In vitro activity of cefditoren and other comparators against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis causing community-acquired respiratory tract infections in China

The aim of this study was to evaluate the in vitro activity of cefditoren and comparators against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis causing community-acquired respiratory tract infections (CARTIs). A total of 391 Streptococcus pneumoniae, 266 H. influenzae, and 76 M. catarrhalis were isolated from 10 centers located at 6 cities in China from January 2009 to May 2010. The microdilution method was used to determine minimum inhibitory concentrations (MICs). The pneumococci comprised 189 (48.3%) penicillin susceptible, 129 (33.0%) penicillin intermediate, and 73 (18.7%) penicillin resistant. Moxifloxacin and levofloxacin showed the highest activity (99.2% and 97.7%, respectively) against Streptococcus pneumoniae, followed by parenteral penicillin G (95.7%), cefditoren (83.1%) and amoxicillin-clavulanic acid (79.3%). Among the 266 H. influenzae isolates, 26 (9.8%) were ampicillin-resistant β-lactamase-producing strains and 24 (9.0%) were ampicillin-resistant β-lactamase-nonproducing strains (BLNAR). Most of antimicrobial agents demonstrated good activity (>97% susceptibility) against H. influenzae except ampicillin, cefuroxime, and cefaclor, which showed relatively lower activity (81.2%, 88.7%, and 88%, respectively). Cefditoren showed excellent activity with the lowest MIC(50) and MIC(90) (≤0.016/0.064 μg/mL) among all tested drugs, which is independent of β-lactamase production or ampicillin resistance. Cefditoren at a concentration of 0.5 μg/mL inhibited all BLNAR strains. Seventy of 76 isolates of M. catarrhalis produced β-lactamase. Cefditoren also showed excellent activity with MIC(90) of 0.064 μg/mL against β-lactamase-nonproducing strains and 0.5 μg/mL against β-lactamase-producing strains. In conclusion, the excellent intrinsic activity of cefditoren suggests that it may be a good choice for the treatment of CARTIs caused by Streptococcus pneumoniae, H. influenzae, and M. catarrhalis in China, while the activity should be closely monitored.     

In vitro activity of cefditoren against clinical isolates of penicillin-susceptible and penicillin-intermediate strains of Streptococcus pneumoniae isolated in Germany, 1992-1998

This study investigates the susceptibility to cefditoren of penicillin-susceptible strains of invasive Streptococcus pneumoniae (n = 312) and of penicillin-intermediate strains of S. pneumoniae (n = 30) isolated mainly from patients with respiratory tract infections. The MIC(90)s of penicillin-susceptible and -intermediate isolates were as follows: cefditoren, < or =0.06 and 1 mg/L; penicillin G, < or =0.06 and 0.5 mg/L. Cefditoren showed the highest activity against the penicillin-intermediate strains investigated compared with the other beta-lactam antibiotics and is therefore considered to be a promising agent for the treatment of infections caused by pneumococci with reduced penicillin susceptibility.     

肺炎链球菌对泰利霉素等抗菌药物的体外抗菌活性

目的了解本院分离的肺炎链球菌对泰利霉素等抗菌药物的体外抗菌活性。方法对本院2005--2007年从各种临床标本收集的97株肺炎链球菌，用K—B纸片法进行药敏试验，测定这些菌株对泰利霉素等3种新近上市和其他7种临床常用抗菌药物的耐药性。结果97株肺炎链球菌对泰利霉素和利奈唑胺的敏感率均为100％，对喹奴普丁-达福普汀也未发现耐药菌株，只是有18．8％的菌株表现为中介。其他抗菌药物的耐药情况如下：对红霉素、克林霉素、万古霉素、左氧氟沙星、氯霉素和四环素的耐药率分别为60．8%、58．8％、0％、2．1％、12．8%和64．5％，对青霉素的敏感率为85．6％。结论本院尚未用于临床的3种新近上市的抗菌药物泰利霉素、利奈唑胺和喹奴普丁-达福普汀，对本院分离的肺炎链球菌有良好的体外抗菌活性。而上述细菌对红霉素、林可霉素以及四环素有较高的耐药性。     

In vitro activities of five fluoroquinolone compounds against strains of Streptococcus pneumoniae with resistance to other antimicrobial agents.

Ciprofloxacin, clinafloxacin, PD 131628, sparfloxacin, and trovafloxacin were tested against 236 strains of Streptococcus pneumoniae, most of which were resistant to other agents. Resistance to multiple antibiotics did not affect the organism's susceptibility to the fluoroquinolones. The fluoroquinolones with in vitro antipneumococcal activity might be particularly useful against strains that are resistant to the more traditional therapeutic agents.     

