The impact of diabetes mellitus on the emergence of multi-drug resistant tuberculosis and treatment failure in TB-diabetes comorbid patients: a systematic review and meta-analysis.

Background: The existence of Type 2 Diabetes Mellitus (DM) in tuberculosis (TB) patients is very dangerous for the health of patients. One of the major concerns is the emergence of MDR-TB in such patients. It is suspected that the development of MDR-TB further worsens the treatment outcomes of TB such as treatment failure and thus, causes disease progression. Aim: To investigate the impact of DM on the Emergence of MDR-TB and Treatment Failure in TB-DM comorbid patients. Methodology: The PubMed database was systematically searched until April 03, 2022 (date last searched). Thirty studies met the inclusion criteria and were included in this study after a proper selection process. Results: Tuberculosis-Diabetes Mellitus patients were at higher risk to develop MDR-TB as compared to TB-non-DM patients (HR 0.81, 95% CI: 0.60-0.96, p < 0.001). Heterogeneity observed among included studies was moderate (I2 = 38%). No significant change was observed in the results after sub-group analysis by study design (HR 0.81, 95% CI: 0.61-0.96, p < 0.000). In the case of treatment failure, TB-DM patients were at higher risk to experience treatment failure rates as compared to TB-non-DM patients (HR 0.46, 95% CI: 0.27-0.67, p < 0.001). Conclusion: The results showed that DM had a significant impact on the emergence of MDR-TB in TB-diabetes comorbid patients as compared to TB-non-DM patients. DM enhanced the risk of TB treatment failure rates in TB-diabetes patients as compared to TB-non-DM patients. Our study highlights the need for earlier screening of MDR-TB, thorough MDR-TB monitoring, and designing proper and effective treatment strategies to prevent disease progression.

Antibiotics for preventing infection at the surgical site: Single dose vs. multiple doses.

Background: Surgical site infections are common and expensive infections that can cause fatalities or poor patient outcomes. To prevent these infections, antibiotic prophylaxis is used. However, excessive antibiotic use is related to higher costs and the emergence of antimicrobial resistance. Objectives: The present meta-analysis aimed to compare the effectiveness of a single dosage versus several doses of antibiotics in preventing the development of surgical site infections. Methods: PubMed was used to find clinical trials evaluating the effectiveness of a single dosage versus several doses of antibiotics in avoiding the development of surgical site infections. The study included trials that were published between 1984 and 2022. Seventy-four clinical trials were included in the analysis. Odds ratios were used to compare groups with 95% confidence intervals. The data were displayed using OR to generate a forest plot. Review Manager (RevMan version 5.4) was used to do the meta-analysis. Results: Regarding clean operations, there were 389 surgical site infections out of 5,634 patients in a single dose group (6.90%) and 349 surgical site infections out of 5,621 patients in multiple doses group (6.21%) (OR = 1.11, lower CI = 0.95, upper CI = 1.30). Regarding clean-contaminated operations, there were 137 surgical site infections out of 2,715 patients in a single dose group (5.05%) and 137 surgical site infections out of 2,355 patients in multiple doses group (5.82%) (OR = 0.87, lower CI = 0.68, upper CI = 1.11). Regarding contaminated operations, there were 302 surgical site infections out of 3,262 patients in a single dose group (9.26%) and 276 surgical site infections out of 3,212 patients in multiple doses group (8.59%) (OR = 1.11, lower CI = 0.84, upper CI = 1.47). In general, there were 828 surgical site infections out of 11,611 patients in a single dose group (7.13%) and 762 surgical site infections out of 11,188 patients in multiple doses group (6.81%) (OR = 1.05, lower CI = 0.93, upper CI = 1.20). The difference between groups was not significant. Conclusion: The present study showed that using a single-dose antimicrobial prophylaxis was equally effective as using multiple doses of antibiotics in decreasing surgical site infections.

Tackling antimicrobial resistance in primary care facilities across Pakistan: Current challenges and implications for the future.

