Activity of moxifloxacin and other quinolones against pneumococci resistant to first-line agents, or with high-level ciprofloxacin resistance

The activity of moxifloxacin and other quinolones was assessed against 288 epidemiologically diverse isolates of Streptococcus pneumoniae, many of them resistant to one or more first-line agents and/or with increased ciprofloxacin resistance (minimum inhibitory concentrations, MICs 16- > 64 mg/l compared with 1-2 mg/l for most isolates). Moxifloxacin and grepafloxacin were the most active quinolone analogues, inhibiting about 90% of the isolates at < or = 1 mg/l, whereas levofloxacin inhibited 64% of isolates at < = 1 mg/l and ciprofloxacin inhibited 42%. Moxifloxacin also was the most active agent against isolates with elevated ciprofloxacin resistance (MIC 16- > 64 mg/l): moxifloxacin MICs of around 4 mg/l were seen for most such isolates, compared with 16-32 mg for levofloxacin and grepafloxacin. The activity of moxifloxacin against pneumococci resistant to one or more first-line agent suggests it will have a useful therapeutic role, although its activity against highly ciprofloxacin resistant isolates seems marginal.     

Comparative activities of six different fluoroquinolones against 9,682 clinical bacterial isolates from 20 European university hospitals participating in the European SENTRY surveillance programme

The in-vitro activities of gatifloxacin, trovafloxacin, levofloxacin, sparfloxacin, ofloxacin, and ciprofloxacin were tested against 9,682 clinical bacterial isolates from 20 European university hospitals participating in the European SENTRY surveillance programme. Gatifloxacin and trovafloxacin exhibited the highest activities against Gram-positive cocci, while levofloxacin, ofloxacin, ciprofloxacin, and gatifloxacin were the most active against Enterobacteriaceae. Ciprofloxacin and levofloxacin showed the highest antimicrobial activities against Pseudomonas spp., while gatifloxacin and trovafloxacin were the most active against Acinetobacter spp. and Stenotrophomonas maltophilia. All Haemophilus spp. and Moraxella catarrhalis isolates were fully susceptible to all quinolones tested. Overall, the new quinolones, showed improved activity against Gram-positive cocci and Gram-negative non-fermenters while retaining their broad-spectrum activity against Gram-negative bacilli.     

Comparative in vitro activity of ciprofloxacin and other unrelated antimicrobials against bacterial respiratory tract pathogens

Ciprofloxacin is a new fluorinated 4-quinolone with a broad spectrum of antimicrobial activity which includes both Gram-negative and Gram-positive bacteria. In this study the in vitro activity of ciprofloxacin has been determined against bacteria associated with respiratory tract infections and compared with that of other antimicrobial agents used in the therapy of such infections. Ciprofloxacin (MIC90 0.008 mg/l) was highly active against Haemophilus influenzae, including isolates producing beta-lactamase which were resistant to amoxycillin. Ciprofloxacin (MIC90 0.06 mg/l) was also highly active against Branhamella catarrhalis, again including those isolates resistant to amoxycillin as a result of beta-lactamase production. Isolates of Streptococcus pneumoniae were less susceptible to ciprofloxacin (MIC90 2 mg/l) but were highly susceptible to amoxycillin (MIC90 less than 0.12 mg/l) and erythromycin (MIC90 0.25 mg/l). Isolates of Klebsiella aerogenes were highly susceptible to ciprofloxacin (MIC90 0.06 mg/l) but much less so to amoxycillin, sulfamethoxazole, trimethoprim, oxytetracycline and erythromycin. Ciprofloxacin (MIC90 0.5 mg/l) was very active against Staphylococcus aureus, including those isolates resistant to amoxycillin and flucloxacillin, and against Mycoplasma pneumoniae. Together with rifampicin and erythromycin, ciprofloxacin was highly active against Legionella pneumophila (MIC90 0.015 mg/l). These results suggest that clinical evaluation of ciprofloxacin in the treatment of respiratory tract infections is justified.     

In vitro activity of gemifloxacin against clinical isolates of Neisseria gonorrhoeae with and without mutations in the gyrA gene

The MIC of gemifloxacin and five other quinolones was tested against 31 clinical isolates of Neisseria gonorrhoeae; strains were analyzed for the presence of mutations in both the gyrA and parC genes. Only seven strains were resistant to nalidixic acid due to a mutation in the gyrA gene but not in the parC gene, with six and two considered intermediate to ciprofloxacin and levofloxacin, respectively. The activity of gemifloxacin was similar to that of trovafloxacin and moxifloxacin, but was more active than nalidixic acid, ciprofloxacin or levofloxacin against the gyrA mutant strains. Gemifloxacin is a valid therapeutic alternative to treat infections with N. gonorrhoeae, retaining its activity against strains already presenting a mutation in gyrA.     

