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Importance: In the US, 50% of all pediatric outpatient antibiotics prescribed are unnecessary or inappropriate. Less is known about the appropriateness of pediatric outpatient antibiotic prescribing., Objective: To identify the overall percentage of outpatient antibiotic prescriptions that are optimal according to guideline recommendations for first-line antibiotic choice and duration., Design, Setting, and Participants: This cross-sectional study obtained data on any clinical encounter for a patient younger than 20 years with at least 1 outpatient oral antibiotic, intramuscular ceftriaxone, or penicillin prescription filled in the state of Tennessee from January 1 to December 31, 2022, from IQVIA's Longitudinal Prescription Claims and Medical Claims databases. Each clinical encounter was assigned a single diagnosis corresponding to the lowest applicable tier in a 3-tier antibiotic tier system. Antibiotics prescribed for tier 1 (nearly always required) or tier 2 (sometimes required) diagnoses were compared with published national guidelines. Antibiotics prescribed for tier 3 (rarely ever required) diagnoses were considered to be suboptimal for both choice and duration., Main Outcomes and Measures: Primary outcome was the percentage of optimal antibiotic prescriptions consistent with guideline recommendations for first-line antibiotic choice and duration. Secondary outcomes were the associations of optimal prescribing by diagnosis, suboptimal antibiotic choice, and patient- and clinician-level factors (ie, age and Social Vulnerability Index) with optimal antibiotic choice, which were measured by odds ratios (ORs) and 95% CIs calculated using a multivariable logistic regression model., Results: A total of 506 633 antibiotics were prescribed in 488 818 clinical encounters (for 247 843 females [50.7%]; mean [SD] age, 8.36 [5.5] years). Of these antibiotics, 21 055 (4.2%) were for tier 1 diagnoses, 288 044 (56.9%) for tier 2 diagnoses, and 197 660 (39.0%) for tier 3 diagnoses. Additionally, 194 906 antibiotics (38.5%) were optimal for antibiotic choice, 259 786 (51.3%) for duration, and 159 050 (31.4%) for both choice and duration. Acute otitis media (AOM) and pharyngitis were the most common indications, with 85 635 of 127 312 (67.3%) clinical encounters for AOM and 42 969 of 76 865 (55.9%) clinical encounters for pharyngitis being optimal for antibiotic choice. Only 257 of 4472 (5.7%) antibiotics prescribed for community-acquired pneumonia had a 5-day duration. Optimal antibiotic choice was more likely in patients who were younger (OR, 0.98; 95% CI, 0.98-0.98) and were less socially vulnerable (OR, 0.84; 95% CI, 0.82-0.86)., Conclusions and Relevance: This cross-sectional study found that less than one-third of antibiotics prescribed to pediatric outpatients in Tennessee were optimal for choice and duration. Four stewardship interventions may be targeted: (1) reduce the number of prescriptions for tier 3 diagnoses, (2) increase optimal prescribing for AOM and pharyngitis, (3) provide clinician education on shorter antibiotic treatment courses for community-acquired pneumonia, and (4) promote optimal antibiotic prescribing in resource-limited settings.

