Characteristics and outcomes of urinary tract infections caused by Enterococci: A multicenter retrospective study from two tertiary hospitals in Saudi Arabia.

Enterococci are Gram-positive coccus bacteria that are normally present in the gastrointestinal tract and ordinarily function commensally with humans. Very few studies have investigated the characteristics of enterococcal infections. We aimed to characterize patients with urinary tract infections (UTIs) due to Enterococci and their outcomes. This was a retrospective cohort study between June 2012-November 2022. Patients who had clinically and microbiologically confirmed Enterococcal UTI based on a urine culture positive for E. faecalis or E. faecium with a count of ≥105 CFU/mL and having urinary tract symptoms were included. A total of 396 patients were eligible and included. The patients had a median age of 61 years and were mostly females (56.8 %). The most common characteristics were hospitalization in a non-ICU ward, having a urinary catheter, and recent use of antibiotics within the last 3 months (66.4 %, 59.3 %, and 51.8 %, respectively). Infection with E. faecalis was more common than E. faecium (77.3 % vs. 22.7 %). However, the latter exhibited higher rates of antibiotic resistance (P < 0.001 to several antibiotics) and was associated with significantly higher median C-reactive protein level (26.7 vs. 13 mg/dL; P = 0.025), mortality (23 % vs. 10.1 %; P = 0.002), and median length of stay (25 vs. 11.5 days; P < 0.001). We found that most patients with enterococcal UTIs had a history of having a urinary catheter and recent antibiotic use and were mostly females and hospitalized in non-ICU wards. E. faecium-infected patients experienced more severe episodes and poorer outcomes compared to patients infected with E. faecalis; thus, would need more aggressive therapy.

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.

Long-term Cardiovascular Adverse Events Induced by Fluoroquinolones: A Retrospective Case-control Study.

ABSTRACT: A correlation is already established between fluoroquinolones (FQs) use and cardiovascular events (CVEs), such as QT prolongation; however, serious events such as aortic aneurysm and valve regurgitation have also been reported with FQs. Several unstudied factors could contribute to the development of different CVEs that were not previously evaluated with FQ therapy. Therefore, we aimed to assess the incidence of different serious CVEs after completion of FQ therapy and potential associating factors. This was a retrospective case-control study of inpatients who received ciprofloxacin, levofloxacin, or moxifloxacin for ≥3 days. Patients' echocardiograms were evaluated for the development of aortic or valvular disease or worsening of an existing condition after completion of therapy. Of 373 included patients, 83 developed new valvular disease or worsening of an existing disease, where tricuspid valve regurgitation was the most common CVE (50/83; 60.2%), followed by mitral valve diseases (48/83; 57.8%). Aortic valve regurgitation occurred more commonly with moxifloxacin compared with ciprofloxacin and levofloxacin (17.8% vs. 6.7% and 10.7%, respectively; P = 0.01). Median time to CVE detection ranged 93-166 days for all FQs. The receipt of moxifloxacin and elevated baseline QT interval were associated with an increased CVEs risk (adjusted odds ratio 3.26; 95% confidence interval, 1.31-8.11 and adjusted odds ratio 1.02; 95% confidence interval, 1.00-1.04, respectively). Other factors did not show such association. The lack of association of different factors with the occurrence of CVEs indicates that all patients receiving FQ therapy, especially moxifloxacin, should be monitored during the first-year after therapy. Alternatively, other antibiotics with a better safety profile may be considered.

Clinical and cost-effectiveness analysis of carbapenems versus ciprofloxacin in the treatment of urinary tract infections due to extended spectrum ß-lactamase-producing Enterobacterales.