Multicentre study of the in vitro evaluation of moxifloxacin and other quinolones against community acquired respiratory pathogens.

The in vitro activity of moxifloxacin was compared with that of ciprofloxacin, levofloxacin, ofloxacin and trovafloxacin against 710 strains (180 Streptococcus pneumoniae, 180 Haemophilus influenzae, 160 Moraxella catarrhalis and 190 Streptococcus pyogenes) isolated from patients with community-acquired respiratory tract infections. MIC values for moxifloxacin, trovafloxacin were 0.25/0.25, 0.03/0.03, 0.06/0.03 and 0.125/0.0125 mg/l for S. pneumoniae, H. influenzae, M. catharralis and S. pyogenes. Based upon the MIC(90) values and the MIC distributions, moxifloxacin and trovafloxacin were the most active of the quinolones tested. They showed enhanced activity against Gram-positive organisms including penicillin non susceptible S. pneumoniae strains. Moxifloxacin was also highly active against ciprofloxacin-resistant S. pneumoniae strains.     

Comparative in vitro activity and pharmacodynamics of five fluoroquinolones against clinical isolates of Streptococcus pneumoniae

STUDY OBJECTIVE: To compare in vitro activity and pharmacodynamics of five fluoroquinolones against clinical isolates of Streptococcus pneumoniae. DESIGN: In vitro analysis. SETTING: University research laboratory. INTERVENTION: Minimum inhibitory concentrations (MICs) were determined for penicillin and five fluoroquinolones by E test for 201 S. pneumoniae isolates. Serum concentration-time profiles were simulated for the following regimens: ciprofloxacin 750 mg orally every 12 hours and 400 mg intravenously every 8 hours; levofloxacin 500 mg orally and intravenously every 24 hours; trovafloxacin 200 mg orally and intravenously every 24 hours; gatifloxacin 400 mg orally and intravenously every 24 hours; and clinafloxacin 200 mg orally and intravenously every 12 hours. MEASUREMENTS AND MAIN RESULTS: Free 24-hour areas under the serum concentration-time curves (AUC0-24) were calculated using the trapezoidal rule, and the average AUC0-24:MIC ratio was calculated for each regimen. Differences in ratios among agents were determined by analysis of variance (Scheffe post hoc test, p < 0.05). For intravenous dosing, the average AUC0-24:MIC for gatifloxacin, clinafloxacin, trovafloxacin, ciprofloxacin, and levofloxacin was 146, 142, 122, 71, and 61, respectively. For both oral and intravenous regimens, gatifloxacin and clinafloxacin ratios were significantly greater than those for trovafloxacin, levofloxacin, and ciprofloxacin (p < or = 0.007). Ratios for trovafloxacin were significantly greater than those for levofloxacin and ciprofloxacin (p < 0.0001), and levofloxacin and ciprofloxacin ratios were not significantly different from each other. CONCLUSION: Gatifloxacin and clinafloxacin achieve significantly higher AUC0-24:MIC ratios for S. pneumoniae than trovafloxacin, levofloxacin, and ciprofloxacin. Large comparative studies are necessary to determine the clinical significance of these findings.     

Comparative in vitro activity of gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin and trovafloxacin against 4151 Gram-negative and Gram-positive organisms

Gatifloxacin, grepafloxacin, moxifloxacin and trovafloxacin are fluoroquinolones with enhanced Gram-positive activity while retaining broad-spectrum activity against Gram-negative pathogens. Levofloxacin and ciprofloxacin are older quinolones with broad activity against Gram-negative pathogens and borderline activity against some Gram-positive organisms. We compared the in vitro activity of these compounds against 4151 Gram-negative and -positive organisms. Gatifloxacin, grepafloxacin, moxifloxacin and trovafloxacin were highly active against penicillin sensitive and resistant Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes and Streptococcus agalactiae. Ciprofloxacin and levofloxacin were active but less potent. All compounds were highly active (overall) against Gram-negative pathogens with ciprofloxacin being the most active agent against Pseudomonas aeruginosa. Our data indicate that the advanced fluoroquinolones will be important compounds for treating infections caused by Gram-positive and Gram-negative pathogens.     

