scholarly journals 1463. Activity of Delafloxacin against Multi-Drug-Resistant Fastidious Respiratory Pathogens from European Medical Centers (2014-2019)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S733-S733
Author(s):  
Dee Shorttidge ◽  
Jennifer M Streit ◽  
Michael D Huband ◽  
Robert K Flamm
Keyword(s):  
Active Agent ◽  
The United States ◽  
Multidrug Resistant ◽  
Respiratory Pathogens ◽  
Services Research ◽  
In Vitro Susceptibility ◽  
Amoxicillin Clavulanate ◽  
Tract Infections ◽  
Research Grant

Abstract Background Delafloxacin (DLX) is an anionic fluoroquinolone (FQ) that has been approved in the United States and in Europe for the treatment of acute bacterial skin and skin structure infections and was recently approved in the US for treatment of community-acquired bacterial pneumonia (CABP). In the present study, in vitro susceptibility (S) results for DLX and comparator agents were determined for CABP pathogens including Streptococcus pneumoniae (SPN), Haemophilus influenzae (HI), H. parainfluenzae (HP) and Moraxella catarrhalis (MC) clinical isolates from European hospitals participating in the SENTRY Program during 2014-2019. Methods A total of 2,835 SPN, 1,484 HI, 959 MC, and 20 HP isolates were collected from community-acquired respiratory tract infections (CARTI) during 2014-2019 from European hospitals. Sites included only 1 isolate/patient/infection episode. Isolate identifications were confirmed at JMI Laboratories. Susceptibility testing was performed according to CLSI broth microdilution methodology, and EUCAST (2020) breakpoints were applied where applicable. Other antimicrobials tested included levofloxacin (LEV) and moxifloxacin (MOX; not tested in 2015). Multidrug-resistant (MDR) SPN isolates were categorized as being nonsusceptible (NS) to amoxicillin-clavulanate, erythromycin (ERY), and tetracycline; other SPN phenotypes were ERY-NS, or penicillin (PEN)-NS. β-lactamase (BL) presence was determined for HI, HP, and MC. Results The activities of the 3 FQs are shown in the table. The most active agent against SPN was DLX, with the lowest MIC50/90 values of 0.015/0.03 mg/L. DLX activities were the same when tested against the MDR or PEN-NS for SPN phenotypes. ERY-NS isolates had DLX MIC50/90 results of 0.015/0.03 mg/L. DLX was the most active FQ against HI, HP, and MC. BL presence did not affect FQ MIC values for HI or MC; only 1 HP isolate was BL-positive. Conclusion DLX demonstrated potent in vitro antibacterial activity against SPN, HI, HP, and MC. DLX was active against MDR SPN that were NS to the agents commonly used as treatments for CABP. These data support the utility of DLX in CABP including when caused by antibiotic resistant strains. Table 1 Disclosures Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Robert K. Flamm, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)

scholarly journals 1582. Delafloxacin Activity Against Drug-Resistant Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, and Moraxella catarrhalis from US Medical Centers (2014–2018)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S577-S578
Author(s):  
Dee Shortridge ◽  
Jennifer M Streit ◽  
Michael D Huband ◽  
Robert K Flamm
Keyword(s):  
Streptococcus Pneumoniae ◽  
Haemophilus Influenzae ◽  
Moraxella Catarrhalis ◽  
Active Agent ◽  
The United States ◽  
Multidrug Resistant ◽  
In Vitro Susceptibility ◽  
Amoxicillin Clavulanate ◽  
Tract Infections