Antimicrobial resistance is a global public health threat. Antimicrobial-resistant infections are on the rise and are associated with increased morbidity, mortality, and health care costs. Infants and children are affected by transmission of antimicrobial-resistant zoonotic pathogens through the food supply, direct contact with animals, environmental pathways, and contact with infected or colonized humans. Although the judicious use of antimicrobial agents is necessary for maintaining the health and welfare of humans and animals, it must be recognized that all use of antimicrobial agents exerts selective pressure that increases the risk of development of resistance. This report describes historical and recent use of antibiotics in animal agriculture, reviews the mechanisms of how such use contributes to development of resistance and can adversely affect child health, and discusses US initiatives to curb unnecessary use of antimicrobial agents in agriculture., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: Acute otitis media (AOM) accounts for roughly 25% of antibiotics prescribed to children annually. Despite national guidelines that recommend short (5-7 days) durations of antibiotics for children 2 years and older with AOM, most receive long (10 day) courses. This study aims to evaluate antibiotic durations prescribed for children aged 2-17 years with uncomplicated AOM across two pediatric academic health systems, and to assess the variability in prescribed durations between and within each system., Methods: Electronic medical record data from 135 care locations at two health systems were retrospectively analyzed. Outpatient encounters for children aged 2-17 years with a diagnosis of AOM from 2019 to 2022 were included. The primary outcome was the percent of 5-day prescriptions. Secondary outcomes included the proportion of 7-day prescriptions, 10-day prescriptions, prescriptions for nonfirst-line antibiotics, cases associated with treatment failure, AOM recurrence, and adverse drug events., Results: Among 73 198 AOM encounters for children 2 years and older, 61 612 (84%) encounters resulted in an antibiotic prescription. Most prescriptions were for 10 days (45 689; 75%), 20% were for 7 days (12 060), and only 5% were for 5 days (3144). Treatment failure, AOM recurrence, adverse drug events, hospitalizations, and office, emergency department or urgent-care visits for AOM within 30 days after the index visit were rare., Conclusions: Despite national guidelines that recommend shorter durations for children with uncomplicated AOM, 75% of our cohort received 10-day durations. Shortening durations of therapy for AOM could reduce antibiotic exposure and should be a priority of pediatric antibiotic stewardship programs., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

Antibiotics are widely used in neonatal intensive care units (NICUs). We conducted a cross-sectional analysis of antibiotic use across US NICUs to evaluate overall, broad-spectrum, and combination antibiotic use. Patterns of antibiotic use varied by medical versus surgical service line, hospital, and geographic location.

Background: The utility of procalcitonin testing in the pediatric intensive care unit (PICU) is not known. We sought to determine the impact of a procalcitonin-guided antibiotic treatment algorithm implemented with antibiotic stewardship (AS) guidance vs. usual care on antibiotic use in critically ill children., Methods: Single center, pragmatic, randomized prospective clinical trial of critically ill children admitted to an ICU setting and started on intravenous antibiotics from February 15, 2018, to April 11, 2019. Patients were assigned on a monthly basis to either the procalcitonin or usual care arm. The procalcitonin arm had procalcitonin testing on hospital days 0, 1, 2, and 4 and stewardship assistance with algorithm result interpretation. Both arms had routine AS audit and feedback. The primary outcome was median antibiotic days of therapy per patient in the first 14-days after enrollment., Results: Among 270 patients, 137 were in the procalcitonin arm and 133 in the usual care arm. Antibiotic days of therapy (DOT) were not significantly different between the procalcitonin arm (6.6, IQR: 3.1-10.9) and the usual care arm (7.6, IQR: 3-11.8; P = 0.37). More AS recommendations were made in the procalcitonin vs. control arm (54 vs. 37; P = 0.03). Adherence with algorithm-based antibiotic recommendations was high in the procalcitonin arm (70%)., Conclusions: We found no difference in antibiotic DOT between study arms. This trial was underpowered but demonstrates feasibility of using a procalcitonin-guided antibiotic treatment algorithm with AS audit and feedback in the PICU., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Management of febrile pediatric patients with cancer with an absolute neutrophil count of 500/µL or greater is unclear. The Esbenshade Vanderbilt (EsVan) risk prediction models have been shown to predict bloodstream infection (BSI) likelihood in this population, and this study sought to prospectively validate and implement these models in clinical practice., Methods: Data were prospectively collected on febrile pediatric patients with cancer with a central venous catheter from April 2015 to August 2019 at a single site, at which the models (EsVan: 2015 to 2017; EsVan2: October 2017 to 2019) were initially developed and subsequently implemented for clinical management in well-appearing nonseverely neutropenic individuals. It was recommended that patients with low BSI risk (< 10%) be discharged home without antibiotics, those with intermediate BSI risk (10%-39.9%) be administered an antibiotic before discharge, and those with high BSI risk (> 40%) be admitted on broad-spectrum antibiotics. Seven-day outcomes were then collected and EsVan models were prospectively validated and C-statistics estimated., Results: In 937 febrile, nonsevere neutropenia episodes, frequencies of low-, intermediate-, and high-risk episodes were 88.9%, 8.6%, and 2.3% respectively. BSI incidence was 4.2% (39 of 937). Within risk groups, low-risk BSI incidence was 1.9% (16 of 834) with BSI incidence of 13.6% and 54.5% for intermediate- and high-risk episodes, respectively. Empirical intravenous antibiotics were administered in 21.1% of low-risk episodes at presentation and at 7 days postpresentation, 72.3% of episodes never required intravenous antibiotics. There were no deaths or clinical decompensations attributable to antibiotic delay. For BSI detection, EsVan and EsVan2 models applied to the new cohort achieved C-statistics of 0.802 and 0.824, respectively., Conclusion: Prospective, real-time clinical utilization of the EsVan models accurately predicts BSI risk and safely reduces unnecessary antibiotic use in febrile, nonseverely neutropenic pediatric patients with cancer.

