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1881. Bacteriophages as adjuvant to antibiotics for the treatment of periprosthetic joint infection caused by multidrug-resistant <i>Pseudomonas aeruginosa</i>. Full Text available with Trip Pro

Bacteriophages as adjuvant to antibiotics for the treatment of periprosthetic joint infection caused by multidrug-resistant Pseudomonas aeruginosa. We documented the adjunctive bacteriophage therapy to treat a chronic relapsing periprosthetic joint infection of the knee and chronic osteomyelitis of the femur, caused by multidrug-resistant Pseudomonas aeruginosa The combined antibiotic/phage treatment eradicated the infection and no side effects to phages were observed.Copyright © 2019

2019 Antimicrobial Agents and Chemotherapy

1882. Conjugative delivery of CRISPR-Cas9 for the selective depletion of antibiotic-resistant enterococci. Full Text available with Trip Pro

show that these CRISPR-Cas-encoding delivery plasmids, or CRISPR-Cas antimicrobials, can reduce the occurrence of antibiotic resistance in enterococcal populations in a sequence-specific manner. Furthermore, we demonstrate that deployment of CRISPR-Cas antimicrobials in the murine intestine reduces the occurrence of antibiotic-resistant E. faecalis by several orders of magnitude. Finally, we show that E. faecalis donor strains harboring CRISPR-Cas antimicrobials are immune to uptake of antibiotic (...) Conjugative delivery of CRISPR-Cas9 for the selective depletion of antibiotic-resistant enterococci. The innovation of new therapies to combat multidrug-resistant (MDR) bacteria is being outpaced by the continued rise of MDR bacterial infections. Of particular concern are hospital-acquired infections (HAIs) recalcitrant to antibiotic therapies. The Gram-positive intestinal pathobiont Enterococcus faecalis is associated with HAIs and some strains are MDR. Therefore, novel strategies to control E

2019 Antimicrobial Agents and Chemotherapy

1883. Impact of Antibiotic Gut Exposure on the Temporal Changes in Microbiome Diversity. Full Text available with Trip Pro

Impact of Antibiotic Gut Exposure on the Temporal Changes in Microbiome Diversity. Although the global deleterious impact of antibiotics on the intestinal microbiota is well known, temporal changes in microbial diversity during and after an antibiotic treatment are still poorly characterized. We used plasma and fecal samples collected frequently during treatment and up to one month after from 22 healthy volunteers assigned to a 5-day treatment by moxifloxacin (n = 14) or no intervention (n = 8 (...) ], 27.7) and 47.4% of the number of OTUs (min, 30.4; max, 48.3). As a consequence of both the long fecal half-life of moxifloxacin and the susceptibility of the gut microbiota to moxifloxacin, bacterial diversity indices did not return to their pretreatment levels until days 16 and 21, respectively. Finally, the model characterized the effect of moxifloxacin on bacterial diversity biomarkers and provides a novel framework for analyzing antibiotic effects on the intestinal microbiome.Copyright © 2019

2019 Antimicrobial Agents and Chemotherapy

1884. Role of the <i>msaABCR</i> Operon in Cell Wall Biosynthesis, Autolysis, Integrity, and Antibiotic Resistance in Staphylococcus aureus. Full Text available with Trip Pro

Role of the msaABCR Operon in Cell Wall Biosynthesis, Autolysis, Integrity, and Antibiotic Resistance in Staphylococcus aureus. Staphylococcus aureus is an important human pathogen in both community and health care settings. One of the challenges with S. aureus as a pathogen is its acquisition of antibiotic resistance. Previously, we showed that deletion of the msaABCR operon reduces cell wall thickness, resulting in decreased resistance to vancomycin in vancomycin-intermediate S. aureus (...) in teichoic acid content in the msaABCR mutant. Therefore, we propose that deletion of the msaABCR operon results in decreased peptidoglycan cross-linking, leading to increased susceptibility toward cell wall-targeting antibiotics, such as β-lactams and vancomycin. Moreover, we also observed significantly downregulated transcription of early cell wall-synthesizing genes, supporting the finding that msaABCR mutant cells have decreased peptidoglycan synthesis. More specifically, the msaABCR mutant

2019 Antimicrobial Agents and Chemotherapy

1885. Debridement, antibiotics and implant retention is a viable treatment option for early periprosthetic joint infection presenting more than four weeks after index arthroplasty. (Abstract)

