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Background The BioFire FilmArray Pneumonia Panel (BFPP), a multiplex PCR panel for the diagnosis of lower respiratory tract infections, has been proposed as a tool for antimicrobial stewardship. Few studies evaluate real-world implementation of the BFPP and no studies focus exclusively on children. Our institution implemented BFPP testing without restrictions. Methods We conducted a retrospective cohort study in children hospitalized at St. Louis Children's Hospital to (1) characterize the use of the BFPP in pediatric patients and (2) assess how results impacted antibiotic use. We included all BFPP tests obtained during the first year after the introduction of the test, September 2021 through August 2022. The primary outcome was change in antibiotic therapy within 24 hours of results, which was compared to the potential change in antibiotic therapy determined by two infectious diseases clinicians. Results One hundred sixty-nine tests from 126 patients were included. Nine patients were immunocompromised and 19 had chronic tracheostomy. The majority of tests were sent from tracheal aspirate specimens (92%) and from patients in an intensive care unit (94%). Only 51% of tests were obtained due to respiratory failure or suspected pneumonia. For 80% of test results, there was potential to change antibiotics, but change occurred in only 46% of tests in practice. Antibiotic escalation was more common (26%) than de-escalation (15%) or discontinuation (4.1%). Conclusions In a cohort of pediatric patients tested with the BFPP, the majority of tests were sent from tracheal aspirates and less than half of tests were associated with a change in antibiotics. [ABSTRACT FROM AUTHOR]

Background Nontuberculous mycobacteria are environmental organisms that cause infections leading to chronic, debilitating pulmonary disease, among which Mycobacterium avium complex (MAC) is the most common species. Methods We described patterns of macrolide-based multidrug antibiotic therapies for MAC pulmonary disease (MAC-PD) in US Medicare beneficiaries with bronchiectasis between January 2006 and December 2014. MAC therapy was defined as a multidrug regimen containing a macrolide plus ≥1 other drug targeting MAC-PD (rifamycin, ethambutol, fluoroquinolone, or amikacin) prescribed concomitantly for >28 days. Results We identified 9189 new MAC therapy users, with a mean age (standard deviation) of 74 (6 years) at the start of therapy; 75% female and 87% non-Hispanic white. A guideline-based regimen (a macrolide, ethambutol, and rifamycin, with or without amikacin) was prescribed for 51% of new MAC therapy users at treatment start, of whom 41% were continuing guideline-based therapy at 6 months, and only 18% at 12 months. Of all new MAC therapy users, by 18 months only 11% were still receiving MAC treatment, 55% had discontinued therapy, and 34% were censored owing to death or the end of the study period. Conclusions Overall, nearly half of new MAC therapy users were prescribed a non–guideline-recommended macrolide-based therapy, including regimens commonly associated with promoting macrolide resistance. Treatment discontinuation was common, and once discontinued, only a few beneficiaries resumed therapy at a later time. Our study adds important data to the current literature on treatment patterns for MAC-PD among older US populations. Future research should examine treatment patterns using more contemporary data sources. [ABSTRACT FROM AUTHOR]