Abstract Background Delafloxacin (DLX) is an anionic fluoroquinolone (FQ) antimicrobial that was approved in 2017 by the United States (US) Food and Drug Administration for the treatment of acute bacterial skin and skin structure infections. DLX recently successfully completed a clinical trial for the treatment of community-acquired bacterial pneumonia (CABP). In the present study, in vitro susceptibility (S) results for DLX and comparator agents were determined for CABP pathogens including Streptococcus pneumoniae (SPN), Haemophilus influenzae (HI), H. parainfluenzae (HP) and Moraxella catarrhalis (MC) clinical isolates from US hospitals participating in the SENTRY Program during 2014–2018. Methods A total of 1,975 SPN, 1,128 HI, 684 MC, and 43 HP isolates were collected from community-acquired respiratory tract infections (CARTI) during 2014–2018 from US hospitals. Sites included only 1 isolate/patient/infection episode. Isolate identifications were confirmed at JMI Laboratories. Susceptibility testing was performed according to CLSI broth microdilution methodology, and CLSI (2019) breakpoints were applied where applicable. Other antimicrobials tested included levofloxacin (LEV) and moxifloxacin (MOX; not tested in 2015). Multidrug-resistant (MDR) SPN isolates were categorized as being nonsusceptible (NS) to amoxicillin-clavulanate, erythromycin, and tetracycline; other SPN phenotypes were LEV-NS or penicillin (PEN)-NS. β-Lactamase (BL) presence was determined for HI, HP, and MC. Results The activities of the 3 FQs are shown in the table. The most active agent against SPN was DLX, with the lowest MIC50/90 values of 0.015/0.03 mg/L. DLX activities were similar when tested against the MDR or PEN-NS for SPN phenotypes. LEV-NS isolates had DLX MIC50/90 results of 0.12/0.25 mg/L. DLX was the most active FQ against HI, HP, and MC. BL presence did not affect FQ MIC values for HI or MC; only 2 HP isolates were BL-positive. Conclusion DLX demonstrated potent in vitro antibacterial activity against SPN, HI, HP, and MC. DLX was active against MDR SPN that were NS to the agents commonly used as treatments for CABP. DLX had excellent activity against LEV-NS SPN. These data support the continued study of DLX as a potential treatment for CABP. Disclosures All authors: No reported disclosures.

scholarly journals Evaluation of In Vitro Activity of Ceftaroline Tested against Streptococcus pneumoniae Isolates from United States Hospitals: Results from 7 Years of the AWARE Surveillance Program (2010–2016)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S378-S378
Author(s):  
Michael A Pfaller ◽  
Rodrigo E Mendes ◽  
Leonard R Duncan ◽  
Robert K Flamm ◽  
Helio S Sader
Keyword(s):  
United States ◽  
The United States ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Amoxicillin Clavulanate ◽  
Infection Types ◽  
Research Grant

Abstract Background Ceftaroline (CPT) is a broad-spectrum cephalosporin with activity against S. pneumoniae (SPN), including multidrug-resistant (MDR) strains. CPT fosamil is approved for clinical use in the United States (US) to treat community-acquired bacterial pneumonia (CABP). The AWARE Program monitors the in vitro activity of CPT against clinical bacteria from various infection types. We evaluated the activity of CPT against isolated SPN clinical isolates from US hospitals collected in 2010 through 2016. Methods A total of 8,768 isolates were consecutively collected (1 per patient) from 47 medical centers in 2010–2016 and tested for susceptibility (S) to CPT and comparator agents using CLSI broth microdilution methods. Resistant subgroups included isolates that were nonsusceptible (NS) to penicillin (PCN), ceftriaxone (CRO), amoxicillin-clavulanate (AMC), erythromycin (ERY), clindamycin (CM), and levofloxacin (LEV) as well as MDR (NS to ≥3 classes of agents) and extensively drug resistant (XDR; NS to ≥5 classes). Results CPT inhibited 99.99% of SPN isolates at ≤0.5 mg/L (only 1 isolate had a CPT MIC of 1 mg/L) and remained active against all SPN-resistant (R) subgroups, including PCN-NS (8.7% at ≥4 mg/L), CRO-NS (6.9% at ≥2 mg/L), MDR (21.7%), and XDR (8.4%) strains. CPT activity remained stable against all R subgroups each year. MDR and XDR frequency decreased from 25.0% and 14.1% in 2011 to 17.8% and 3.2% in 2015, respectively; and S to PCN, CRO, AMC, CM, trimethoprim-sulfamethoxazole (TMX), and tetracycline (TET) increased in the same period (Table). The CPT-NS isolate had multiple substitutions in the penicillin binding proteins (PBP), mainly PBP2x, when compared with reference sequences, and showed 31 amino acid alterations in MurM. For MDR isolates, CPT (99.9%S), tigecycline (99.9%S), linezolid (100.0%S), and vancomycin (100.0%S) were the most active agents. Conclusion CPT demonstrated potent and consistent (2010–2016) activity against SPN, including several R phenotypes and the less S serotypes. SPN S to many antibiotics increased from 2011 to 2015, but remained stable in 2015–2016. Increases in S rates could be related to the anti-pneumococcal vaccine PVC-13 introduced in 2010. Disclosures M. A. Pfaller, Allergan: Research Contractor, Research grant; R. E. Mendes, Allergan: Research Contractor, Research grant; L. R. Duncan, Allergan: Research Contractor, Research grant; R. K. Flamm, Allergan: Research Contractor, Research grant; H. S. Sader, Allergan: Research Contractor, Research grant

scholarly journals Comparison of the In Vitro Susceptibility of Ceftolozane-Tazobactam With the Cumulative Susceptibility Rates of Standard Antibiotic Combinations When Tested Against Pseudomonas aeruginosa From ICU Patients With Bloodstream Infections or Pneumonia