Debridement, antibiotics and implant retention is a viable treatment option for early periprosthetic joint infection presenting more than four weeks after index arthroplasty. Success of debridement, antibiotics and implant retention (DAIR) in early periprosthetic joint infection (PJI) largely depends on the presence of a mature biofilm. At what time point DAIR should be disrecommended is unknown. This multicenter study evaluated the outcome of DAIR in relation to time after index (...) arthroplasty.We retrospectively evaluated PJIs occurring within 90 days after surgery and treated with DAIR. Patients with bacteremia, arthroscopic debridements and a follow-up <1 year were excluded. Treatment failure was defined as 1) any further surgical procedure related to infection 2) PJI-related death, 3) long-term suppressive antibiotics.769 patients were included. Treatment failure occurred in 294 patients (38%) and was similar between time-intervals from index arthroplasty to DAIR: week 1-2: 42% (95

2019 Clinical Infectious Diseases

1886. The Overton window and a less dogmatic approach to antibiotics. Full Text available with Trip Pro

The Overton window and a less dogmatic approach to antibiotics. Recent trials in infectious disease have led to reconsidering traditional treatment of infectious disease-changing the duration or type of traditional antibiotics or evaluating new antibiotics for approval. These trials have used the non-inferiority trial approach. The non-inferiority trial design and recent infectious disease trials of relevance are discussed in this viewpoint.To analyze recent trials in infectious disease

2019 Clinical Infectious Diseases

1887. Inappropriate Empirical Antibiotic Treatment in High-risk Neutropenic Patients With Bacteremia in the Era of Multidrug Resistance. (Abstract)

Inappropriate Empirical Antibiotic Treatment in High-risk Neutropenic Patients With Bacteremia in the Era of Multidrug Resistance. We aimed to describe the current rates of inappropriate empirical antibiotic treatment (IEAT) in oncohematological patients with febrile neutropenia (FN) and its impact on mortality.This was a multicenter prospective study of all episodes of bloodstream infection (BSI) in high-risk FN patients (2006-2017). Episodes receiving IEAT were compared with episodes

2019 Clinical Infectious Diseases

1888. An Integrated Safety Summary of Omadacycline, a Novel Aminomethylcycline Antibiotic. Full Text available with Trip Pro

An Integrated Safety Summary of Omadacycline, a Novel Aminomethylcycline Antibiotic. Omadacycline is a semisynthetic tetracycline antibiotic. Phase III clinical trial results have shown that omadacycline has an acceptable safety profile in the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Similar to most tetracyclines, transient nausea and vomiting and low-magnitude increases in liver aminotransferases were the most frequent

2019 Clinical Infectious Diseases

1889. Each Additional Day of Antibiotics is Associated with Lower Gut Anaerobes in Neonatal Intensive Care Unit Patients. Full Text available with Trip Pro

Each Additional Day of Antibiotics is Associated with Lower Gut Anaerobes in Neonatal Intensive Care Unit Patients. Discontinuation of inappropriate antimicrobial therapy is an important target for stewardship intervention. The drug and duration-dependent effects of antibiotics on the developing neonatal gut microbiota needs to be precisely quantified.In this retrospective, cross-sectional study, we performed 16S rRNA sequencing on stool swab samples collected from neonatal intensive care unit (...) (NICU) patients within 7 days of discontinuation of therapy who received either ampicillin and tobramycin (AT), ampicillin and cefotaxime (AC), or ampicillin, tobramycin and metronidazole (ATM). We compared taxonomic composition within term and preterm infant groups between treatment regimens. We calculated adjusted effect estimates for antibiotic type and duration of therapy on the richness of obligate anaerobes and known butyrate-producers in all infants.A total of 72 infants were included

2019 Clinical Infectious Diseases

1890. Optimizing Contact Precautions to Curb the Spread of Antibiotic-resistant Bacteria in Hospitals: A Multicenter Cohort Study to Identify Patient Characteristics and Healthcare Personnel Interactions Associated With Transmission of Methicillin-resistant Sta Full Text available with Trip Pro

Optimizing Contact Precautions to Curb the Spread of Antibiotic-resistant Bacteria in Hospitals: A Multicenter Cohort Study to Identify Patient Characteristics and Healthcare Personnel Interactions Associated With Transmission of Methicillin-resistant Sta Healthcare personnel (HCP) acquire antibiotic-resistant bacteria on their gloves and gowns when caring for intensive care unit (ICU) patients. Yet, contact precautions for patients with methicillin-resistant Staphylococcus aureus (MRSA

2019 Clinical Infectious Diseases

1891. Effectiveness of Oral Vancomycin for Prevention of Healthcare Facility-Onset Clostridioides difficile Infection in Targeted Patients During Systemic Antibiotic Exposure. Full Text available with Trip Pro

