Use Of First-line Antibiotics Research Articles

Antibiotic utilization and resistance in diarrheagenic Escherichia coli isolated from children under 5 Years in Nakuru County: a case-control study

Background: Children under the age of 5 years continue to suffer the ravaging effects of microbial resistance. Majority of the infections associated with this age are of bacterial and viral nature. Highest mortalities in this age group are those associated with enteric and diarrheal diseases. Diarrheagenic Escherichia coli (DEC) is among the leading causes of these diseases due to their ubiquitous nature. Methods: The study adopted a case-control design and aimed at investigating antibiotic utilization and resistance in DEC strains isolated from children under 5 years in Nakuru County. A total sample size of 384 children were considered. Stool samples from anal swabs were obtained and cultured on Eosin Methylene Blue (EMB). Antimicrobial susceptibility testing was done using the Kirby-Bauer disk diffusion method to segregate the resistant DEC isolates against amoxicillin, ampicillin, erythromycin, cefoxitin and nalidixic acid. Results: All the DEC (n=192, 100%) strains were resistant to amoxicillin, n=168, 87.5% were resistant to ampicillin, n=156, 81.3% to erythromycin n=72, 37.5% to cefoxitin and only n=64, 33.3% to nalidixic acid. Based on demographic factors, it was that observed self-medication leads among factors contributing to the observed trend in antimicrobial resistance (AMR). Other factors such the length of antibiotic use did not show any level of significance (p<0.05). Conclusions: Thus, we conclude that a conglomerate of several factors is associated with the rising cases of AMR among the DEC strains. Notably, the use of first-line antibiotics especially the β-lactams poses a critical health concern being the most resisted class of antibiotics. Therefore, the current study unravels the need to remediate the effects of AMR among the DEC strains through proper formulation and implementation of guidelines on antibiotic usage.

Impact of antimicrobial stewardship interventions on peripartum antibiotic prescribing in patients with penicillin allergy

Beta-lactam antibiotics (eg, penicillins, cephalosporins, and carbapenems) are preferred for group B streptococcus prophylaxis, intra-amniotic infection, and cesarean surgical site infection prophylaxis. Non-beta-lactam alternatives are associated with inferior efficacy and contribute to higher rates of surgical site infection and longer lengths of stay. Most patients who report a penicillin allergy can tolerate penicillins without any adverse reaction. There are low rates of cross-reactivity between penicillins and other beta-lactams, including cephalosporins and carbapenems. Efforts to evaluate penicillin allergy and promote the use of beta-lactams are needed. This study aimed to evaluate whether an antimicrobial stewardship intervention improved the use of first-line antibiotics for peripartum indications in patients with a reported penicillin allergy, following updates to institutional guidelines. This was a retrospective study of adult patients presenting for vaginal or cesarean delivery at 2 hospitals within a healthcare system. Patients received at least 1 dose of antibiotics for a peripartum indication between May 1, 2018, and October 31, 2018 (preintervention group) and May 1, 2020, to October 31, 2020 (postintervention group). The stewardship intervention bundle, which was implemented between March 2019 and April 2020, included updates to institutional antibiotic guidelines, reclassification of severe penicillin allergy, development of obstetrical prophylaxis and treatment order sets, promotion of allergy referral services, and establishment of a physician champion. The primary outcome was the composite rates of patients with reported penicillin allergy who received a preferred antibiotic for a peripartum indication. The secondary measures included maternal and neonatal outcomes. A total of 192 patients with a history of documented penicillin allergy were evaluated (96 patients in the preintervention group and 96 patients in the postintervention group). Hives were the most commonly reported index symptom in both groups (40/96 [41.7%] vs 39/96 [40.6%]; P=.883). After stewardship interventions, there was a significant increase in the rate of preferred antibiotic use (33/96 [34.3%] vs 81/96 [84.3%]; P<.001). The effect was the greatest in patients with nonsevere allergy (14/76 [18.4%] vs 68/82 [82.9%]; P<.001). There was no difference in the rates of postpartum endometritis, 30-day readmission, 90-day surgical site infection, or neonatal early-onset sepsis between the pre- and postintervention groups. Of note, 1 patient in the postintervention group experienced itching, and another patient developed a rash, both of which resolved with medical management. A comprehensive antibiotic stewardship intervention was associated with a 50% increase in the use of preferred antibiotics for peripartum indications in patients with penicillin allergy. Allergic reactions with first-line beta-lactams were minimal and manageable.

Antibiotic Stewardship and Treatment of Uncomplicated Urinary Tract Infection (UTI) in Children and Adolescents in the Emergency Department of a Community Hospital.

