Comparative activity of telithromycin against typical community-acquired respiratory pathogens

OBJECTIVES: Respiratory tract infections (RTIs) remain a significant cause of morbidity and mortality. Major bacterial pathogens in RTIs, such as Streptococcus pneumoniae, have exhibited increasing resistance to a variety of antibiotics during the past decades. Telithromycin, the first ketolide, was designed especially to overcome this resistance. The present study was conducted to assess the comparative activity of telithromycin against typical RTI pathogens in Austria. METHODS: A total of 1,015 bacterial isolates was tested, including S. pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Haemophilus influenzae. MICs of the following antimicrobials: penicillin G, ampicillin (for H. influenzae), azithromycin, clarithromycin, erythromycin A and telithromycin were determined using the NCCLS broth microdilution method. RESULTS: Telithromycin showed excellent activity against S. pneumoniae, with 99.8% of all isolates being susceptible. Penicillin remained active with an MIC50 and MIC90 of 0.007 mg/L. Nevertheless, a notable increase in penicillin intermediate-resistant and resistant isolates, from 4.9% in 1996 to the present rate of 10%, was observed. There was also a distinct rise in the resistance levels of S. pneumoniae against the macrolides. All tested isolates of S. pyogenes were susceptible to penicillin and telithromycin, and only low levels of resistance against telithromycin were found in S. aureus (2.2%, MIC90 of 0.5 mg/L). No telithromycin-resistant isolate of H. influenzae could be detected. CONCLUSIONS: This study demonstrates the rising prevalence of resistance among S. pneumoniae not only to penicillin but also to other antimicrobials. It also shows the value of telithromycin as an attractive option for the empirical treatment of community-acquired RTIs in an era of widespread antibacterial resistance.     

Antimicrobial resistance among isolates of respiratory tract infection pathogens from the southern United States: data from the PROTEKT US surveillance program 2000/2001

BACKGROUND: PROTEKT US (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin in the United States) was established in 2000 to monitor antimicrobial resistance among respiratory tract pathogens across the United States. METHODS: During 2000 to 2001, 75 southern US centers collected 3,867 Streptococcus pneumoniae, 1,455 Streptococccus pyogenes and 1,042 Haemophilus influenzae. RESULTS: Overall, 46.1% of S. pneumoniae isolates were nonsusceptible to penicillin, 35.8% were resistant to erythromycin, and 0.5% were resistant to fluoroquinolones. Against S. pneumoniae the most active agents were telithromycin (99.7% susceptible), linezolid (99.8%) and the fluoroquinolones (levofloxacin 99.4%, gatifloxacin 99.5%). The prevalence of erythromycin-resistant S. pyogenes isolates was 4.5%. Telithromycin, at concentration of < or = 1 mg/L, inhibited 99.9% of S. pyogenes. The prevalence of beta-lactamase positive H. influenzae was 26.2%. Telithromycin was active (MIC90 4 mg/L) against H. influenzae, irrespective of beta-lactamase production. CONCLUSION: The prevalence of penicillin and macrolide resistance among respiratory tract pathogens from the southern United States is high. Fluoroquinolone resistance is low. Telithromycin is highly active against respiratory tract pathogens with reduced susceptibility to beta-lactams, macrolides, and fluoroquinolones.     

Antimicrobial susceptibility of community-acquired respiratory tract pathogens in North America in 1999-2000: findings of the PROTEKT surveillance study