Bacterial strain-independent AUC/MIC and strain-specific dose-response relationships reflecting comparative fluoroquinolone anti-pseudomonal pharmacodynamics in an in vitro dynamic model

To compare the antimicrobial effects (AMEs) of two quinolones in terms of the AUC/MIC- and dose (D)-response relationships, five differentially susceptible clinical isolates of Pseudomonas aeruginosa were exposed to decreasing concentrations of ciprofloxacin (two 12-h doses with T(1/2) = 4 h) and trovafloxacin (a single dose with T(1/2) = 9.2 h). The simulated AUC/MICs of ciprofloxacin ranged from 58 to 932 and those of trovafloxacin, from 54 to 466 h. The intensity of the AME (I(E)) correlated well with log AUC/MIC for both ciprofloxacin and trovafloxacin (r(2) = 0.99 and 0.97, respectively) in a strain-independent fashion. At a given AUC/MIC ratio, AMEs of trovafloxacin were greater than ciprofloxacin. However, based on the respective I(E)-logD curves, 200 mg trovafloxacin produced a slightly greater AME than 2 x 500 mg ciprofloxacin only with the most susceptible P. aeruginosa. With the less susceptible P. aeruginosa ciprofloxacin was more efficient than trovafloxacin. This study suggests that both bacterial strain-independent AUC/MIC- and the respective strain-specific dose-response relationships of the AME are important for comprehensive pharmacodynamic evaluation of antimicrobial agents.     

In vitro activity of sitafloxacin compared with several fluoroquinolones against Streptococcus anginosus and Streptococcus constellatus

The in vitro activities of sitafloxacin and seven other fluoroquinolones a (ciprofloxacin, tosufloxacin, sparfloxacin, levofloxacin, T-3811ME, moxifloxacin and trovafloxacin) were examined by the microdilution method against 79 clinically isolated 'Streptococcus milleri' group (SMG) microorganisms. No statistically significant differences were found between the minimum inhibitory concentrations (MIC(50) and MIC(90)) against Streptococcus anginosus and Streptococcus constellatus. Sitafloxacin was the most active agent of the eight fluoroquinolones tested against SMG, with a MIC(90) of 0.06 microg/mL, which was 8 times more active than ciprofloxacin and 16 times more active than levofloxacin. Although none of the SMG strains showed high resistance to any of the fluoroquinolones tested, three agents (trovafloxacin, sitafloxacin and T-3811ME) had low MICs against 23 SMG strains against which levofloxacin had a MIC> 1 microg/mL. In conclusion, several fluoroquinolones have low MICs against SMG, but sitafloxacin has the lowest.     

Antibacterial activity of gatifloxacin against various fresh clinical isolates in 2002

Antibacterial activities of gatifloxacin (GFLX) and other antibacterial drugs against various fresh clinical strains (800 isolates) isolated from specimens of patients in 2002 were compared. GFLX was more active than levofloxacin and ciprofloxacin against Gram-positive bacteria such as methicillin susceptible Staphylococcus aureus and Streptococcus pneumoniae. For these isolates, clarithromycin and azithromycin were less active (MIC90; > 16- > 64 micrograms/mL), GFLX was more active than cefdinir. For Escherichia coli, Klebsiella pneumoniae, Acinetobacter species, Haemophilus influenzae and Moraxella (Branhamella) catarrhalis, three quinolones including GFLX were potently active (MIC90; < or = 0.06-0.5 microgram/mL). Pseudomonas aeruginosa isolated from urinary tract infections were resistant to three quinolones including GFLX (MIC90; 32-64 micrograms/mL), however P. aeruginosa isolated from respiratory and otolaryngological infections were more susceptible (MIC90; 0.5-2 micrograms/mL). Quinolones were less active against Neisseria gonorrhoeae as compared with the cephem antibiotics tested, but GFLX was the most active against N. gonorrhoeae among the quinolones tested. In this study, we investigated activity of GFLX against fresh clinical strains isolated early in 2002, GFLX is widely and potently active against S. aureus, S. pneumoniae and various Gram-negative bacteria.     

