In vitro activity of daptomycin against 297 staphylococcal isolates.

The in vitro activity of daptomycin against 297 clinical isolates of Staphylococcus aureus and S. epidermidis sensu strictu was compared with the activities of cephalothin, dicloxacillin, tobramycin, and vancomycin. Minimal inhibitory concentrations (MICs) were determined by an agar dilution method. Cephalothin and dicloxacillin showed the highest activity against S. aureus on a weight-for-weight basis, all isolates being inhibited by 0.5 mg/l or less of either agent. Cephalothin was somewhat more active against S. epidermidis than was dicloxacillin. Daptomycin and vancomycin exhibited high and similar activity against both S. aureus and S. epidermidis (MIC90% = 1 and 2 mg/l, respectively). Tobramycin was highly active against S. aureus, but the activity against S. epidermidis was greatly variable (MIC range less than or equal to 0.03 - greater than or equal to 16 mg/l). The activity of daptomycin was markedly influenced by the test medium; the MICs were generally 32 times higher when the isolates were tested on Iso-Sensitest agar than on Mueller-Hinton agar. Supplementation of Iso-Sensitest agar with increasing concentrations of calcium potentiated the activity of daptomycin substantially, the results obtained on Iso-Sensitest agar supplemented with 20 mg Ca2+/l being similar to those obtained on Mueller-Hinton agar.

In vitro studies of fleroxacin (Ro 23-6240), a new trifluorinated quinolone derivative.

The in vitro activity of fleroxacin (Ro 23-6240) against 441 bacterial isolates was compared with those of ciprofloxacin, ofloxacin, amoxycillin, cefadroxil, cefuroxime and tobramycin. An agar dilution method was used for the determination of minimal inhibitory concentrations (MICs). Ciprofloxacin showed the highest activity against the Enterobacteriaceae, 95% of the isolates were inhibited by 0.06 mg/l, but fleroxacin and ofloxacin were also highly active (MIC 90% = 0.5 and 0.25 mg/l, respectively). Ciprofloxacin was the most active agent against Pseudomonas aeruginosa (MIC 90% = 0.12 mg/l), whereas the activities of fleroxacin and ofloxacin were more variable. Tobramycin was highly active against P. aeruginosa, 75% of the isolates were inhibited by 0.5 mg/l or less. The quinolones and tobramycin exhibited high activity against Acinetobacter calcoaceticus, the great majority of the isolates being susceptible to 0.5 mg/l or less of any agent. All the quinolones showed high activity against Staphylococcus aureus, but fleroxacin was less active against Staphylococcus epidermidis and Staphylococcus saprophyticus than were the other derivatives. The pneumococcal and streptococcal isolates were markedly less susceptible to fleroxacin than to the other quinolones tested (MIC range 4-32 mg/l). All isolates of Haemophilus influenzae and Neisseria gonorrhoeae were inhibited by the lowest concentration of the quinolones employed in the study (0.03 mg/l). Cefuroxime was also highly active against N. gonorrhoeae, whether the strains were beta-lactamase-producing or not, but was somewhat less active against H. influenzae. The quinolones displayed moderate and similar activity against Bacteroides fragilis isolates (MIC range 1-16 mg/l). The MICs of fleroxacin against gram-negative rods were generally 4-16 times higher at pH 8.8 than those obtained at pH 5.8 and 7.3. The activity against gram-positive cocci was not markedly influenced by changes in pH.

In vitro activities of ciprofloxacin, ofloxacin, norfloxacin and rosoxacin compared with cinoxacin and trimethoprim.

The in vitro activities of ciprofloxacin, ofloxacin, norfloxacin, rosoxacin, cinoxacin and trimethoprim have been compared. An agar dilution method has been employed for the measurement of minimal inhibitory concentrations (MICs). 426 clinical, bacterial urinary isolates mainly from hospitalised patients were included; all common urinary tract pathogens were represented. The newer quinolones were highly active against Enterobacteriaceae species, Pseudomonas aeruginosa and Acinetobacter calcoaceticus. Ciprofloxacin was the most active agent against these organisms (MICs less than or equal to 2 mg/l). A few strains of Escherichia coli and Klebsiella were resistant to rosoxacin (MIC greater than or equal to 128 mg/l). Cinoxacin and trimethoprim were considerably less active against gram-negative strains. The new quinolones were also active against staphylococci of various species and enterococci (MICs less than or equal to 4 mg/l) except for rosoxacin for which 16 mg/l was needed to inhibit all gram-positive isolates. Cinoxacin was virtually inactive against this group whereas trimethoprim showed variable activity.

Ro 17-2301: in vitro comparison with aztreonam, imipenem, ceftazidime, cefotaxime and netilmicin.

The in vitro activity of the novel monobactam antibiotic, Ro 17-2301 has been compared with those of aztreonam, imipenem, ceftazidime, cefotaxime and netilmicin. A total of 438 clinical isolates of aerobic gram-negative rods were employed and an agar dilution method was used for measurement of MIC. Ro 17-2301 was highly active against a wide variety of Enterobacteriaceae species (MIC range less than or equal to 0.03-8, MIC50 less than or equal to 0.03, MIC90 0.06 mg/l). The activity of aztreonam parallelled that of Ro 17-2301 although the latter seemed to have more uniformly high activity against Klebsiella sp. The other agents showed generally high activity against Enterobacteriaceae except netilmicin against Providencia stuartii (MIC50 4, MIC90 greater than or equal to 16 mg/l). Activity against Pseudomonas aeruginosa. was more variable. Ro 17-2301 and aztreonam were moderately active (MIC50 2, MIC90 8 and 16 mg/l, respectively). Imipenem was the most active agent against Acinetobacter, whereas Ro 17-2301 was moderately active. In conclusion, Ro 17-2301 shows impressive activity against Enterobacteriaceae and moderate activity against Acinetobacter and P. aeruginosa. Ro 17-2301 may well prove to be a useful agent in the treatment of gram-negative infections.