A retrospective, cross-sectional study of children with suspected urinary tract infections (UTIs) 3 months to 18 years of age who had a urinalysis and urine culture (UC) during an emergency department (ED) visit between 2019 and 2020 was performed. Chi-square, Fisher exact, and independent samples T tests were used as appropriate. Median age was 6.6 years (interquartile range = 3.3-12.4). Urinalysis positivity was 92.8%, of which 81.9% of children were prescribed a first-line antibiotic. First-line antibiotic use was 82.7%. Positive UC rate was 84.7%, with 84% receiving a first-line antibiotic (P = .025). The correlation between a positive urinalysis and a positive UC was 80.8% (P < .001). Change of antibiotics based on the uropathogen of positive UCs was 6.3% (P < .001). The urinalysis and UC guided the diagnosis and treatment of UTIs. First-line antibiotics can be safely administered in the ED and prescribed for positive urinalyses. Studies are needed to evaluate the discontinuation of antibiotics with negative UCs as part of antibiotic stewardship initiatives.

Delabeling penicillin and other antibiotic allergies in solid organ transplantation patients.

Immunocompromised populations including solid organ transplant (SOT) recipients have a high likelihood of need for antibiotic therapy for treatment of infection as well as for prophylaxis. Antibiotic allergy is commonly reported and often leads to the use of alternative, second-line antibiotics, which have been associated with poor outcomes, increased adverse effects, and higher cost. Formal allergy assessment and allergy testing can serve as an important antimicrobial stewardship tool in optimizing antibiotic regimens for this patient population. A PubMed search with relevant keywords was performed. Review of relevant professional society guidelines was also performed. Documented penicillin and sulfonamide allergies are common impediments to the treatment and prophylaxis of immunocompromised populations, but are rarely formally evaluated in practice; however, there is evidence that most patients with documented allergy to these antibiotics can, in fact, tolerate penicillins and sulfonamide antibiotics. Implementation of an antibiotic allergy evaluation and testing program has been shown to increase the use of first-line antibiotics and can be cost saving. Antibiotic allergies have significant clinical consequences, especially in immunocompromised populations. Evaluation of these allergies to prevent the avoidance of first-line antibiotics should be a standard part of the workflow for these patients, prior to transplant. Programs can be tailored to the available personnel and resources of the organization.

How effective is a brief educational intervention on prescribing first-line antibiotics in acute cystitis? A quasi-experimental study among general practitioners in Croatia

AimTo assess the effectiveness of a brief educational intervention on prescribing first-line antibiotics in acute cystitis.MethodsThis quasi-experimental before-after study was conducted over a period of eight months. We collected prescribing data related to urinary tract infections four months before the educational intervention and four months after it. Aggregate data on office visits, diagnoses, and issued prescriptions were collected from each practice’s electronic medical records based on monthly reports.ResultsOverall, 3581 prescriptions were issued: 1717 before and 1864 after the intervention. The total number of prescriptions increased by 8.5%. The use of first-line antibiotics increased by 21.2%, the use of fluoroquinolones decreased by 6.6%, while the use of beta-lactams remained unchanged. After the intervention, nitrofurantoin was the most prescribed first-line antibiotic. The proportion of women who were prescribed first-line antibiotic did not reach the acceptable range (80%-100%) according to the European Surveillance of Antimicrobial Consumption quality indicators. The proportion of fluoroquinolones (17.9%) use was well above the acceptable range (0%-5%).ConclusionA brief educational intervention proved to be a useful method in adopting better prescribing habits. Of particular importance is the considerable increase in the use of nitrofurantoin due to its reliable efficacy against multidrug-resistant urinary pathogens.

1135. The Effect of Penicillin Allergy Labels on Antibiotic Prescribing for Children Diagnosed with Upper Respiratory Tract Infections in Two Primary Care Networks