Background: Although endemic to much of the global population, few studies have examined Helicobacter pylori (H. pylori) in US refugee populations. This study investigates the prevalence of H. pylori infection and barriers to treatment in the International Family Medicine Clinic (IFMC), a primary care refugee clinic, in central Virginia. Materials and Methods: We conducted a chart review of 188 refugee patients of the IFMC who were referred for an H. pylori test between January 1, 2019, and December 31, 2020. Recorded measures included patient demographics, H. pylori test result, treatment of initial infection, completion of test of cure (TOC), TOC results, salvage therapy, and barriers to treatment. Binary logistic regression was performed to examine the association between demographic factors and H. pylori test results. Results: Of the 171 patients who completed an H. pylori test, 94 tested positive (54.9%). Of the 93 patients that were subsequently treated, 76 were treated with clarithromycin triple therapy (82%). Forty‐eight patients (52%) completed a TOC after completing treatment, and 21 (43%) of these patients remained positive, indicating persistent infection. Eighteen patients (90%) who remained positive for H. pylori were subsequently treated with quadruple therapy. Patients under 18 (OR = 0.25, p < 0.01) and patients with a history of previous H. pylori (OR = 0.44, p < 0.05) were less likely to have positive results on initial H. pylori testing. Common barriers to treatment included pregnancy, religious observance (e.g., fasting), and health system complications (e.g., prior authorization for medications, cost of treatment). Conclusions: The prevalence of H. pylori among refugees at the IFMC was higher than the overall prevalence estimate for the United States, which is consistent with previous studies. This work represents an updated picture of H. pylori prevalence among refugees in the United States and contributes to the identification of treatment barriers. Significance statement: This article describes a chart review of recently resettled adult and children refugees treated at the main family medicine clinic at a large University‐based medical center from 2019 to 2020. Results include the prevalence of H. pylori infection among those tested, treatment resistance based on patients that required additional rounds of treatment for eradication, and identified barriers to treatment completion. This study adds to the scant literature on epidemiology of H. pylori infection among refugee populations in the United States, especially considering the importance of refugee and immigrant populations to the burden of H. pylori infection in North America. [ABSTRACT FROM AUTHOR]

Background: Infection is the most common cause of mortality within the first year after lung transplantation (LTx). The management of perioperative antibiotic therapy is a major issue, but little is known about worldwide practices.Methods: We sent by email a survey dealing with 5 daily clinical vignettes concerning perioperative antibiotic therapy to 180 LTx centers around the world. The invitation and a weekly reminder were sent to lung transplant specialists for a single consensus answer per center during a 3-month period.Results: We received a total of 99 responses from 24 countries, mostly from Western Europe (n = 46) and the USA (n = 34). Systematic screening for bronchial recipient colonization before LTx was mostly performed with sputum samples (72%), regardless of the underlying lung disease. In recipients without colonization, antibiotics with activity against gram-negative bacteria resistant strains (piperacillin / tazobactam, cefepime, ceftazidime, carbapenems) were reported in 72% of the centers, and antibiotics with activity against methicillin-resistant Staphylococcus aureus (mainly vancomycin) were reported in 38% of the centers. For these recipients, the duration of antibiotics reported was 7 days (33%) or less (26%) or stopped when cultures of donor and recipients were reported negatives (12%). In recipients with previous colonization, antibiotics were adapted to the susceptibility of the most resistant strain and given for at least 14 days (67%).Conclusion: Practices vary widely around the world, but resistant bacterial strains are mostly targeted even if no colonization occurs. The antibiotic duration reported was longer for colonized recipients. [ABSTRACT FROM AUTHOR]

Purpose: Ceftazidime–avibactam is a novel β-lactam/β-lactamase inhibitor combination recently approved in Europe and the USA for the treatment of adults with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), among other indications. In the phase III REPROVE trial (NCT01808092), ceftazidime–avibactam demonstrated non-inferiority to meropenem for the treatment of patients with nosocomial pneumonia (NP), including VAP. As ceftazidime–avibactam was not studied in patients with NP prior to REPROVE, selecting an appropriate dosage regimen in the "perfect storm" of NP required careful consideration of potential determinants and confounders of response specific to the NP patient population. Methods: This review describes the series of preclinical studies and pharmacokinetic/pharmacodynamic (PK/PD) analyses that supported ceftazidime–avibactam dosage selection for patients with NP/VAP (2000/500 mg by 2-h intravenous infusion every 8 h, adjusted for renal function). In parallel, important considerations for antibiotic dosage selection in patients with NP are highlighted, including adequate drug penetration into the lungs, the suitability of murine-derived plasma PK/PD targets, evaluation of MIC distributions against clinical bacterial isolates from patients with NP, and consideration of PK in patients with NP, who are often critically ill. These analyses also supported the European approval of ceftazidime–avibactam for adults with HAP, including VAP, before the completion of REPROVE. Conclusions: This work serves as a successful practical example of dosage design for a new antibacterial drug therapy in the indication of NP, including VAP, where previous drug therapies have failed, possibly as a result of evaluation of too few variables, thereby limiting the accuracy of pharmacodynamic predictions. [ABSTRACT FROM AUTHOR]