BACKGROUND: Urinary tract infections (UTIs) are the most common infectious diseases in both hospital and community settings. The management of UTIs caused by extended spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) has become more complicated given the limited options of effective antibiotic agents besides the amplification of total healthcare costs. METHODS: This was a retrospective cohort study conducted among hospitalized patients between January 2018 and March 2020. Adults diagnosed with UTI due to ESBL-PE with at least 2 days of admission were included. Excluded were patients with concomitant infection, polymicrobial UTI, and pregnant women. The primary endpoints were clinical cure and incremental cost-effectiveness ratio (ICER). Clinical cure, hospitalization, and antibiotics costs were considered to evaluate ICER. The secondary endpoints included microbiological eradication, length of stay (LOS), and 30-day readmission. RESULTS: Of 102 patients, 89 received a carbapenem and 13 received ciprofloxacin. The patients had similar baseline characteristics, including history of hospitalization and UTI within 3 months. No difference was observed in clinical cure rates (86.5% vs. 100%, P = 0.159), microbiological eradication (93.1% vs. 100%, P = 0.639), median LOS (6 days in both groups, P = 0.773), and 30-day readmission rates (41.6% vs. 46.2%, P = 0.755). The ICER of carbapenem to ciprofloxacin was - 7,626.05, indicating that ciprofloxacin was more cost-effective compared with carbapenems. CONCLUSION: Ciprofloxacin had comparable cure rates with carbapenems, lower risk of 30-day readmission, and was more cost-effective for the treatment of UTI due to ESBL-PE. Therefore, it should be considered as a valuable option if ESBL-PE showed susceptibility to it.

Factors influencing future career interests of pharmacy interns in Saudi Arabia: a survey from 25 colleges of pharmacy.

BACKGROUND: Hundreds of pharmacists graduate from pharmacy colleges in Saudi Arabia, and various factors influence their choice of career pathway. Very few single-institution studies assessed career choices of pharmacy students with or without evaluating the influencing factors. Therefore, this study aimed to evaluate career choices and the associating factors of pharmacy interns from multiple colleges in Saudi Arabia. METHODS: This was a cross-sectional study that surveyed pharmacy interns from 25 pharmacy colleges in Saudi Arabia using an online questionnaire. The survey was sent during the last rotation month in the internship year (May-June 2022). RESULTS: Of 454 participants, 411 (90.5%) were enrolled in Doctor of Pharmacy programs. While most participants were interested in becoming clinical pharmacists (n = 183; 40.3%), a considerable number were also interested in working in different sectors of pharmaceutical companies and industry (n = 127; 28%). Internship training significantly correlated with selecting clinical pharmacy specialist career (r = 0.19; P = 0.0001), whereas salary/financial incentives significantly influenced the choice of working as sales and marketing representatives and pharmacy product specialists in pharmaceutical companies (r = 0.29 and 0.24; P < 0.0001 for both). College courses correlated with choosing academia in pharmaceutical sciences (r = 0.20; P < 0.0001), whereas summer training correlated with the community pharmacy career (r = 0.11; P = 0.02). CONCLUSION: Pharmacy colleges should utilize results from this study to enhance the exposure of pharmacy students during their academic years to different pharmacy career pathways by allowing the opportunity to shadow pharmacists from different sectors as part of college courses, inviting previous graduates, and activating the role of academic advisors in career orientation.

Views and perceptions of the public toward COVID-19 vaccine in Saudi Arabia.

Background: Numerous surveys studied individuals' decision to receive COVID-19 vaccine but the motives behind accepting or refusing COVID-19 vaccines are not yet fully understood. We aimed to more qualitatively explore the views and perceptions toward COVID-19 vaccines in Saudi Arabia to provide recommendations to mitigate the vaccine hesitancy issue. Methods: Open-ended interviews were conducted between October 2021-January 2022. The interview guide included questions about beliefs in vaccine efficacy and safety, and previous vaccination history. The interviews were audio-recorded, transcribed verbatim, and the content was analyzed using thematic analysis. Nineteen participants were interviewed. Results: All of the interviewees were vaccine acceptors; however, three participants were hesitant as they felt they were forced to receive it. Several themes emerged as the reasons to accept or refuse the vaccine. The key reasons behind vaccine acceptance were the sense of obligation to fulfill a governmental command, trust in the government decisions, vaccine availability, and the impact of family/friends. The main reason behind vaccine hesitancy was doubts regarding vaccine efficacy and safety and that vaccines were pre-invented, and the pandemic is made-up. Participants' sources of information included social media, official authorities, and family/friends. Conclusion: Findings from this study show that the convenience of receiving the vaccine, the abundance of credible information from the Saudi authorities, and the positive influence of family/friends were among the major factors that encouraged the public in Saudi Arabia to get vaccinated against COVID-19. Such results may inform future policies regarding encouraging the public to receive vaccines in cases of pandemic.

Evaluation of grit and its associated factors among undergraduate pharmacy students from 14 Asian and Middle Eastern countries amid the COVID-19 pandemic.