In vitro susceptibility of 4903 bacterial isolates to gemifloxacin--an advanced fluoroquinolone

The in vitro activity of gemifloxacin against over 4900 bacterial isolates was determined by microbroth dilution with interpretation in accordance with NCCLS guidelines. Susceptibility results were compared with those for ciprofloxacin, gatifloxacin, levofloxacin and moxifloxacin. Gemifloxacin and the other fluoroquinolones were not affected by either beta-lactamase production or penicillin-resistance in Streptococcus pneumoniae. The MIC90 values for gemifloxacin were: S. pneumoniae 0.063 mg/l; Haemophilus influenzae 0.016 mg/l; Moraxella catarrhalis 0.008 mg/l, methicillin-susceptible Staphylococcus aureus 0.063 mg/l; methicillin-susceptible Streptococcus pyogenes 0.031 mg/l; Enterobacteriaceae 0.031-0.16 mg/l; Pseudomonas aeruginosa 4 mg/l; Neisseria meningitidis 0.008 mg/l. The MIC90 for gemifloxacin was lower than those for the other quinolones tested against S. pneumoniae (ciprofloxacin 2-4 mg/l, gatifloxacin 0.5 mg/l, levofloxacin 1-2 mg/l, moxifloxacin 0.25 mg/l). This study confirms the enhanced potent activity of gemifloxacin against Gram-positive pathogens, its broad-spectrum, Gram-negative activity and indicates that gemifloxacin is likely to have an important role in treating patients with Gram-positive and/or Gram-negative infections.     

Increased antibacterial activity of DW286, a novel fluoronaphthyridone antibiotic, against Staphylococcus aureus strains with defined mutations in DNA gyrase and topoisomerase IV

To investigate the activity of DW286, a new fluoronaphthyridone, the quinolone resistance determining regions (QRDRs) of gyrA, gyrB, grlA and grlB genes in 64 Staphylococcus aureus clinical isolates were analyzed and the MICs of DW286 and comparator quinolones determined. Double and triple mutants in gyrA and grlA were resistant to ciprofloxacin, sparfloxacin, trovafloxacin and gemifloxacin but susceptible to DW286 (MIC 0.25-0.5 mg/l). The fourth alteration, Ser85Pro of GyrA was required to make a strain resistant to DW286 (MIC 4-32 mg/l). For a strain with the mutations at GyrA Ser84Leu and GrlA Ser80Phe, the MBC of DW286 was two-fold higher than its corresponding MIC, in contrast to ciprofloxacin which was not bactericidal.     

Susceptibility of Brucella melitensis to fluoroquinolones

In vitro activity of four fluoroquinolones and four other antibacterial agents was tested against clinical isolates of Brucella melitensis. Initially all the 146 isolates studied were inhibited by 0.06-0.5 mg/l of ciprofloxacin and fleroxacin and 0.12-0.5 mg/l of pefloxacin or norfloxacin. One of these isolates developed resistance during therapy with ciprofloxacin, with a rise in MIC from 0.06 mg/l to more than 5.0 mg/l. This strain also showed cross-resistance to all other quinolones. All the isolates remained susceptible to tetracycline, gentamicin, rifampicin and trimethoprim-sulfamethoxazole. None of the quinolones showed in vitro synergy with other antibiotics.     

Antimicrobial resistance trends in community-acquired respiratory tract pathogens in the Western Pacific Region and South Africa: report from the SENTRY antimicrobial surveillance program, (1998-1999) including an in vitro evaluation of BMS284756

From 1998 to 1999, a large number of community-acquired respiratory tract isolates of Streptococcus pneumoniae (n=566), Haemophilus influenzae (n=513) and Moraxella catarrhalis (n=228) were collected from 15 centres in Australia, Hong Kong, Japan, China, the Philippines, Singapore, South Africa and Taiwan through the SENTRY Antimicrobial Surveillance Program. Isolates were tested against 26 antimicrobial agents using the NCCLS-recommended methods. Overall, 40% of S. pneumoniae isolates were resistant to penicillin with 18% of strains having high-level resistance (MIC > or =2 mg/l). Rates of erythromycin and clindamycin resistance were 41 and 23%, respectively. Penicillin-resistant strains showed high rates of resistance to other antimicrobial agents: 96% to trimethoprim-sulphamethoxazole (TMP-SMX), 84% to tetracycline and 81% to erythromycin. A significant proportion of penicillin-susceptible strains was also resistant to erythromycin (21%), tetracycline (29%) and TMP-SMZ (26%). Small numbers of strains were resistant to levofloxacin (0.7%), trovafloxacin (0.4%) and grepafloxacin (1.3%) where as all strains remained uniformly susceptible to quinupristin/dalfopristin and BMS284756 (MIC(90), 0.06 mg/l), a new desfluoroquinolone. beta-lactamases were, produced by 20% H. influenzae isolates and only rare strains showed intrinsic resistance to amoxycillin. Other beta-lactam agents showed good activity with rates of resistance less than 2% and all isolates showed susceptibility to cefixime, ceftibuten, cefepime and cefotaxime. Rates of resistance to tetracycline and chloramphenicol were also relatively low at 3%. The majority (98%) of M. catarrhalis isolates was found to be beta-lactamase-positive and resistant to penicillins, however, resistance to erythromycin and tetracycline was also low at 1.8%. Both H. influenzae and M. catarrhalis isolates were uniformly susceptible to the new desfluoroquinolone and tested fluoroquinolones.     

