Posts filed under ‘Infecciones respiratorias’

Comparative In Vitro Activity of Omadacycline against Dog and Cat Bite Wound Isolates.

Antimicrob Agents Chemother. 2018 Mar 27;62(4). pii: e02551-17.

Goldstein EJC1,2, Citron DM3, Tyrrell KL3, Leoncio E3, Merriam CV3.

Abstract

Omadacycline was tested against 125 isolates recovered from infected cat and dog bites in humans.

Its activity was similar to that of other compounds in the tetracycline class, and it was active against strains exhibiting tetracycline resistance.

Against anaerobic isolates, resistance to tetracyclines was more prominent and omadacycline was the most active of the group.

All isolates had omadacycline MICs of <1 μg/ml, with the exception of Eikenella corrodens, which showed reduced susceptibility to the entire tetracycline group.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914009/pdf/e02551-17.pdf

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November 18, 2018 at 11:58 am

In Vitro Activities of Omadacycline and Comparators against Anaerobic Bacteria.

Antimicrob Agents Chemother. 2018 Mar 27;62(4). pii: e00047-18.

Stapert L1, Wolfe C1, Shinabarger D1, Marra A2, Pillar C1.

Abstract

Omadacycline (OMC), a broad-spectrum aminomethylcycline, has shown clinical efficacy in anaerobic acute bacterial skin and skin structure infections (ABSSSI) and in animal models of intra-abdominal anaerobic infections.

Here, the in vitro activity of OMC against clinically relevant anaerobes was similar to that of tigecycline, with MIC90 values of 1 to 8 μg/ml against Bacteroides spp., 0.5 μg/ml against Clostridium difficile, Prevotella spp., and Porphyromonas asaccharolytica, 1 μg/ml against Peptostreptococcus spp., and 16 μg/ml against Clostridium perfringens.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5913939/pdf/e00047-18.pdf

November 18, 2018 at 11:56 am

Surveillance of Omadacycline Activity Tested against Clinical Isolates from the United States and Europe as Part of the 2016 SENTRY Antimicrobial Surveillance Program.

Antimicrob Agents Chemother. 2018 Mar 27;62(4). pii: e02327-17.

Pfaller MA1,2, Huband MD3, Shortridge D1, Flamm RK1.

Abstract

Omadacycline was tested against 21,000 bacterial isolates collected prospectively from medical centers in Europe and the United States during 2016.

Omadacycline was active against Staphylococcus aureus (MIC50/MIC90, 0.12/0.25 mg/liter), including methicillin-resistant S. aureus (MRSA); streptococci (MIC50/MIC90, 0.06/0.12 mg/liter), including Streptococcus pneumoniae, viridans group streptococci, and beta-hemolytic streptococci; Enterobacteriaceae, including Escherichia coli (MIC50/MIC90, 0.5/2 mg/liter); Haemophilus influenzae (MIC50/MIC90, 1/1 mg/liter); and Moraxella catarrhalis (MIC50/MIC90, 0.25/0.25 mg/liter).

Omadacycline merits further study in serious infections where resistant pathogens may be encountered

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5913935/pdf/e02327-17.pdf

 

November 18, 2018 at 11:55 am

Safety and Pharmacokinetics of the Aminomethylcycline Antibiotic Omadacycline Administered to Healthy Subjects in Oral Multiple-Dose Regimens.

Antimicrob Agents Chemother. 2018 Jan 25;62(2). pii: e01487-17.

Bundrant LA1, Tzanis E2, Garrity-Ryan L3, Bai S2, Chitra S2, Manley A2, Villano S2.

Abstract

Omadacycline, a first-in-class aminomethylcycline antibiotic, is related to tetracyclines but is structurally modified to circumvent mechanisms of resistance to tetracyclines.

Omadacycline demonstrates potent activity against a broad range of pathogens, including drug-resistant strains, and is in late-stage development for treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia.

Previous studies support an intravenous-to-oral transition regimen with 300-mg once-daily oral dosing.

This phase 1 study investigated the pharmacokinetics and safety/tolerability of multiple oral omadacycline doses higher than 300 mg.

Using a 3-period crossover design, healthy adults were randomized to receive oral omadacycline at 300, 450, and 600 mg in variable sequence (n = 26) or placebo (n = 7) once daily for 5 consecutive days per period. In plasma, omadacycline maximum concentration and total exposure increased with increasing dose but were less than dose proportional.

The kinetics of omadacycline plasma accumulation were similar between dose levels; exposure on day 5 was ∼50% higher than that on day 1.

Omadacycline plasma concentrations on day 1 of 450-mg dosing were similar to those on day 5 of 300-mg dosing.

All doses were generally well tolerated, but the 600-mg dose was associated with more gastrointestinal adverse events.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786815/pdf/e01487-17.pdf

November 18, 2018 at 11:54 am

Pharmacokinetics and Safety of Omadacycline in Subjects with Impaired Renal Function.

Antimicrob Agents Chemother. 2018 Jan 25;62(2). pii: e02057-17.

Berg JK1, Tzanis E2, Garrity-Ryan L3, Bai S2, Chitra S2, Manley A2, Villano S2.

Abstract

Many antibiotics require dose adjustments in patients with renal impairment and/or in those undergoing hemodialysis.

Omadacycline, the first aminomethylcycline antibiotic in late-stage clinical development, displays activity against a broad spectrum of bacterial pathogens, including drug-resistant strains.