Effectiveness of Oral Vancomycin for Prevention of Healthcare Facility-Onset Clostridioides difficile Infection in Targeted Patients During Systemic Antibiotic Exposure. Limited retrospective data suggests prophylactic oral vancomycin may prevent Clostridioides difficile infection (CDI). We sought to evaluate the effectiveness of oral vancomycin for the prevention of health care facility-onset CDI (HCFO-CDI) in targeted patients.We conducted a randomized, prospective, open-label study at Novant (...) Health Forsyth Medical Center in Winston-Salem, North Carolina between October 2018 and April 2019. Included patients were randomized 1:1 to either oral vancomycin (dosed at 125 mg once daily while receiving systemic antibiotics and continued for 5 days post completion of systemic antibiotics [OVP]), or no prophylaxis. The primary endpoint was incidence of HCFO-CDI. Secondary endpoints included incidence of community-onset healthcare facility-associated CDI (CO-HCFA-CDI), incidence of vancomycin

2019 Clinical Infectious Diseases

1892. Evaluation of infection rates with narrow versus broad-spectrum antibiotic regimens in civilian gunshot open-fracture injury. (Abstract)

Evaluation of infection rates with narrow versus broad-spectrum antibiotic regimens in civilian gunshot open-fracture injury. Civilian gunshot open-fracture injuries portray a significant health burden to patients. Use of antibiotics is endorsed by guideline recommendations for the prevention of post-traumatic infections, however, antimicrobial selection and their associated outcomes remains unclear. Therefore, we sought to compare infectious and other clinical outcomes between three (...) antimicrobial cohorts in patients with gunshot-related fractures requiring operative intervention.Patients were identified by retrospectively querying the University of Kentucky Trauma Registry for gunshot wound victims. A narrow regimen, an expanded gram-negative regimen, and a regimen containing a fluoroquinolone antimicrobial were identified for comparison. The primary outcome was a composite of infections at or before 14 days of hospitalization. Secondary endpoints included hospital length of stay

2019 American Journal of Emergency Medicine

1893. Antibiotic Prophylaxis During Catheter-Managed Postoperative Urinary Retention After Pelvic Reconstructive Surgery: A Randomized Controlled Trial. Full Text available with Trip Pro

Antibiotic Prophylaxis During Catheter-Managed Postoperative Urinary Retention After Pelvic Reconstructive Surgery: A Randomized Controlled Trial. To estimate whether nitrofurantoin prophylaxis decreases the incidence of culture-documented urinary tract infection for women with catheter-managed urinary retention after pelvic reconstructive surgery.This double-blind, placebo-controlled, randomized trial was conducted at five academic institutions. Women with urinary retention after surgery

2019 Obstetrics and Gynecology

1894. Antibiotic Use Without Indication During Delivery Hospitalizations in the United States. Full Text available with Trip Pro

Antibiotic Use Without Indication During Delivery Hospitalizations in the United States. To analyze trends in unindicated antibiotic use during vaginal delivery hospitalization.This study used an administrative database to analyze antibiotic use during delivery hospitalizations from January 2006 to March 2015. Women were classified by mode of delivery and whether they had an evidence-based indication for antibiotics. Indications for antibiotics included preterm prelabor rupture of membranes (...) (PROM), cesarean delivery, group B streptococcus (GBS) colonization, chorioamnionitis, endometritis, urinary tract infections, and other infections. The Cochran-Armitage test was used to assess trends of antibiotic administration. Unadjusted and adjusted analyses for antibiotic receipt including demographic, hospital, and obstetric and medical factors were performed with unadjusted and adjusted risk ratios (RRs) with 95% CIs as measures of association.A total of 5,536,756 delivery hospitalizations

2019 Obstetrics and Gynecology

1895. A 2-Year Pragmatic Trial of Antibiotic Stewardship in 27 Community Nursing Homes. Full Text available with Trip Pro

A 2-Year Pragmatic Trial of Antibiotic Stewardship in 27 Community Nursing Homes. To determine if antibiotic prescribing in community nursing homes (NHs) can be reduced by a multicomponent antibiotic stewardship intervention implemented by medical providers and nursing staff and whether implementation is more effective if performed by a NH chain or a medical provider group.Two-year quality improvement pragmatic implementation trial with two arms (NH chain and medical provider group).A total (...) of 27 community NHs in North Carolina that are typical of NHs statewide, conducted before announcement of the US Centers for Medicare and Medicaid Services antibiotic stewardship mandate.Nursing staff and medical care providers in the participating NHs.Standardized antibiotic stewardship quality improvement program, including training modules for nurses and medical providers, posters, algorithms, communication guidelines, quarterly information briefs, an annual quality improvement report

2019 Journal of the American Geriatrics Society Controlled trial quality: uncertain

1896. The Effect of Expert Feedback on Antibiotic Prescribing in Pediatrics: Experimental Evidence. Full Text available with Trip Pro