Objective: To characterize the prevalence of and seasonal and regional variation in inpatient antibiotic use among hospitalized US children in 2017-2018., Design: We conducted a cross-sectional examination of hospitalized children. The assessments were conducted on a single day in spring (May 3, 2017), summer (August 2, 2017), fall (October 25, 2017), and winter (January 31, 2018). The main outcome of interest was receipt of an antibiotic on the study day., Setting: The study included 51 freestanding US children's hospitals that participate in the Pediatric Health Information System (PHIS)., Patients: This study included all patients <18 years old who were admitted to a participating PHIS hospital, excluding patients who were admitted solely for research purposes., Results: Of 52,769 total hospitalized children, 19,174 (36.3%) received antibiotics on the study day and 6,575 of these (12.5%) received broad-spectrum antibiotics. The overall prevalence of antibiotic use varied across hospitals from 22.3% to 51.9%. Antibiotic use prevalence was 29.2% among medical patients and 47.7% among surgical patients. Although there was no significant seasonal variation in antibiotic use prevalence, regional prevalence varied, ranging from 32.7% in the Midwest to 40.2% in the West (P < .001). Among units, pediatric intensive care unit patients had the highest prevalence of both overall and broad-spectrum antibiotic use at 58.3% and 26.6%, respectively (P < .001)., Conclusions: On any given day in a national network of children's hospitals, more than one-third of hospitalized children received an antibiotic, and 1 in 8 received a broad-spectrum antibiotic. Variation across hospitals, setting and regions identifies potential opportunities for enhanced antibiotic stewardship activities.

Background: While there is increasing knowledge about the gut microbiome, the factors influencing and the significance of the gut resistome are still not well understood. Infant gut commensals risk transferring multidrug-resistant antibiotic resistance genes (ARGs) to pathogenic bacteria. The rapid spread of multidrug-resistant pathogenic bacteria is a worldwide public health concern. Better understanding of the naïve infant gut resistome may build the evidence base for antimicrobial stewardship in both humans and in the food industry. Given the high carriage rate of extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in Asia, we aimed to evaluate community prevalence, dynamics, and longitudinal changes in antibiotic resistance gene (ARG) profiles and prevalence of ESBL-producing E. coli and K. pneumoniae in the intestinal microbiome of infants participating in the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, a longitudinal cohort study of pregnant women and their infants., Methods: We analysed ARGs in the first year of life among 75 infants at risk of eczema who had stool samples collected at multiple timepoints using metagenomics., Results: The mean number of ARGs per infant increased with age. The most common ARGs identified confer resistance to aminoglycoside, beta-lactam, macrolide and tetracycline antibiotics; all infants harboured these antibiotic resistance genes at some point in the first year of life. Few ARGs persisted throughout the first year of life. Beta-lactam resistant Escherichia coli and Klebsiella pneumoniae were detected in 4 (5.3%) and 32 (42.7%) of subjects respectively., Conclusion: In this longitudinal cohort study of infants living in a region with high endemic antibacterial resistance, we demonstrate that majority of the infants harboured several antibiotic resistance genes in their gut and showed that the infant gut resistome is diverse and dynamic over the first year of life.