BackgroundIn pediatric inpatient settings, unconfirmed penicillin allergy labels (PALs) are associated with increased broad-spectrum antibiotic use, costs, and adverse events. However, 90% of antibiotics are prescribed in the outpatient setting and 70% of these antibiotics are given for upper respiratory tract infections (URTI.) Little is known about the effect of PALs on antibiotic prescribing in the pediatric outpatient population.MethodsA retrospective birth cohort was created of children born between January 1st 2010 and June 30th 2020 and seen at one of 91 Texas Children’s Pediatrics or Children’s Hospital of Philadelphia primary care clinics. Children with an ICD10 code for an URTI and an antibiotic prescription were stratified into those with or without a penicillin allergy label at the time of the infection. Rates of second-line and broad-spectrum antibiotic use were compared.ResultsThe birth cohort included 334,465 children followed for 1.2 million person-years. An antibiotic was prescribed for 696,782 URTIs and the most common diagnosis was acute otitis media. Children with PALs were significantly more likely to receive second-line antibiotics (OR 35.0, 95% CI 33.9-36.1) and broad-spectrum antibiotics (OR 23.9, 95% CI 23.2-24.8.) Children with PALs received more third generation cephalosporins (60% vs. 15%) and more macrolide antibiotics (25% vs. 3%) than those without a PAL. Overall, 18,015 children (5.4%) acquired a PAL during the study period, which accounted for 23% of all second-line antibiotic prescriptions and 17% of all broad-spectrum antibiotic use for URTIs. Multivariable logistic regression for receipt of second-line antibiotics for upper respiratory tract infections ConclusionPALs are common and account for a substantial proportion of second-line and broad-spectrum antibiotic use in pediatric outpatients treated for URTIs. Efforts to de-label children with PALs are likely to increase first-line antibiotic use and decrease broad-spectrum antibiotic use for URTIs, the most common indication for antibiotic prescribing to children.Disclosures Debra Palazzi, MD, MEd, AAP (Other Financial or Material Support, PREP ID Editorial Board, PREP ID Course)AHRQ (Research Grant or Support)Elsevier (Other Financial or Material Support, Royalties for writing and editing chapters)JAMA Pediatrics (Board Member)

Anatomy of a successful stewardship intervention: Improving perioperative prescribing in penicillin-allergic patients.

To evaluate whether a series of quality improvement interventions to promote safe perioperative use of cephalosporins in penicillin-allergic patients improved use of first-line antibiotics and decreased costs. Before-and-after trial following several educational interventions. Academic medical center. This study included patients undergoing a surgical procedure involving receipt of a perioperative antibiotic other than a penicillin or carbapenem between January 1, 2017, and August 31, 2019. Patients with and without a penicillin allergy label in their electronic medical record were compared with respect to the percentage who received a cephalosporin and average antibiotic cost per patient. A multidisciplinary team from infectious diseases, allergy, anesthesiology, surgery, and pharmacy surveyed anesthesiology providers about their use of perioperative cephalosporins in penicillin-allergic patients. Using findings from that survey, the team designed a decision-support algorithm for safe utilization and provided 2 educational forums to introduce this algorithm, emphasizing the safety of cefazolin or cefuroxime in penicillin-allergic patients without history of a severe delayed hypersensitivity reaction. The percentage of penicillin-allergic patients receiving a perioperative cephalosporin improved from ∼34% to >80% following algorithm implementation and the associated educational interventions. This increase in cephalosporin use was associated with a ∼50% reduction in antibiotic cost per penicillin-allergic patient. No significant adverse reactions were reported. An educational antibiotic stewardship intervention produced a significant change in clinician behavior. A simple intervention can have a significant impact, although further study is needed regarding whether this response is sustained and whether an educational intervention is similarly effective in other healthcare systems.

Enabling antibiotic allergy evaluations and reintroduction of first-line antibiotics for patients with cystic fibrosis

BackgroundPatients with cystic fibrosis (CF) often have a history of antibiotic adverse drug reactions (ADRs) that pose a barrier to receiving recommended first-line treatment. Targeted antibiotic allergy evaluations are increasingly recognized as an important strategy for optimization of antimicrobial stewardship. ObjectiveTo improve first-line antibiotic use in patients with CF with antibiotic ADRs by streamlining access to antibiotic allergy evaluations and standardizing documentation of plans for antibiotic reintroduction. MethodsWe incorporated allergy evaluations into a multidisciplinary CF clinic and used telemedicine when allergy evaluations could not be performed during CF clinic. Standard documentation of antibiotic allergy plans was used to enable safe reintroduction of first-line antibiotics by CF providers. ResultsStrategies used in this study allowed 81.3% (26 of 32) of patients with CF to receive allergy evaluations and antibiotic allergy plans for prioritized antibiotics (penicillin, cephalosporin, sulfonamide), with removal of 41.0% (16 of 39) of prioritized antibiotic ADRs. Only 5.1% (2 of 39) of prioritized antibiotic ADRs evaluated required strict avoidance after evaluation. There were 9 patients who received at least 1 prioritized antibiotic, with 66.6% (6 of 9) of these patients given the antibiotic after only 1 allergy evaluation visit. Furthermore, these strategies allowed allergy evaluations of 23 nonprioritized antibiotics to occur, with removal of the ADR in 39.1% (9 of 23) and use of 77.8% (7 of 9) of nonprioritized antibiotics after removal. ConclusionIncorporating allergy evaluations into a multidisciplinary CF clinic can liberalize first-line antibiotic use in patients with CF. Standard documentation of antibiotic allergy plans allowed antibiotic reintroduction to occur even before complete removal of documented antibiotic ADRs.