2019 ◽  
Vol 6 (6) ◽  
Author(s):  
Dee Shortridge ◽  
Michael A Pfaller ◽  
S J Ryan Arends ◽  
Janet Raddatz ◽  
Daryl D DePestel ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bloodstream Infections ◽  
The United States ◽  
Multidrug Resistant ◽  
In Vitro Susceptibility ◽  
Patients At Risk ◽  
Seriously Ill Patients ◽  
Tract Infections ◽  
Hospital Acquired

Abstract Background Pseudomonas aeruginosa remains an important cause of hospital-acquired infections in the United States and is frequently multidrug-resistant (MDR). The Infectious Diseases Society of America guidelines recommend empiric combination therapy that includes an antipseudomonal β-lactam with an aminoglycoside or fluoroquinolone likely to cover ≥95% of P. aeruginosa infections in seriously ill patients at risk of having an MDR pathogen. Ceftolozane is an antipseudomonal cephalosporin, combined with the β-lactamase inhibitor tazobactam. Ceftolozane-tazobactam is approved for treatment of complicated urinary tract infections and complicated intra-abdominal infections. A phase 3 clinical trial for the treatment of hospital-acquired pneumonia including ventilator-associated pneumoniae was recently completed. We compared the in vitro susceptibility rate of ceftolozane-tazobactam with the cumulative susceptibility rates of antibiotic combinations commonly used against P. aeruginosa. Methods Isolates were collected from intensive care unit patients hospitalized in 32 US hospitals from 2011 to 2017. The susceptibilities of 1543 P. aeruginosa isolates from bloodstream infections (198 isolates, 12.8%) or pneumonia (1345 isolates, 87.2%) were determined for ceftolozane-tazobactam and comparators. Results The most active antimicrobials were colistin (99.4% susceptible), amikacin (98.1% susceptible), and ceftolozane-tazobactam (96.5% susceptible). The susceptibilities to other antipseudomonal β-lactams and fluoroquinolones were <84%. A cumulative susceptibility of ≥95% was reached for cefepime, ceftazidime, meropenem, and piperacillin-tazobactam only in combination with amikacin due to the lower susceptibilities of gentamicin, ciprofloxacin, and levofloxacin. Monotherapies that exceeded 95% were ceftolozane-tazobactam, amikacin, and colistin. Conclusions Ceftolozane-tazobactam monotherapy is likely to be active against more isolates than a combination of another β-lactam and a fluoroquinolone or gentamicin for serious P. aeruginosa infections.

scholarly journals In Vitro Evaluation of Delafloxacin Activity when Tested Against Contemporary community-Acquired Bacterial Respiratory Tract Infection Isolates (2014–2016): Results from the Sentry Antimicrobial Surveillance Program

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S369-S369 ◽  
Author(s):  
Dee Shortridge ◽  
Jennifer M Streit ◽  
Michael D Huband ◽  
Paul R Rhomberg ◽  
Robert K Flamm
Keyword(s):  
Respiratory Tract ◽  
Drug Application ◽  
The United States ◽  
Community Acquired Pneumonia ◽  
Surveillance Program ◽  
In Vitro Susceptibility ◽  
Antimicrobial Surveillance ◽  
Tract Infections ◽  
Research Grant

