How to design and implement an outpatient antimicrobial stewardship programme.

Antimicrobial stewardship programmes in the outpatient setting have recently become an area of focus in an effort to improve antimicrobial prescribing. The Centers for Disease Control and Prevention and The Joint Commission have recently addressed this concern and provided a framework for the implementation of an outpatient stewardship programme. This manuscript offers detailed guidance on how to design and implement an outpatient antimicrobial stewardship programme and reviews the literature on current strategies. Challenges related to initiating and maintaining outpatient stewardship efforts are also discussed. This article is part of the Antibiotic stewardship Special Issue: https://www.drugsincontext.com/special_issues/antimicrobial-stewardship-a-focus-on-the-need-for-moderation.

Affective domain predictors of PharmD student pursuit of and successful matching for postgraduate pharmacy residency training.

PURPOSE: A study was conducted to identify significant associations between affective domain (AD) features identified using the Birkman Method assessment and students' likelihood to pursue and to successfully match for postgraduate residency training (PGRT), while controlling for demographic and academic variables known to impact PGRT match rates. METHODS: A retrospective analysis of 3 graduating classes of PharmD students from 2 colleges of pharmacy was performed. Data points such as PGRT match results, PGRT pursuit, student demographics, academic performance information, and AD data from the Birkman assessment were analyzed. Regression analysis was used to identify statistically significant associations between demographic, academic performance, and AD variables with both pursuit of PGRT and successful matching for PGRT. RESULTS: Data from 503 students were evaluated, with 211 (42%) pursuing PGRT. A variety of AD variables were significantly associated with pursuing PGRT and matching for PGRT. Two groups of actionable variables emerged: (1) variables associated with a lesser likelihood of pursuing PGRT but a greater likelihood of successful matching, and (2) variables associated with a greater likelihood of pursuing PGRT and a lesser likelihood of successful matching. CONCLUSION: Early identification of students' AD features along with specific interventions to promote PGRT pursuit in those less likely to pursue but more likely to match, as well as interventions to promote successful matching in students most likely to pursue but less likely to match for PGRT, is a strategy for possibly optimizing PharmD student career path planning and PGRT match success that merits further evaluation.

Pharmacokinetic evaluation of cefiderocol for the treatment of multidrug resistant Gram-negative infections.

INTRODUCTION: Cefiderocol is a siderophore cephalosporin antibiotic and first of its kind approved by the Food and Drug Administration for the treatment of complicated urinary tract infections (cUTI) and hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) in patients 18 years or older caused by susceptible organisms. Cefiderocol's unique mechanism of iron chelation improves Gram-negative membrane penetration as the bacteria's iron uptake mechanism recognizes the chelated iron antibiotic and iron for entry. This also allows for the evasion of cefiderocol from cell entry-related resistance mechanisms. AREAS COVERED: This review covers the mechanism of action, resistance mechanisms, pharmacokinetics in various patient populations, and pharmacodynamics. Relevant literature evaluating efficacy and safety are discussed. EXPERT OPINION: Limited treatment options are available for the treatment of carbapenem-resistantorganisms. Clinical trials have demonstrated that cefiderocol is no worse than alternative treatment options for cUTIs and HABP/VABP, but more data are currently available to support the use of beta-lactam beta-lactamase inhibitor agents, where susceptible. Mortality differences demonstrated in patients with pneumonia and bloodstream infections must further be explored and logistical and practical considerations regarding susceptibility testing and use as monotherapy vs. combination therapy must be considered prior to confidently recommending cefiderocol for regular use in systemic infections.

Evaluation of Treatment Practices for Urinalyses and Urine Cultures at an Outpatient Multiple Sclerosis Clinic.

