Activity of Faropenem against Middle Ear Fluid Pathogens from Children with Acute Otitis Media in Costa Rica and Israel

When tested against nine strains of pneumococci and six of Haemophilus influenzae of various resistotypes, faropenem failed to select for resistant mutants after 50 days of consecutive subculture in subinhibitory concentrations. Faropenem also yielded low rates of spontaneous mutations against all organisms of both species. By comparison, resistant clones were obtained with macrolides, ketolides, and quinolones.Streptococcus pneumoniae is the leading bacterial cause of community-acquired pneumonia. The incidence of pneumococci resistant to penicillin G and other ␤-lactam and non-␤-lactam compounds is increasing worldwide (8,10). Although introduction of a pediatric conjugated vaccine has led to a significant decrease in systemic infections caused by drug-resistant pneumococci, this decrease has not been mirrored in pneumococcal community-acquired respiratory tract infections caused by resistant strains. Also, nonvaccine serotypes with raised penicillin G MICs have recently appeared (15). There is thus still a need for new agents to treat these infections.Haemophilus influenzae is a second major cause of community-acquired respiratory infections in children and adults. In countries such as the United States, where the H. influenzae type b vaccine is widely used, H. influenzae type b has been replaced by untypeable H. influenzae strains (18). The major resistance mechanism in H. influenzae in the United States and Europe is ␤-lactamase production (TEM-1 and ROB-1). The incidence of ␤-lactamase-negative, ampicillin-resistant (BLNAR) strains in the US is Ͻ1% (18). The incidences of BLNAR strains are high in France and Japan and are reportedly on the rise in other countries (18). Of the ␤-lactams available for treatment of infections caused by this organism, cefixime and cefpodoxime are the most potent, followed by amoxicillin-clavulanate and cefuroxime (18). Despite relatively low MICs, the pharmacokinetic and pharmacodynamic properties of macrolides and ketolides cast doubt on their clinical efficacy against H. influenzae (18).Faropenem medoxomil (6,9,16,17) is an oral penem to be introduced for oral treatment of pediatric and adult community-acquired respiratory tract infections. This compound has low MICs against S. pneumoniae as well as H. influenzae (16,17). This study uses single-and multistep methodologies to examine the capability of faropenem compared with those of amoxicillin-clavulanate, cefuroxime, cefdinir, azithromycin, telithromycin, levofloxacin, and moxifloxacin to select for resistant mutants of nine S. pneumoniae and six H. influenzae strains of various resistotypes. Intravenous carbapenems, such as imipenem and meropenem, were not included, because we felt that the drugs tested should all be orally available.For testing of S. pneumoniae strains, three penicillin-susceptible, three penicillin-intermediate-resistant, and three penicillin-resistant strains were chosen. Of these, three were erythromycin susceptible; one strain had erm(B), two had mef(A), one had erm(B) plus mef(A), and one had an L4 ...

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confidence: 99%

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confidence: 99%

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In Vitro Capability of Faropenem To Select for Resistant Mutants of Streptococcus pneumoniae and Haemophilus influenzae

Kosowska-Shick

Clark

Credito

et al. 2008

“…Comparison of the MIC 90 s of the oral ␤-lactams showed that faropenem was the most active agent against isolates from children younger than 2 years, with an MIC 90 of 1 g/ml, compared with amoxicillin-clavulanate and cefdinir, with MIC 90 s of 8 and Ͼ8 g/ml, respectively. The more potent activity of faropenem compared with those of other ␤-lactams against pediatric isolates of S. pneumoniae was also confirmed in another study that evaluated middle ear fluid isolates from children with acute otitis media in Costa Rica and Israel, showing that it was typically two-to fourfold more active than amoxicillin-clavulanate (27). In contrast, no levofloxacinresistant S. pneumoniae was detected in isolates from children 14 years old or younger.…”

Section: Discussionmentioning

confidence: 54%

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

Critchley

Brown

Traczewski

et al. 2007

Self Cite

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 communityacquired 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 ␤-lactams, azithromycin, and SXT was higher among S. pneumoniae isolates from children than those from adults. ␤-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 g/ml for S. pneumoniae, 1 g/ml for H. influenzae, and 0.5 g/ml for M. catarrhalis, suggesting that faropenem shows promise as a treatment option for respiratory infections caused by contemporary resistant phenotypes.Community-acquired respiratory tract infections are among the most prevalent and serious infections in the United States and represent the leading cause of physician office visits. The bacterial pathogens most frequently isolated from respiratory tract infection specimens are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Although many community-acquired respiratory tract infections are treated empirically without culture guidance, the emergence of resistance in respiratory pathogens continues to threaten this practice (12,13,18,19). Of particular concern are the emergence and dissemination of S. pneumoniae strains with high-level resistance to penicillin (MICs, Ն8 g/ml) (24) and strains that are multidrug resistant (MDR) to several antibiotic classes (7,15,22). Among H. influenzae and M. catarrhalis clinical isolates, the production of ␤-lactamase continues to compromise the use of amoxicillin as a treatment option (8).The continued prevalence of resistance among respiratory pathogens warrants t...

“…Faropenem is an oral penem with excellent activity against the primary bacterial pathogens responsible for communityacquired respiratory tract infections, including non-penicillinsusceptible S. pneumoniae, ␤-lactamase-producing Haemophilus influenzae, and ␤-lactamase-producing Moraxella catarrhalis isolates (6,12,25,28). Faropenem demonstrates lower MICs (MIC 90 , 1 g/ml) than other ␤-lactams and macrolides for panresistant non-vaccine serotype 19A S. pneumoniae strains, which are spreading in the United States (5,22).…”

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confidence: 99%

Binding of Faropenem and Other β-Lactam Agents to Penicillin-Binding Proteins of Pneumococci with Various β-Lactam Susceptibilities

Kosowska-Shick

McGhee

Appelbaum

2009

Faropenem demonstrated low MICs (<1 g/ml) for all penicillin-susceptible and nonsusceptible pneumococci and exhibited very strong abilities to bind to Streptococcus pneumoniae penicillin-binding proteins (PBPs), except for PBP2X. The lower faropenem affinity for PBP2X did not affect MICs for any strains tested, and only imipenem had lower MICs, with much lower binding affinities for all PBPs tested, than faropenem.