Abstract Background Delafloxacin (DLX) is a broad-spectrum fluoroquinolone (FQ) antibacterial that has completed clinical development (oral and intravenous formulations) with the new drug application currently under the Food and Drug Administration review for the treatment of acute bacterial skin and skin structure infections (ABSSSI). DLX is also in clinical trials for community-acquired bacterial pneumonia. In this study, in vitro susceptibility results for DLX and comparator agents were determined for clinical isolates from community-acquired respiratory tract infections (CA-RTI) collected in medical centers in the United States and Europe participating in the SENTRY surveillance program during 2014–2016. Methods A total of 3,093 isolates that included 1,673 Streptococcus pneumoniae (SPN), 805 Haemophilus influenzae (HI) and 555 Moraxella catarrhalis (MC) were collected during 2014–2016 and included only 1 isolate/patient/infection episode. Isolate identifications were confirmed at JMI Laboratories. Susceptibility testing was performed according to CLSI reference broth microdilution methodology, and results were interpreted per CLSI (2017) breakpoints. Other antibacterials tested included levofloxacin (LVX) and penicillin. Β-lactamase production for HI and MC was determined by the nitrocephin disk test. Results DLX demonstrated potent in vitro activity against SPN (MIC50/90 0.015/0.03 mg/L). Activity remained the same for penicillin-intermediate or -resistant isolates. For 23 LVX nonsusceptible SPN, the DLX MIC50/90 were 0.12/0.25 mg/L with all isolates having DLX MIC values ≤1 mg/L. For HI, the DLX MIC50/90 were ≤0.001/0.004 mg/L, and for MC the MIC50/90 were 0.008/0.008 mg/L. DLX activity was unaffected by the presence of β-lactamase for either HI or MC. Activity of DLX was similar for US and European isolates. Conclusion Delafloxacin demonstrated potent in vitro antibacterial activity against CA-RTI pathogens, including SPN, HI, and MC. These data support the continued study of DLX as a potential treatment for community-acquired pneumonia. Disclosures D. Shortridge, Melinta Therapeutics: Research Contractor, Research grant; J. M. Streit, Melinta Therapeutics: Research Contractor, Research grant; M. D. Huband, Melinta Therapeutics: Research Contractor, Research grant; P. R. Rhomberg, Melinta Therapeutics: Research Contractor, Research grant; R. K. Flamm, Melinta Therapeutics: Research Contractor, Research grant

scholarly journals In Vitro Activities of Peptide Deformylase Inhibitors against Gram-Positive Pathogens

2002 ◽  
Vol 46 (4) ◽  
pp. 1117-1118 ◽  
Author(s):  
R. Wise ◽  
J. M. Andrews ◽  
J. Ashby
Keyword(s):  
Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Active Agent ◽  
Peptide Deformylase ◽  
Gram Positive ◽  
Similar Activity ◽  
Amoxicillin Clavulanate ◽  
Tract Infections

ABSTRACT The activities of six peptide deformylase (PDF) inhibitors against 107 respiratory tract pathogens were studied and compared to those of ciprofloxacin and amoxicillin-clavulanate. Against Streptococcus pneumoniae, BB-83698 and BB-83815 were the most active PDF inhibitors (MIC at which 90% of the organisms tested were inhibited [MIC90], 0.25 μg/ml). Five of the agents showed similar activity against Moraxella catarrhalis (MIC90, 0.12 μg/ml). All PDF inhibitors were less active against Haemophilus influenzae; BB-3497 was the most active agent (MIC90, 2 μg/ml). Five agents were studied against Chlamydia spp. and showed activity similar to that of ciprofloxacin (MIC, 0.5 to 4 μg/ml). This study demonstrates that PDF inhibitors have the potential to be developed for the treatment of respiratory tract infections.

scholarly journals Ceftazidime/Avibactam: Who Says You Can’t Teach an Old Drug New Tricks?

2016 ◽  
Vol 19 (4) ◽  
pp. 448 ◽  
Author(s):  
Katie E. Barber ◽  
Jessica K. Ortwine ◽  
Ronda L Akins
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
The United States ◽  
Phase Iii ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
Tract Infections ◽  
Abdominal Infections