Introduction: Grit is proposed as an essential trait for academic achievement. Thus, evaluating its current status and the associated factors could aid academic support planning. Objective: The present study aimed to assess grit level and its related factors among undergraduate pharmacy students from 14 countries amid the COVID-19 pandemic. Methods: A cross-sectional survey-based study was conducted among pharmacy students from 14 countries in Asia and the Middle East. A 31-item questionnaire was developed, validated, and pilot-tested, including the validated short scale for grit assessment. The data was collected between 1 February and 15 April 2022. Descriptive and inferential statistics were employed as appropriate. Results: A total of 2665 responses were received, mainly from females (68.7 %), living in urban areas (69.2 %) and studying at private universities (59.1 %). The average grit score on a scale of 5 was 3.15 ± 0.54. The responses revealed higher favourable responses to items on the perseverance of efforts (34.9 % to 54 %) compared to items on the consistency of interests (26.5 % to 31.1 %). Students who did not exercise (AOR: 0.47, 95 %CI: 0.33-0.67) or exercised irregularly (AOR: 0.64, 95 %CI: 0.45-0.90) were less likely to have higher grit scores than those who exercised regularly. Additionally, students who did not receive COVID-19 vaccination (AOR: 0.50, 95 %CI: 0.36-0.71) or received only one dose (AOR: 0.67, 95 %CI: 0.46-0.99) were less likely to have higher grit scores than those who received their booster vaccination. Interestingly, students who chose the pharmacy program as their only available or reasonable choice (AOR: 0.33, 95 %CI: 0.17-0.62) and students from public universities (AOR: 0.82, 95 %CI: 0.68-0.98) were less likely to have higher grit scores. On the other hand, students who did not face educational challenges with online learning (AOR: 1.19, 95 %CI: 1.003-1.416) and students with excellent (AOR: 2.28, 95 %CI: 1.57-3.31) and very good (AOR: 2.16, 95 %CI: 1.53-3.04) academic performance were more likely to have higher grit scores. Conclusion: The findings revealed moderate grit levels. Higher grit levels were thought to be associated with several personal, lifestyle and academic factors. Further interventions to support students' grit attributes are required, particularly concerning the consistency of interests.

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

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

Elevated MICs of Susceptible Antipseudomonal Cephalosporins in Non-Carbapenemase-Producing, Carbapenem-Resistant Pseudomonas aeruginosa: Implications for Dose Optimization.

The present study evaluated the in vitro potency of ceftazidime and cefepime among carbapenem-resistant Pseudomonas aeruginosa isolates collected as part of a global surveillance program and assessed the pharmacodynamic implications using previously published population pharmacokinetics. When susceptible, MICs resulted at the high end of distribution for both ceftazidime and cefepime, thus 6 g/day was required to achieve optimal pharmacodynamic profiles. These findings should be considered in the clinic and for the application of CLSI susceptibility breakpoints.

The ERACE-PA Global Surveillance Program: Ceftolozane/tazobactam and Ceftazidime/avibactam in vitro Activity against a Global Collection of Carbapenem-resistant Pseudomonas aeruginosa.

The cephalosporin-ß-lactamase-inhibitor-combinations, ceftolozane/tazobactam and ceftazidime/avibactam, have revolutionized treatment of carbapenem-resistant Pseudomonas aeruginosa (CR-PA). A contemporary assessment of their in vitro potency against a global CR-PA collection and an assessment of carbapenemase diversity are warranted. Isolates determined as CR-PA by the submitting site were collected from 2019-2021 (17 centers in 12 countries) during the ERACE-PA Global Surveillance Program. Broth microdilution MICs were assessed per CLSI standards for ceftolozane/tazobactam, ceftazidime/avibactam, ceftazidime, and cefepime. Phenotypic carbapenemase testing was conducted (modified carbapenem inactivation method (mCIM)). mCIM positive isolates underwent genotypic carbapenemase testing using the CarbaR, the CarbaR NxG, or whole genome sequencing. The MIC50/90 was reported as well as percent susceptible (CLSI and EUCAST interpretation). Of the 807 isolates, 265 (33%) tested carbapenemase-positive phenotypically. Of these, 228 (86%) were genotypically positive for a carbapenemase with the most common being VIM followed by GES. In the entire cohort of CR-PA, ceftolozane/tazobactam and ceftazidime/avibactam had MIC50/90 values of 2/ > 64 and 4/64 mg/L, respectively. Ceftazidime/avibactam was the most active agent with 72% susceptibility per CLSI compared with 63% for ceftolozane/tazobactam. For comparison, 46% of CR-PA were susceptible to ceftazidime and cefepime. Against carbapenemase-negative isolates, 88 and 91% of isolates were susceptible to ceftolozane/tazobactam and ceftazidime/avibactam, respectively. Ceftolozane/tazobactam and ceftazidime/avibactam remained highly active against carbapenem-resistant P. aeruginosa, particularly in the absence of carbapenemases. The contemporary ERACE-PA Global Program cohort with 33% carbapenemase positivity including diverse enzymology will be useful to assess therapeutic options in these clinically challenging organisms with limited therapies.