BACKGROUND: Patients with multiple sclerosis (MS) experience disease flares that can be precipitated by the presence of infection. Discerning asymptomatic bacteriuria from urinary tract infection (UTI) in patients with MS is complicated by lower urinary tract dysfunction, leading to potentially inappropriate antimicrobial use. In this study the antimicrobial treatment practices for positive urine cultures in patients with MS were evaluated. METHODS: In this single-center, retrospective study, positive cultures in patients with MS were included. The primary outcome was the proportion of patients appropriately treated with or without antimicrobial therapy. Secondary end points included antimicrobial selection and urinalysis positivity. RESULTS: Two hundred thirty-six cultures from 139 patients were evaluated. Treatment was inappropriate in 81 of 201 treated cultures (40%). Frequency, nocturia, dysuria, and foul-smelling urine were reported by patients in 54 (23%), 10 (4%), 25 (11%), and 14 (6%) cultures, respectively. The antimicrobial selected was too broad in spectrum for 35 of 201 (17%). Of those, fluoroquinolones were the agents used in 33 of 35 cases (94%). A urinalysis was sent in 203 cases (86%), with 197 (84%) positive for at least one predefined positivity criteria. CONCLUSIONS: Urinalyses and urine cultures are performed frequently in patients with MS, often independent of symptoms. Patients with MS could be treated for asymptomatic bacteriuria at higher rates than the general population, and traditional urinary symptoms may not be appropriate indicators of infection. Empirical therapy for UTI is frequently used in this population, often resulting in inappropriate and/or too broad of antimicrobial therapy.

Contemporary Perspective on the Treatment of Acinetobacter baumannii Infections: Insights from the Society of Infectious Diseases Pharmacists.

The purpose of this narrative review is to bring together the most recent epidemiologic, preclinical, and clinical findings to offer our perspective on best practices for managing patients with A. baumannii infections with an emphasis on carbapenem-resistant A. baumannii (CRAB). To date, the preferred treatment for CRAB infections has not been defined. Traditional agents with retained in vitro activity (aminoglycosides, polymyxins, and tetracyclines) are limited by suboptimal pharmacokinetic characteristics, emergence of resistance, and/or toxicity. Recently developed and US Food and Drug Administration (FDA)-approved ß-lactam/ß-lactamase inhibitor agents do not provide enhanced activity against CRAB. On balance, cefiderocol and eravacycline demonstrate potent in vitro activity and are well tolerated, but clinical data for patients with CRAB infections do not yet support widespread use. Given that CRAB has the capacity to infect vulnerable patients and preferred regimens have not been identified, we advocate for combination therapy. Our preferred regimen for critically ill patients infected, or considered to be at high risk for CRAB, includes meropenem, polymyxin B, and ampicillin/sulbactam. Importantly, site of infection, severity of illness, and local epidemiology are essential factors to be considered in selecting combination therapies. Molecular mechanisms of resistance may unveil preferred combinations at individual centers; however, such data are often unavailable to treating clinicians and have not been linked to improved clinical outcomes. Combination strategies may also pose an increased risk for antibiotic toxicity and Clostridioides difficile infection, and should therefore be balanced by understanding patient goals of care and underlying health conditions. Promising therapies that are in clinical development and/or under investigation include durlobactam-sulbactam, cefiderocol combination regimens, and bacteriophage therapy, which may over time eliminate the need for the continued use of polymyxins. Future goals for CRAB management include pathogen-focused treatment paradigms that are based on molecular mechanisms of resistance, local susceptibility rates, and the availability of well-tolerated, effective treatment options.

Candida auris Urinary Tract Infections and Possible Treatment.

Candida auris is a globally emerging pathogen that has been identified in urinary tract infections (UTIs) worldwide. The novel pathogen is characterized by common misidentification, difficult eradication, and multidrug resistance. To date, there is a paucity of data to guide the optimal management of C. auris UTIs. This review provides an overview of C. auris as an etiologic agent of UTIs, a comprehensive review of published data on C. auris UTIs, and a proposed treatment algorithm based on patient clinical status, the presence or absence of clinical infection, comorbidities, infection, and therapy history. Echinocandin and liposomal amphotericin B are recommended as first-line agents for most patients with C. auris isolated in the urine, with a focus on infection control measures and appropriate follow-up criteria. A variety of combination therapies, flucytosine, and amphotericin B bladder irrigations are offered as potential alternatives in the event of infection persistence or recurrence. The treatment approach centers on the aggressive treatment of C. auris in most patients, with the goal of preventing subsequent invasive spread, multi-drug resistance, and ultimate mortality. Published literature on C. auris urinary isolation and treatment is imperative for the future evolution of evidence-based treatment recommendations for this unique pathogen of concern.