Canadian Pseudomonas aeruginosa susceptibility study from 48 medical centers: focus on ciprofloxacin

We tested 1503 clinical isolates of Pseudomonas aeruginosa, from 48 Canadian medical centers, against ciprofloxacin and 11 other antimicrobial agents to determine in vitro activity. The frequency of susceptibility was highest for carbenicillin and ticarcillin (91% each) followed by imipenem and ceftazadime (90% each). Overall susceptibility (≤1.0 mg/l) to ciprofloxacin was 84% while resistance (≥4.0 mg/l) was 12%. Ciprofloxacin resistant isolates were more common from urinary tract specimens than from specimens collected from the respiratory and/or skin and soft tissue. Isolates from cystic fibrosis patients were more resistant to all agents tested than isolates from non-cystic fibrosis patients.     

In vitro activities of fourteen antimicrobial agents against obligately anaerobic bacteria

The in vitro activities of fourteen antimicrobial agents were tested against 292 clinical isolates of obligately anaerobic bacteria using the broth microdilution technique. Taking all strains as a group the MIC(50/90) (mg/l) values were metronidazole and imipenem 0.25/1, meropenem 0.25/0.5, trovafloxacin 0.25/1, gatifloxacin and moxifloxacin 0.5/2, levofloxacin 2/16, ciprofloxacin 4/32, clindamycin 0.5/8, amoxycillin/clavulanate 1/4, doxycycline and chloramphenicol 2/4, erythromycin 4/>32 and penicillin G 16/>32.     

In vitro fluoroquinolone-resistant mutants of Salmonella enterica serotype Enteritidis: analysis of mechanisms involved in resistance

This study analysed the mechanisms involved in the acquisition of resistance to quinolones in mutants obtained in vitro of Salmonella enterica serotype Enteritidis. Two nalidixic acid-resistant (minimal inhibitory concentrations, MIC>256 mg/l), ciprofloxacin-susceptible (MIC 0.5 mg/l) clinical isolates of Salmonella Enteritidis with a mutation at amino acid codon Ser-83 of the gyrA gene were grown on plates containing increasing concentrations of ciprofloxacin. The increase in MIC to ciprofloxacin, sparfloxacin and trovafloxacin was totally or partially associated with over-expression of an AcrAB-like efflux pump. In addition, unidentified mechanism(s) may have been involved in the increased MIC to these antimicrobials. This study demonstrated that AcrAB-like efflux pumps appear to play a relevant role in the increase in MIC to some quinolones although, other, as yet undefined, mechanisms may be involved.     

Pathogen occurrence and antimicrobial resistance trends among urinary tract infection isolates in the Asia-Western Pacific Region: report from the SENTRY Antimicrobial Surveillance Program, 1998-1999

Worldwide surveillance of antimicrobial resistance among urinary tract pathogens is useful to determine important trends and geographical variation for common Gram-positive and -negative species. The most common causative uropathogens often have intrinsic or acquired resistance mechanisms which include ESBL production among enteric bacilli, multi-drug resistant staphylococci and non-fermentative Gram-negative bacilli such as Pseudomonas aeruginosa and Acinetobacter spp. and vancomycin-resistant Enterococcus spp. This study evaluates pathogen frequency and the resistance rates among urinary tract infection (UTI) pathogens in 14 medical centres in the Asia-Pacific region between 1998 and 1999. The isolates were referred to a central monitor for reference NCCLS broth microdilution testing, identification confirmation and patient demographic analysis. Over 50% of the 958 pathogens were Escherichia coli and Klebsiella spp. followed by P. aeruginosa, Enterococcus spp. and Enterobacter spp. Susceptibility for the three enteric bacilli was high for carbapenems (100%), 'fourth-generation' cephalosporins (cefepime 94.9-98.6%) and amikacin (> or = 93.0%). Beta-lactamase inhibitor compounds were more active against E. coli (piperacillin/tazobactam; > 90% susceptible) than the other two enteric species and all other tested agents had a narrower spectra of activity. The rank order of anti-pseudomonal agents was amikacin (91.5% susceptible)> imipenem > piperacillin/tazobactam > tobramycin > ceftazidime and cefepime (77.4 and 76.4% susceptible, respectively). Susceptibility to quinolones for the P. aeruginosa isolates was only 63.2-67.0%. Only one vancomycin-intermediate Enterococcus spp. (van C phenotype) was detected among the 103 strains tested. Newer fluoroquinolones (gatifloxacin; MIC(50), mg/l) were more potent against enterococci than ciprofloxacin (MIC(50), 2 mg/l) and high-level resistance to aminoglycosides was common (41.7%). The data presented are compared to studies of similar design from other areas which are part of the SENTRY surveillance network.     

