Respiratory tract pathogens isolated from patients hospitalized with suspected pneumonia: frequency of occurrence and antimicrobial susceptibility patterns from the SENTRY Antimicrobial Surveillance Program (United States and Canada, 1997).

Thirty-seven sentinel hospitals (29 in the United States [US]; eight in Canada) collected bacterial isolates from hospitalized patients with a diagnosis of pneumonia. The antimicrobial susceptibility patterns of these pathogens were determined to more than 60 agents (40 reported) using the reference broth microdilution method described by the National Committee for Clinical Laboratory Standards. The five most frequently recorded species among the 2757 isolates collected during the study were (no. tested/%): Staphylococcus aureus (632/22.9%), Pseudomonas aeruginosa (498/18. 1%), Haemophilus influenzae (284/10.3%), Klebsiella spp. (240/8.7%), and Streptococcus pneumoniae (213/7.7%). There was a significant difference in the susceptibility to antimicrobials between the US and Canada for S. aureus to oxacillin (50.1% versus 93.8% susceptible, respectively), gentamicin (78.7% versus 97.8%), and fluoroquinolones (49.5 to 53.0% versus 89.8 to 94.9%). Amikacin (92. 8% susceptible) was the most active antimicrobial agent against P. aeruginosa, and meropenem was the most potent beta-lactam. Against H. influenzae, most drugs retained a high level of activity, whilst against the S. pneumoniae, only the newer fluoroquinolones (gatifloxacin, levofloxacin, sparfloxacin) remained highly effective in vitro. Only two antimicrobial agents (imipenem and meropenem) were >99% active against the Klebsiella spp. and Enterobacter spp. isolated in this survey (possess extended spectrum beta-lactamases or hyperproduction of Amp C cephalosporins); cefepime (95.6-100.0% susceptible) was significantly more active than other cephalosporins tested. Clonal, epidemic outbreaks of multiply resistant strains were very rare in monitored hospitals. In conclusion, important differences exist between the US and Canada in the susceptibility patterns of some respiratory tract pathogens to commonly used antimicrobial agents with Canadian strains generally being more susceptible to currently available antimicrobial agents.

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 beta-lactamase production or penicillin resistance. Cefditoren had MIC50/MIC90 results for Moraxella catarrhalis and Haemophilus influenzae of 0.12/0.5 and < or = 0.008/0.015 microgram/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 micrograms cefditoren/mL, and the highest recorded MIC was 4 micrograms/mL. Cefditoren appears to be a very promising beta-lactam possessing the greatest potency and potential spectrum versus contemporary (1997) respiratory tract pathogens.

Comparative in vitro evaluation of dirithromycin tested against recent clinical isolates of Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae, including effects of medium supplements and test conditions on MIC results.

The use of macrolides for treatment of respiratory complaints has been complicated by susceptibility test conditions that adversely effect the in vitro test results and perceived potencies of these compounds. Dirithromycin was studied as to its in vitro activity compared to other macrolides as well as the effects that environmental incubation variations and inoculum concentrations may have on susceptibility results. Dirithromycin was less active than other macrolides tested (azithromycin clarithromycin, erythromycin) against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis with MIC90 values of 16, 32, and 1 microgram/ml, respectively; an activity that was most similar to roxithromycin. This reduced activity may be compensated by the superior pharmacokinetic properties that dirithromycin possesses compared to other members in its class. Method variation studies show that incubation in CO2 environments increase the MIC values for all macrolide compounds and dirithromycin was most effected by pH changes in three in vitro methods tested (Etest [AB BIODISK, Solna, Sweden] broth microdilution, and disk diffusion). Variations in inoculum concentration had minimal effect on dirithromycin potency. In addition the variability (lack of reproducibility) of the test results with dirithromycin were not significant. Dirithromycin is an alternative therapeutic choice among macrolide compounds for treatment of community-acquired respiratory infections caused by various streptococci, Legionella pneumophilia, Mycoplasma pneumoniae and M. catarrhalis, and also possesses a modest in vitro potency versus H. influenzae coupled with excellent pharmacokinetic properties. In vitro tests with dirithromycin will continue to be problematic for H. influenzae because of the adverse effects of recommended CO2 incubation for some standardized methods or commercial products (Etest).

BAY 12-8039, a novel fluoroquinolone. Activity against important respiratory tract pathogens.

BAY 12-8039 or moxifloxacin is a new 8-methoxyquinolone with documented, improved activity against Gram-positive cocci and anaerobic bacteria. This study tested 1250 commonly isolated respiratory tract pathogens (251 Moraxella catarrhalis, 499 Haemophilus influenzae, 500 Streptococcus pneumoniae) from 1996-1997 clinical infections at more than 30 medical centers. Among the M. catarrhalis strains (81% beta-lactamase-positive) the BAY 12-8039 MIC90 was 0.06 microgram/mL, a potency equal to ofloxacin but less than all other tested fluoroquinolones (ciprofloxacin, clinafloxacin, levofloxacin, sparfloxacin, trovafloxacin). The H. influenzae strains were generally less susceptible to BAY 12-8039 (MIC90, 0.03 microgram/mL) than the tested fluoroquinolones, and the other comparison compounds were less active overall. All S. pneumoniae strains were susceptible to BAY 12-8039 at < or = 0.25 microgram/mL (MIC90, 0.06-0.12 microgram/mL), a value equal-potent to trovafloxacin. This new fluoroquinolone, BAY 12-8039, appears promising for the treatment of community-acquired respiratory tract infections caused by common bacterial species.

Comparative in vitro activity of gatifloxacin against Stenotrophomonas maltophilia and Burkholderia species isolates including evaluation of disk diffusion and E test methods.

The in vitro activity of gatifloxacin, a new fluoroquinolone, was compared to that of five other fluoroquinolones against 105 Stenotrophomonas maltophilia isolates and 52 Burkholderia spp. isolates. The gatifloxacin MICs were determined using the broth microdilution method and the E test (AB Biodisk, Sweden); these methods were compared for test accuracy, and 5 microg disk zone diameters were compared for interpretive accuracy using the standardized disk diffusion method. In terms of potency, gatifloxacin was most similar to sparfloxacin and trovafloxacin against Stenotrophomonas maltophilia (MIC50, 0.5-1 mg/l) and Burkholderia spp. (MIC50, 1-2 mg/l). This activity was greater than that of ciprofloxacin, levofloxacin or ofloxacin (MIC50, > or = 2 mg/l) against Stenotrophomonas maltophilia isolates but comparable to that of levofloxacin against the Burkholderia spp. (60% susceptible at < or = 2 mg/l). The E test results compared well with the reference dilution test results (81-97% at +/- 1 log2 dilution). The disk diffusion test using previously suggested breakpoints for other bacteria (> or = 18 mm or < or = 2 mg/l for susceptible and < or = 14 mm or > or = 8 mg/l for resistant) also performed well, at > 90% categorical agreement. The activity of gatifloxacin is comparable to that of other newer quinolones against isolates of Stenotrophomonas maltophilia and Burkholderia spp., and susceptibility testing using simple qualitative and quantitative methods appears to function well with these drug/organism combinations.