Objective: To identify patient and provider characteristics associated with high-volume antibiotic prescribing for children in Tennessee, a state with high antibiotic utilization., Design: Cross-sectional, retrospective analysis of pediatric (aged <20 years) outpatient antibiotic prescriptions in Tennessee using the 2016 IQVIA Xponent (formerly QuintilesIMS) database., Methods: Patient and provider characteristics, including county of prescription fill, rural versus urban county classification, patient age group, provider type (nurse practitioner, physician assistant, physician, or dentist), physician specialty, and physician years of practice were analyzed., Results: Tennessee providers wrote 1,940,011 pediatric outpatient antibiotic prescriptions yielding an antibiotic prescribing rate of 1,165 per 1,000 population, 50% higher than the national pediatric antibiotic prescribing rate. Mean antibiotic prescribing rates varied greatly by county (range, 39-2,482 prescriptions per 1,000 population). Physicians wrote the greatest number of antibiotic prescriptions (1,043,030 prescriptions, 54%) of which 56% were written by general pediatricians. Pediatricians graduating from medical school prior to 2000 were significantly more likely than those graduating after 2000 to be high antibiotic prescribers. Overall, 360 providers (1.7% of the 21,798 total providers in this dataset) were responsible for nearly 25% of both overall and broad-spectrum antibiotic prescriptions; 20% of these providers practiced in a single county., Conclusions: Fewer than 2% of providers account for 25% of pediatric antibiotic prescriptions. High antibiotic prescribing for children in Tennessee is associated with specific patient and provider characteristics that can be used to design stewardship interventions targeted to the highest prescribing providers in specific counties and specialties.

Competing Interests: POTENTIAL CONFLICT OF INTEREST: Vizient pays Dr Fox’s affiliation, the University of Utah Drug Information Service, to provide them with drug shortage data; no funds are directly paid to Dr Fox; and Drs Banerjee, Thurm, and Hersh have indicated they have no potential conflicts of interest to disclose.

The prevalence of pediatric antimicrobial stewardship programs (ASPs) is increasing in acute care facilities across the United States. Over the past several years, the evidence base used to inform effective stewardship practices has expanded, and regulatory interest in stewardship programs has increased. Here, we review approaches for established, hospital-based pediatric ASPs to adapt and report standardized metrics, broaden their reach to specialized populations, expand to undertake novel stewardship initiatives, and implement rapid diagnostics to continue their evolution in improving antimicrobial use and patient outcomes.

Diagnostics are a cornerstone of the practice of infectious diseases. However, various limitations frequently lead to unmet clinical needs. In most other domains, diagnostics focus on narrowly defined questions, provide readily interpretable answers, and use true gold standards for development. In contrast, infectious diseases diagnostics must contend with scores of potential pathogens, dozens of clinical syndromes, emerging pathogens, rapid evolution of existing pathogens and their associated resistance mechanisms, and the absence of gold standards in many situations. In spite of these challenges, the importance and value of diagnostics cannot be underestimated. Therefore, the Antibacterial Resistance Leadership Group has identified diagnostics as 1 of 4 major areas of emphasis. Herein, we provide an overview of that development, highlighting several examples where innovation in study design, content, and execution is advancing the field of infectious diseases diagnostics., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Antibacterial resistance is increasing globally and has been recognized as a major public health threat. Antibacterial stewardship is the coordinated effort to improve the appropriate use of antibiotics with the aim to decrease selective pressure for multidrug-resistant organisms in order to preserve the utility of antibacterial agents. This article describes the activities of the Antibacterial Resistance Leadership Group (ARLG) in the area of antibacterial stewardship. To date, the ARLG has focused intensely on development of rapid diagnostic tests, which (when coupled with educational and institutional initiatives) will enable the robust stewardship that is needed to address the current crisis of antibacterial resistance. In addition to exploring the effectiveness of stewardship techniques in community hospitals, the ARLG has also developed strategy trials to assess the feasibility of reducing antibacterial usage while preserving patient outcome., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