Purpose: Gram-negative resistance continues to rise with treatment options becoming more limited. Ceftazidime/avibactam was recently approved in the United States and Europe, which combines an established third-generation cephalosporin with a new, unique, non-β-lactam β-lactamase inhibitor. This review conducts a thorough examination of structure, pharmacology, spectrum of activity, pharmacokinetics/pharmacodynamics, in vitro and clinical efficacy and safety/tolerability of ceftazidime/avibactam, as well as detailed future directions for the agent. Methods: Pubmed and clinicaltrials.gov searches, as well as abstracts from the 2015 Interscience Conference on Antimicrobial Agents and Chemotherapy/International Society of Chemotherapy (ICAAC/ICC) and ID Week meetings and the 2016 American Society of Microbiology Microbe meeting, were conducted from January 2004 – September 2016. Relevant search terms included ceftazidime, ceftazidime/avibactam, avibactam, NXL104 and AVE1330A. The US package insert for ceftazidime/avibactam (02/2015) and European public assessment report (06/2016) were also reviewed. Results: In vitro susceptibility for ceftazidime/avibactam displayed potent activity against many Enterobacteriaceae including extended-spectrum-β-lactamase (ESBL) and carbapenemase-producing strains, as well as Pseudomonas aeruginosa. Phase II clinical trials utilized for approval demonstrated comparable safety and efficacy to imipenem/cilistatin for treatment of complicated urinary tract infections (70.4% vs. 71.4%) and combined with metronidazole compared to meropenem in complicated intra-abdominal infections (91.2% vs 93.4%). Phase III data displayed non-inferior efficacy of ceftazidime/avibactam compared to doripenem for complicated urinary tract infections (70.2% vs 66.2%) and combined with metronidazole compared to meropenem in complicated intra-abdominal infections (82.5% vs 84.9%), as well as comparable safety. Ceftazidime/avibactam was well-tolerated but does require renal adjustments. Additionally, 3 case series and a single case report have demonstrated the potential for ceftazidime/avibactam against multidrug resistant organisms for compassionate use or failure after previous therapy. Conclusion: By adding avibactam to ceftazidime, clinicians’ antimicrobial armamentarium is expanded, potentially increasing the ability to combat multi-drug resistant gram-negative pathogens, particularly ESBL and carbapenemase-producing organisms, as well as Pseudomonas aeruginosa. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals National and Regional Assessment of Antimicrobial Resistance among Community-Acquired Respiratory Tract Pathogens Identified in a 2005-2006 U.S. Faropenem Surveillance Study

2007 ◽  
Vol 51 (12) ◽  
pp. 4382-4389 ◽  
Author(s):  
Ian A. Critchley ◽  
Steven D. Brown ◽  
Maria M. Traczewski ◽  
Glenn S. Tillotson ◽  
Nebojsa Janjic
Keyword(s):  
United States ◽  
Respiratory Tract ◽  
Respiratory Infections ◽  
Empirical Therapy ◽  
The United States ◽  
Respiratory Pathogens ◽  
Study Objective ◽  
Tract Infections ◽  
Resistance Rates

ABSTRACT Surveillance studies conducted in the United States over the last decade have revealed increasing resistance among community-acquired respiratory pathogens, especially Streptococcus pneumoniae, that may limit future options for empirical therapy. The objective of this study was to assess the scope and magnitude of the problem at the national and regional levels during the 2005-2006 respiratory season (the season when community-acquired respiratory pathogens are prevalent) in the United States. Also, since faropenem is an oral penem being developed for the treatment of community-acquired respiratory tract infections, another study objective was to provide baseline data to benchmark changes in the susceptibility of U.S. respiratory pathogens to the drug in the future. The in vitro activities of faropenem and other agents were determined against 1,543 S. pneumoniae isolates, 978 Haemophilus influenzae isolates, and 489 Moraxella catarrhalis isolates collected from 104 U.S. laboratories across six geographic regions during the 2005-2006 respiratory season. Among S. pneumoniae isolates, the rates of resistance to penicillin, amoxicillin-clavulanate, and cefdinir were 16, 6.4, and 19.2%, respectively. The least effective agents were trimethoprim-sulfamethoxazole (SXT) and azithromycin, with resistance rates of 23.5 and 34%, respectively. Penicillin resistance rates for S. pneumoniae varied by region (from 8.7 to 22.5%), as did multidrug resistance rates for S. pneumoniae (from 8.8 to 24.9%). Resistance to β-lactams, azithromycin, and SXT was higher among S. pneumoniae isolates from children than those from adults. β-Lactamase production rates among H. influenzae and M. catarrhalis isolates were 27.4 and 91.6%, respectively. Faropenem MICs at which 90% of isolates are inhibited were 0.5 μg/ml for S. pneumoniae, 1 μg/ml for H. influenzae, and 0.5 μg/ml for M. catarrhalis, suggesting that faropenem shows promise as a treatment option for respiratory infections caused by contemporary resistant phenotypes.