Antibiotic utilization within 18 community hospitals in the United States: A 5-year analysis.

BACKGROUND: Antibiotic overuse is associated with antibiotic resistance. We evaluated antibiotic utilization defined by days of therapy/1000 patient days (DOT/1000 PD) in various community hospitals across the United States. METHODS: Community hospitals within the Cardinal Health Drug Cost Opportunity Analytics database were evaluated for the availability of DOT/1000 PD data between 2012 to 2016 for overall and specific antibiotic use and the following classes: narrow-spectrum ß-lactams (ampicillin, nafcillin, oxacillin, cefazolin, and cephalexin), non-carbapenem antipseudomonal ß-lactams (piperacillin/tazobactam, ceftazidime, and cefepime), carbapenems, anti-methicillin-resistant Staphylococcus aureus agents (vancomycin, linezolid, daptomycin, and tigecycline), and fluoroquinolones. Antibiotic utilization and change in utilization during the study period was calculated using linear regression (ß coefficient). RESULTS: Eighteen hospitals had antibiotic utilization data available. Hospitals were primarily urban (72%) with an average of 209 total beds and 22 intensive care unit beds. Mean number of pharmacists in these hospitals was nine with a mean pharmacist: bed ratio of 0.05. While all hospitals had antimicrobial stewardship programs established during the study period, only 78% and 22% had infectious diseases (ID) physician and ID pharmacist on staff, respectively. A decrease in antipseudomonal ß-lactams (excluding carbapenems) and fluoroquinolones was observed (ß coefficients = -1.2 and -2.6, respectively), all other antibiotic classes had increased utilization. CONCLUSION: Overall antibiotic utilization increased over 5 years. The increase in narrow-spectrum ß-lactams utilization along with the reduction in the use of antipseudomonal ß-lactams and fluoroquinolones indicate appropriate antimicrobial stewardship. Institutional antibiotic utilization should be evaluated for appropriateness to limit the overuse of broad-spectrum antibiotics in an effort to reduce resistance development.

Comparison of three current Clostridioides difficile infection guidelines: IDSA/SHEA, ESCMID, and ACG guidelines.

PURPOSE: Clostridioides difficile infection (CDI) is a widely recognized condition associated with comorbidity and decreased patient quality of life. Certain professional medical organizations develop clinical practice guidelines for major diseases. This is done in an effort to streamline the universal clinical practice and ensure that a more accurate diagnosis and better treatments are offered to respective patients for optimal outcomes. However, as new data evolve, constant update of these guidelines becomes essential. While these guidelines provide up-to-date recommendations, they are not published around the same time; thus, their recommendations may vary depending on evidence available prior to guidelines preparation and publication. METHODS: Recommendations and corresponding justifications from three major CDI guidelines between 2013 and 2017 were pooled and compared, and notable differences were highlighted while providing an insight and a final recommendation from a clinical standpoint. RESULTS: Most recommendations were consistent among all three guidelines. One notable difference was in the specification of candidates for CDI diagnosis, where it would be recommended to mainly test patients with three or more diarrheal episodes over 24 h, if they had no other clear reason for the diarrhea. Another conflicting point was regarding the treatment of non-severe CDI where vancomycin can be considered for older or sicker patients; however, metronidazole still remains a reasonable option based on recent data, some of which were not cited in the most recent guidelines of IDSA/SHEA. CONCLUSION: Overall, it is prudent to follow these guidelines with critical appraisal to fulfill the goal of achieving optimum patient outcomes.

Antibiotic use and duration in association with Clostridioides difficile infection in a tertiary academic medical center: A retrospective case-control study.