We describe a 16-year-old neutropenic patient from the Middle East with bloodstream infection caused by two carbapenemase-producing Escherichia coli isolates that we characterized by whole-genome sequencing. While one displayed meropenem resistance and was blaNDM positive, the other demonstrated meropenem susceptibility yet harbored blaOXA181 (which encodes a blaOXA48-like enzyme). This report highlights the challenge of laboratory detection of blaOXA48-like enzymes and the clinical implications of genotypic resistance detection in carbapenemase-producing Enterobacteriaceae., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Background: The value of rapid, panel-based molecular diagnostics for positive blood culture bottles (BCBs) has not been rigorously assessed. We performed a prospective randomized controlled trial evaluating outcomes associated with rapid multiplex PCR (rmPCR) detection of bacteria, fungi, and resistance genes directly from positive BCBs., Methods: A total of 617 patients with positive BCBs underwent stratified randomization into 3 arms: standard BCB processing (control, n = 207), rmPCR reported with templated comments (rmPCR, n = 198), or rmPCR reported with templated comments and real-time audit and feedback of antimicrobial orders by an antimicrobial stewardship team (rmPCR/AS, n = 212). The primary outcome was antimicrobial therapy duration. Secondary outcomes were time to antimicrobial de-escalation or escalation, length of stay (LOS), mortality, and cost., Results: Time from BCB Gram stain to microorganism identification was shorter in the intervention group (1.3 hours) vs control (22.3 hours) (P < .001). Compared to the control group, both intervention groups had decreased broad-spectrum piperacillin-tazobactam (control 56 hours, rmPCR 44 hours, rmPCR/AS 45 hours; P = .01) and increased narrow-spectrum β-lactam (control 42 hours, rmPCR 71 hours, rmPCR/AS 85 hours; P = .04) use, and less treatment of contaminants (control 25%, rmPCR 11%, rmPCR/AS 8%; P = .015). Time from Gram stain to appropriate antimicrobial de-escalation or escalation was shortest in the rmPCR/AS group (de-escalation: rmPCR/AS 21 hours, control 34 hours, rmPCR 38 hours, P < .001; escalation: rmPCR/AS 5 hours, control 24 hours, rmPCR 6 hours, P = .04). Groups did not differ in mortality, LOS, or cost., Conclusions: rmPCR reported with templated comments reduced treatment of contaminants and use of broad-spectrum antimicrobials. Addition of antimicrobial stewardship enhanced antimicrobial de-escalation., Clinical Trials Registration: NCT01898208., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objective: To compare vancomycin serum trough concentrations and 24-hour area under the serum concentration-versus-time curve (AUC24) among very low-birth-weight (VLBW) premature infants before and after implementation of an institution-wide increase in neonatal vancomycin dosing., Study Design: We performed a retrospective analysis of vancomycin concentrations among preterm VLBW neonates before (2007-2010) and after (2010-2013) implementation of a new vancomycin dosing protocol consisting of increased vancomycin daily dose and frequency of administration., Results: Neonates weighing < 1,500 g and receiving the new vancomycin dosing regimen had lower rates of undetectable trough concentrations (24 vs. 50%, p = 0.04), higher median trough concentrations (10.8 vs. 5.9 µg/mL, p = 0.003), a higher proportion of goal trough concentrations of 10 to 20 µg/mL (35 vs. 4%, p = 0.005), and a significantly higher vancomycin AUC24 (438 vs. 320 mg·h/L, p = 0.004) compared with historical controls., Conclusion: Increasing the vancomycin daily dose and dosing frequency led to an increase in vancomycin trough concentrations and AUC24, and a decrease in the proportion of undetectable (< 5.0 µg/mL) troughs, without an increase in toxicity among VLBW premature neonates., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Vancomycin treatment failure has been associated with low serum vancomycin trough concentrations, prompting recommendations to increase the daily doses in adults and children. Despite more aggressive vancomycin dosing, there continues to be significant variability in vancomycin trough concentrations in pediatric patients., Methods: To determine if vancomycin trough concentrations in pediatric patients differ by age and weight, we reviewed records of hospitalized patients who received vancomycin between 2008 and 2012. Patients were divided into groups that received vancomycin 40 mg/kg/day (2008-2009) or 60 mg/kg/day (2010-2012). Vancomycin trough concentrations were compared between groups and within the 60 mg/kg/day group, stratified by patient age and weight., Results: After increasing the vancomycin dose from 40 to 60 mg/kg/day, initial trough concentrations increased significantly in patients younger than 2 and greater than 6 years of age, but not in patients between the ages of 2 and 5 years. In the 60 mg/kg/day group, only 16.7% of patients between 2 and 5 years of age had initial trough concentrations in the therapeutic range (10-20 μg/ml). Initial trough concentrations were therapeutic in a greater proportion of patients ages 6-12 years (38.7%) and 13-18 years (63.0%). Patients between the ages of 13 and 18 had the highest proportion of supratherapeutic initial vancomycin trough concentrations (14.8%). Patients weighing over 50 kg had significantly higher trough concentrations than patients  50 kg or less (17.1 μg/ml vs 9.3 μg/ml, p<0.001)., Conclusion: Although increasing the vancomycin dose from 40 to 60 mg/kg/day led to a significant increase in vancomycin trough concentrations, a large proportion of patients receiving 60 mg/kg/day of vancomycin had trough concentrations outside of the therapeutic range. Specifically, patients younger than 6 years tended to have low trough concentrations, whereas adolescents and children over 50 kg were more likely to have elevated trough concentrations. Vancomycin dosing strategies in pediatric patients should consider age and weight as well as renal function and indication., (© 2013 Pharmacotherapy Publications, Inc.)