Background: Nontuberculous mycobacteria are environmental organisms that are increasingly causing chronic and debilitating pulmonary infections, of which Mycobacterium avium complex (MAC) is the most common pathogen. MAC pulmonary disease (MAC-PD) is often difficult to treat, often requiring long-term multidrug antibiotic therapy., Research Question: Is there an association between various guideline-based three-drug therapy (GBT) regimens and (1) therapy-associated adverse events or (2) regimen change/discontinuation, within 12 months of therapy initiation?, Study Design and Methods: In a retrospective cohort study, we examined tolerability outcomes of GBT regimens for MAC-PD in 4,626 US Medicare beneficiaries with bronchiectasis, who were prescribed a GBT as initial antibiotic treatment for presumed MAC-PD during 2006 to 2014. Using multivariable Cox proportional hazard regression, we estimated adjusted hazard ratios (aHRs) to compare the risk of adverse events and regimen change/discontinuations within 12 months of therapy initiation in various GBT regimens., Results: The cohort had a mean age ± SD of 77.9 ± 6.1 years at treatment start, were mostly female (77.7%), and were mostly non-Hispanic White (87.2%). The risk of regimen change/discontinuation within 12 months of therapy was higher for clarithromycin-based regimens than azithromycin-based regimens (aHR, 1.12; 95% CI, 1.04-1.20 with rifampin; aHR, 1.11; 95% CI, 0.93-1.32 with rifabutin as the companion rifamycin), and for rifabutin-containing regimens than rifampin-containing regimens (aHR, 1.49; 95% CI, 1.33-1.68 with azithromycin; aHR, 1.47; 95% CI, 1.27-1.70 with clarithromycin as the companion macrolide). The aHR comparing regimen change/discontinuation with clarithromycin-ethambutol-rifabutin and azithromycin-ethambutol-rifampin was 1.64 (95% CI, 1.43-1.64)., Interpretation: Overall, an azithromycin-based regimen was less likely to be changed or discontinued than a clarithromycin-based regimen, and a rifampin-containing regimen was less likely to be changed or discontinued than a rifabutin-containing regimen within 12 months of therapy start. Our work provides a population-based assessment on the tolerability of multidrug antibiotic regimens used for the treatment of MAC-PD., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: E. H. has served on an advisory board for AN2 pharmaceuticals and received consult fees. K. L. W. has grants or contracts from Insmed; and has received consulting fees from Insmed, Paratek, RedHill Biopharma, Spero Therapeutics, and AN2 pharmaceuticals. T. K. M. has grants or contracts from Insmed, the Centered Outcomes Research Institute, and the Lung Health Foundation; has received consulting fees from Insmed, RedHill Biopharma, and Spero Therapeutics; has received payment or honoraria from France Foundation, Astra Zeneca, Novartis, and Insmed; and has a leadership or fiduciary role in the Toronto NTM patient group. None declared (J. H. K., K. F. C., M. M., S. K. B.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

In this multicenter retrospective cohort study of over 1 million patients at 150 US hospitals, proton pump inhibitors increased the odds of a patient having hospital-onset Clostridium difficile infection as did third and fourth generation cephalosporins, carbapenems, and piperacillin/tazobactam. These findings support appropriate prescribing of acid-suppression therapy and high-risk antibiotics. [ABSTRACT FROM AUTHOR]