Antimicrobial activity and in vitro susceptibility test development for cefditoren against Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus species

Cefditoren, a third generation orally administered aminothiazolyl cephalosporin, has demonstrated bactericidal activity against many Gram positive and negative bacterial pathogens and stability against clinically important beta-lactamases. Cefditoren was compared to cefaclor, cefixime, and penicillins against 1 435 recently isolated strains of streptococci (312 Streptococcus pneumoniae, 165 viridans group streptococci, 142 beta-haemolytic streptococci), Haemophilus influenzae (521 strains), and Moraxella catarrhalis (295 strains). Streptococcus pneumoniae and viridans group streptococci had penicillin nonsusceptible rates of 37.8 and 35.8%, respectively. Cefditoren (MIC(90) in microg/ml/% susceptible) activity against all tested H. influenzae (0.03/100) and M. catarrhalis (0.06-0.5/100) was comparable to cefixime and significantly greater than cefaclor. Cefditoren (MIC(90), 0.5 microg/ml) was 4- to 128-fold more active than comparison beta-lactams against the pneumoococci and was the most potent beta-lactam (including penicillin) versus beta-haemolytic streptococci. Cefditoren pharmacokinetics demonstrate a T(1/2) of 1.5-2 h and C(max) values of 2.8 and 4.6 microg/ml, respectively with 200 or 400 mg doses of cefditoren pivoxil; plasma concentrations exceed 1 microg/ml for 4 to 6 hours (33-50% of dosing interval). Consequently, a susceptible MIC of /= 18 and >/= 15 mm (5-microg disk) for all cited fastidious species tested. Categorical agreement between MIC and disk tests was 94.6 to 100% with a correlation coefficient (r) range of 0.50 to 0.90 for streptococci. H. influenzae intermethod comparison results using the same interpretive criteria were in complete agreement, but exhibited a low r = 0.39. Cefditoren clearly possesses the most potent activity among currently studied oral cephalosporins or penicillin against commonly isolated bacterial pathogens causing bronchitis, pneumonia, sinusitis, or pharyngitis and was active against nearly all penicillin-resistant streptococci at 相似文献   

In vitro evaluation of a novel orally administered cephalosporin (cefditoren) tested against 1249 recent clinical isolates of Haemophilus influenzae,Moraxella catarrhalis,and Streptococcus pneumoniae

Cefditoren (formerly ME-1206), a new orally administered cephalosporin, was evaluated in vitro against 1249 recently isolated strains of Streptococcus pneumoniae (500 strains), Moraxella catarrhalis (250 strains), and Haemophilus influenzae (499 strains). Reference National Committee for Clinical Laboratory Standards methods were used and the strains were representative for the current rates of β-lactamase production or penicillin resistance. Cefditoren had MIC₅₀/MIC₉₀ results for Moraxella catarrhalis and Haemophilus influenzae of 0.12/0.5 and ≤0.008/0.015 μg/mL, respectively. The pneumococci were consistently twofold to eightfold more susceptible to cefditoren than other oral cephalosporins or penicillins. The MIC₉₀ for penicillin-resistant S. pneumoniae was only 2 μg cefditoren/mL, and the highest recorded MIC was 4 μg/mL. Cefditoren appears to be a very promising β-lactam possessing the greatest potency and potential spectrum versus contemporary (1997) respiratory tract pathogens.     

Susceptibility of Streptococcus pneumoniae and Haemophilus influenzae to cefditoren, and provisional interpretive criteria

In vitro cefditoren antimicrobial activity was tested by broth microdilution and disk diffusion methods against 300 Streptococcus pneumoniae and 299 Haemophilus influenzae isolates. MICs were also determined for three comparison drugs. The MICs of cefditoren were very comparable to those of cefotaxime against both species. If penicillin-resistant pneumococci are to be considered not susceptible to cefditoren, the tentative MIC breakpoints for cefditoren of < or = 0.25 microg/ml for susceptible and > or 1.0 microg/ml for resistant could be selected. With these breakpoints, all penicillin-susceptible pneumococci were cefditoren-susceptible, as were 85% of penicillin-intermediate strains. Provisional zone diameter breakpoints would be > or = 26 mm for susceptible and < or = 20 mm for resistant. If penicillin-resistant pneumococcal infections are shown to clinically respond to cefditoren therapy, then a susceptible MIC breakpoint of < or = 1.0 microg/ml would be appropriate, with a corresponding zone diameter breakpoint of > or = 21 mm. A susceptible MIC breakpoint of < or = 0.5 or < or = 1.0 microg/ml is appropriate for H. influenzae, but lack of correlation between cefditoren MICs and disk diffusion zone diameters when testing H. influenzae leads us to make no recommendations at this time regarding cefditoren disk tests for H. influenzae.     