Previous literature has attributed the use of certain antibiotics to Clostridioides difficile infection (CDI); however, the time from administration to CDI onset is not adequately evaluated. We aimed to determine the type of antibiotics and duration of therapy associated with the highest CDI incidence at a tertiary academic medical center. This was a retrospective, case-control study of adult inpatients who received at least one course of antibiotic treatment. Patients were divided into either cases or controls. For cases, their first episode of CDI was a determining factor. Primary outcome were the types of antibiotics associated with risk of CDI development and the median time of antibiotic usage defining this risk. Of 601 patients who developed CDI, 313 were included as cases while 150 of 291 who received antibiotics but did not develop CDI were included as controls. Cefepime and cefazolin were significantly associated with increased risk for CDI with odds ratios of 3.01 (95% CI, 1.96-4.65; P < 0.001) and 1.71 (95% CI, 1.02-2.95; P < 0.05), respectively. Cefepime was associated with CDI after a median time of 8 days while CDI may have occurred after 6 days of therapy with cefazolin. Use of antineoplastic agents was significantly associated with CDI (odds ratio, 2.32; 95% CI, 1.35-4.13; P < 0.01). Antibiotic use increased the risk of CDI, particularly with cefepime and cefazolin with a median time to incidence of 8 and 6 days, respectively. CDI risk was also increased with the use of antineoplastic agents.

Clinical use comparison of a semiautomated PCR with fluorescent ribotyping for typing of Clostridium difficile.

Molecular typing of Clostridium difficile is performed to assess strain relatedness or place strains within an epidemiological context. Different C. difficile ribotyping systems are available. However, a common strain library does not exist. We aimed to compare ribotyping results of 29 clinical C. difficile isolates by two methods: semiautomated PCR-ribotyping and fluorescent PCR-ribotyping. For certain ribotypes (n = 16/29; 55.2 %), the inter-laboratory reproducibility was consistent among multiple samples from individual subjects, while 54.8 % (n = 14/29) were discordant. Additionally, 11/29 ribotypes (38 %) and 12/29 ribotypes (41 %) did not match with known reference strains in the semiautomated PCR-fluorescent ribotyping systems' libraries, respectively. The identification of 027 ribotype by both systems was consistent for 75 % of the isolates. Discriminatory indices for the semiautomated PCR-ribotyping and fluorescent PCR-ribotyping systems are 0.906 and 0.886, respectively. Although ribotyping provides important epidemiologic insights, the lack of a common strain library makes interpretation of results using different ribotyping protocols difficult.

Eravacycline Pharmacokinetics and Challenges in Defining Humanized Exposure In Vivo.

We assessed the pharmacokinetic profile of eravacycline, a novel antibiotic of the tetracycline class, and determined the dose in an immunocompetent murine thigh infection model that would provide free-drug exposure similar to that observed in humans after the administration of 1 mg/kg intravenously (i.v.) every 12 h (q12h). Eravacycline demonstrated a nonlinear protein-binding profile. The 2.5-mg/kg i.v. q12h dose in mice resulted in an area under the concentration-time curve for the free, unbound fraction of the drug of 1.64 mg · h/liter, which closely resembles the human exposure level.

In Vitro Pharmacodynamics of Human Simulated Exposures of Telavancin against Methicillin-Susceptible and -Resistant Staphylococcus aureus with and without Prior Vancomycin Exposure.

Telavancin is a lipoglycopeptide with potent activity against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA). The activity of telavancin against MRSA and MSSA after prior vancomycin exposure was studied in an in vitro pharmacodynamic model. Two clinical MRSA and two MSSA isolates, all with vancomycin MICs of 2 µg/ml, were subjected to humanized free drug exposures of vancomycin at 1 g every 12 h (q12h) for 96 h, telavancin at 750 mg q24h for 96 h, and vancomycin at 1 g q12h for 72 h followed by telavancin at 750 mg q24h for 48 h (120 h total). The microbiological responses were measured by changes from 0 h in log10 CFU/ml at the end of experiments and area under the bacterial killing and regrowth curves over 96 h (AUBC0-96). The control isolates grew to 8.8 ± 0.3 log10 CFU/ml. Initially, all regimens caused -4.5 ± 0.9 reductions in log10 CFU/ml by 48 h followed by slight regrowth over the following 48 to 72 h. After 96 h, vancomycin and telavancin achieved -3.7 ± 0.9 and -3.8 ± 0.8 log10 CFU/ml changes from baseline, respectively (P = 0.74). Sequential exposure to telavancin after vancomycin did not result in additional CFU reductions or increases, with ultimate log10 CFU/ml reductions of -4.3 ± 1.1 at 96 h and -4.2 ± 1.3 at 120 h (P > 0.05 for all comparisons at 96 h). The AUBC0-96 was significantly smaller for the regimen of telavancin for 96 h than for the regimens of vancomycin for 96 h and vancomycin followed by telavancin (P ≤ 0.04). No resistance was observed throughout the experiment. Against these MRSA and MSSA isolates with vancomycin MICs of 2 µg/ml, telavancin was comparable with vancomycin and its activity was unaffected by prior vancomycin exposure.