Data from completed phase 3 studies of omadacycline for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP) showed intravenous (i.v.) to once-daily oral omadacycline to be clinically effective and well tolerated.

To determine if the dosing of omadacycline should be adjusted in patients with impaired renal function, a phase 1 study examining the pharmacokinetics (PK) and safety of i.v. omadacycline (100 mg) was conducted in subjects with end-stage renal disease (ESRD) on stable hemodialysis (n = 8) and in matched healthy subjects (n = 8). i.v. administration of omadacycline produced similar plasma concentration-time profiles in subjects with ESRD and healthy subjects.

Further, in subjects with ESRD, similar values of the PK parameters were observed when omadacycline was administered i.v. after or before dialysis.

The mean area under the concentration-time curve from time zero extrapolated to infinity in plasma was 10.30 μg · h/ml when omadacycline was administered to ESRD subjects after dialysis, 10.20 μg · h/ml when omadacycline was administered to ESRD subjects before dialysis, and 9.76 μg · h/ml when omadacycline was administered to healthy subjects.

The mean maximum observed concentration of omadacycline in plasma in ESRD subjects was 1.88 μg/ml when it was administered after dialysis and 2.33 μg/ml when it was administered before dialysis, and in healthy subjects it was 1.92 μg/ml.

The 100-mg i.v. dose of omadacycline was generally safe and well tolerated in both ESRD and healthy subjects.

This study demonstrates that no dose adjustment is necessary for omadacycline in patients with impaired renal function or on days when patients are receiving hemodialysis.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786750/pdf/e02057-17.pdf

November 18, 2018 at 11:52 am

Managing community acquired pneumonia in the elderly – the next generation of pharmacotherapy on the horizon.

Expert Opin Pharmacother. 2017 Aug;18(11):1039-1048.

Amalakuhan B1,2, Echevarria KL1,2, Restrepo MI1,2.

Abstract

Community acquired pneumonia (CAP) is associated with high rates of morbidity and mortality, especially among the elderly.

Antibiotic treatment for CAP in the elderly is particularly challenging for many reasons, including compliance issues, immunosuppression, polypharmacy and antimicrobial resistance.

There are few available antibiotics that are able to address these concerns.

Areas covered: After a systematic review of the current literature, we describe seven novel antibiotics that are currently in advanced stages of development (phase 3 and beyond) and show promise for the treatment of CAP in those over the age of 65.

These antibiotics are: Solithromycin, Pristinamycin, Nemonaxacin, Lefamulin, Omadacycline, Ceftobiprole and Delafloxacin.

Using a novel conceptual framework designed by the present authors, known as the ‘San Antonio NIPS model‘, we evaluate their strengths and weaknesses based on their ability to address the unique challenges that face the elderly.

Expert opinion: All seven antibiotics have potential value for effective utilization in the elderly, but to varying degrees based on their NIPS model score.

The goal of this model is to reorganize a clinician’s focus on antibiotic choices in the elderly and bring attention to a seldom discussed topic that may potentially become a health-care crisis in the next decade

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092187/pdf/nihms-1500383.pdf

November 18, 2018 at 11:47 am

Surveillance of Omadacycline Activity against Clinical Isolates from a Global Collection (North America, Europe, Latin America, Asia-Western Pacific), 2010-2011.

Antimicrob Agents Chemother. 2017 Apr 24;61(5). pii: e00018-17.

Pfaller MA1,2, Huband MD1, Rhomberg PR1, Flamm RK3.

Abstract

Omadacycline is a broad-spectrum aminomethylcycline in late-stage clinical development for the treatment of acute bacterial skin and skin structure infections and community-acquired pneumonia as an oral and an intravenous once-daily formulation.

In this study, omadacycline and comparators were tested against 69,246 nonduplicate bacterial isolates collected prospectively during 2010 and 2011 from medical centers in Asia-Pacific (11,397 isolates), Europe (23,490 isolates), Latin America (8,038 isolates), and North America (26,321 isolates).

Omadacycline was tested by broth microdilution following Clinical and Laboratory Standards Institute M07-A10 (2015) methods.

A total of 99.9% of Staphylococcus aureus isolates were inhibited by ≤2 μg/ml of omadacycline (MIC50/90, 0.12/0.25 μg/ml), including 100.0% of methicillin-susceptible S. aureus isolates and 99.8% of methicillin-resistant S. aureus isolates.

Omadacycline potencies were comparable for Streptococcus pneumoniae (MIC50/90, 0.06/0.06 μg/ml), viridans group streptococci (MIC50/90, 0.06/0.12 μg/ml), and beta-hemolytic streptococci (MIC50/90, 0.06/0.12 μg/ml) regardless of species and susceptibility to penicillin.

Omadacycline was active against Enterobacteriaceae and was most active against Escherichia coli (MIC50/90, 0.5/2 μg/ml), Enterobacter aerogenes (MIC50/90, 2/4 μg/ml), Klebsiella oxytoca (MIC50/90, 1/4 μg/ml), and Citrobacter spp. (MIC50/90, 1/4 μg/ml).

Omadacycline was active against Haemophilus influenzae (MIC50/90, 1/1 μg/ml) regardless of β-lactamase status and against Moraxella catarrhalis (MIC50/90, 0.12/0.25 μg/ml).

The potent activity of omadacycline against Gram-positive and Gram-negative bacteria indicates that omadacycline merits further study in serious infections in which multidrug resistance and mixed Gram-positive and Gram-negative infections may be a concern.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5404553/pdf/e00018-17.pdf

November 18, 2018 at 11:45 am

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