In vitro and in vivo activities of meropenem and comparable antimicrobial agents against Haemophilus influenzae, including beta-lactamase-negative ampicillin-resistant strains.

The in vitro activity of ampicillin, cefotaxime, meropenem, panipenem, imipenem and biapenem was assayed using ampicillin-susceptible, beta-lactamase-positive and beta-lactamase-negative ampicillin-resistant (BLNAR) Haemophilus influenzae isolated recently in Japan. Against ampicillin-susceptible isolates, cefotaxime was the most potent (MIC(90) 0.016 mg/mL). Both cefotaxime and meropenem (MIC(90) of both, 0.5 mg/L) were the most potent against beta-lactamase-positive isolates. Against BLNAR isolates, meropenem (MIC(90) 0.5 mg/L) was the most potent. In murine bronchopneumonia caused by ampicillin-susceptible and BLNAR H. influenzae, cefotaxime showed the best efficacy, followed by meropenem. Our results indicate that meropenem could be a useful intravenous agent for infections caused by H. influenzae, including BLNAR strains.     

In vitro activity of ABT-773, a new ketolide, against recent clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis

The in vitro activity of ABT-773 was evaluated against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates. ABT-773 was the most active antimicrobial tested against S. pneumoniae. ABT-773 and azithromycin were equivalent in activity against H. influenzae and M. catarrhalis and more active than either clarithromycin or erythromycin.     

In vitro activity of rosoxacin against Haemophilus influenzae

The in vitro activity of rosoxacin was compared to that of ampicillin, cefoxitin, chloramphenicol, and rifampin, against 94 clinical isolates of Haemophilus influenzae. The results indicated that rosoxacin had significantly better in vitro activity against H. influenzae than the other antibiotics evaluated in this study. In addition, rosoxacin was an effective antimicrobial agent against isolates of H. influenzae that were resistant to ampicillin due to beta-lactamase production.     

Comparative in vitro activity of telithromycin against macrolide-resistant and -susceptible Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae

OBJECTIVES: The first objective was to investigate the in vitro activity of telithromycin against respiratory tract pathogens in comparison with other antimicrobial agents. The second objective was to identify the influence of the erm(B) and mef(A) genes on the susceptibility of Streptococcus pneumoniae to telithromycin. METHODS: The in vitro activity of telithromycin against S. pneumoniae, Moraxella catarrhalis and Haemophilus influenzae, isolated from the UK and 40 macrolide-resistant S. pneumoniae from four different countries was compared with a variety of antimicrobial agents. The 140 isolates were examined for the presence of the erm(B) and mef(A) genes. The impact of 5% CO(2) on susceptibility testing was also investigated. RESULTS: Telithromycin showed greatest activity against S. pneumoniae, but also had good activity against M. catarrhalis and H. influenzae, which was independent of their resistance profiles to other antibiotics. The MIC(90) of telithromycin for S. pneumoniae was 0.12 mg/L, which was 64-fold lower than the lowest macrolide MIC; 21% of the S. pneumoniae were macrolide resistant. Thirty-eight per cent of the macrolide-resistant strains were erm(B)-positive and 62% were mef(A)-positive, but no strain contained both genes. The activity of telithromycin was similar to that of azithromycin against both M. catarrhalis and H. influenzae, Erythromycin was slightly less active: 1% and 8% of M. catarrhalis and H. influenzae, respectively, were resistant to erythromycin, but none were resistant to telithromycin. Five per cent of the S. pneumoniae strains and 4% of the H. influenzae strains changed from telithromycin susceptible to non-susceptible entirely because of the incubation conditions. The MIC(50)s and MIC(90)s of S. pneumoniae, M. catarrhalis and H. influenzae increased by one dilution when incubated in CO(2). CONCLUSIONS: Telithromycin has shown high in vitro activity against S. pneumoniae, including those strains that are macrolide susceptible and resistant as well as M. catarrhalis and H. influenzae. This study has also demonstrated that there is no cross-resistance between erythromycin and telithromycin. The impact of 5% CO(2) on susceptibility testing should be investigated further before providing definite guidelines on telithromycin susceptibility testing.     

Activity of gemifloxacin against Streptococcus pneumoniae and Haemophilus influenzae

This review focuses on the activity of gemifloxacin, a new respiratory fluoroquinolone, against the two most important bacterial pathogens associated with lower respiratory tract infections, namely Streptococcus pneumoniae and Haemophilus influenzae.     

