1591. Updated Fluoroquinolone MIC Breakpoints: Impact on Susceptibility Rates in the United States

Abstract Background In 2015 USCAST, the National Advisory Committee for the United States (US) to EUCAST, produced a report (Version 1.0) on their website (www.uscast.org) re-evaluating fluoroquinolone (FQ) breakpoint interpretive criteria (IC) based on analysis of current microbiology and pharmacokinetic/pharmacodynamic (PK/PD) data. EUCAST initiated a consultative process using USCAST analyses in an effort to update FQ IC, released in 2017. CLSI formed an ad-hoc working group in late 2015 to review the USCAST FQ document and formulate questions about content. In 2018, USCAST released V1.3 of the FQ document and CLSI subsequently published updated FQ MIC IC in the M100-S29 (2019) document. This study evaluated the impact on susceptibility (S) rates for US surveillance data that these IC changes created. Methods Clinical isolates (reference broth microdilution MIC) from 2016–2018 US SENTRY Program were analyzed for S based on current and previous IC. FQ results for ciprofloxacin (CIP), levofloxacin (LEV), and moxifloxacin (MOX) were evaluated. Benchmark S comparison data for meropenem, cefepime, piperacillin–tazobactam and delafloxacin (new FQ) were also included. Results S rates for Enterobacteriaceae (ENT;Figure) were reduced by 3.8/3.7% for CIP/LEV (CLSI) and 2.3/2.5% (EUCAST). MOX-S rate vs. ENT declined 5.7% (EUCAST). Although reductions in S occurred for most organism groups, K. pneumoniae (6.0/5.5% for CIP/LEV [CLSI] and 4.0/4.2% [EUCAST]) and S. marcescens (7.4/4.1% for CIP/LEV [CLSI] and 4.1/5.0% [EUCAST]) reductions were among the largest changes. For Pseudomonas aeruginosa (PSA), CIP-S decreased 6.8% and LEV-S 10.1% (CLSI); but potential for false-S results remain using CLSI IC (5 pathogens). Conclusion USCAST’s comprehensive analyses of FQ IC in 2015 led to revised breakpoints for most organism/drug combinations among ENT and PSA compared with those being used before. USCAST analysis was most influenced by PK/PD in vivo data as current clinical outcomes data by MIC was limited. Awareness and interactions (both formal and informal) among breakpoint setting organizations has modified FQ ICs which are lower than previously recommended, and although not perfectly harmonized in time and detail, this represents a successful model. Disclosures All authors: No reported disclosures.

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Tasked with a Challenging Objective: Why Do Neutrophils Fail to Battle Pseudomonas aeruginosa Biofilms

Pathogens ◽

10.3390/pathogens8040283 ◽

2019 ◽

Vol 8 (4) ◽

pp. 283 ◽

Cited By ~ 3

Author(s):

Jennifer Geddes-McAlister ◽

Abirami Kugadas ◽

Mihaela Gadjeva

Keyword(s):

United States ◽

Pseudomonas Aeruginosa ◽

Bacterial Infections ◽

The United States ◽

Multidrug Resistant ◽

Bacterial Biofilms ◽

Spectroscopy Analysis ◽

Mass Spectroscopy Analysis ◽

Novel Therapeutic

Multidrug-resistant (MDR) bacterial infections are a leading cause of mortality, affecting approximately 250,000 people in Canada and over 2 million people in the United States, annually. The lack of efficacy of antibiotic-based treatments is often caused by inability of the drug to penetrate bacterial biofilms in sufficient concentrations, posing a major therapeutic challenge. Here, we review the most recent information about the architecture of Pseudomonas aeruginosa biofilms in vivo and describe how advances in imaging and mass spectroscopy analysis bring about novel therapeutic options and challenge existing dogmas.

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Pharmacodynamic Evaluation of the Activities of Six Parenteral Vancomycin Products Available in the United States

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03710-14 ◽

2014 ◽

Vol 59 (1) ◽

pp. 622-632 ◽

Cited By ~ 10

Author(s):

Arnold Louie ◽

Michael T. Boyne ◽

Vikram Patel ◽

Clayton Huntley ◽

Weiguo Liu ◽

...