More than 400 000 vascular grafts are inserted annually in the USA. Graft insertion is complicated by infection in 0.5–4% of cases. Vascular graft infections (VGIs) are becoming one of the most frequent prosthesis-related infections and are associated with considerable mortality, ranging from 10 to 25% within 30 days following the diagnosis. Treatment of VGI is based on urgent surgical removal of the infected graft followed by prolonged antibiotherapy. Data regarding the best antibiotherapy to use are lacking since no well designed trial to study antimicrobial treatment of VGI exists. Moreover, since VGIs demonstrate very specific pathophysiology, guidelines on other material-related infections or infective endocarditis treatment cannot be entirely applied to VGI. A French multidisciplinary group gathering infectious diseases specialists, anaesthesiologists, intensivists, microbiologists, radiologists and vascular surgeons was created to review the literature dealing with VGI and to make some proposals regarding empirical and documented antibiotic therapy for these infections. This article reveals these proposals. [ABSTRACT FROM AUTHOR]

A non-systematic review of the published scientific evidence has been carried out on the duration of empirical antibiotic treatment in surgical intra-abdominal infections (IIA) with effective focus control. Given the progressive increase in antibiotic resistance, it is urgent to have strategies to reduce the pressure on the microbiota. The American guidelines made by Mazuski et al. of 2017 1 , as the central axis in the recommendations of the duration of empirical antibiotic treatment in intra-abdominal infections with control of the focus and a bibliographic search of all the articles that contained the keywords in Pubmed and Google Scholar is added. 21 articles referring to the duration of empirical antibiotic treatment in intra-abdominal infection with control of the focus are collected. With the American guidelines and these articles, a proposal is prepared for the duration of empirical antibiotic treatment in patients without risk factors between 24 and 72 h. And in those who present risk factors, it should be individualized with active monitoring every 24 h of fever, paralytic ileus and leukocytosis (FIL), before an early detection of complications or the need for changes in antibiotic treatment. Short treatments are just as effective as those of longer durations and are associated with fewer adverse effects, therefore, daily adjusting and reassessing the duration of empirical antibiotic treatment is essential for better practice., (Copyright © 2022 The Author(s). Published by Elsevier España, S.L.U. All rights reserved.)

Abstract: Hormonal and antimicrobial therapies are essential to regulate and maintain healthy reproduction in domestic animals. The appropriate and legal use of these compounds is ultimately the responsibility of the veterinarian and other users, with a primary mission to directly protect and promote the health of animals, and indirectly the health of people. The appropriate use of these products is defined by the Federal Food, Drug, and Cosmetic Act, 21 United States of America § 301 et seq and implementing regulations in the Code of Federal Regulations. In the past, use of a drug in an animal for an unapproved use violated this Act. However, passage of the Animal Medicinal Drug Use Clarification Act 1994 legalized the extra-label use of certain animal and human drugs in veterinary practice for treating diseases. This manuscript reviews currently approved hormonal and antimicrobial drugs for use in theriogenology. Considering the ever increasing knowledge in the area of veterinary reproduction, particularly in the treatment and control of reproduction using antimicrobials and hormones, it would be beneficial to widen the therapeutic options in these categories. The potential for widening the therapeutic options is also discussed in this review, by providing a non-exhaustive but essential list of potential new drugs for use in clinical animal reproduction (theriogenology). [Copyright &y& Elsevier]

The article determines whether postponed oxygenation assessment delays initiation of antibiotic therapy and adversely affects intensive care unit survival in patients with severe community-acquired pneumonia in the U.S. Early oxygenation assessment was associated with antibiotic delivery and better intensive care unit survival. Those data suggest the potential value of an early care bundle focusing on implementation of oxygenation assessment immediately after arrival to the emergency department.