The PROTEKT surveillance study commenced in 1999 to examine the antimicrobial susceptibility of community-acquired respiratory pathogens. We report here the results from 2371 isolates collected during 2000 by North American centers (Canada, n = 7; USA, n = 8). Overall, 21.3% of pneumococci (n = 687) were penicillin G-resistant (Canada, 10.3%; USA, 32.6%). Corresponding rates of erythromycin resistance were 16.3% and 31.5%. Telithromycin inhibited all penicillin- and erythromycin-resistant isolates at < or =1 microg/ml. Among 612 Hemophilus influenzae isolates, 22.4% were beta-lactamase-positive. Antimicrobial susceptibility of H. influenzae varied between 82.4% (clarithromycin) and 100% (cefpodoxime, levofloxacin). Importantly, one isolate was found to be resistant to both moxifloxacin and ciprofloxacin. Most Moraxella catarrhalis isolates were highly susceptible to the antimicrobials tested, except ampicillin. All Streptococcus pyogenes isolates (n = 382) were penicillin-susceptible and 5.2% were non-susceptible to erythromycin. S. pyogenes showed cross-resistance to other macrolides yet remained inhibited by telithromycin at < or =0.5 microg/ml. Methicillin resistance among Staphylococcus aureus was common (19.9%), particularly in the USA. The PROTEKT study confirms the widespread prevalence of antimicrobial resistance among common respiratory pathogens in North America, and hence the need for continued surveillance to guide optimal empiric therapy for community-acquired respiratory tract infections.     

Antibacterial resistance of community-acquired respiratory tract pathogens recovered from patients in Germany and activity of the Ketolide Telithromycin: results from the PROTEKT surveillance study (1999-2000)

BACKGROUND: The Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin (PROTEKT) longitudinal global surveillance study examines the antibacterial susceptibility of community-acquired respiratory pathogens. METHODS AND RESULTS: Data from isolates collected in Germany in 1999-2000 in the PROTEKT study show that 8.3% of pneumococcal isolates (n = 325) had reduced susceptibility to penicillin and 2.2% were fully resistant. Erythromycin resistance was 15.7% overall and particularly high in Leipzig (31.6%). All penicillin- and erythromycin-resistant strains were inhibited by telithromycin (MIC < or =0.5 mg/l) and linezolid (MIC < or =2 mg/l). Beta-lactamase was produced by 3.2% of Haemophilus influenzae (9/284) and 89.5% of Moraxella catarrhalis strains (111/124). All Streptococcus pyogenes isolates (n = 87) were susceptible to penicillin, although 9.2% were resistant to macrolides. CONCLUSIONS: Penicillin resistance in Germany remains low; however, the prevalence of antimicrobial resistance among common respiratory pathogens is rising, particularly against macrolides. Continued surveillance is necessary to guide optimal empirical therapy, and new antimicrobials, like telithromycin, need to be developed with improved potency against target pathogens and low propensity for the development of resistance.     

In vitro activity of telithromycin against respiratory tract pathogens in comparison with other antimicrobial agents

This study was done to evaluate the in vitro activity of a new ketolide telithromycin in comparison with clarithromycin, erythromycin, moxifloxacin and levofloxacin against Streptococcus pneumoniae (n = 67), Haemophilus influenzae (n = 139), and Moraxella catarrhalis (n = 46)collected between January and June 2003 in Hong Kong. Among the H. influenzae isolates, 25.2% produced beta-lactamase, while 97.8% of M. catarrhalis isolates produced beta-lactamase. Half of the S. pneumoniae isolates were nonsusceptible to penicillin, and 90.9% of these strains were resistant to clarithromycin and erythromycin. One (1.5%) S. pneumoniae strain was resistant to levofloxacin (MIC = 8 mg/l) and all isolates were sensitive to moxifloxacin and telithromycin with MIC <1 mg/l. H. influenzae isolates were sensitive to all fluoroquinolones tested and 2.2% of H. influenzae were resistant to clarithromycin. M. catarrhalis isolates were sensitive except 1 strain which was resistant to levofloxacin (MIC = 4 mg/l) and moxifloxacin (8 mg/l). All M. catarrhalis strains were sensitive to telithromycin with MIC90 = 0.5 mg/l. Telithromycin demonstrated high activity and no resistance was found in all these major respiratory tract pathogens.     