A Learning Collaborative to Improve Antibiotic Prescribing in Primary Care Pediatric Practices.

An American Academy of Pediatrics State Chapter organized a 6-month, mostly online quality improvement learning collaborative to improve antibiotic prescribing and patient education for upper respiratory infection (URI) and acute otitis media (AOM). Practices submitted data on quality measures at baseline, monthly, and 4 months post-project. Fifty-three clinicians from 6 independent, private primary care pediatric practices participated. Use of first-line antibiotics for AOM increased from 63.5% at baseline to 80.4% 4 months post-project. Use of safety-net antibiotic prescriptions (SNAP) for AOM increased from 4.5% to 16.9%. Educating patients about management for URI increased from 66.1% to 88.0% and for AOM from 20.4% to 85.6%. Practices maintained high performance for not prescribing antibiotics for URI (94.4% to 96.2%). Leveraging local relationships and national resources, this replicable antibiotic stewardship project engaged independent private practices to improve patient education for URI and AOM and prescribing and use of SNAP for AOM.

Evaluation of the Quality of Antibiotic Prescribing in Primary Care: A Multicenter Longitudinal Study From Shenzhen, China.

Background: Currently, there is no comprehensive evaluation of the quality of antibiotic prescribing in China’s primary care facilities based on longitudinal data. Methods: We randomly selected 11 community health centers in Shenzhen, China, and collected all outpatient prescriptions of these centers from 2010 to 2015. To evaluate the quality of antibiotic prescribing, we used six quality indicators for analysis, including number of antibiotics per 100 consultations, ratio between broad-spectrum and narrow-spectrum antibiotics (B/N ratio), percentage of first-line antibiotics recommended by guidelines, percentage of oral antibiotics with a duration exceeding the guideline recommendation, and new pediatric-specific indicators such as percentage of antibiotics with amoxicillin (A index) and ratio between amoxicillin and broad-spectrum antibiotics (A/B ratio). Results: During the study period, 571,362 outpatient consultations resulted in antibiotic prescriptions, which contained 706,411 antibiotics. The overall number of antibiotics per 100 consultations decreased significantly from 93.50 in 2010 to 19.98 in 2015 (p = 0.004), but the B/N ratio showed an upward trend over time (p = 0.009). In different populations and different common infections, the number of antibiotics used decreased to varying degrees, while the B/N ratio increased to varying degrees, with the most obvious change in children <5 years. The percentage of first-line antibiotics for common infections was not high, ranging from 3.45 to 44.25% during 2014–2015. The percentage of oral antibiotics with an exceeded duration ranged from 0.70 to 19.39%. Moreover, the A index and A/B ratio in children remained low for a long time, which was 0.76% and 0.01 in 2015. Conclusion: A review of antibiotic prescribing in Shenzhen, China, showed a substantial reduction in antibiotic use in primary care. However, problems such as widespread use of broad-spectrum antibiotics, insufficient use of first-line antibiotics and low use of amoxicillin were prevalent. Improving and optimizing the quality of antibiotic prescribing, particularly in children prescriptions, will be the focus of future antibiotic stewardship in China.

785. Association between Prevalence of Laboratory-Identified Clostridioides difficile Infections (CDIs) and CDI Antibiotic Treatment in U.S. Acute Care Hospitals, 2018