Background: Use of outpatient parenteral antimicrobial therapy (OPAT) in pediatrics is widespread and may be increasing. Recent data quantifying use and characteristics of pediatric OPAT are lacking., Methods: To evaluate the number of children receiving OPAT each year and their associated characteristics and outcomes, we conducted a retrospective review of all patients discharged with OPAT from the Mayo Clinic Children's Hospital between August 1, 2010 and December 31, 2011., Results: During the study period, there were 126 pediatric hospital discharges with OPAT (2.5% of all discharges). OPAT was used most commonly to treat bone and joint (21%), bloodstream (15%), intra-abdominal (13%) and soft tissue (9%) infections. A positive culture or serology result was found in 86 (68%) OPAT courses. The most frequently used antibiotics were ceftriaxone (17%), cefazolin (16%) and cefepime (13%). The median duration of OPAT was 12 days. Thirty-six courses (29%) resulted in catheter- or antibiotic-associated complications. Weekly laboratory monitoring was more common when OPAT was managed by the infectious disease service (88%) versus other services (20%). Among 123 courses with follow-up, 109 (89%) resulted in cure, and 13 (11%) were treatment failures., Conclusion: At our children's hospital, 2.5% of hospitalized patients were discharged with OPAT. In one-third of OPAT courses children developed catheter- or antibiotic-associated complications. Opportunities to increase the role of pediatric infectious disease in OPAT initiation and management should be explored.

Background: A rapid increase in multidrug-resistant Gram-negative infections has led to a reemergence of colistin use globally. Although it is well described among adults, colistin use and its associated toxicities in children are poorly understood. We report findings from the largest case series of pediatric colistin use to date., Methods: We queried pediatric infectious diseases specialists from the Emerging Infections Network to identify members who had prescribed intravenous colistin within the past 7 years. We collected relevant demographic and clinical data. Bivariate analyses and multivariable logistic regression were performed., Results: Two hundred twenty-nine pediatric infectious diseases specialists completed the survey (84% response); 22% had prescribed colistin to children. Among respondents, 92 cases of colistin use from 25 institutions were submitted. The most commonly targeted organisms were multidrug-resistant Pseudomonas (67.4%), multidrug-resistant Acinetobacter -baumanii (11.9%), carbapenemase-producing Enterobacteriaceae (13.0%) and extended-spectrum β-lactamase producing Enterobacteriaceae (5.4%). Development of resistance to colistin was observed in 20.5% of patients. Additional antimicrobial therapy was administered to 84% of patients, and 22% of children experienced nephrotoxicity (not associated with dosage or interval of colistin prescribed). Renal function returned to baseline in all patients. Children aged ≥13 years had approximately 7 times the odds of developing nephrotoxicity than younger children, even after controlling for receipt of additional nephrotoxic agents (odds ratio 7.16; 95% confidence interval: 1.51-14.06; P = 0.013). Four children exhibited reversible neurotoxicity., Conclusions: Most pediatric infectious diseases specialists have no experience prescribing colistin. Colistin use in children has been associated primarily with nephrotoxicity and, to a lesser extent, neurotoxicity, both of which are reversible. Emergence of resistance to colistin is concerning.