Study objectives: To evaluate the impact of a multifactorial intervention to improve the quality, efficiency, and patient understanding of care for community-acquired pneumonia. Design: Times series cohort study. Setting: Four academic health centers in the New York City metropolitan area. Patients or participants: All consecutive adults hospitalized for pneumonia during a 5-month period before (n = 1,013) and after (n = 1,081) implementation of an inpatient quality improvement (QI) initiative. Interventions: A multidisciplinary team of opinion leaders developed evidence-based treatment guidelines and critical pathways, conducted educational sessions with physicians, distributed pocket reminder cards, promoted standardized orders, and developed bilingual patient education materials. Measurements and results: The average age was 71.4 years, and 44.1% of cases were low risk, 36.8% were moderate risk, and 19.2% were high risk. The preintervention and postintervention groups were well matched on age, sex, race, nursing home residence, pneumonia severity, initial presentation, and most major comorbidities. The intervention increased the use of guideline- recommended antimicrobial therapy from 78.1 to 83.4% (p = 0.003). There was also a borderline decrease in the proportion of patients being discharged prior to becoming clinically stable, from 27.0 to 23.5% (p = 0.06). However, there were no improvements in the other targeted indicators, including time to first dose of antibiotics, proportion receiving antibiotics within 8 h, timely switch to oral antibiotics, timely discharge, length of stay, or patient education outcomes. Conclusions: This real-world QI program was able to improve modestly on some quality indicators, but not effect resource use or patient knowledge of their disease. Changing physician and organizational behavior in academic health centers will require the development and implementation of more intensive. system-oriented strategies. [ABSTRACT FROM AUTHOR]

Background Empiric therapy is a mainstay of the inpatient management of urinary tract infections (UTIs), and the choice of empiric antibiotic is shaped by local epidemiology and patient risk factors and comorbidities. Pathogen identification (ID) and antibiotic susceptibility testing (AST) provide information that can guide adjustments in therapy, allowing de-escalation to more targeted, narrow-spectrum antibiotics. Methods Real-world data (hospital billing claims) from 2017 was used to extract relevant information from general hospitals on inpatients with bacterial UTIs including patient demographics and antibiotics line of therapy progression. Patients were projected to the USA national event totals and validated with other projection-related data sources (HCUP) and secondary market research. Data obtained in the claims analysis was validated by primary market research (PMR). Results Analysis of 33M claims identified 169K patients with a code for UTI; in at least one-third of patients, there were no codes associated with ID/AST assays. Among those with codes for ID/AST assays, the vast majority were performed in the first 3 days following hospital admission. Approximately two-thirds of patients with associated ID/AST codes were already receiving an antibiotic when the assays were performed, which was assumed to be the empiric treatment. Analysis of the line of antibiotic therapy progression in patients where ID/AST was performed identified subsequent changes in antibiotic prescribing in approximately one-third of patients within 3 days, compatible with changes due to delivery of conclusive results and were interpreted as a transition from empiric to targeted treatment. Conclusion To the best of our knowledge, this is the first attempt at understanding the impact of ID/AST assays on prescribing practices with basis on analysis of claims data. Our results align with PMR conducted by DRG internally, supporting the validity of this methodology. Although this claims analysis delivers reliable data when claims are associated with ID/AST assays, it is limited by incompletely filled claims, which may underestimate the use of these assays. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background: The impact of antibiotic timing on sepsis outcomes remains controversial due to conflicting results from previous studies., Objectives: This study investigated the association of door-to-antibiotic time with long-term mortality in ED patients with sepsis., Methods: This retrospective cohort study included nontrauma adult ED patients with clinical sepsis admitted to four hospitals from 2013 to 2017. Only patients' first eligible encounter was included. Multivariable logistic regression was used to measure the adjusted association between door-to-antibiotic time and 1-year mortality. Secondary analyses used alternative antibiotic timing measures (antibiotic initiation within 1 or 3 h and separate comparison of antibiotic exposure at each hour up to hour 6), alternative outcomes (hospital, 30-day, and 90-day mortality), and alternative statistical methods to mitigate indication bias., Results: Among 10,811 eligible patients, median door-to-antibiotic time was 166 min (interquartile range, 115-230 min), and 1-year mortality was 19%. After adjustment, each additional hour from ED arrival to antibiotic initiation was associated with a 10% (95% CI, 5-14; P < .001) increased odds of 1-year mortality. The association remained linear when each 1-h interval of door-to-antibiotic time was independently compared with door-to-antibiotic time ≤ 1 h and was similar for hospital, 30-day, and 90-day mortality. Mortality at 1 year was higher when door-to-antibiotic times were > 3 h vs ≤ 3 h (adjusted OR, 1.27; 95% CI, 1.13-1.43) but not > 1 h vs ≤ 1 h (adjusted OR, 1.26; 95% CI, 0.98-1.62)., Conclusions: Delays in ED antibiotic initiation time are associated with clinically important increases in long-term, risk-adjusted sepsis mortality., (Copyright © 2019 American College of Chest Physicians. All rights reserved.)