Baseline study to determine in vitro activities of daptomycin against gram-positive pathogens isolated in the United States in 2000-2001

The activity of daptomycin was assessed by using 6,973 gram-positive bacteria isolated at 50 United States hospitals in 2000 and 2001. Among the isolates of Streptococcus pneumoniae (n = 1,163) collected, the rate of penicillin resistance was 16.1%; rates of oxacillin resistance among Staphylococcus aureus isolates (n = 1,018) and vancomycin resistance among Enterococcus faecium isolates (n = 368) were 30.0 and 59.5%, respectively. Multidrug-resistant (MDR) phenotypes (isolates resistant to three or more different chemical classes of antimicrobial agents) accounted for 14.2% of S. pneumoniae isolates, 27.1% of S. aureus isolates, and 58.4% of E. faecium isolates. For all gram-positive species tested, MICs at which 90% of the isolates tested were inhibited (MIC(90)s) and MIC ranges for directed-spectrum agents (daptomycin, quinupristin-dalfopristin, and linezolid) were identical or highly similar for isolates susceptible or resistant to other agents or MDR. Daptomycin had a MIC(90) of 0.12 micro g/ml for both penicillin-susceptible and -resistant isolates of S. pneumoniae. Against oxacillin-resistant S. aureus daptomycin had a MIC(90) of 0.5 micro g/ml, and it had a MIC(90) of 4 micro g/ml against both vancomycin-susceptible and -resistant E. faecium. The MIC(90)s for daptomycin and other directed-spectrum agents were unaffected by the regional or anatomical origin of isolates or patient demographic parameters (patient age, gender, and inpatient or outpatient care). Our results confirm the gram-positive spectrum of activity of daptomycin and that its activity is independent of susceptibility or resistance to commonly prescribed and tested antimicrobial agents. This study may serve as a baseline to monitor future changes in the susceptibility of gram-positive species to daptomycin following its introduction into clinical use.     

Comparative in vitro activity of older and newer fluoroquinolones against respiratory tract pathogens

The aim of this study was to evaluate the antibacterial activity of older (ciprofloxacin and ofloxacin) and newer (moxifloxacin, grepafloxacin, sparfloxacin and levofloxacin) fluoroquinolones. Minimal inhibitory concentrations (MICs) were determined, according to the NCCLS guidelines, against the following respiratory tract pathogens: penicillin-susceptible and -resistant Streptococcus pneumoniae, beta-lactamase-positive and beta-lactamase-negative Haemophilus influenzae and beta-lactamase-positive Moraxella catarrhalis. In addition, we evaluated the minimal bactericidal concentrations of the same antibiotics against all the pneumococci and the haemophili. Finally, the activity of ciprofloxacin, ofloxacin, sparfloxacin and moxifloxacin against 15 pneumococci were investigated by time-kill analysis. All fluoroquinolones tested exhibited a similar, good activity against H. influenzae and M. catarrhalis. Against S. pneumoniae, irrespective of penicillin susceptibility, moxifloxacin, grepafloxacin, sparfloxacin and levofloxacin exhibited excellent activity, better than ciprofloxacin and ofloxacin. Time-kill analysis showed that 99.9% killing of all strains was obtained after 24 h with moxifloxacin at 2 x MIC, whereas other antimicrobials obtained similar results at 4 x MIC. Moxifloxacin is characterized by an improved activity against respiratory pathogens, including penicillin-resistant and -susceptible S. pneumoniae. Its activity is not influenced by beta-lactamase production. These results suggest that moxifloxacin represents a promising alternative for treatment of respiratory tract infections.     