scholarly journals In Vitro Activity of Lefamulin Against a Global Collection of Bacterial Pathogens Commonly Causing Community-Acquired Bacterial Pneumonia (CABP, SENTRY 2015)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S373-S373 ◽  
Author(s):  
Susanne Paukner ◽  
Helio S Sader ◽  
Jennifer M Streit ◽  
Robert K Flamm ◽  
Steven P Gelone
Keyword(s):  
Respiratory Tract ◽  
Bacterial Pathogens ◽  
Bloodstream Infections ◽  
Vitro Activity ◽  
Asia Pacific ◽  
Respiratory Pathogens ◽  
In Vitro Activity ◽  
Tract Infections ◽  
Research Grant

Abstract Background CABP is the number one reason for death by infectious diseases worldwide and emerging resistance complicates its treatment. Lefamulin is the first semi-synthetic pleuromutilin antibiotic for IV and oral use in humans. It is currently in Phase 3 trials for the treatment of CABP in adults. Lefamulin effectively and selectively inhibits bacterial translation by binding to the peptidyl transferase center (PTC) via four H-bonds and other interactions at the A- and P-site resulting in an “induced fit.” This study investigated the activity of lefamulin and comparators against a contemporary set of bacterial pathogens associated with community-acquired respiratory infections collected worldwide. Methods Unique patients’ isolates (n = 2817) were collected globally in US (19.7%), Europe (36.9%), Latin America (5.7%) and Asia-Pacific region (37.6%) (30 countries, 116 sites) from adult and pediatric patients with respiratory tract infection (88.0%), bloodstream infections (5.5%) and other infections (2.4%). Lefamulin and comparators were tested by CLSI broth microdilution and susceptibility was determined using the CLSI (2017) breakpoints. Results LEF was the most potent compound tested, with 99.7% of all S. pneumoniae isolates being inhibited at a concentration of ≤0.25 mg/L (MIC50/90 values of 0.06/0.12 mg/L) and its activity was not affected by resistance to other antibiotic classes. S. pneumoniae isolates were largely susceptible to levofloxacin (99.1%) and ceftriaxone (96.5%), while 34.5%, 23.3% and 16.8% of isolates were resistant to macrolides, tetracycline and clindamycin, respectively. Lefamulin also showed potent activity against H. influenzae (MIC50/90 of 0.5/1 mg/L), including 22.0% of ß-lactamase producing strains, and M. catarrhalis (0.06/0.12 mg/L). Conclusion Lefamulin demonstrated potent in vitro activity against this global collection of contemporary respiratory pathogens and its activity was unchanged regardless of resistance phenotype to the other antibiotic classes including macrolides, ß-lactams, tetracyclines or fluoroquinolones. These data support the continued clinical development of lefamulin for the treatment of respiratory tract infections, including CABP. Disclosures S. Paukner, Nabriva Therapeutics: Employee and Shareholder, Salary; H. S. Sader, Nabriva Therapeutics: Research Contractor, Research grant; J. M. Streit, Nabriva Therapeutics: Research Contractor, Research grant; R. K. Flamm, Nabriva Therapeutics: Research Contractor, Research grant; S. P. Gelone, Nabriva Therapeutics: Employee and Shareholder, Salary

scholarly journals 1353. In Vitro Activity of Lefamulin (LEF) Against Bacterial Pathogens Commonly Causing Community-Acquired Bacterial Pneumonia (CABP): 2016 SENTRY Data From the United States

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S414-S414 ◽  
Author(s):  
Susanne Paukner ◽  
Robert K Flamm ◽  
Steven P Gelone ◽  
Helio S Sader
Keyword(s):  
United States ◽  
Ribosomal Subunit ◽  
The United States ◽  
Vitro Activity ◽  
Surveillance Program ◽  
Respiratory Pathogens ◽  
In Vitro Activity ◽  
Medical Centers ◽  
Tract Infections