In vitro activity of a new broad-spectrum, beta-lactamase-stable oral cephalosporin, cefixime, in comparison with other drugs, against Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis and Streptococcus pneumoniae.

Cefixime, a new orally absorbed iminomethoxyaminothiazolyl cephalosporin, was tested against some microorganisms involved in upper and lower respiratory tract infections such as Haemophilus (influenzae and parainfluenzae), Moraxella catarrhalis and Streptococcus pneumoniae, isolated in the period from November 1990 to April 1991. Its activity was compared to nine other antimicrobial agents: erythromycin, trimethoprim-sulfamethoxazole, ampicillin, amoxicillin-clavulanate, cefaclor, ceftazidime, ceftriaxone, cefotaxime and ofloxacin. Cefixime inhibits 90% of S. pneumoniae, H. influenzae and H. parainfluenzae, both beta-lactamase producers (BLP) or not (NBLP) at concentrations of less than 0.25 mg/l. It inhibits 90% of M. catarrhalis (BLP and NBLP) at concentrations of less than 1 mg/l. In general, cefixime has a superior in vitro activity with respect to cefaclor and the other cephalosporins as well as erythromycin and amoxicillin (the last one in BLP strains). In the evaluation of the antibacterial activity of beta-lactam against Haemophilus and M. catarrhalis, the authors observed different indications in the guidelines for ampicillin. Cefixime is not destroyed by the plasmid-mediated beta-lactamase produced by Haemophilus sp. and M. catarrhalis (TEM and ROB in Haemophilus strains and BRO in M. catarrhalis). In view of its excellent in vitro activity against the commonly encountered respiratory tract pathogens, cefixime is indicated in the therapy of these infections.     

Moxifloxacin: a comparison with other antimicrobial agents of in-vitro activity against Streptococcus pneumoniae

Two hundred representative isolates, including 26 strains of Streptococcus pneumoniae with intermediate resistance to penicillin, were selected from a collection obtained from blood cultures of patients with bacteraemic pneumococcal pneumonia. The MICs of moxifloxacin (BAY 12-8039), grepafloxacin, sparfloxacin, levofloxacin, ofloxacin, ciprofloxacin, erythromycin, tetracycline and penicillin G were determined by a standard agar dilution technique. Moxifloxacin had the highest in-vitro activity against S. pneumoniae (MIC90 = 0.25 mg/L; MIC range 0.06-0.25 mg/L). The MIC90 values were one dilution lower than those obtained with sparfloxacin and grepafloxacin, three dilutions lower than those obtained with levofloxacin, and four dilutions lower than those of ofloxacin and ciprofloxacin.     

Activity of moxifloxacin and twelve other antimicrobial agents against 216 clinical isolates of Streptococcus pneumoniae

BACKGROUND: An increased incidence of macrolide resistance in penicillin-resistant Streptococcus pneumoniae has been described. METHODS: With this in mind, 216 S. pneumoniae isolates were evaluated for their in vitro susceptibility to a new fluoroquinolone, moxifloxacin, which was compared with penicillin, amoxicillin, cefuroxime, cefotaxime, ceftriaxone, erythromycin, clarithromycin, ciprofloxacin, sparfloxacin, ofloxacin, vancomycin and teicoplanin. A broth microdilution assay was performed in cation- adjusted Mueller-Hinton broth with 5% (v/v) lysed horse blood according to NCCLS guidelines. RESULTS: Erythromycin resistance was observed in all the 22 penicillin-resistant S. pneumoniae (10.1%). All the penicillin- susceptible S. pneumoniae were susceptible to cephalosporins, whereas all the penicillin-resistant ones showed resistance to cefuroxime and only intermediate susceptibility to cefotaxime and ceftriaxone. The 216 tested strains were inhibited by sparfloxacin and moxifloxacin at concentrations of 0.12-0.5 mg/l and 0.06-0.25 mg/l, respectively, regardlesss of whether the strain was penicillin and/or erythromycin resistant. Seven penicillin-resistant strains displayed resistance to ofloxacin. All isolates were susceptible to vancomycin; teicoplanin MIC values ranged from 0.03 to 0.12 mg/l. The excellent in vitro activity of moxifloxacin against S. pneumoniae was not affected by penicillin and/or macrolides. CONCLUSION: Moxifloxacin appears to be a promising choice for the treatment of pneumococcal infections, including situations where therapeutic choices are limited due to penicillin and macrolide resistance.