Background Clostridioides difficile infections (CDIs) are an urgent public health threat, accounting for 223,900 infections and 12,800 deaths in hospitalized patients annually. In early 2018, the Infectious Disease Society of America (IDSA) recommended oral vancomycin or fidaxomicin as the first-line antibiotics for CDIs. To track the uptake of IDSA’s recommendations, we evaluated the association between CDI prevalence and use of first-line antibiotics in hospitals reporting to the Centers for Disease Control and Prevention’s (CDC’s) National Healthcare Safety Network (NHSN).MethodsWe matched 2018 hospital-level, NHSN data on laboratory-identified CDIs with NHSN antimicrobial use (AU) data for the same time period. Hospitals that submitted < 6 months of either data type in 2018 were excluded. The association between quarterly hospital-level CDI prevalence rates per 100 patient-admissions and use of CDI antibiotics (oral vancomycin plus fidaxomicin) per 1,000 days-present was evaluated using Pearson’s linear correlation coefficient and using Goodman and Kruskal’s gamma (G) on ordinal quartiles to assess rates of discordant pairs.ResultsAmong the 2735 hospital-level quarters based on 714 hospitals included in the study, CDI prevalence (median: 0.46 per 100 patient-admissions) and CDI antibiotic use (median: 8.85 antibiotic-days per 1,000 days-present) demonstrated only a moderately positive correlation (r = 0.48). Among hospitals in the highest quartile for CDI prevalence, 5.1% were in the lowest quartile for antibiotic use. Among hospitals in the highest quartile for antibiotic use, 5.3% were in the lowest quartile for CDI prevalence, and 54.2% were in the highest quartile for CDI prevalence (G = 0.60; 95% CI: 0.57–0.63).Correlation of hospital-level Clostridioides difficile infection (CDI) prevalence rates and oral vancomycin and fidaxomicin use in U.S. acute care hospitals, 2018 Distribution of hospital-level Clostridioides difficile infection (CDI) prevalence rates and oral vancomycin and fidaxomicin use in ordinal quartiles (Q1–Q4) to access rates of discordant pairs ConclusionThe moderate correlation and discordant rates suggest that vancomycin and fidaxomicin are less frequently used as primary antibiotics in some hospitals; whereas in others, CDI antibiotic use is occurring in the absence of positive laboratory tests for CDI. To further investigate this discordance, there is a need to assess hospitals’ prescribing and testing practices in an ongoing manner. These findings may be useful to serve as baseline for measuring progress of appropriateness of treatment and testing for CDIs.Disclosures All Authors: No reported disclosures

126. Implementation of the core elements of an outpatient antimicrobial stewardship program in pediatric emergency departments and urgent care clinics

BackgroundWe used the Center for Disease Control and Prevention’s 4 core elements (commitment, action for policy and practice, tracking and reporting, education and expertise) to establish an outpatient antibiotic stewardship program (ASP) in 2 pediatric emergency departments (EDs) and 3 urgent care clinics (UCCs) of a healthcare system.MethodsThe outpatient ASP team consists of infectious diseases (ID) physicians, a pharmacist, and data analyst collaborating with ED and UCC providers. We placed a commitment letter in every exam room. We coach and support frontline providers to lead and sustain quality improvement (QI) projects. A monthly report evaluates rates of antibiotic use for viral infections and first-line antibiotic use for bacterial infections. We also compare rates of respiratory diagnoses and overall antibiotic use for all respiratory infections among the different sites. We developed an outpatient antibiotic handbook summarizing diagnosis and treatment recommendations for commonly encountered infections. Progress on prescribing trends and positive reinforcement are shared with providers during cookie rounds at bi-annual division meetings. We provide lectures, workshops, and newsletter articles on wise use of antibiotics.ResultsPre-implementation data showed < 5% antibiotic use for common pediatric viral infections and >85% use of first-line antibiotics for common bacterial infections. Trends in the report help us identify site-specific improvement opportunities we are working with frontline providers on addressing. In 2 years, our QI efforts have resulted in an increase in safety-net antibiotic prescriptions for acute otitis media in the EDs from 0.4% to over 7.5%, and a decrease in the percentage of rapid streptococcal testing performed in children < 3years old from 13% to 5% in one UCC (Figure 1). We have completed 15 cookie rounds attended by all ED/UCC core providers. In a survey completed by 61 providers, 85% found the handbook to be very beneficial, and 97% report it impacts their daily practice (Table 1).Figure 1: Annotated control charts of 2 quality improvement projects. A. Increase in safety-net antibiotic prescriptions offered to children diagnosed with acute otitis media in the emergency department. B. decrease in the percentage of streptococcal rapid antigen detection tests performed on children younger than 3 years of age in one urgent care clinic ConclusionSeeking leadership support and most importantly engaging frontline providers allowed us to be successful in implementing the suggested core elements of an outpatient ASP and maximize existing resources.Disclosures Brian R. Lee, MPH, PhD, Merck (Grant/Research Support)

Multi-Label Random Forest Model for Tuberculosis Drug Resistance Classification and Mutation Ranking.

Resistance prediction and mutation ranking are important tasks in the analysis of Tuberculosis sequence data. Due to standard regimens for the use of first-line antibiotics, resistance co-occurrence, in which samples are resistant to multiple drugs, is common. Analysing all drugs simultaneously should therefore enable patterns reflecting resistance co-occurrence to be exploited for resistance prediction. Here, multi-label random forest (MLRF) models are compared with single-label random forest (SLRF) for both predicting phenotypic resistance from whole genome sequences and identifying important mutations for better prediction of four first-line drugs in a dataset of 13402 Mycobacterium tuberculosis isolates. Results confirmed that MLRFs can improve performance compared to conventional clinical methods (by 18.10%) and SLRFs (by 0.91%). In addition, we identified a list of candidate mutations that are important for resistance prediction or that are related to resistance co-occurrence. Moreover, we found that retraining our analysis to a subset of top-ranked mutations was sufficient to achieve satisfactory performance. The source code can be found at http://www.robots.ox.ac.uk/~davidc/code.php.