Keyword(s):

United States ◽

Drug Exposure ◽

The United States ◽

Mouse Serum ◽

Infection Model ◽

Population Pharmacokinetic ◽

Bacterial Killing ◽

The Impact

ABSTRACTA recent report found that generic parenteral vancomycin products may not havein vivoefficacies equivalent to those of the innovator in a neutropenic murine thigh infection model despite having similarin vitromicrobiological activities and murine serum pharmacokinetics. We compared thein vitroandin vivoactivities of six of the parenteral vancomycin products available in the United States. Thein vitroassessments for the potencies of the vancomycin products included MIC/minimal bactericidal concentration (MBC) determinations, quantifying the impact of human and murine serum on the MIC values, and time-kill studies. Also, the potencies of the vancomycin products were quantified with a biological assay, and the human and mouse serum protein binding rates for the vancomycin products were measured. Thein vivostudies included dose-ranging experiments with the 6 vancomycin products for three isolates ofStaphylococcus aureusin a neutropenic mouse thigh infection model. The pharmacokinetics of the vancomycin products were assessed in infected mice by population pharmacokinetic modeling. No differences were seen across the vancomycin products with regard to anyin vitroevaluation. Inhibitory sigmoid maximal bacterial kill (Emax) modeling of the relationship between vancomycin dosage and the killing of the bacteria in micein vivoyielded similarEmaxand EC50(drug exposure driving one-halfEmax) values for bacterial killing. Further, there were no differences in the pharmacokinetic clearances of the 6 vancomycin products from infected mice. There were no important pharmacodynamic differences in thein vitroorin vivoactivities among the six vancomycin products evaluated.

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The rise in climate change-induced federal fishery disasters in the United States

PeerJ ◽

10.7717/peerj.11186 ◽

2021 ◽

Vol 9 ◽

pp. e11186

Author(s):

Lyall Bellquist ◽

Vienna Saccomanno ◽

Brice X. Semmens ◽

Mary Gleason ◽

Jono Wilson

Keyword(s):

Climate Change ◽

United States ◽

Harmful Algal Blooms ◽

Algal Blooms ◽

Ad Hoc ◽

The United States ◽

Societal Benefit ◽

Disaster Assistance ◽

Environmental Events ◽

The Impact

Commercial, recreational, and indigenous fisheries are critical to coastal economies and communities in the United States. For over three decades, the federal government has formally recognized the impact of fishery disasters via federal declarations. Despite these impacts, national syntheses of the dynamics, impacts, and causes of fishery disasters are lacking. We developed a nationwide Federal Fishery Disaster database using National Oceanic and Atmospheric Administration (NOAA) fishery disaster declarations and fishery revenue data. From 1989-2020, there were 71 federally approved fishery disasters (eleven are pending), which spanned every federal fisheries management region and coastal state in the country. To date, we estimate fishery disasters resulted in $2B (2019 USD) in Congressional allocations, and an additional, conservative estimate of $3.2B (2019 USD) in direct revenue loss. Despite this scale of impact, the disaster assistance process is largely ad hoc and lacks sufficient detail to properly assess allocation fairness and benefit. Nonetheless, fishery disasters increased in frequency over time, and the causes of disasters included a broad range of anthropogenic and environmental factors, with a recent shift to disasters now almost exclusively caused by extreme environmental events (e.g., marine heatwaves, hurricanes, and harmful algal blooms). Nationwide, 84.5% of fishery disasters were either partially or entirely attributed to extreme environmental events. As climate change drives higher rates of such extreme events, and as natural disaster assistance requests reach an all-time high, the federal system for fisheries disaster declaration and mitigation must evolve in order to effectively protect both fisheries sustainability and societal benefit.