Antibacterial Efficacy of Eravacycline In Vivo against Gram-Positive and Gram-Negative Organisms.

Members of the tetracycline class are frequently classified as bacteriostatic. However, recent findings have demonstrated an improved antibacterial killing profile, often achieving ≥3 log10 bacterial count reduction, when such antibiotics have been given for periods longer than 24 h. We aimed to study this effect with eravacycline, a novel fluorocycline, given in an immunocompetent murine thigh infection model over 72 h against two methicillin-resistant Staphylococcus aureus (MRSA) isolates (eravacycline MICs = 0.03 and 0.25 µg/ml) and three Enterobacteriaceae isolates (eravacycline MICs = 0.125 to 0.25 µg/ml). A humanized eravacycline regimen, 2.5 mg/kg of body weight given intravenously (i.v.) every 12 h (q12h), demonstrated progressively enhanced activity over the 72-h study period. A cumulative dose response in which bacterial density was reduced by more than 3 log10 CFU at 72 h was noted over the study period in the two Gram-positive isolates, and eravacycline performed similarly to comparator antibiotics (tigecycline, linezolid, and vancomycin). A cumulative dose response with eravacycline and comparators (tigecycline and meropenem) over the study period was also observed in the Gram-negative isolates, although more variability in bacterial killing was observed for all antibacterial agents. Overall, a bacterial count reduction of ≥3 log was achieved in one of the three isolates with both eravacycline and tigecycline, while meropenem achieved a similar endpoint against two of the three isolates. Bactericidal activity is typically defined in vitro over 24 h; however, extended regimen studies in vivo may demonstrate an improved correlation with clinical outcomes by better identification of antimicrobial effects.

Multidrug-Resistant Pseudomonas aeruginosa Infection in a Child with Cystic Fibrosis.

We describe a pediatric cystic fibrosis patient who developed a pulmonary exacerbation due to two multidrug-resistant (MDR) Pseudomonas aeruginosa isolates. In addition to these MDR organisms, the case was further complicated by ß-lactam allergy. Despite the MDR phenotype, both isolates were susceptible to an antimicrobial combination.

A pilot study to assess bacterial and toxin reduction in patients with Clostridium difficile infection given fidaxomicin or vancomycin.

BACKGROUND: To assess the effect of fidaxomicin and vancomycin on Clostridium difficile toxins and correlation with clinical and microbiologic outcomes. METHODS: Hospitalized patients with C. difficile infection were randomly assigned a 10-day course of fidaxomicin or vancomycin. Stool samples collected at baseline (day 0), mid-therapy (days 3-5), end of therapy (days 10-13) and follow-up (days 19-38) were assessed for quantity of toxins A and B as well as spore and vegetative cells counts. Correlation of toxins concentrations with microbiologic and clinical findings were evaluated. RESULTS: Among 34 patients 12 had detectable toxin concentrations at baseline seven were randomized to fidaxomicin and five to vancomycin. Overall both fidaxomicin and vancomycin resulted in drop of both toxins concentrations by midpoint of therapy. The drop in toxin A concentrations was maintained up to the follow-up period with fidaxomicin but not with vancomycin even in patients who developed recurrence. Patients who developed recurrence in the fidaxomicin group had lower concentrations of toxin B versus the recurrence patient of vancomycin group. Presence of vegetative cells and spores was significantly linked with high toxin A (P = 0.003 and <0.001 respectively) and toxin B (P = 0.007 and <0.001 respectively) concentrations across time points. Toxin B concentrations but not A significantly correlated with stool consistency (P < 0.001) and frequency (P = 0.05). CONCLUSIONS: Fidaxomicin was associated with sustained reduction of both toxins up to 30 days post therapy versus vancomycin. Multiple clinical or microbiologic observations were correlated with toxin A or B concentrations.

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.