Results from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme: report of the 2001 data from 15 United States medical centres

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme is an international surveillance network of more than 100 medical centres where meropenem is the primary therapeutic carbapenem. Institutions have been monitored since 1997 (1999 in United States (US)) using National Committee for Clinical Laboratory Standards (NCCLS) reference susceptibility methods to monitor in vitro activity of meropenem and selected other broad-spectrum antimicrobial agents. In 2001, a total of 2874 strains were processed from the 15 US medical centres. Molecular methods were associated with MIC methods as needed for defining epidemic spread of resistant strains. The meropenem MIC(90) values were 0.03 mg/l for Citrobacter spp., Escherichia coli and Klebsiella spp.; 0.06 mg/l for Proteus mirabilis and Serratia spp. and 0.12 mg/l for Enterobacter spp. This potency was 8-16-fold greater than that of imipenem and the meropenem spectrum of activity versus the Enterobacteriaceae was the broadest of all tested antimicrobial agents. Only piperacillin/tazobactam (MIC(9), 64 mg/l) and tobramycin (MIC(90), 4 mg/l) were active against more than 90.0% of Pseudomonas aeruginosa at the NCCLS susceptible breakpoint, and the carbapenems were the most active compounds against Acinetobacter spp. However, Acinetobacter spp. isolates were resistant to all of the antimicrobial agents tested and the molecular typing results suggested that they were epidemiologically related. Only ciprofloxacin and ceftazidime had significantly reduced activity against oxacillin-susceptible staphylococci (87.9-92.6% susceptible. These 2001 US MYSTIC Programme results demonstrated no significant decline in carbapenem activity or susceptibility rates compared with the previously monitored years (1999-2000). Most apparent were the decreasing susceptibility rates for ciprofloxacin and ceftazidime against staphylococci. Continued surveillance in these institutions appears warranted as sites of high potential emerging resistance risk.     

Susceptibility of Canadian isolates of Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae to oral antimicrobial agents

We measured the susceptibility of Canadian isolates of three respiratory tract pathogens (Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae) to several currently approved antimicrobial agents by two different methods. We also measured the susceptibility of isolates to seven fluoroquinolones. Beta-lactamase was produced by 123/566 (21.7%) of H. influenzae isolates compared with 178/200 (89%) of M. catarrhalis isolates. For S. pneumoniae 83/374 (22.2%) isolates were penicillin resistant and of these 2.1% (8/374) showed high level resistance (MIC≥2 mg/l). Regardless of methodology, all fluoroquinolones were highly active against H. influenzae (MIC₉₀ ≤0.031 mg/l) and M. catarrhalis (MIC₉₀ ≤0.064 mg/l) isolates. Susceptibility of H. influenzae to cefuroxime and amoxycillin/clavulanic acid was 99–100% whereas 84–85.5% were susceptible to cefaclor and cefprozil. Azithromycin susceptibility ranged from 82.6 to 99.2% depending on the method. M. catarrhalis isolates were uniformly susceptible to all agents tested except amoxycillin. Cross-resistance in S. pneumoniae to all non-quinolone agents was concurrent with increasing penicillin resistance as shown by increasing MIC₉₀ values. For the fluoroquinolones tested, the rank order of potency based on MIC₉₀ values was as follows: gemifloxacin (0.031–0.063 mg/l), trovafloxacin (0.125 mg/l), moxifloxacin (0.125–0.25 mg/l), grepafloxacin (0.125–0.25 mg/l), gatifloxacin (0.5 mg/l), levofloxacin (1 mg/l) and ciprofloxacin (2 mg/l). Our study confirms either a high or increasing prevalence of antimicrobial resistant respiratory pathogens in Canada and also compares the new and old fluoroquinolones and their potential role as therapy for community-acquired infections. The prevalence of β-lactamase positive H. influenzae may have decreased from levels reported in previous studies.