The Effect of Expert Feedback on Antibiotic Prescribing in Pediatrics: Experimental Evidence. Background. Inappropriate prescribing of antibiotics, which is common in pediatric care, is a key driver of antimicrobial resistance. To mitigate the development of resistance, antibiotic stewardship programs often suggest the inclusion of feedback targeted at individual providers. Empirically, however, it is not well understood how feedback affects individual physicians' antibiotic prescribing (...) decisions. Also, the question of how physicians' characteristics, such as clinical experience, relate to antibiotic prescribing decisions and to responses to feedback is largely unexplored. Objective. To analyze the causal effect of descriptive expert feedback (and individual characteristics) on physicians' antibiotic prescribing decisions in pediatrics. Design. We employed a randomized, controlled framed field experiment, in which German pediatricians (n=73) decided on the length of first-line

2019 Medical Decision Making Controlled trial quality: uncertain

1897. Umbilical catheters as vectors for generalized bacterial infection in premature infants regardless of antibiotic use. Full Text available with Trip Pro

Umbilical catheters as vectors for generalized bacterial infection in premature infants regardless of antibiotic use. Introduction. Umbilical catheterization offers unique vascular access that is only possible in the neonatal setting due to unobstructed umbilical vessels from foetal circulation. With the cut of the umbilical cord, two arteries and a vein are dissected, allowing quick and painless catheterization of the neonate. Unfortunately, keeping the umbilical access sterile is challenging (...) blood cultures. The patients with the most intense bacterial catheter colonization presented with sepsis around removal time or a couple of days later, especially if they were extremely premature and exhibited very low birth weight. Catheterization time did not play a major role.Conclusion. Umbilical catheters are vectors for skin microflora transmission to the bloodstream via biofilm formation, regardless of antibiotic use and the duration of catheterization, especially in preterm neonates.

2019 Journal of Medical Microbiology

1898. Restoring the activity of the antibiotic aztreonam using the polyphenol epigallocatechin gallate (EGCG) against multidrug-resistant clinical isolates of <i>Pseudomonas aeruginosa</i>. Full Text available with Trip Pro

Restoring the activity of the antibiotic aztreonam using the polyphenol epigallocatechin gallate (EGCG) against multidrug-resistant clinical isolates of Pseudomonas aeruginosa. Introduction. Pseudomonas aeruginosa is an important Gram-negative pathogen that is intrinsically multidrug-resistant (MDR) and frequently associated with healthcare-associated outbreaks. With increasing resistance to antibiotics and with very few novel drugs under development, clinicians often use combinations (...) demonstrate that synergy between aztreonam and EGCG exists [fractional inhibitory concentration indices (FICIs) 0.02-0.5], with the combination affording significantly (P=<0.05) enhanced bacterial killing, with a >3 log10 reduction in colony-forming units ml-1 at 24 h. EGCG was able to restore susceptibility to aztreonam to a level equal to or below the breakpoint set by the European Committee for Antimicrobial Susceptibility Testing. In G. mellonella, the combination was superior to monotherapy

2019 Journal of Medical Microbiology

1899. Antimicrobial resistance in methicillin-resistant <i>Staphylococcus aureus</i> to newer antimicrobial agents. Full Text available with Trip Pro

Antimicrobial resistance in methicillin-resistant Staphylococcus aureus to newer antimicrobial agents. Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) result in significant morbidity and mortality for patients in both community and health care settings. This is primarily due to the difficulty in treating MRSA, which is often resistant to multiple classes of antibiotics. Understanding the mechanisms of antimicrobial resistance (AMR) in MRSA provides insight (...) into the optimal use of antimicrobial agents in clinical practice and also underpins critical aspects of antimicrobial stewardship programs. In this review we delineate the mechanisms, prevalence, and clinical importance of resistance to antibiotics licensed in the past 20 years that target MRSA, as well as new drugs in the pipeline which are likely to be licensed soon. Current gaps in scientific knowledge about MRSA resistance mechanisms are discussed, and topics in the epidemiology of AMR in S. aureus

2019 Antimicrobial Agents and Chemotherapy

1900. First-line antibiotic selection in outpatient settings. Full Text available with Trip Pro

First-line antibiotic selection in outpatient settings. Using the 2014 IBM MarketScan Commercial Database, we compared antibiotic selection for pharyngitis, sinusitis, and acute otitis media in retail clinics, emergency departments, urgent cares, and offices. Only 50% of visits for these conditions received recommended first-line antibiotics. Improving antibiotic selection for common outpatient conditions is an important stewardship target.

2019 Antimicrobial Agents and Chemotherapy

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