Improving Antibiotic Prescribing for Pediatric Urinary Tract Infections in Outpatient Settings

To determine if a multicomponent intervention was associated with increased use of first-line antibiotics (cephalexin or sulfamethoxazole and trimethoprim) among children with uncomplicated urinary tract infections (UTIs) in outpatient settings. The study was conducted at Kaiser Permanente Colorado, a large health care organization with ∼127 000 members <18 years of age. After conducting a gap analysis, an intervention was developed to target key drivers of antibiotic prescribing for pediatric UTIs. Intervention activities included development of new local clinical guidelines, a live case-based educational session, pre- and postsession e-mailed knowledge assessments, and a new UTI-specific order set within the electronic health record. Most activities were implemented on April 26, 2017. The study design was an interrupted time series comparing antibiotic prescribing for UTIs before versus after the implementation date. Infants <60 days old and children with complex urologic or neurologic conditions were excluded. During January 2014 to September 2018, 2142 incident outpatient UTIs were identified (1636 preintervention and 506 postintervention). Pyelonephritis was diagnosed for 7.6% of cases. Adjusted for clustering of UTIs within clinicians, the proportion of UTIs treated with first-line antibiotics increased from 43.4% preintervention to 62.4% postintervention (P < .0001). The use of cephalexin (first-line, narrow spectrum) increased from 28.9% preintervention to 53.0% postintervention (P < .0001). The use of cefixime (second-line, broad spectrum) decreased from 17.3% preintervention to 2.6% postintervention (P < .0001). Changes in prescribing practices persisted through the end of the study period. A multicomponent intervention with educational and process-improvement elements was associated with a sustained change in antibiotic prescribing for uncomplicated pediatric UTIs.

Knowledge and Practice Discordance in Treating Urinary Tract Infections.

Urinary tract infections (UTIs) are a common condition in women. Guidelines have been published on the diagnosis and management of such infections with the twin goals of improved patient safety and avoiding unnecessary health care costs. In this study we evaluated both physicians' knowledge of these guidelines, and whether that knowledge translates to their clinical practice. We performed a retrospective chart review of UTI management before and after an educational intervention in a family medicine residency. Two control sites were also included. We also assessed physicians' knowledge of current UTI management guidelines using an anonymous quiz. At the intervention site, guideline adherence improved following the educational session. Inappropriate culture use decreased from 88% to 68% (P<.005) while first-line antibiotic use increased from 68% to 92% (P<.005). No such benefits were seen at the control sites. The control and intervention site providers did not differ in knowledge of antibiotic choice on the quiz (86% and 88% correct respectively, P=.85), but all control providers felt routine cultures were appropriate, whereas only 38% of the intervention providers did (P<.05). A simple educational intervention made an impact on the management of UTI. Our results also highlighted that knowledge and practice are not always aligned.

Cross-sectional survey on the use and impact of the Danish national antibiotic use guidelines for companion animal practice

BackgroundThe Danish antibiotic use guidelines for companion animal practice were published by the Danish Veterinary Association in 2012. Since then, national surveillance data indicate a 10% reduction in the total use of antibiotics for companion animals, particularly a marked reduction in the use of third generation cephalosporins. The aim of the study was to assess if and how the guidelines have impacted diagnostic and antibiotic prescription habits of the users, and to identify user perceived barriers to implementation.ResultsAn online questionnaire was sent to all 882 members of the Danish Small Animal Veterinary Association in October 2015. The survey was completed by 151 veterinarians. Respondents most frequently consulted the recommendations on skin and urinary tract infections (UTI), and users generally reported a high degree of adherence to the recommendations. Sixty-five per cent indicated that the guidelines had influenced their habits in one or more of the areas being investigated, i.e. perioperative use of antibiotics, use of first line antibiotics for the treatment of pyoderma or UTI, and/or use of microbiological diagnostics. Perioperative use of antibiotics for clean surgeries was uncommon, irrespective of whether respondents had consulted the relevant recommendations or not. On the contrary, significant differences in the prescribing habits between guideline users and non-users were observed for pyoderma and UTI, suggesting an impact of the guidelines towards more prudent antimicrobial use. The diagnostic habits were examined in a subgroup of 63 guideline users. Of those, 19 and 39% reported frequent use of culture and susceptibility (C&S) testing prior to treating pyoderma and UTI respectively, whereas 68–84% reported C&S testing in the event of poor response to treatment or recurrence of infections. The main barriers for implementation of therapeutic recommendations were confidence in old prescribing practices and unavailability of recommended drugs. The main barriers for C&S testing were good experience with empiric treatment, and the owners’ financial situation.ConclusionsThe findings suggest a positive influence of the national antibiotic guidelines on prescription patterns among companion animal practitioners in Denmark. Sustained campaign activity is encouraged and should include promotion of bacteriological testing.