Antimicrobial activity of advanced-spectrum fluoroquinolones tested against more than 2000 contemporary bacterial isolates of species causing community-acquired respiratory tract infections in the United States (1999)

In vitro activity of four newer fluoroquinolones (clinafloxacin, gemifloxacin, moxifloxacin, sitafloxacin) and an equal number control drugs in the same class (ciprofloxacin, grepafloxacin, levofloxacin, trovafloxacin) was determined by reference dilution tests against 2156 recent United States clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. All the fluoroquinolones demonstrated excellent in vitro activity against these pathogens. Streptococcus pneumoniae isolates were fully susceptible to clinafloxacin, sitafloxacin, and gemifloxacin at 0.5 microg/ml, and over 98% of sampled strains had MICs of 相似文献   

Contemporary evaluation of the in vitro activity and spectrum of cefdinir compared with other orally administered antimicrobials tested against common respiratory tract pathogens (2000-2002)

Cefdinir is an oral cephalosporin approved by the Food and Drug Administration in 1997 for the treatment of acute exacerbation of chronic bronchitis, pharyngitis-tonsillitis, community-acquired pneumonia, acute maxillary sinusitis, and uncomplicated skin and skin structure infections in adults and adolescents, and acute otitis media, pharyngitis-tonsillitis, and uncomplicated skin and skin structure infections in children. Although cefdinir showed similar activity to other cephalosporins in the early studies, very limited data has been generated over the last decade. In this report, we summarize the contemporary in vitro activity and spectrum of cefdinir in comparison to numerous other orally administrated antimicrobials available for treatment of community-acquired respiratory infections. A total of 8,326 non-duplicate recent clinical isolates, including Haemophilus influenzae (3,438), Moraxella catarrhalis (1,688), and Streptococcus pneumoniae (3,200), were collected from 35 medical centers in North America during 2000 through 2002, and susceptibility tested by reference broth microdilution methods. Pneumococcal susceptibility patterns for beta-lactams and macrolides were also analyzed according to the year of isolation and the age group of the patients. Cefdinir had the greatest activity against H. influenzae among the cephalosporins tested with susceptibility rates of 97.1 to 99.0%. All of the agents tested had complete or near complete activity against M. catarrhalis. Against S. pneumoniae, cefdinir and other cephalosporins showed similar susceptibility patterns, but improved rates were observed in 2002 (78.5-79.4%) when compared to the previous monitored period (71.8-74.5%). This increase in susceptibility was mainly because of a declining the occurrence of high-level penicillin resistance (MIC >/=2 microg/ml) across all age groups. Macrolide resistance also decreased among S. pneumoniae in 2002 when compared to 2000 through 2001; however, resistance to levofloxacin continued to increase from 0.9% in 2000 to 1.4% in 2002. These results indicate a significant change in emerging beta-lactam resistance patterns (including cefdinir) with a decrease possibly influenced by greater pneumococcal vaccine use in children and the elderly. These rates of increased susceptibility could sustain and enhance the clinical activity of orally administered beta-lactams such as cefdinir.     

头孢丙烯及其他4种抗生素对社区获得性呼吸道感染病原菌体外抗菌活性比较

目的 :调查头孢丙烯及其他 4种抗生素对社区获得性呼吸道感染细菌的体外抗菌活性。方法 :肺炎链球菌、流感嗜血杆菌和卡他莫拉菌用全自动细菌分析系统的革兰阳性菌鉴定卡GPI、奈瑟及嗜血杆菌鉴定卡NHI做最终鉴定。药物敏感性试验采用Etest方法测定MIC。结果 :共计测定了 15 5株肺炎链球菌、97株流感嗜血杆菌、2 0株卡他莫拉菌、12株苯唑西林敏感的金黄色葡萄球菌 ,19株 β 溶血链球菌的药物敏感性试验。结果表明肺炎链球菌对 5种常用抗生素的敏感率分别为 :头孢丙烯 90 .3%、头孢克罗 85 .2 % ,阿奇霉素 2 5 .8%、青霉素 80 .6 %、阿莫西林 克拉维酸为 94 .2 %。流感嗜血杆菌对头孢丙烯和头孢克罗敏感率均为 97.9%。结论 :头孢丙烯对社区获得性呼吸道感染的 5种主要病原菌均显示了很高的体外抗菌活性。     

The Alexander Project 1996-1997: latest susceptibility data from this international study of bacterial pathogens from community-acquired lower respiratory tract infections