Objective: To better understand the epidemiology of drug-resistant Escherichia coli across health care and community settings., Patients and Methods: We conducted a population-based cohort study of the incidence of antibiotic-resistant E coli bacteriuria among different patient groups. All urine cultures with monomicrobial growth of E coli obtained from Olmsted County, Minnesota, residents from January 1, 2005, through December 31, 2009, were identified. The initial isolate per patient per year was included. Analyses were stratified by patient age and location of infection onset (ie, nosocomial, health care associated, and community associated)., Results: We evaluated 5619 E coli isolates and the associated patients. During the study period, the incidence of drug-resistant bacteriuria did not change among children but increased significantly among adults of all ages, most markedly among elderly patients older than 80 years. In elderly patients, the incidence of bacteriuria with isolates resistant to fluoroquinolones increased from 464 to 1116 per 100,000 person-years (P<.001), and the incidence of bacteriuria with isolates resistant to fluoroquinolones plus trimethoprim-sulfamethoxazole increased from 274 to 512 per 100,000 person-years (P<.05). When analyzed by location of infection onset, incidence of bacteriuria with isolates resistant to trimethoprim-sulfamethoxazole, fluoroquinolones, trimethoprim-sulfamethoxazole plus fluoroquinolones, extended-spectrum cephalosporins, and more than 3 drug classes increased significantly among community-associated but not among nosocomial or health care-associated cases., Conclusion: In this population-based study, the incidence of antibiotic-resistant E coli bacteriuria nearly doubled during the 5-year study period among elderly patients and those with community-associated isolates. These patient groups should be targets of interventions to slow the emergence and spread of antibiotic-resistant E coli., (Copyright © 2012 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to beta-lactam antibiotics because it expresses penicillin-binding protein 2a (PBP2a), a low-affinity penicillin-binding protein. An investigational broad-spectrum cephalosporin, ceftobiprole (BPR), binds PBP2a with high affinity and is active against MRSA. We hypothesized that BPR resistance could be mediated by mutations in mecA, the gene encoding PBP2a. We selected BPR-resistant mutants by passage in high-volume broth cultures containing subinhibitory concentrations of BPR. We used strain COLnex (which lacks chromosomal mecA) transformed with pAW8 (a plasmid vector only), pYK20 (a plasmid carrying wild-type mecA), or pYK21 (a plasmid carrying a mutant mecA gene corresponding to five PBP2a mutations). All strains became resistant to BPR by day 9 of passaging, but MICs continued to increase until day 21. MICs increased 256-fold (from 1 to 256 microg/ml) for pAW8, 32-fold (from 4 to 128 microg/ml) for pYK20, and 8-fold (from 16 to 128 mug/ml) for pYK21. Strains carrying wild-type or mutant mecA developed six (pYK20 transformants) or four (pYK21 transformants) new mutations in mecA. The transformation of COLnex with a mecA mutant plasmid conferred BPR resistance, and the loss of mecA converted resistant strains into susceptible ones. Modeling studies predicted that several of the mecA mutations altered BPR binding; other mutations may have mediated resistance by influencing interactions with other proteins. Multiple mecA mutations were associated with BPR resistance in MRSA. BPR resistance also developed in the strain lacking mecA, suggesting a role for chromosomal genes.

BackgroundRapid blood culture diagnostics are of unclear benefit for patients with gram-negative bacilli (GNB) bloodstream infections (BSIs). We conducted a multicenter, randomized, controlled trial comparing outcomes of patients with GNB BSIs who had blood culture testing with standard-of-care (SOC) culture and antimicrobial susceptibility testing (AST) vs rapid organism identification (ID) and phenotypic AST using the Accelerate Pheno System (RAPID).MethodsPatients with positive blood cultures with Gram stains showing GNB were randomized to SOC testing with antimicrobial stewardship (AS) review or RAPID with AS. The primary outcome was time to first antibiotic modification within 72 hours of randomization.ResultsOf 500 randomized patients, 448 were included (226 SOC, 222 RAPID). Mean (standard deviation) time to results was faster for RAPID than SOC for organism ID (2.7 [1.2] vs 11.7 [10.5] hours; P