Trends in anti-bacterial resistance among Streptococcus pneumoniae isolated in the USA, 2000–2003: PROTEKT US years 1–3

Jenkins, Stephen G.; Farrell, David J.; Patel, Manish; Lavin, Bruce

doi:10.1016/j.jinf.2005.04.015

Cited by 54 publications

(65 citation statements)

References 24 publications

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“…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%

“…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).…”

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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: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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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“…Molecular epidemiology studies have shown that the prevalence of these two mechanisms among macrolide-resistant pneumococci varies in different geographical areas. In the United States (18), Canada (15), and the United Kingdom (2), the efflux system is more common, while in Spain (34), Italy (24), and other European countries (29), the ribosomal modification is prevalent. In addition, isolates carrying both resistance determinants are becoming increasingly common in several areas of the globe (12,19,23) and have also been found, although rarely, in Italy (24,25).…”

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confidence: 99%

The mef (E)-Carrying Genetic Element (mega) of Streptococcus pneumoniae : Insertion Sites and Association with Other Genetic Elements

Grosso

Camilli

Iannelli

et al. 2006

Antimicrob Agents Chemother

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The structure of the macrolide efflux genetic assembly (mega) element, its genomic locations, and its association with other resistance determinants and genetic elements were investigated in 16 Streptococcus pneumoniae isolates carrying mef(E), of which 1 isolate also carried tet(M) and 4 isolates also carried tet(M) and erm(B). All isolates carried a mega element of similar size and structure that included the operon mef(E)-msr(D) encoding the efflux transport system. Among tetracycline-susceptible isolates, six different integration sites were identified, five of which were recognized inside open reading frames present in the R6 genome. In the five isolates also carrying tet(M), mega was inserted in different genetic contexts. In one isolate, it was part of previously described Tn916-like element Tn2009. In another isolate, mega was inserted in a transposon similar to Tn2009 that also included an erm(B) element. This new composite transposon was designated Tn2010. Neither Tn2009 nor Tn2010 could be transferred by conjugation to pneumococcal or enterococcal recipients. In the three isolates in which mega was not physically linked with tet(M), this gene was associated with erm(B) in transposon Tn3872, a Tn916-like element. Homologies between the chromosomal insertions of these composite transposons and sequences of multidrug-resistant pneumococcal genomes in the databases indicate the presence of preferential sites for the integration of composite Tn916-like elements carrying multiple resistance determinants in S. pneumoniae.

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“…For example, M. catarrhalis was widely recognized as a pathogen in COPD only in the last 1520 years [Sethi and Murphy, 2004]. Antimicrobial resistance has emerged among pathogens implicated in COPD, including b lactam and macrolide resistance in S. pneumoniae, b lactamase production in H. influenzae and M. catarrhalis and fluoroquinolone resistance in P. aeruginosa [Jenkins et al 2005;Hoban and Felmingham, 2002]. Pharmacodynamic/pharmacokinetic studies suggest that full-dose intermittent treatment with a potent antibiotic is less likely to induce antibiotic resistance than continuous low-dose regimens [File and Hadley, 2002].…”

Section: New Approaches To Long Term Antibiotics In Copdmentioning

confidence: 99%

The benefits of long-term systemic antimicrobial therapy in chronic obstructive pulmonary disease

Berim

Sethi

2011

Ther Adv Respir Dis

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Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are major contributors to the morbidity and mortality associated with this disease. Current approaches that likely reduce chronic obstructive pulmonary disease (COPD) exacerbations include smoking cessation, influenza and pneumococcal vaccinations, long-acting bronchodilator and inhaled corticosteroid therapy, pulmonary rehabilitation, and mucolytic drugs. However, with optimal treatment using all of these modalities, we are only able to reduce exacerbations by about 40%. A significant proportion of COPD exacerbations are bacterial, therefore long-term antimicrobial therapy could have a role in preventing exacerbations. Long-term antibiotic treatment in COPD regimens that are being evaluated include low-dose macrolide therapy, pulsed fluoroquinolone administration and the use of inhaled antibiotics. Although initial results have been promising with significant reductions in exacerbations with these regimens, additional studies are required to identify the appropriate patient and regimen and elucidate the riskbenefit as well as cost effectiveness of long-term antibiotics in COPD.

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Trends in anti-bacterial resistance among Streptococcus pneumoniae isolated in the USA, 2000–2003: PROTEKT US years 1–3

Cited by 54 publications

References 24 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

The mef (E)-Carrying Genetic Element (mega) of Streptococcus pneumoniae : Insertion Sites and Association with Other Genetic Elements

The benefits of long-term systemic antimicrobial therapy in chronic obstructive pulmonary disease

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