Antibiotics are gradually becoming less effective against bacteria worldwide, and this issue is of particular concern in economically-developing nations like Pakistan. We undertook a scoping review in order to review the literature on antimicrobial use, prescribing, dispensing and the challenges associated with antimicrobial resistance in primary care (PC) settings in Pakistan. Furthermore, this review aims to identify potential solutions to promote appropriate use of antimicrobials in Pakistan. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) checklist, a comprehensive scoping review was conducted to review the literature of antimicrobials used, prescribed and dispensed in PC settings in Pakistan. Google Scholar and Pub-Med were searched for the period 2000-2023. Papers were analyzed on the basis of eligibility i.e., included antimicrobial use, prescribing and dispensing practices by general population at homes, by prescribers in outpatient departments of hospitals and by pharmacists/dispensers in community pharmacies, respectively. Two researchers analyzed the articles thoroughly and disagreements were resolved through discussion with a third reviewer. Both quantitative and qualitative research studies were eligible for inclusion. Additionally, the selected papers were grouped into different themes. We identified 4070 papers out of which 46 studies satisfied our eligibility criteria. The findings revealed limited understanding of antimicrobial resistance (AMR) by physicians and community pharmacists along with inappropriate practices in prescribing and dispensing antibiotics. Moreover, a notable prevalence of self-medication with antibiotics was observed among the general population, underscoring a lack of awareness and knowledge concerning proper antibiotic usage. Given the clinical and public health implications of AMR, Pakistan must prioritize its policies in PC settings. Healthcare professionals (HCPs) need to reduce inappropriate antibiotic prescribing and dispensing, improve their understanding of the AWaRe (access, watch and reserve antibiotics) classification and guidance, monitor current usage and resistance trends, as well as implement antimicrobial stewardship (ASP) activities starting in targeted locations.

Knowledge, attitude, and perception of community pharmacists towards antimicrobial stewardship in Saudi Arabia: A descriptive cross-sectional study.

Background: Antimicrobial resistance is of paramount concern globally. Community pharmacists (CPs) play a vital role in supporting judicious antimicrobial use in the community as they are the key healthcare providers at a public level. This study aimed to assess the knowledge, attitude, and perception of CPs towards antimicrobial stewardship at the community level in Saudi Arabia. Methods: A self-administered questionnaire was distributed to all community pharmacies in four major cities of Saudi Arabia. A simple random sampling approach was used to select pharmacies in each chain. Results: A total of 520 CPs responded to the survey with a response rate of 98.6 %. Most of the pharmacists (n = 479, 92.1 %) accepted that antimicrobial stewardship programs are essential tools to limit injudicious usage of antimicrobials at the community level. Interestingly, very few (n = 105, 21 %) agreed to recommend antibiotics for common illnesses, including upper respiratory tract infections, cold, and flu without a valid prescription. Further, we found a significant role of Saudi health authorities, e.g., Saudi food & drug authorities and the Ministry of Health, in restricting antimicrobials sale in community pharmacies without a valid prescription. Conclusion: Our study findings revealed that CPs had good knowledge about antimicrobial stewardship in Saudi Arabia. The CPs play an active role in the optimization of antimicrobial therapy and infections caused by different microbes. Strict policies by the Saudi health care authority regarding the restricted dispensing of antimicrobials are welcomed by the CPs and thus may contribute toward lowering of antimicrobial resistance burden on the patients and Saudi health care authorities.

Dose Optimization of Colistin: A Systematic Review.

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

Work readiness scale for pharmacy interns and graduates: A cross-sectional study.

INTRODUCTION: As the number of unemployment among pharmacy graduates increases, the Saudi Ministry of Labor implemented extra measures to facilitate their training and hiring by the private sectors. Nevertheless, there is a paucity of data regarding pharmacy graduates' work readiness (WR). Hence, we aim to assess their WR and identify predicting factors associated with WR among pharmacy graduates' in Saudi Arabia. METHODS: A 46-item self-reported pre-validated anonymous work readiness scale (WRS) survey with a 5-point Likert scale was administered to pharmacy senior students and graduates using Qualtrics XM® survey tool over the month of May 2020. The main outcome was to assess WRS for pharmacy interns and graduates and identify factors associated with work readiness. RESULTS: A total of 617 participants have participated in this survey, out of which 46.5% were freshly graduated pharmacists and 19.6% were pharmacy interns. Most participants (82.3%) were PharmD candidates or graduates. Around two-third of participants (63%) have successfully completed all survey items. The maximum points scored was 223 out of 230, and the median overall score was found to be 175. There was no significant association with gender, age, or type of university regarding overall scores. However, a statistically significant odds ratio was observed with PharmD program type and previous pharmaceutical marketing training (OR = 1.778, 95% CI = 1.143-2.765: OR = 0.618, 95% CI = 0.432-0.884, respectively). CONCLUSION: The overall median score shows a good work readiness level among pharmacy students/graduates in Saudi Arabia; however, PharmD program graduates exposed to advance pharmacy training, including the pharmaceutical marketing experience, have higher work readiness odds than Bpharm graduates. Further studies involving other related perspectives, such as stakeholders, employers, and preceptors, would give a clear image of pharmacy graduates' job readiness levels.