Abstract Background LEF, the first pleuromutilin antibiotic for IV and oral use in humans, is in Phase 3 clinical trials for the treatment of CABP in adults. In the first of these to be completed, LEF demonstrated noninferiority to moxifloxacin ± linezolid. LEF inhibits bacterial translation by binding the 50S ribosomal subunit at the A- and P-sites in the peptidyl transferase center. CABP is a leading cause of infectious diseases in the United States and increasing antibacterial resistance complicates its treatment. This study investigated the in vitro activity of LEF and comparators against a contemporary set of bacterial respiratory pathogens collected in the United States. Methods Isolates (n = 1674, 1/patient) were collected from 32 medical centers in the United States as part of the SENTRY Surveillance Program. LEF and comparators were tested by CLSI broth microdilution methods, and susceptibility was determined using the CLSI (2018) breakpoints. Results LEF was the most active compound against Streptococcus pneumoniae (MIC50/90 of 0.12/0.12 µg/mL), and its activity was not affected by resistance to other antibiotic classes. S. pneumoniae isolates were susceptible to levofloxacin (99.1%) and ceftriaxone (97.7%), whereas only 53.9%, 63.9%, and 80.4% of isolates were susceptible to macrolides, penicillin (oral), and tetracycline, respectively. LEF also showed potent activity against Staphylococcus aureus (MIC50/90 of 0.06/0.12 µg/mL), including methicillin-resistant (MRSA) isolates (MIC50/90 of 0.06/0.12 µg/mL, 87.1% resistant to erythromycin), Haemophilus influenzae, (MIC50/90 of 0.5/1 µg/mL, 26.9% β-lactamase producing), and Moraxella catarrhalis (MIC50/90 0.06/0.06 µg/mL, 96.5% β-lactamase positive) (figure). Conclusion LEF displayed potent in vitro activity against a contemporary collection of respiratory pathogens from the United States. LEF was active regardless of resistance phenotype to other antibiotic classes including β-lactams, tetracyclines, or macrolides. These results further support the clinical development of lefamulin for the treatment of CABP or other respiratory tract infections. Disclosures S. Paukner, Nabriva: Employee and Shareholder, Salary. R. K. Flamm, Nabriva: Research Contractor, Research grant. S. P. Gelone, Nabriva Therapeutics: Employee, Equity, Shareholder and Salary. Achaogen: Shareholder, Equity, Shareholder. H. S. Sader, Nabriva Therapeutics: Research Contractor, Research support.

scholarly journals Evaluation of Current Activities of Fluoroquinolones against Gram-Negative Bacilli Using Centralized In Vitro Testing and Electronic Surveillance

2001 ◽  
Vol 45 (1) ◽  
pp. 267-274 ◽  
Author(s):  
Daniel F. Sahm ◽  
Ian A. Critchley ◽  
Laurie J. Kelly ◽  
James A. Karlowsky ◽  
David C. Mayfield ◽  
...  
Keyword(s):  
The United States ◽  
Multidrug Resistant ◽  
Fluoroquinolone Resistance ◽  
Electronic Surveillance ◽  
Surveillance Network ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
Resistance Patterns ◽  
Clinically Significant

ABSTRACT Given the propensity for Enterobacteriaceae and clinically significant nonfermentative gram-negative bacilli to acquire antimicrobial resistance, consistent surveillance of the activities of agents commonly prescribed to treat infections arising from these organisms is imperative. This study determined the activities of two fluoroquinolones, levofloxacin and ciprofloxacin, and seven comparative agents against recent clinical isolates ofEnterobacteriaceae, Pseudomonas aeruginosa,Acinetobacter baumannii, and Stenotrophomonas maltophilia using two surveillance strategies: 1) centralized in vitro susceptibility testing of isolates collected from 27 hospital laboratories across the United States and 2) analysis of data from The Surveillance Network Database-USA, an electronic surveillance network comprising more than 200 laboratories nationwide. Regardless of the surveillance method, Enterobacteriaceae,P. aeruginosa, and A. baumannii demonstrated similar rates of susceptibility to levofloxacin and ciprofloxacin. Susceptibilities to the fluoroquinolones approached or exceeded 90% for all Enterobacteriaceae except Providenciaspp. (≤65%). Approximately 70% of P. aeruginosa and 50% of A. baumanii isolates were susceptible to both fluoroquinolones. Among S. maltophilia isolates, 50% more isolates were susceptible to levofloxacin than to ciprofloxacin. Overall, the rate of ceftazidime nonsusceptibility amongEnterobacteriaceae was 8.7%, with fluoroquinolone resistance rates notably higher among ceftazidime-nonsusceptible isolates than ceftazidime-susceptible ones. Multidrug-resistant isolates were present among all species tested but were most prevalent for Klebsiella pneumoniae andEnterobacter cloacae. No gram-negative isolates resistant only to a fluoroquinolone were encountered, regardless of species. Thus, while levofloxacin and ciprofloxacin have maintained potent activity against Enterobacteriaceae, the potential for fluoroquinolone resistance, the apparent association between fluoroquinolone and cephalosporin resistance, and the presence of multidrug resistance in every species examined emphasize the need to maintain active surveillance of resistance patterns among gram-negative bacilli.

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