The Alexander Project was established in 1992 to examine antimicrobial susceptibilities of bacterial isolates from community-acquired infections of the lower respiratory tract. Testing of a range of compounds was undertaken in a central laboratory. From 1992 to 1995, isolates were collected from geographically separated areas in countries in the European Union and various states in the USA. In 1996, the study was extended to include centres in Mexico, Brazil, Saudi Arabia, South Africa, Hong Kong and other European countries not included previously. Data generated by the project during 1996-1997 confirm France and Spain as European centres with high rates of resistance to penicillin among isolates of Streptococcus pneumoniae. Both intermediate (MIC 0. 12-1 mg/L) and resistant (MIC 2 mg/L) phenotypes are present. Combined resistance rates (intermediate and resistant) were >/=50% in 1997. Combined resistance rates in excess of 20% were found in the Republic of Ireland, Portugal, the Slovak Republic and Hungary. Penicillin resistance continues to evolve in the USA, with combined resistance rates of 16.4% (1996) and 18.6% (1997). In the new, non-European centres, e.g. Mexico and, in particular, Hong Kong (where resistant strains accounted for 50% of all isolates of S. pneumoniae in 1996 and 55.5% in 1997), there are centres where rates of resistance are high. Macrolide resistance is increasing generally among both penicillin-resistant and penicillin-susceptible isolates of S. pneumoniae. There is variation between countries, and in four out of the 16 centres for which both 1996 and 1997 data are available, rates of macrolide resistance have fallen. Overall, the percentage of S. pneumoniae strains that is resistant to macrolides exceeds the percentage that is resistant to penicillin. In 1996, 16. 5% of all S. pneumoniae isolates were resistant to macrolides compared with 10.4% resistant to penicillin, and in 1997 respective rates were 21.9% and 14.1%. beta-Lactamase production was the principal mechanism of resistance observed among isolates of Haemophilus influenzae. However, considerable variation in the percentage of isolates producing beta-lactamase (0-37.1%) was observed within this species. Within Europe, in the Republic of Ireland, France and Belgium, more than 15% of isolates were beta-lactamase producers. In Spain rates were as high as 31.7%. Outside Europe and the USA high rates were described in Mexico (25%), Saudi Arabia (27.9%, 16.7%) and Hong Kong (37.1%, 28.9%). Of H. influenzae from the USA, 30.4% were beta-lactamase producers in 1996 and 23.3% in 1997. beta-Lactamase production among isolates of Moraxella catarrhalis was observed in >90% of the isolates tested in 1996 and 1997.     

In vitro activity of moxifloxacin(BAY 12-8039) against respiratory tract pathogens from six Latin-American countries

The in vitro antibacterial activity of moxifloxacin (BAY 12-8039) was evaluated against 636 isolates of respiratory tract pathogens. The isolates were collected from July 1997 to August 1998 in the frame of a multinational Latin American study. E-test strips calibrated to read moxifloxacin MIC ranges from 0.002 to 32 microg/ml were used in susceptibility testing. Weekly quality control tests in each laboratory ensured reproducibility. Laboratories from Argentina, Brazil, Chile, Colombia, Mexico and Uruguay participated. MIC(90) for moxifloxacin were as follows: Streptococcus pneumoniae (304 isolates) 0.25 microg/ml, Haemophilus influenzae (135 isolates) 0.125 microg/ ml, Streptococcus pyogenes (66 isolates) 0.25 microg/ml, Moraxella catarrhalis (62 isolates) 0. 25 microg/ml and methicillin-sensitive Staphylococcus aureus (69 isolates) 0.25 microg/ml. These results agreed with reports from other areas. Moxifloxacin showed excellent activity against respiratory pathogens from participant countries.     