Association between graduates' factors and success rate on the Saudi Pharmacist Licensure Examination: A single-Institution cross-sectional study.

INTRODUCTION: The Saudi Pharmacists Licensure Examination's (SPLE) initial results were revealed in February 2020, which showed enormous inconsistency with the passing rates. Hence, we aimed to investigate the predictors of pharmacy graduates' success rate on the SPLE of a single-college in Saudi Arabia. METHODS: In a cross-sectional study of 2019-graduates, data were collected via-phone interviews and retrieved from the college's database. Graduates' data were retrieved from the college's database, which includes high school grade point average (GPA), General Aptitude Test, Scholastic Achievement Admission Test, preparatory year GPA, pharmacy GPA, and all courses' grades. The data collected via-phone interview includes information that was not recorded in the college's database, such as date of birth, SPLE score, and the number of SPLE attempts. We only included students who agreed to be interviewed and had attempted the SPLE at least once. We developed a prediction model using correlational analyses and stepwise multiple linear regression to examine graduates' factors in predicting success on the SPLE. RESULTS: Out of the 149 graduates, 105 fulfilled the inclusion criteria. Around 84% of them passed the SPLE. Correlation analyses showed a significant direct correlation between preparatory year GPA and pharmacy GPA with SPLE scores (r = 0.228, P = 0.0193 and r = 0.533, P < 0.0001, respectively). In addition, the results showed that all of the four SPLE content areas were positively correlated with SPLE scores (P < 0.0001). The stepwise multivariable regression showed that being a male graduate and scoring high-grade points in pharmacology and therapeutics courses were significantly associated with high SPLE scores (P = 0.0053, P = 0.0256, and P = 0.0001, respectively). CONCLUSION: This single cross-sectional study found that being a male, pharmacology GPA, and therapeutics GPA were significantly associated with a higher SPLE score. Further studies should focus on the GPA cut off below which we should give remediation to improve SPLE passing rate.

Single ß-lactams versus combinations as empiric therapy for infections with Pseudomonas aeruginosa: assessing the in vitro susceptibility.

Background: While the value of combination versus monotherapy of infections with Pseudomonas aeruginosa infection is a subject of debate, increasing antimicrobial resistance of this pathogen makes it difficult to select appropriate empiric regimens. We evaluated the probability that P. aeruginosa would be susceptible to ß-lactams either as monotherapy or as part of a combination regimen.Methods: Contemporary non-duplicate isolates of P. aeruginosa derived from blood or the respiratory tract of patients hospitalized in the United States were investigated. Minimum inhibitory concentrations were determined using broth microdilution methods for amikacin (AMK), cefepime (FEP), ceftazidime (CAZ), ceftolozane/tazobactam (C/T), ciprofloxacin (CIP), fosfomycin (FOF), meropenem (MEM), piperacillin/tazobactam (TZP) and tobramycin (TOB). Susceptibility to a regimen was derived from the minimum inhibitory concentrations value of the beta-lactam plus the minimum inhibitory concentrations value of the additional agent.Results: In 1209 P. aeruginosa, susceptibility to C/T exceeded 90%, while susceptibility to FEP, CAZ, MEM and TZP ranged from 73 to 78%. For antibiotic combinations, the addition of the 2nd agent AMK, TOB, CIP or FOF raised the susceptibility to FEP, CAZ, MEM and TZP, whereas very little added activity was noted for C/T due to the intrinsic potency of this compound alone.Conclusions: While the addition of AMK, TOB, CIP or FOF markedly increased the probability that an active regimen would be selected for empirical therapy with FEP, CAZ, MEM and TZP, C/T alone had higher activity than the combinations.

In vitro potency of antipseudomonal ß-lactams against blood and respiratory isolates of P. aeruginosa collected from US hospitals.