Online availability of fish antibiotics and documented intent for self-medication.

Self-medication and antibiotic utilization without healthcare oversight may lead to delayed appropriate treatment, transmission of communicable infections, untoward adverse events, and contribute to antimicrobial resistance. Previous data suggest people obtain over-the-counter (OTC) animal antibiotics for their personal use. This study examined the availability of OTC fish antibiotics online and the documented intent for self-medication. The authors conducted a web-based cross-sectional study using Google search engine to identify vendor websites selling fish antibiotics in the United States. Vendor websites were included if product information, consumer reviews, and comments were publicly available. Nine fish antibiotics were chosen due to their possibility of having consequences to human misuse. The cost and availability of fish antibiotics was recorded. The proportion of reviews and comments related to human consumption was calculated. Consumer review traffic based on "likes" and "dislikes" received was compared between human- and non-human consumption-related reviews. Selected fish antibiotics were purchased and evaluated for physical appearance and compared to FDA-approved available equivalents. We found 24 website vendors with online ordering available for OTC fish antibiotics. Cost varied significantly by antibiotic and quantity ranging from USD $8.99 to $119.99. There were 2,288 reviews documented for the 9 selected antibiotics being sold. Among consumer reviews, 2.4% were potentially associated with human consumption. Human consumption-related reviews constituted 30.2% of all "likes" received and 37.5% of all "dislikes" received. Human consumption-related reviews received an average of 9.2 likes compared to 0.52 likes for non-human consumption-related reviews. The 8 fish antibiotics purchased were consistent with FDA-approved equivalents in physical appearance. Although infrequent, antibiotics intended for fish use are being purchased online without a prescription for self-medication to circumvent professional medical care. Reviews related to human consumption generate significant online traffic compared to reviews unrelated to human consumption.

Prediction of trimethoprim/sulfamethoxazole resistance in community-onset urinary tract infections.

OBJECTIVES: This study aimed to predict trimethoprim/sulfamethoxazole (SXT) resistance in patients with community-onset urinary tract infection (UTI) due to Enterobacteriaceae based on patient-specific risk factors. METHODS: This was a retrospective case-control study in Prisma Health facilities in central South Carolina, USA, including three community hospitals, affiliated emergency departments and ambulatory clinics, including adult patients with community-onset UTI due to Enterobacteriaceae (1 April 2015 to 29 February 2016). Multivariate logistic regression was used to examine risk factors for SXT resistance. RESULTS: Among 351 unique patients with community-onset UTI, 71 (20.2%) had SXT-resistant Enterobacteriaceae urinary isolates. Overall, median age was 64 years and 252 (71.8%) were female. A multivariate model identified prior urinary infection/colonisation with SXT-resistant Enterobacteriaceae (OR=8.58, 95% CI 3.92-18.81; P<0.001) and SXT use within past 12 months (OR=2.58, 95% CI 1.13-5.89; P=0.02) as predictors of SXT resistance among urinary isolates. Most patients with UTI (285; 81.2%) had no risk factors for SXT resistance. SXT resistance rates increased from 13% in the absence of risk factors to 31% in patients with prior SXT use, 66% in those with prior urinary infection/colonisation with SXT-resistant Enterobacteriaceae and 73% in the presence of both risk factors. CONCLUSION: SXT resistance in Enterobacteriaceae urinary isolates may be predicted based on prior urine culture results and SXT use within the previous year. Utilisation of a patient-specific antibiogram may allow empirical SXT use in patients with community-onset UTI in the absence of risk factors for resistance.

