safety of topical application of clotrimazole versus others in the treatment of oropharyngeal candidiasis (OPC). METHOD: Four electronic databases, registries of ongoing trials, and manual search were used to identify randomized controlled trials (RCTs) that compared the efficacy of clotrimazole to other antifungal agents in patients who were clinically diagnosed with oral candidiasis up to November 1st, 2019. Primary outcomes were clinical response and mycological cure rates. Secondary outcomes include relapse rate, incidence of systemic infections, and compliance. Adverse effects were also evaluated. RESULTS: Sixteen RCTs with a total of 1685 patients were included. Half of the eligible studies were considered at high risk of performance bias and more than a third, at high risk of reporting bias. Our analysis showed no significant difference in clinical response between clotrimazole and all other antifungal agents. However, clotrimazole was less effective in terms of mycologic cure and relapse rate. Sensitivity analysis comparing clotrimazole to other topical antifungal agents only showed no differences in clinical response, microbiologic cure or relapse. Further sensitivity analysis showed significant efficacy of fluconazole over clotrimazole. CONCLUSION: This meta-analysis indicated that clotrimazole is less effective than fluconazole but as effective as other topical therapies in treating OPC. Well-designed high-quality RCT is needed to validate these findings.

Eosinopenia and Binary Toxin Increase Mortality in Hospitalized Patients With Clostridioides difficile Infection.

BACKGROUND: Patients with Clostridioides difficile infection (CDI) with either eosinopenia or infected with a binary toxin strain have increased likelihood of mortality. However, the relationship between binary toxin and eosinopenia to synergistically increase mortality has not been studied in humans. We hypothesized that patients with CDI due to binary toxin strains and concomitant peripheral eosinopenia would have a higher likelihood of inpatient mortality. METHODS: This multicenter, retrospective cohort study included adult patients with CDI of known ribotypes stratified by eosinopenia, defined as an absence of eosinophils in the peripheral blood (Houston cohort). The primary outcome was inpatient mortality. Results were supported by a separate national cohort of veterans with CDI (Veterans' cohort). RESULTS: In the Houston cohort, a total of 688 patients from 13 institutions in 6 cities were included. Of these, 132 (19%) had an eosinophil count of 0.0 cells/µL (0.0 cells*109/L) and 109 (16%) were infected with a binary toxin strain. After adjusting for covariates, the combination of eosinopenia and infection with a binary toxin strain was an independent predictor of inpatient mortality (odds ratio [OR], 7.8; 95% confidence interval [CI], 1.9-33.2; P = .005). In the separate Veterans' cohort (n = 790), this combination was also a significant predictor of inpatient mortality (OR, 6.1; 95% CI, 1.5-23.9; P = .009). CONCLUSIONS: In conclusion, the combination of eosinopenia and CDI due to a binary toxin strain was correlated with increased mortality in hospitalized patients from 2 independent cohorts. Prospective studies should further study this important subset of patients at the time of CDI diagnosis.

Comparing the efficacy and safety of faecal microbiota transplantation with bezlotoxumab in reducing the risk of recurrent Clostridium difficile infections: a systematic review and Bayesian network meta-analysis of randomised controlled trials.

OBJECTIVES: The risk of recurrent Clostridium difficile infections (RCDIs) is high when treated with standard antibiotics therapy (SAT) alone. It is suggested that the addition of faecal microbiota transplantation (FMT) or bezlotoxumab after SAT reduces the risk of RCDI. In the absence of head-to-head randomised controlled trials (RCTs), this review attempts to compare the efficacy and safety of bezlotoxumab with FMT in reducing the risk of RCDI in hospitalised patients. DESIGN: A systematic review and Bayesian network meta-analysis. DATA SOURCE: A comprehensive search from inception to 30 February 2019 was conducted in four databases (Medline/PubMed, Embase, Scopus, ClinicalTrials.gov). ELIGIBILITY CRITERIA: RCTs reporting the resolution of diarrhoea associated with RCDI without relapse for at least 60 days after the end of treatments as the primary outcome. DATA EXTRACTION AND SYNTHESIS: We extracted author, year of publication, study design and binomial data that represented the resolution of diarrhoea or adverse events of monoclonal antibodies and FMT infusion. Random-effects models were used for resolution rate of RCDI and adverse events. The Cochrane Risk of Bias tool was used to assess the quality of included RCTs. RESULTS: Out of 1003 articles identified, seven RCTs involving 3043 patients contributed to the review. No difference was reported between single or multiple infusions of FMT and bezlotoxumab in resolving RCDI, (OR 1.53, 95% credible interval (CrI) 0.39 to 5.16) and (OR 2.86, 95% CrI 1.29 to 6.57), respectively. Patients treated with SAT alone or bezlotoxumab with SAT showed significantly lower rates of diarrhoea than FMT (OR 0, 95% CrI 0 to 0.09) and (OR 0, 95% CrI 0 to 0.19), respectively. There was no difference in terms of other adverse events. CONCLUSIONS: This is the first network meta-analysis that has compared the recently Food and Drug Administration-approved monoclonal antibody bezlotoxumab with FMT for resolving RCDI. The quality of the included RCTs was variable. The findings of this study suggested no difference between single or multiple infusions of FMT and bezlotoxumab. However, FMT was associated with a higher rate of non-serious diarrhoea as opposed to SAT used alone or in combination with bezlotoxumab.