Comparative in vitro and bactericidal activities of telithromycin against penicillin-nonsusceptible, levofloxacin-resistant, and macrolide-resistant Streptococcus pneumoniae by time-kill methodology

Kays, Michael B.; Lisek, Christopher R.; Denys, Gerald A.

doi:10.1016/j.ijantimicag.2006.09.024

Cited by 7 publications

(7 citation statements)

References 38 publications

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“…One erythromycin-susceptible S. pneumoniae isolate and two erythromycin-resistant S. pneumoniae isolates, including mefA-positive and ermB-positive strains, were tested (16,21,26,27,29,30). The AUC 0-24 /MIC values of S-013420 required for activity against S. pneumoniae were determined.…”

Section: Resultsmentioning

confidence: 99%

“…This result is supported by characterization of the concentration-dependent bactericidal activity of S-013420 which was indicated by timekill kinetics (12a). As for S. pneumoniae, other studies of macrolide antibiotics also showed that AUC 0-24 /MIC was the dominant parameter which correlated with antibacterial activity and characterized concentration-dependent bactericidal activity (16,21,26,27,29,30). The dominant PK/PD parameter for determination of the efficacy of macrolide antimicrobials was considered to be AUC/MIC, regardless of the bacterial species.…”

Section: Discussionmentioning

confidence: 99%

“…The bacterial cell suspension was incubated at 37°C for 24 h under conditions simulating various time-concentration curves of S-013420. A portion of the bacterial cell suspension was collected at 0, 1, 2, 4, 6,8,10,12,14,16,18,20,22, and 24 h. After two washings, the collected samples were serially diluted 10-fold with the growth medium. Next, these samples were mixed with about 10 ml of the agar medium and the number of colonies was counted after incubation at 35 to 37°C for 1 to 3 days.…”

Section: Methodsmentioning

confidence: 99%

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In Vitro Pharmacokinetic and Pharmacodynamic Evaluation of S-013420 against Haemophilus influenzae and Streptococcus pneumoniae

Homma

Hori

Ohshiro

et al. 2010

Antimicrob Agents Chemother

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The pharmacokinetic (PK)/pharmacodynamic (PD) parameters and the antibacterial activity of S-013420, a novel bicyclolide, against Haemophilus influenzae and Streptococcus pneumoniae, including macrolide-resistant isolates, were investigated using an in vitro PD model. Various time-concentration curves were artificially constructed by modifying the PK data obtained in phase I studies. The activity against H. influenzae was evaluated using two parameters, that is, the area above the killing curve (AAC) and the viable cell reduction at 24 h. The relationships between the antibacterial activity of S-013420 and the three PK/PD parameters were investigated by fitting the data to the sigmoid maximum effective concentration model In antimicrobial chemotherapy, the pharmacokinetic (PK)/ pharmacodynamic (PD) concept has recently been used during drug development to determine susceptibility breakpoints, predict clinical efficacy, and optimize the antimicrobial regimen (1, 4, 13). Generally, antimicrobials can be categorized according to the dominant parameter of three PK/PD parameters correlated with antibacterial activity. These three parameters (1) are the area under the concentration-time curve from 0 to 24 h (AUC 0-24 )/MIC, the peak concentration (C max )/MIC, and the cumulative percentage of a 24-h period that the drug concentration exceeds the MIC under steady-state PK conditions (%T MIC ). Nonclinical PK/PD characterizations of antimicrobials using in vitro PD models or in vivo infection models have been reported (2,5,26,29). In general, AUC 0-24 /MIC is the dominant PK/PD parameter for macrolides, ketolides, and quinolones, while C max /MIC is the main parameter for quinolones and aminoglycosides and %T MIC is that for ␤-lactams (1, 4). Overall, nonclinical PK/PD data have agreed well with data obtained for infected patients, and a PK/PD evaluation would be helpful for cutting costs, addressing ethical issues, and shortening the duration of clinical trials (1, 4).Community-acquired respiratory tract infections (RTIs), such as community-acquired pneumonia, acute exacerbations of chronic bronchitis, sinusitis, and acute otitis media, are among the most common infectious diseases for which oral antibiotics are prescribed in primary clinical settings and are mainly caused by Streptococcus pneumoniae and Haemophilus influenzae (6). The macrolide antimicrobials, including clarithromycin and azithromycin, are often used for the treatment of community-acquired RTIs. However, the decreased susceptibility of S. pneumoniae to macrolide agents is a key problem worldwide. Recent reports have suggested that pneumococcal macrolide resistance rates were about 35% in some regions (7,14,23). In S. pneumoniae, two main mechanisms of macrolide resistance were reported, i.e., active efflux due to mef genes and ribosomal modification mediated by erm genes (11). S-013420 (EDP-420, EP-013420) is a novel bicyclolide (bridged bicyclic macrolide) that is characterized by a 6,11-O-bridged structure discovered by Enanta Pharmaceuticals, Inc. ...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

In Vitro Pharmacokinetic and Pharmacodynamic Evaluation of S-013420 against Haemophilus influenzae and Streptococcus pneumoniae

Homma

Hori

Ohshiro

et al. 2010

Antimicrob Agents Chemother

View full text Add to dashboard Cite

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“…The procedure was performed in triplicates for each organism. Bactericidal activity was defined as a P 3 log 10 reduction (P99.9% reduction) in CFU/ml (Kays, Lisek, & Denys, 2007;Soberon, Sgariglia, Sampietro, Quiroga, & Vattuone, 2007).…”

Section: Time-kill Assaymentioning

confidence: 99%

Assessment of antibacterial activity of fractions from burdock leaf against food-related bacteria

Lou

Wang

et al. 2010

Food Control

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“…Ketolides prove slightly more effi cient against gram-positive organisms, causing a 1-4 log decrease in CFU of S. aureus, S. pneumoniae, or S. pyogenes over 24 h Drago et al 2005 ;Kays et al 2007 ;Woosley et al 2010 ). Their killing activity develops over time but is also concentration dependent; it is infl uenced by the bacterial inoculum (Boswell et al 1998 ).…”

Section: In Vitro Pharmacodynamic Modelsmentioning

confidence: 99%

Macrolides and Ketolides

Bambeke

2013

Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics

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Macrolides and ketolides are characterized by a very wide tissular distribution, which is related to their capacity to accumulate in the acidic compartments of the cells. This property is considered an advantage, because it concentrates the drug at the site of infection. Yet, the low serum levels consecutive to this tissular distribution may favor the selection of resistance. Macrolides are essentially bacteriostatic and ketolides are slowly bactericidal. The pharmacodynamic indice that best predicts effi cacy is the free 24 h-AUC/MIC ratio for both subclasses. Despite their high concentration inside the cells, macrolides and ketolides remain bacteriostatic against intracellular bacteria, with a potency similar to that observed extracellularly. New formulations have been developed to optimize patient's adherence (extended release tablets) or to further increase antibiotic concentration at the site of infection (powders for inhalation).

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Comparative in vitro and bactericidal activities of telithromycin against penicillin-nonsusceptible, levofloxacin-resistant, and macrolide-resistant Streptococcus pneumoniae by time-kill methodology

Cited by 7 publications

References 38 publications

In Vitro Pharmacokinetic and Pharmacodynamic Evaluation of S-013420 against Haemophilus influenzae and Streptococcus pneumoniae

In Vitro Pharmacokinetic and Pharmacodynamic Evaluation of S-013420 against Haemophilus influenzae and Streptococcus pneumoniae

Assessment of antibacterial activity of fractions from burdock leaf against food-related bacteria

Macrolides and Ketolides

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