Ceftazidime: in vitro comparison with cephalothin, cefuroxime, and netilmicin. A Norwegian study.

The in vitro activity of ceftazidime has been compared with those of cephalothin, cefuroxime, and netilmicin against a variety of gram-positive and gram-negative bacteria in order to register sensitivity patterns in the western part of Norway. An agar dilution method was used for minimal inhibitory concentration (MIC) determination. Ceftazidime was the most active agent against Enterobacteriaceae; all isolates being inhibited by 2 mg/l or less, whereas netilmicin was slightly less active, especially against Providencia. Cephalothin and cefuroxime were markedly less active than the other two agents against Enterobacteriaceae. Ceftazidime and netilmicin were active against our Pseudomonas aeruginosa isolates (MICs less than or equal to 4 and less than or equal to 8 mg/l, respectively). Only netilmicin had useful activity against Acinetobacter calcoaceticus. Ceftazidime was the least active agent against Staphylococcus aureus; nearly all the isolates had MICs of 4-8 mg/l. Cefuroxime was the most active agent against Bacteroides fragilis, whereas ceftazidime was inactive. Ceftazidime may, in the future, be a useful alternative to the aminoglycosides in the treatment of serious gram-negative infections, particularly when P. aeruginosa might be involved.

N-formimidoyl thienamycin: in vitro comparison with cefoxitin and tobramycin against clinical, bacterial isolates.

The in vitro activity of the novel beta-lactam antibiotic, N-formimidoyl thienamycin (N-f thienamycin) has been compared with those of cefoxitin and tobramycin. An agar dilution method was employed. N-f thienamycin was active against all Enterobacteriaceae isolates (MIC less than or equal to 4 mg/l). All Pseudomonas aeruginosa isolates were inhibited by 2 mg/l. N-f thienamycin was also active against Acinetobacter calcoaceticus (96 per cent inhibited by 0.5 mg/l) and Gram-positive cocci. All enterococci were inhibited by 2 mg/l. The drug was active against Haemophilus influenzae (MIC less than or equal to 1 mg/l) and the Bacteroides fragilis group (MIC less than or equal to 0.5 mg/l). Cefoxitin was inactive against most Enterobacter and A. calcoaceticus isolates and all P. aeruginosa and enterococcal isolates. Tobramycin was virtually inactive against Gram-positive cocci other than Staphylococcus aureus. N-f thienamycin thus has a broad spectrum of in vitro activity, greater than that of cefoxitin and tobramycin, and may therefore be useful in the treatment of serious infection, particularly when the aetiology is unknown.

The in vitro activity of gentamicin, tobramycin and netilmicin against 500 clinical isolates of bacteria. A comparative study using three different test media.

The in vitro activities of the three aminoglycoside antibiotics, gentamicin, and tobramycin have been compared against 500 isolates of Enterobacteriaceae, Pseudomonas aeruginosa and Staphylococcus aureus. An agar dilution method was employed with three sensitivity media: Iso-Sensitest Agar, Mueller-Hinton Agar and PDM-Antibiotic Sensitivity Medium. All three aminoglycosides were highly active against S. aureus (MIC less than or equal to 0.5 mg/l) and the majority of Enterobacteriaceae (MIC90 approx. 1 mg/l). Tobramycin showed the highest activity against P. aeruginosa (MIC less than or equal to 1 mg/l). No major difference in measured MIC were found on the three media. Gentamicin and netilmicin were somewhat less active against P. aeruginosa on Mueller-Hinton Agar. MICs for tobramycin against Enterobacteriaceae were a little higher on PDM than on the other two agars. Our results show that measured MIC varied very little on the three sensitivity media. All media are suitable for routine use, provided that control strains are employed.

Ceftriaxone: in vitro activity against 410 bacterial isolates compared with cefotaxime.

The in vitro activity of the two new cephalosporins, cefotaxime and ceftriaxone, against 410 bacterial isolates was compared using an agar dilution method. Both compounds were highly active against Enterobacteriaceae, including indole-positive Proteus and Providencia; the great majority of the isolates were inhibited by 0.06 mg/l of either drug. Activity against Pseudomonas aeruginosa and Staphylococcus aureus was moderate, and enterococci were resistant. All Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae isolates were susceptible to 0.03 mg/l of either drug. The isolates belonging to the Bacteroides fragilis group were inhibited over a wide range of concentrations and some were highly resistant (MIC greater than or equal to 64 mg/l). There were no significant differences in the antibacterial activity of the two drugs against our isolates. Both drugs may be of potential use in the treatment of serious infections caused by Enterobacteriaceae; they may prove to be a useful alternative to the aminoglycosides.

The in vitro activity of moxalactam against 430 clinical, bacterial isolates.

The in vitro activity of the novel beta-lactam antibiotic moxalactam against 430 bacterial isolates was determined by an agar dilution method. Moxalactam was highly active against Enterobacteriaceae including indole-positive Proteus and Providencia, all isolates being susceptible to 1.0 microgram/ml or less. The drug was somewhat less active against Gram-positive cocci and Pseudomonas aeruginosa, and enterococci were highly resistant. All Haemophilus influenzae isolates were inhibited by 0.06 microgram/ml or less. Activity against Bacteroides fragilis was good but wide variations of minimal inhibitory concentrations were noted. Moxalactam may become a useful alternative to the aminoglycosides in the treatment of serious infections caused by Gram-negative bacteria.