Comparative in vitro activity of the new quinolone gemifloxacin (SB-265805) with other fluoroquinolones against respiratory tract pathogens

The in vitro activity of gemifloxacin (SB-265805) was compared with that of other fluoroquinolones against 302 clinical isolates of Streptococcus pneumoniae, 300 clinical isolates of Haemophilus influenzae and 28 clinical isolates of Moraxella catarrhalis, including multiply resistant strains. Gemifloxacin at 0.12 mg/L inhibited all microorganisms tested. MIC(90) values of gemifloxacin, trovafloxacin, grepafloxacin and levofloxacin against all (630) isolates tested were 0.03, 0.12, 0.12 and 1 mg/L, respectively. MIC(90) values of the same fluoroquinolones against S. pneumoniae were 0.06, 0.25, 0.12 and 1 mg/L, respectively.     

In vitro activity of trimethoprim alone compared with trimethoprim-sulfamethoxazole and other antimicrobials against bacterial species associated with upper respiratory tract infections

Trimethoprim-sulfamethoxazole has been used to treat various respiratory tract infections. Nevertheless, for many patients, intolerance of the sulfonamide component precludes use of this combination. This study examined the activity of trimethoprim alone in comparison to that of trimethoprim-sulfamethoxazole and other antimicrobials against bacterial species implicated in respiratory tract infections. For Haemophilus influenzae, minimal inhibitory concentrations of trimethoprim were equal to or one dilution greater than those of trimethoprim-sulfamethoxazole, with 56 of 58 strains inhibited by the former at ≤0.25 μg/ml. All oxacillin-susceptible Staphylococcus aureus and 96.7% of Streptococcus pyogenes were inhibited by trimethoprim ≤2 μg/ml. In contrast, only 50% of Streptococcus pneumoniae were inhibited by this concentration of trimethoprim, whereas 93.3% were susceptible to the combination at ≤2/38 μg/ml. All oxacillin-resistant S. aureus and all Moraxella catarrhalis were resistant to trimethoprim, although many of the former and all of the latter were susceptible to trimethoprim-sulfamethoxazole.     

In vitro activity of telithromycin against macrolide-susceptible and macrolide-resistant pharyngeal isolates of group A streptococci in the United States

In vitro susceptibility testing of 2,797 group A streptococcus (GAS) isolates demonstrated that telithromycin was fully active against all macrolide-susceptible strains and among 80 of 115 macrolide-resistant GAS expressing the M phenotype. Telithromycin resistance was identified in 2 of 45 strains expressing the inducible macrolide-lincosamide-streptogramin B phenotype and four of nine isolates expressing the constitutive macrolide-lincosamide-streptogramin B resistance phenotype.     

Comparative in vitro activity of carbapenem antibiotics against respiratory pathogens isolated in recent years

We investigated the antibacterial activity of 12 antibiotics, including 4 carbapenems, against 200 strains of respiratory pathogens isolated in 1997, and compared the results with those obtained in 1993. The strains examined were 38 strains of methicillin-susceptible Staphylococcus aureus (MSSA), 32 strains of methicillin-resistant S. aureus (MRSA), 22 strains of penicillin-susceptible Streptococcus pneumoniae (PSSP), 10 strains of penicillin-resistant S. pneumoniae (PRSP), 53 strains of Pseudomonas aeruginosa, 19 strains of Moraxella catarrhalis, and 26 strains of Haemophilus influenzae. In 1993, 100 strains were examined. The minimal inhibitory concentration data of the present study showed that imipenem and panipenem were more active than the other agents against gram-positive bacteria, and that meropenem and biapenem were more active than the other agents against gram-negative bacteria. By comparing these results with those obtained in 1993, it was found that increase of resistance to carbapenem antibiotics was not observed against all the strains tested in this study. Thus, it can be stated that carbapenem antibiotics retain their position as the drug of first choice for severe infections. Received: January 4, 1999 / Accepted: May 26, 1999     

The Alexander Project 1998-2000: susceptibility of pathogens isolated from community-acquired respiratory tract infection to commonly used antimicrobial agents