We discuss the management of GBS positive women with PPROM, an aspect of obstetrical management that remains controversial despite the publication of new randomized control trials in recent years. Clinical practice guidelines from several countries' national organizations are compared and contrasted, and areas of uncertainty are identified., (Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.)

Despite evidence supporting the effectiveness of best practices of infection prevention and management, many surgeons worldwide fail to implement them. Evidence-based practices tend to be underused in routine practice. Surgeons with knowledge in surgical infections should provide feedback to prescribers and integrate best practices among surgeons and implement changes within their team. Identifying a local opinion leader to serve as a champion within the surgical department may be important. The "surgeon champion" can integrate best clinical practices of infection prevention and management, drive behavior change in their colleagues, and interact with both infection control teams in promoting antimicrobial stewardship., Competing Interests: Not applicable.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Pulmonary Exacerbations (PEx) are associated with increased morbidity and mortality in individuals with CF. PEx management practices vary widely, and optimization through interventional trials could potentially improve outcomes. The object of this analysis was to evaluate current physician treatment practices and patient outcomes for PEx., Methods: The Standardized Treatment of Pulmonary Exacerbations (STOP) observational study enrolled 220 participants ≥12years old admitted to the hospital for PEx at 11 U.S. CF centers. Spirometry and daily symptom scores were collected during the study. Physicians were surveyed on treatment goals and their management practices were observed. Treatment outcomes were compared to stated goals., Results: The mean (SD) duration of IV antibiotic treatment was 15.9 (6.0) days. Those individuals with more severe lung disease (<50% FEV 1 ) were treated nearly two days longer than those with >50% FEV 1 . Physician-reported FEV 1 improvement goals were 10% (95% CI: 5%, 14%) lower for patients with 6-month baseline FEV 1 ≤50% predicted compared with those with 6-month baseline FEV 1 >50% predicted. There were clinically and statistically significant improvements in symptoms from the start of IV antibiotic treatment to the end of IV antibiotic treatment and 28days after the start of treatment. The mean absolute increase in FEV 1 from admission was 9% predicted at end of IV antibiotic treatment, and 7% predicted at day 28. Only 39% fully recovered lost lung function, and only 65% recovered at least 90% of lost lung function. Treatment was deemed successful by 84% of clinicians, although 6-month baseline FEV 1 was only recovered in 39% of PEx., Conclusions: In this prospective observational study of PEx, treatment regimens and durations showed substantial variation. A significant proportion of patients did not reach physician's treatment goals, yet treatment was deemed successful., (Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Pelvic inflammatory disease (PID) is a gynaecological inflammatory disorder with a high incidence that can lead to sequelae such as infertility, ectopic pregnancy and chronic pelvic pain. The International Union against Sexually Transmitted Infections (IUSTI) and the US Centers for Disease Control and Prevention (CDC) have issued treatment recommendations for the management of PID. The purpose of this review is to summarise the available evidence for the use of IUSTI- and CDC-recommended antibiotic therapies for PID. The main differences between recommendations concern alternative regimens for inpatient treatment and the use of oral moxifloxacin as an alternative outpatient regimen in the IUSTI guidelines. There is evidence supporting the use of the recommended antibiotic regimens, although with some variation in reported cure rates. This variation can be explained, in part, by the different diagnostic and evaluation criteria used in different trials. Adverse events that require discontinuation of antibiotic therapy are rarely observed. The main limitation of the current available evidence is the short-term follow-up, which does not allow full evaluation of the risks of long-term sequelae., (Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)