BACKGROUND: Challenges due to multidrug resistant (MDR) Gram-negative bacterial pathogens such as P. aeruginosa (PSA) are increasing globally. Suboptimal antimicrobial therapy of infections caused by PSA is associated with increased morbidity and mortality. As a result, antimicrobial susceptibility (%S) studies are pivotal to identifying trends in antimicrobial resistance that inform decisions regarding choice of antimicrobial therapy. This study assessed the in vitro potency of 7 antipseudomonal agents including ceftolozane/tazobactam (C/T) against PSA collected from numerous sites across the US. METHODS: Multiple US hospitals provided non-duplicate respiratory and blood isolates of PSA for potency testing. MICs against PSA were determined using broth microdilution methods according to CLSI for 7 antimicrobials with antipseudomonal activity: aztreonam (ATM), cefepime (FEP), ceftazidime (CAZ), C/T, imipenem (IPM), meropenem (MEM) and piperacillin/tazobactam (TZP). %S was defined per CLSI or FDA breakpoint criteria. RESULTS: Thirty-five hospitals geographically spread across the US provided a total of 1,209 PSA isolates. Of the antibiotics assessed, %S to C/T was the highest at 95% with an MIC50 of 0.5 mg/L and MIC90 of 2 mg/L. In comparison, other %S (MIC50/MIC90) was as follows: ATM 66% (8/32); FEP 76% (4/32); CAZ 78% (4/64); IPM 68% (2/16); MEM 74% (0.5/16); and TZP 73% (8/128). CONCLUSIONS: For this geographically diverse PSA population, C/T demonstrated the highest overall susceptibility (95%). Other antipseudomonal agents inclusive of the carbapenems displayed susceptibilities of 66-78%. In the era of escalating PSA resistance to the ß-lactams, the potency of C/T may represent an important clinical option.

In Vivo Efficacy of Humanized WCK 5222 (Cefepime-Zidebactam) Exposures against Carbapenem-Resistant Acinetobacter baumannii in the Neutropenic Thigh Model.

Herein, we describe the in vivo efficacy of human-simulated WCK 5222 (cefepime-zidebactam) exposure against carbapenem-resistant Acinetobacter baumannii strains in a neutropenic murine thigh infection model. Five of the six isolates examined expressed OXA-23 or OXA-24. WCK 5222, despite showing MICs of 16 to 64 mg/liter, produced remarkable in vivo activity; human-simulated exposure showed a decline in the bacterial burden for all isolates (mean reduction, -2.09 ± 1.01 log10 CFU/thigh), while a lack of activity was observed with cefepime and zidebactam monotherapies.

Patient preferences for treatment of acute bacterial skin and skin structure infections in the emergency department.

BACKGROUND: Limited research has assessed patient preferences for treatment disposition and antibiotic therapy of acute bacterial skin and skin structure infection (ABSSSI) in the emergency department (ED). Understanding patient preference for the treatment of ABSSSI may influence treatment selection and improve satisfaction. METHODS: A survey was conducted across 6 US hospital EDs. Patients with ABSSSI completed a baseline survey assessing preferences for antibiotic therapy (intravenous versus oral) and treatment location. A follow-up survey was conducted within 30-40 days after ED discharge to reassess preferences and determine satisfaction with care. RESULTS: A total of 94 patients completed both baseline and follow-up surveys. Sixty (63.8%) participants had a history of ABSSSI, and 69 (73.4%) were admitted to the hospital. Treatment at home was the most common preference reported on baseline and follow-up surveys. Patients with higher education were 82.2% less likely to prefer treatment in the hospital. Single dose intravenous therapy was the most commonly preferred antibiotic regimen on baseline and follow-up surveys (39.8 and 19.1%, respectively). Median satisfaction scores for care in the ED, hospital, home, and with overall antibiotic therapy were all 8 out of a maximum of 10. CONCLUSIONS: In these patients, the most common preference was for outpatient care and single dose intravenous antibiotics. Patient characteristics including higher education, younger age, and current employment were associated with these preferences. Opportunities exist for improving ABSSSI care and satisfaction rates by engaging patients and offering multiple treatment choices.

Variability in Emergency Medicine Provider Decisions on Hospital Admission and Antibiotic Treatment in a Survey Study for Acute Bacterial Skin and Skin Structure Infections: Opportunities for Antimicrobial Stewardship Education.