Antibiotic susceptibility pattern of Salmonella enterica serovar typhi and Salmonella enterica serovar paratyphi A with special reference to quinolone resistance

Background and Objectives: Typhoid fever is endemic in India. Extensive use of first-line antibiotics has led to the emergence of multi-drug resistant (MDR) Salmonella typhi. Ciprofloxacin has become empirical therapy of choice against MDR salmonellae. Recent year's emergence of low-level ciprofloxacin resistance in salmonellae resulted in delayed response and serious complications. Nalidixic acid (NA) screen test is used as surrogate marker for detection low-level ciprofloxacin resistance. In this study, we evaluated prevalence of MDR and low-level ciprofloxacin resistant S. typhi and Salmonella paratyphi A. Materials and Methods: A total of 50 blood culture isolates of S. typhi and S. paratyphi A were tested for antibiotic susceptibility according to Clinical Laboratory Standards Institute (CLSI) method. Minimal inhibitory concentration (MIC) to ciprofloxacin was carried out by E-test and agar dilution method. Results: Among the 50 salmonella isolates, 80% were S. typhi and 20% were S. paratyphi A. MDR was found in 2% S. typhi. NA resistant salmonellae showed ciprofloxacin MIC ranging from 0.25 to 0.75 μg/ml. One isolate of S. typhi showed ciprofloxacin MIC of 32 μg/ml and was also resistant to ceftriaxone. NA screen test for low-level ciprofloxacin resistance was 100% sensitive and 97.9% specific. Interpretation and Conclusion: NA resistant isolates should be tested for ciprofloxacin MIC to decide therapeutic options. The current CLSI breakpoints may have to be re-evaluated for salmonellae.

Ligand efficiency driven design of new inhibitors of Mycobacterium tuberculosis transcriptional repressor EthR using fragment growing, merging, and linking approaches.

Tuberculosis remains a major cause of mortality and morbidity, killing each year more than one million people. Although the combined use of first line antibiotics (isoniazid, rifampicin, pyrazinamide, and ethambutol) is efficient to treat most patients, the rapid emergence of multidrug resistant strains of Mycobacterium tuberculosis stresses the need for alternative therapies. Mycobacterial transcriptional repressor EthR is a key player in the control of second-line drugs bioactivation such as ethionamide and has been shown to impair the sensitivity of the human pathogen Mycobacterium tuberculosis to this antibiotic. As a way to identify new potent ligands of this protein, we have developed fragment-based approaches. In the current study, we combined surface plasmon resonance assay, X-ray crystallography, and ligand efficiency driven design for the rapid discovery and optimization of new chemotypes of EthR ligands starting from a fragment. The design, synthesis, and in vitro and ex vivo activities of these compounds will be discussed.

Antibiotic prescribing for adults with acute cough/lower respiratory tract infection: congruence with guidelines

European guidelines for treating acute cough/lower respiratory tract infection (LRTI) aim to reduce nonevidence-based variation in prescribing, and better target and increase the use of first-line antibiotics. However, their application in primary care is unknown. We explored congruence of both antibiotic prescribing and antibiotic choice with European Respiratory Society (ERS)/European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for managing LRTI. The present study was an analysis of prospective observational data from patients presenting to primary care with acute cough/LRTI. Clinicians recorded symptoms on presentation, and their examination and management. Patients were followed up with self-complete diaries. 1,776 (52.7%) patients were prescribed antibiotics. Given patients' clinical presentation, clinicians could have justified an antibiotic prescription for 1,915 (71.2%) patients according to the ERS/ESCMID guidelines. 761 (42.8%) of those who were prescribed antibiotics received a first-choice antibiotic (i.e. tetracycline or amoxicillin). Ciprofloxacin was prescribed for 37 (2.1%) and cephalosporins for 117 (6.6%). A lack of specificity in definitions in the ERS/ESCMID guidelines could have enabled clinicians to justify a higher rate of antibiotic prescription. More studies are needed to produce specific clinical definitions and indications for treatment. First-choice antibiotics were prescribed to the minority of patients who received an antibiotic prescription.

