Evaluation of novel antipseudomonal drugs using the serum bactericidal activity test

Serum bactericidal activity against Pseudomonas aeruginosa was determined in six volunteers 1 and 4 h after administration of 2 g ceftazidime, 4 g piperacillin, 500 mg imipenem, 80 mg tobramycin and four combinations of these agents. Ceftazidime produced the highest serum bactericidal titers, killing 100% and 86% of the 50 Pseudomonas aeruginosa strains tested after 1 and 4 h respectively at a serum dilution of 18. Imipenem had lower serum bactericidal titers than ceftazidime, killing 88 % of the isolates after 1 h at a serum dilution of 18. The combination showed only slightly higher titers. Killing curves were determined for nine strains of Pseudomonas aeruginosa using undiluted volunteer serum drawn 1 h after administration of the antibiotics. The combinations ceftazidime/tobramycin and piperacillin/ tobramycin exhibited higher killing activity than the single drugs. As the activity of the aminoglycosides could be underestimated on the basis of their low serum bactericidal titers, it is concluded that determination of these titers is inappropriate for evaluating the efficacy of the aminoglycosides.     

Serum bactericidal activity of gemifloxacin versus clarithromycin against Streptococcus pneumoniae with different susceptibility to quinolones

The objective of this study was to determine serum bactericidal titers (SBT, the highest dilution of serum showing no growth) and the serum bactericidal activity (SBA, i.e. duration of SBT greater than 1:2) as well as the serum bactericidal rate of gemifloxacin and clarithromycin after single doses in healthy male volunteers against Streptococcus pneumoniae. Strains tested had various degrees of susceptibility to penicillin as well as different susceptibility to quinolones due to a different QRDR mutation pattern (parC, gyrA). Serum samples from volunteers (n = 12) who had received a single oral dose of either 320 mg gemifloxacin or 500 mg clarithromycin in an open-label crossover study were obtained over a 24-hour period. SBA was determined, using the microdilution method. SBA of wildtype strains for gemifloxacin ranged from 8.9 to 15.4 h (mean 12.6 h). For gemifloxacin, 2 strains with solitary gyrA mutation had an SBA from 4.5 to 4.7 h (median 4.5 h). One of the 2 strains with a single QRDR mutation in parC displayed an SBA of 4.5 h, comparable to the gyrA mutation strains, whereas the second strain had a nearly twice as long SBA of 8.9 h. Two strains with two mutations (parC and gyrA) did not display any SBA. For clarithromycin, the duration of SBA ranged from 11.3 to 15.5 h (mean 13.6 h) for 6 of the 12 strains with an MIC < or = 0.06 mg/L (no SBA was found for the remaining strains, with an MIC of 0.25 mg/L or higher). In conclusion, a correlation between individual serum concentrations and SBA was found for both antibiotics.     

Comparative in vitro activity of RO 23-6240 (Fleroxacin), a new 4-quinolone derivative

The in vitro activity of RO 23-6240 was compared with that of norfloxacin, ofloxacin and ciprofloxacin as well as four other antimicrobial agents against 345 recent clinical isolates. The MICs of RO 23-6240 againstEnterobacteriaceae andAcinetobacter anitratum was 0.5mg/l. At the same concentration of the compound 90% of staphylococci were inhibited. AgainstEnterococcm faecalis andPseudomonas aeruginosa RO 23-6240 proved less active, having MIC90 values of 4.0 mg/l and 8.0 mg/l, respectively.Enterobacteriaceae and staphylococci strains that were resistant to piperacillin, cefotaxime or tobramycin were susceptible to the compound. In general the activity of RO 23-6240 was comparable to those of norfloxacin and ofloxacin, but less than that of ciprofloxacin.     

Comparison of microscopic and cultural findings in the diagnosis ofGardnerella vaginalis infection

The diagnosis ofGardnerella vaginalis infection on the basis of microscopic and cultural findings was compared. A total of 340 specimens of vaginal secretion were Gram stained and plated on a medium selective forGardnerella vaginalis. Positive culture was obtained in 165 cases. Microscopy was unequivocally positive in 95, doubtful in 58 and negative in 187. Positive microscopy was confirmed by culture in 99%. On the other hand, 21% of (he negative microscopy results gave a false negative diagnosis. Specimens for which microscopy was doubtful were culture positive in 53% of the cases, including 12% with heavy growth. Thus, positive microscopy proved to be sufficient for a reliable diagnosis ofGardnerella vaginalis infection. However, in specimens with negative or doubtful microscopic findings, additional culture is recommended.     

Urinary Excretion and Bactericidal Activities of Gemifloxacin and Ofloxacin after a Single Oral Dose in Healthy Volunteers

In a randomized crossover study, 16 volunteers (8 men, 8 women) received single oral doses of 320 mg of gemifloxacin and 400 mg of ofloxacin on two separate occasions in the fasting state to assess the urinary excretion and urinary bactericidal titers (UBTs) at intervals for up to 144 h. Ofloxacin showed higher concentrations in urine compared with those of gemifloxacin. The median (range) cumulative excretion of gemifloxacin was 29.7% (8.4 to 48.7%) of the parent drug administered, and median (range) cumulative excretion of ofloxacin was 84.3% (46.5 to 95.2%) of the parent drug administered. The UBTs, i.e., the highest twofold dilutions (with antibiotic-free urine as the diluent) of urine that were still bactericidal, were determined for a reference strain and nine uropathogens for which the MICs of gemifloxacin and ofloxacin were as follows: Escherichia coli ATCC 25922, 0.016 and 0.06 microg/ml, respectively; Klebsiella pneumoniae, 0.03 and 0.06 microg/ml, respectively; Proteus mirabilis, 0.125 and 0.125 microg/ml, respectively; Escherichia coli, 0.06 and 0.5 microg/ml, respectively; Pseudomonas aeruginosa, 1 and 4 microg/ml, respectively; Staphylococcus aureus, 0.008 and 0.25 microg/ml, respectively; Enterococcus faecalis, 0.06 and 2 microg/ml, respectively; Staphylococcus aureus, 0.25 and 4 microg/ml, respectively; Enterococcus faecalis, 0.5 and 32 microg/ml, respectively; and Staphylococcus aureus, 2 and 32 microg/ml, respectively. Generally, the UBTs for gram-positive uropathogens were higher for gemifloxacin than for ofloxacin and the UBTs for gram-negative uropathogens were higher for ofloxacin than for gemifloxacin. According to the UBTs, ofloxacin-resistant uropathogens (MICs, >or=4 mg/liter) should also be considered gemifloxacin resistant. Although clinical trials have shown that gemifloxacin is effective for the treatment of uncomplicated urinary tract infections, whether an oral dosage of 320 mg of gemifloxacin once daily is also adequate for the treatment of complicated urinary tract infections has yet to be confirmed.     

Distribution and resistance patterns ofHaemophilus influenzae: A European cooperative study

Distribution and resistance patterns ofHaemophilus influenzae: A European cooperative study