scholarly journals In Vitro Pharmacodynamic Activities of ABT-492, a Novel Quinolone, Compared to Those of Levofloxacin against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis

2004 ◽  
Vol 48 (1) ◽  
pp. 203-208 ◽  
Author(s):  
Shana M. Gunderson ◽  
Robert A. Hayes ◽  
John P. Quinn ◽  
Larry H. Danziger
Keyword(s):  
Streptococcus Pneumoniae ◽  
Haemophilus Influenzae ◽  
Moraxella Catarrhalis ◽  
Maximal Activity ◽  
Community Acquired Pneumonia ◽  
Maximal Effect ◽  
Bacterial Isolates ◽  
Atypical Pathogens ◽  
Time Kill

ABSTRACT ABT-492 is a novel quinolone with potent activity against gram-positive, gram-negative, and atypical pathogens, making this compound an ideal candidate for the treatment of community-acquired pneumonia. We therefore compared the in vitro pharmacodynamic activity of ABT-492 to that of levofloxacin, an antibiotic commonly used for the treatment of pneumonia, through MIC determination and time-kill kinetic analysis. ABT-492 demonstrated potent activity against penicillin-sensitive, penicillin-resistant, and levofloxacin-resistant Streptococcus pneumoniae strains (MICs ranging from 0.0078 to 0.125 μg/ml); β-lactamase-positive and β-lactamase-negative Haemophilus influenzae strains (MICs ranging from 0.000313 to 0.00125 μg/ml); and β-lactamase-positive and β-lactamase-negative Moraxella catarrhalis strains (MICs ranging from 0.001 to 0.0025 μg/ml), with MICs being much lower than those of levofloxacin. Both ABT-492 and levofloxacin demonstrated concentration-dependent bactericidal activities in time-kill kinetics studies at four and eight times the MIC with 10 of 12 bacterial isolates exposed to ABT-492 and with 12 of 12 bacterial isolates exposed to levofloxacin. Sigmoidal maximal-effect models support concentration-dependent bactericidal activity. The model predicts that 50% of maximal activity can be achieved with concentrations ranging from one to two times the MIC for both ABT-492 and levofloxacin and that near-maximal activity (90% effective concentration) can be achieved at concentrations ranging from two to five times the MIC for ABT-492 and one to six times the MIC for levofloxacin.

scholarly journals In Vitro Activities of Novel 2-Fluoro-Naphthyridine-Containing Ketolides

2005 ◽  
Vol 49 (1) ◽  
pp. 309-315 ◽  
Author(s):  
Darren Abbanat ◽  
Glenda Webb ◽  
Barbara Foleno ◽  
Y. Li ◽  
Mark Macielag ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Streptococcus Pneumoniae ◽  
Respiratory Tract ◽  
Haemophilus Influenzae ◽  
Moraxella Catarrhalis ◽  
Bacterial Strains ◽  
Erythromycin A ◽  
Time Kill ◽  
Vitro Protein

ABSTRACT In vitro activities of erythromycin A, telithromycin, and two investigational ketolides, JNJ-17155437 and JNJ-17155528, were evaluated against clinical bacterial strains, including selected common respiratory tract pathogens. Against 46 macrolide-susceptible and -resistant Streptococcus pneumoniae strains, the MIC90 (MIC at which 90% of the isolates tested were inhibited) of the investigational ketolides was 0.25 μg/ml, twofold lower than that of telithromycin and at least 64-fold lower than that of erythromycin A. Against erm(B)-containing pneumococci, the MIC90 of all the ketolides was 0.06 μg/ml. The MIC90 of the investigational ketolides against mef(A)-containing pneumococci or pneumococci with both mef(A) and erm(B) was 0.25 μg/ml, two-and fourfold lower, respectively, than that of telithromycin. In contrast, the MICs of the investigational ketolides against macrolide-resistant S. pneumoniae strains with ribosomal mutations were similar to or, in some cases, as much as eightfold higher than those of telithromycin. Against Haemophilus influenzae, MICs of all the ketolides were ≤2 μg/ml. Against three Moraxella catarrhalis isolates, the MIC of the ketolides was 0.25 μg/ml. The ketolides inhibited in vitro protein synthesis, with 50% inhibitory concentrations ranging from 0.23 to 0.27 μM. In time-kill studies against macrolide-susceptible and erm- or mef-containing pneumococci, the ketolides were bacteriostatic to slowly bactericidal, with 24-h log10 decreases ranging from 2.0 to 4.1 CFU. Intervals of postantibiotic effects for the ketolides against macrolide-susceptible and -resistant S. pneumoniae were 3.0 to 8.1 h.

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 In-vitro activity of levofloxacin against bacterial pathogens collected in China：A ten-year（2009-2018） retrospective study

2020 ◽  
Author(s):  
LU GAN ◽  
Yun Li ◽  
Yuan Lv ◽  
Bo Zheng
Keyword(s):  
Streptococcus Pneumoniae ◽  
Klebsiella Pneumoniae ◽  
Haemophilus Influenzae ◽  
Community Acquired Pneumonia ◽  
Resistance Rate ◽  
Gram Negative Bacteria ◽  
Icu Patients ◽  
Gram Negative ◽  
Resistance Rates

Abstract Background： This study was designed to evaluate the in-vitro activity of levofloxacin against bacterial pathogens collected from Chinese hospitalized patients between 2009 and 2018, and analysis the trends of levofloxacin resistance in China.Methods In this analysis, antimicrobial minimum inhibitory concentrations (MICs) experiments with levofloxacin and controls against a range of Gram-positive and Gram-negative bacteria collected from 2009 to 2018. MICs were determined using the agar dilution method according to the guidelines of Clinical and Laboratory Standards Institute (CLSI)，2019. Antimicrobial susceptibility was determined using CLSI breakpoints. Statistical tests were analysed by Statistical Package for the Social Sciences software (SPSS, Inc., Chicago, IL, USA), calculating the MIC90.Results In the past decade，the antibacterial activities of levofloxacin against Escherichia coli, Enterobacter cloacae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia, which were common gram-negative bacteria, were stable; the resistance rates of these bacteria had no significant changes or decreased slightly. The levofloxacin resistance rates of Staphylococcus aureus and Enterococcus faecalis, which were gram positive bacteria, decreased from 48.4% and 36.9% in 2009-2010 to 22.8% and 25.7% in 2017-2018, respectively, respectively. The levofloxacin resistance rate among Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus pneumoniae, the common pathogens of community acquired pneumonia (CAP), were less than 3%. The levofloxacin resistance rates for Klebsiella pneumoniae and Acinetobacter baumannii increased. No difference in the levofloxacin resistance rates by age group (18-64, 65-74, ≥75 years old age groups) was observed. The resistance rate of strains isolated from ICU patients was usually 10-20% higher than that of non-ICU patients.Conclusion In recent ten years, levofloxacin has continued to be active in-vitro against the strains in its antibacterial spectrum. No significant change of resistance rates was observed and it still has a good antibacterial effect on the main pathogenic bacteria of community-acquired pneumonia, such as Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae and MSSA.

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