Report of oral clarithromycin desensitization

Antibiotic hypersensitivity can lead to significant morbidity, mortality and suboptimal treatment options. Rapid desensitization induces temporary immunological tolerance in a host with type 1 hypersensitivity reaction. We report a case of oral desensitization to clarithromycin. To our knowledge, this is the first protocol published for desensitization to macrolides. A 68-year-old female with a history of giant cell arteritis treated with oral corticosteroids and steroid-induced diabetes presented with small nodules and ulcers on the pre-tibial surface of her legs. Despite multiple courses of oral and parenteral antibiotics for cellulitis, the lesions continued to develop. Skin biopsy of the lesion demonstrated suppurative granuloma formation with acid-fast bacilli on microscopy. The patient reported anaphylaxis to erythromycin 20 years previously and bronchospasm to roxithromycin 5 years previously. She was commenced on rifampicin and moxifloxacin for mycobacterial skin infection, and Mycobacterium chelonaewas subsequently cultured. There was further clinical deterioration and her treatment was changed to doxycycline, intravenous amikacin and intravenous imipenem. Antibiotic susceptibility testing subsequently revealed the isolate was resistant to imipenem, so this was substituted with linezolid. Unfortunately, this was discontinued due to diarrhoea. Intravenous amikacin was not desired as a long-term treatment option due to risk of renal and ototoxicity. Clarithromycin is the treatment of choice for M. chelonae infection [1], but the patient had a strong history of type 1 hypersensitivity with macrolide antibiotics. No published protocol for rapid drug desensitization was available for clarithromycin, so a clarithromycin desensitization protocol was developed (Table 1). The protocol was administered in an intensive care unit with careful observation on a medical ward for 36 h afterwards. No adverse reaction was noted. Table 1 Oral clarithromycin desensitization protocol The patient continued doxycycline and clarithromycin for a total of 18 months. There was an excellent clinical response and no adverse drug reactions were recorded. Serious adverse drug reactions occur in 6.7% of hospitalized patients and rank from the fourth to sixth leading cause of death in these patients [2]. Since 1998 there has been a 2.6-fold increase in serious adverse drug reactions reported to the US Food and Drug Administration [3]. Type 1 (immediate) hypersensitivity reactions occur within minutes to hours of drug administration due to release of vasoactive substances from mast cells and basophils (often IgE-mediated). Clinical manifestations range from urticaria to life-threatening angio-oedema and anaphylaxis. Desensitization procedures were first developed in the 1960s [4]. Rapid desensitization involves incremental exposure to drug antigens at increasing concentrations leading to a therapeutic dose. Antigen-specific mast cell desensitization is thought to be the underlying mechanism for drug desensitization [5]. By inducing temporary clinical and immunological tolerance, patients are able to receive optimal treatment while avoiding or minimizing anaphylaxis and anaphylactoid reactions. Tolerance is maintained only if drug antigens are administered at regular intervals, and repeated desensitizations can also be given [6]. Desensitization protocols have been developed for a variety of drugs including penicillins, cephalosporins, vancomycin, sulfonamides, rifampicin, nonsteroidal anti-inflammatory drugs and chemotherapeutic agents (taxanes, platins). As specific skin prick testing to clarithromycin was not performed in our patient, we cannot be certain that an immediate hypersensitivity reaction would have occurred. However, given her previous immediate hypersensitivity reactions to other 14-membered macrolides erythromycin and roxithromycin, we felt that desensitization to clarithromycin was warranted. Skin prick testing has been well described for penicillins and cephalosporins, and is considered accurate for diagnosing penicillin allergy, as antigenic determinants have been well characterized [7]. Cross-sensitivity within the same antibiotic class is variable, however. There is little information available for diagnostic tests for macrolide allergy, as immediate hypersensitivity reactions are uncommon [8]. A patient in the literature with roxithromycin immediate hypersensitivity demonstrated positive skin prick testing to erythromycin and clarithromycin [9]. These macrolides have a similar chemical structure comprising a 14-membered carbon ring, compared with 15-membered macrolides (azithromycin) and 16-membered macrolides (spiramycin). Use of first-line antibiotics in certain conditions have been shown to have greater efficacy, for example trimethoprim + sulfamethoxazole for Pneumocystis jiroveci pneumonia [10, 11] or penicillin for syphilis, especially in HIV-infected individuals [12]. Macrolide antibiotics have an important role in the treatment of nontuberculous mycobacterial infections [13]. In our case report clarithromycin was a desirable treatment option, and rapid oral desensitization to clarithromycin was successful with no adverse events reported. We believe this is the first published protocol for desensitization to macrolide antibiotics and anticipate that its use can be extended to other centres worldwide.