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

Abstract

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In countries such as the United States, where the H. influenzae type b vaccine is widely used, H. influenzae type b has been replaced by untypeable H. influenzae strains (18).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 ...

Role of Efflux in Antibiotic Resistance of Achromobacter xylosoxidans and Achromobacter insuavis Isolates From Patients With Cystic Fibrosis

“…Other mutations (A1284G and T1325C) have not been described so far. In addition, in two isolates with an MIC of 512 mg/L, we found mutations in the ribosomal protein 4, namely, Q65R (never described) and G69R, previously reported in macrolide-resistant Streptococcus pneumoniae ( Clark et al, 2007 ; Kosowska-Shick et al, 2008 ), linezolid-resistant Staphylococcus epidermidis ( Mendes et al, 2012 ), and CF macrolide-resistant Burkholderia multivorans (G70R; corresponding position) ( Silva et al, 2016 ).…”

Prevalence of Serotype 19A Streptococcus pneumoniae among Isolates from U.S. Children in 2005-2006 and Activity of Faropenem

“…All isolates were susceptible to levofloxacin and telithromycin, agents that are unlikely to be widely used in children because of safety concerns and because telithromycin is not available in pediatric formulation. Faropenem appears to be a possible option for treating pediatric infections because it has low potential for resistance development (21), provided it achieves adequate in vivo activity against U.S. pediatric isolates, such as serotype 19A, that are notoriously resistant to other antimicrobial agents (10,11). Phase 3 studies in adults have shown that faropenem has a good safety profile with a low incidence of diarrhea, nausea, and vomiting and no risk of cardiotoxicity or seizures (12,16).…”

Prevalence of Antibiotics Resistance Among Patients Undergoing Bronchoscopy in Chest Department at Al-Shifa Medical Complex in Gaza Strip, Palestine

“…In the current investigation, monomicrobial growth was found in 100% of the cases. In another study, monomicrobial growth was found in 91.3% of the cases, and 8.7% were polymicrobial 19 . The exact rate of polymicrobial infection is dependent on the laboratory technique.…”