BACKGROUND: Acute bacterial skin and skin structure infections (ABSSSIs) are a frequent cause of emergency department (ED) visits. Providers in the ED have many decisions to make during the initial treatment of ABSSSI. There are limited data on the patient factors that influence these provider decisions. METHODS: An anonymous survey was administered to providers at 6 EDs across the United States. The survey presented patient cases with ABSSSIs ≥75 cm2 and escalating clinical scenarios including relapse, controlled diabetes, and sepsis. For each case, participants were queried on their decision for admission vs discharge and antibiotic therapy (intravenous, oral, or both) and to rank the factors that influenced their antibiotic decision. RESULTS: The survey was completed by 130 providers. For simple ABSSSI, the majority of providers chose an oral antibiotic and discharged patients home. The presence of recurrence or controlled diabetes resulted in more variation in responses. Thirty-four (40%) and 51 (60%) providers chose intravenous followed by oral antibiotics and discharged the recurrence and diabetes cases, respectively. Presentation with sepsis resulted in initiation with intravenous antibiotics (122, 95.3%) and admission (125, 96.1%) in most responses. CONCLUSIONS: Variability in responses to certain patient scenarios suggests opportunities for education of providers in the ED and the development of an ABSSSI clinical pathway to help guide treatment.

Antibacterial Activity of Human Simulated Epithelial Lining Fluid Concentrations of Ceftazidime-Avibactam Alone or in Combination with Amikacin Inhale (BAY41-6551) against Carbapenem-Resistant Pseudomonas aeruginosa and Klebsiella pneumoniae.

The role of inhalational combination therapy when treating carbapenem-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae with newer beta-lactam/beta-lactamase inhibitors has not been established. Using a 72-h in vitro pharmacodynamic chemostat model, we simulated the human exposures achieved in epithelial lining fluid (ELF) following intravenous treatment with ceftazidime-avibactam (CZA) 2.5 g every 8 h (q8h) alone and in combination with inhaled amikacin (AMK-I) 400 mg q12h, a reformulated aminoglycoside designed for inhalational administration, against three P. aeruginosa isolates (CZA [ceftazidime/avibactam] MICs, 4/4 to 8/4 µg/ml; AMK-I MICs, 8 to 64 µg/ml) and three K. pneumoniae isolates (CZA MICs, 1/4 to 8/4 µg/ml; AMK-I MICs, 32 to 64 µg/ml). Combination therapy resulted in a significant reduction in 72-h CFU compared with that of CZA monotherapy against two of three P. aeruginosa isolates (-4.14 log10 CFU/ml, P = 0.027; -1.42 log10 CFU/ml, P = 0.020; and -0.4 log10 CFU/ml, P = 0.298) and two of three K. pneumoniae isolates (0.04 log10 CFU/ml, P = 0.963; -4.34 log10 CFU/ml, P < 0.001; and -2.34 log10 CFU/ml, P = 0.021). When measured by the area under the bacterial growth curve (AUBC) over 72 h, significant reductions were observed in favor of the combination regimen against all six isolates tested. AMK-I combination therapy successfully suppressed CZA resistance development in one K. pneumoniae isolate harboring blaKPC-3 that was observed during CZA monotherapy. These studies suggest a beneficial role for combination therapy with intravenous CZA and inhaled AMK when treating pneumonia caused by carbapenem-resistant Gram-negative bacteria.

Physical compatibility of fosfomycin for injection with select i.v. drugs during simulated Y-site administration.

PURPOSE: The results of a study to determine the physical compatibility of ZTI-01 (fosfomycin for injection) in 0.9% sodium chloride or 5% dextrose during simulated Y-site administration with 37 i.v. antimicrobials and 58 nonantimicrobials are reported. METHODS: Fosfomycin, an epoxide antibiotic with broad-spectrum activity against multidrug-resistant bacteria, is marketed in the United States only in an oral formulation with limited bioavailability, but an i.v. formulation is in development. Fosfomycin for injection and other evaluated drugs were reconstituted according to manufacturer recommendations and further diluted with 0.9% sodium chloride or 5% dextrose to the final desired concentrations. Y-site administration was simulated in glass culture tubes. Incompatibility was defined as changes in visual characteristics or a change in turbidity of >0.5 nephelometric turbidity units over the 120-minute observation period. RESULTS: Of the 95 drugs tested, 16 were incompatible with fosfomycin in 0.9% sodium chloride, and 18 were incompatible with fosfomycin in 5% dextrose; incompatibility was observed with 10 of 37 antimicrobials, including the 3 commercially available amphotericin B products, anidulafungin, caspofungin, ceftaroline, ciprofloxacin, daptomycin, doxycycline, and isavuconazonium sulfate. CONCLUSION: Fosfomycin for injection at a concentration of 30 mg/mL was physically compatible with 73 of 95 (77%) of the i.v. drugs tested at concentrations used clinically in both 0.9% sodium chloride injection and 5% dextrose injection. Twenty-two drugs were deemed incompatible in at least 1 of the 2 diluents.