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Antimicrobial Activity of Murepavadin Tested against Clinical Isolates of Pseudomonas aeruginosa from the United States, Europe, and China

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00311-18 ◽

2018 ◽

Vol 62 (7) ◽

Cited By ~ 14

Author(s):

Helio S. Sader ◽

Glenn E. Dale ◽

Paul R. Rhomberg ◽

Robert K. Flamm

Keyword(s):

United States ◽

Pseudomonas Aeruginosa ◽

Cyclic Peptide ◽

Polymyxin B ◽

The United States ◽

Broth Microdilution ◽

Content Type ◽

Microdilution Method ◽

Medical Centers ◽

Broth Microdilution Method

ABSTRACT Murepavadin (formerly POL7080), a 14-amino-acid cyclic peptide, and comparators were tested by the broth microdilution method against 1,219 Pseudomonas aeruginosa isolates from 112 medical centers. Murepavadin (MIC 50/90 , 0.12/0.12 mg/liter) was 4- to 8-fold more active than colistin (MIC 50/90 , 1/1 mg/liter) and polymyxin B (MIC 50/90 , 0.5/1 mg/liter) and inhibited 99.1% of isolates at ≤0.5 mg/liter. Only 4 isolates (0.3%) exhibited murepavadin MICs of >2 mg/liter. Murepavadin was equally active against isolates from Europe, the United States, and China.

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Activity of Ceftolozane-Tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae Isolates Collected from Respiratory Tract Specimens of Hospitalized Patients in the United States during 2013 to 2015

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02125-17 ◽

2017 ◽

Vol 62 (3) ◽

Cited By ~ 14

Author(s):

Mariana Castanheira ◽

Leonard R. Duncan ◽

Rodrigo E. Mendes ◽

Helio S. Sader ◽

Dee Shortridge

Keyword(s):

United States ◽

Pseudomonas Aeruginosa ◽

The United States ◽

Drug Resistant ◽

Broth Microdilution ◽

Content Type ◽

Extensively Drug Resistant ◽

Encoding Genes ◽

M 14

ABSTRACT The activities of ceftolozane-tazobactam and comparator agents against organisms deemed to be the cause of pneumonia among patients hospitalized in the United States during 2013 to 2015 were evaluated. Organisms included 1,576 Pseudomonas aeruginosa and 2,362 Enterobacteriaceae isolates susceptibility tested using reference broth microdilution methods. Ceftolozane-tazobactam, cefepime, ceftazidime, meropenem, and piperacillin-tazobactam inhibited 96.3%, 84.8%, 83.5%, 80.0%, and 78.6%, respectively, of the P. aeruginosa isolates. Ceftolozane-tazobactam inhibited 77.5 to 85.1% of isolates nonsusceptible to antipseudomonal β-lactams and 86.6% and 71.0% of the 372 (23.6% overall) multidrug- and 155 (9.8%) extensively drug-resistant isolates tested. The activity of this combination was greater than those of other β-lactams evaluated against P. aeruginosa groups across all U.S. census divisions. Ceftolozane-tazobactam was active against 90.6% of the Enterobacteriaceae , being less active than only meropenem (95.6% susceptible) among the β-lactams evaluated. Against 145 Escherichia coli and Klebsiella pneumoniae isolates carrying extended-spectrum-β-lactamase (ESBL)-encoding genes without carbapenemases, ceftolozane-tazobactam inhibited 82.8% of these isolates and was more active than cefepime and piperacillin-tazobactam (15.2% and 74.3% susceptible, respectively). ESBL genes included in this analysis were mainly bla CTX-M-15 -like (89 isolates) and bla CTX-M-14 -like (22) genes but also bla SHV (31) and bla TEM (3). Ceftolozane-tazobactam also displayed activity (84.6% susceptible) against 13 isolates harboring acquired AmpC genes. All β-lactams displayed limited activity against bla KPC -carrying isolates. Ceftolozane-tazobactam was the most active β-lactam tested against P. aeruginosa isolates from isolates that were the probable cause of pneumonia and displayed in vitro activity against Enterobacteriaceae , including isolates resistant to cephalosporins and carrying ESBL genes.

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