OBJECTIVES: The Alexander Project is a continuing surveillance study, begun in 1992, examining the susceptibility of pathogens involved in adult community-acquired respiratory tract infections (CARTI) to a range of antimicrobial agents. MATERIALS AND METHODS: This study tested the susceptibility of isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis collected between 1998 and 2000 to 23 antimicrobials. Minimum inhibitory concentrations of agents were determined using the broth microdilution method and interpreted according to NCCLS and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. RESULTS: In total, 8882 isolates of S. pneumoniae, 8523 isolates of H. influenzae and 874 isolates of M. catarrhalis were collected during 1998-2000 from centres in 26 countries. The world-wide prevalence of penicillin resistance (penicillin MICs > or = 2 mg/l) in isolates of S. pneumoniae was 18.2% over the study period, and the prevalence of macrolide resistance (erythromycin MICs > or = 1 mg/l) in this pathogen was 24.6%. Over the study period, macrolide resistance exceeded penicillin resistance in 19 of the 26 countries included in the study. Of the non-fluoroquinolone agents, the only oral agents to which over 90% of S. pneumoniae isolates were susceptible at both NCCLS and PK/PD breakpoints were amoxicillin (95.1%) and co-amoxiclav (95.5-97.9%). The prevalence of fluoroquinolone-resistant S. pneumoniae (ofloxacin MICs > or = 8 mg/l) was 1.1%. Gemifloxacin was the most potent fluoroquinolone tested against S. pneumoniae (99.9% susceptible). In isolates of H. influenzae, beta-lactamase production was 16.9%, whereas the prevalence of beta-lactamase-negative, ampicillin-resistant strains was low (0.2%). beta-Lactamase production in M. catarrhalis world-wide remained high over the period studied (92.1%). Using PK/PD breakpoints, the most active non-fluoroquinolone agents against H. influenzae were ceftriaxone (100% susceptible), cefixime (99.8%) and co-amoxiclav (98.1-99.6%). Co-amoxiclav, cefdinir and cefixime (100%) were the most active beta-lactams against M. catarrhalis. Both H. influenzae and M. catarrhalis were highly susceptible to the fluoroquinolones. CONCLUSIONS: These data demonstrate the continued evolution of and geographical variation in bacterial resistance and highlight the need for appropriate prescribing of antimicrobials in CARTI, using agents with adequate activity, based on local susceptibility profiles and PK/PD parameters.     

Comparative in vitro activity of a new quinolone, fleroxacin, against respiratory pathogens from patients with cystic fibrosis.

We evaluated fleroxacin, a newer fluoroquinolone, against isolates from sputum from patients with cystic fibrosis. These isolates included rough and mucoid Pseudomonas aeruginosa, Pseudomonas cepacia, Staphylococcus aureus, Haemophilus influenzae, and Escherichia coli. Selected isolates were tested by the broth microdilution method to examine the influence of various pHs, inoculum sizes, and biological fluids (serum or sputum from patients with cystic fibrosis). Fleroxacin MICs for 50 and 90% of isolates of P. aeruginosa were 2.0 and 4 micrograms/ml, those for P. cepacia were 2 and 16 micrograms/ml, those for S. aureus were 0.5 and 1 microgram/ml, those for H. influenzae were 0.06 and 0.06 micrograms/ml, and those for E. coli were 0.01 and 0.03 micrograms/ml, respectively. Fleroxacin activity against mucoid P. aeruginosa was similar to the activities of enoxacin and ofloxacin but eightfold lower than that of ciprofloxacin. It was twofold more active than norfloxacin and enoxacin but was twofold less active than ciprofloxacin, ofloxacin, and nafcillin against S. aureus. Fleroxacin inhibitory activity against P. cepacia was two- to fourfold lower than that of ciprofloxacin but eightfold greater than those of the other quinolones tested. Alterations in pH, diluent, and inoculum size did not significantly affect fleroxacin activity. These results, combined with available pharmacokinetic and tissue distribution data, support the need for clinical evaluation of fleroxacin in pulmonary infections in patients with cystic fibrosis.