A practical guide for pharmacists to successfully implement penicillin allergy skin testing.

PURPOSE: The purpose of this article is to offer practical guidance for pharmacists to successfully implement penicillin allergy skin testing (PAST). SUMMARY: Less than 10% of patients labeled as having a penicillin allergy are confirmed as present upon skin testing. This labeling results in use of alternative antibiotics and thus unwanted adverse consequences including potentiated antimicrobial resistance, increased costs, and worse clinical outcomes. Stewardship guidelines recommend PAST to enhance use of first-line agents; however, this was a weak recommendation with low-quality evidence. Recent efforts and subsequent research since publication of guidelines have demonstrated beneficial effects from increasing use of PAST among stewardship programs to improve outcomes. A number of different models exist demonstrating successful implementation of PAST at various healthcare facilities. There are important logistical factors to consider during implementation of PAST such as target population, optimal preparation, leadership structure, resource availability, and state regulations. Pharmacists as leaders of antimicrobial stewardship teams and experts in drug allergies are a natural fit to help implement PAST in healthcare settings to improve overall outcomes. This article offers guidance to institutions considering implementation of PAST. CONCLUSION: PAST is rapidly becoming an effective, long-term antimicrobial stewardship tool to optimize antimicrobial prescribing in both the inpatient and outpatient settings. Pharmacists have demonstrated significant benefit as providers of PAST services in a variety of healthcare settings with a number of different healthcare professionals.

Production of a biologically active recombinant marsupial growth factor using the methylotrophic yeast Pichia pastoris.

The cytokine stem cell factor (SCF) and its interaction with its receptor c-kit plays an important role in the development of germ cells in eutherians. To investigate the putative roles of the SCF/c-kit system in marsupials, recombinant Australian brushtail possum (Trichosurus vulpecula) SCF was purified after secretion by the methylotrophic yeast Pichia pastoris. The purification procedure utilized Ni2+ affinity chromatography with a poly-histidine tag engineered onto the C-terminus of the recombinant SCE The recombinant possum SCF had a molecular weight of 48 kDa, as determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, and was biologically active with respect to its ability to maintain and induce proliferation of marsupial primordial germ cells in vitro. Furthermore, the recombinant possum SCF stimulated proliferation of the cell line TF1 and this bioactivity could be inhibited using an antibody directed against recombinant mouse SCF. This source of biologically active marsupial SCF may prove useful in future studies of marsupial development.

A calmodulin binding site in the tuberous sclerosis 2 gene product is essential for regulation of transcription events and is altered by mutations linked to tuberous sclerosis and lymphangioleiomyomatosis.

Mutations in the tuberous sclerosis 2 (TSC2) gene product have been genetically linked to the pathology of both tuberous sclerosis (TSC) and the gender-specific lung disease, lymphangioleiomyomatosis (LAM). Both diseases are classified as disorders of cellular migration, proliferation, and differentiation. Earlier studies from our laboratory (1) linked TSC2 with steroid/nuclear receptor signaling. Studies presented here provide evidence for calmodulin (CaM) signaling in the propagation of this TSC2 activity. Far Western screening of a lambda phage human brain cDNA library to identify interacting proteins for the TSC2 gene product (tuberin) yielded multiple clones encoding human CaM. Direct binding with 32P-labeled tuberin demonstrated Ca2+-dependent binding to CaM-Sepharose which was lost upon deletion of the C-terminal 72 residues. The sequence (1740)WIARLRHIKRLRQRIC(1755) was identified as one capable of forming a basic amphipathic helix indicative of CaM binding domains in known calmodulin binding proteins. Studies with a synthetic peptide of this sequence demonstrated very tight Ca2+-dependent binding to CaM as judged by tryptophan fluorescence perturbation studies and phosphodiesterase activation by CaM. Deletion mutagenesis studies further suggested that this CaM binding domain is required for tuberin modulation of steroid receptor function and that mutations in this region may be involved in the pathology of TSC and LAM.