N. X. Chin

In vitro activity of lomefloxacin (SC-47111; NY-198), a difluoroquinolone 3-carboxylic acid, compared with those of other quinolones.

Lomefloxacin (SC-47111; NY-198) is a new difluoroquinolone agent. It inhibited 90% of Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., Proteus mirabilis, Morganella morganii, Proteus vulgaris, Serratia marcescens, Salmonella spp., Shigella spp., Aeromonas spp., Yersinia spp., Haemophilus influenzae, and Neisseria gonorrhoeae at less than or equal to 2 micrograms/ml. Lomefloxacin inhibited 90% of Pseudomonas aeruginosa at 4 micrograms/ml. Lomefloxacin was equal in activity to norfloxacin against Escherichia coli, Klebsiella spp., Enterobacter spp., Haemophilus influenzae, and Neisseria gonorrhoeae but was twofold less active against Proteus spp., Providencia spp., Serratia marcescens, Salmonella spp., and Shigella spp. Ofloxacin was generally 2- to 4-fold more active, and ciprofloxacin was 4- to 16-fold more active. Lomefloxacin inhibited Staphylococcus aureus, including methicillin-resistant isolates, but MICs for 90% of streptococcal species tested were 8 micrograms/ml. In the presence of 9 mM Mg2+, MICs for Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa were increased, as they were when they were tested in urine. A single-step increase in resistance to eightfold above the MIC occurred at a frequency of less than 10(-10), but serial transfer of bacteria in the presence of the agent produced MIC increases. Lomefloxacin had activity and properties comparable to those of many of the new quinolones.

Comparative in vitro activity and beta-lactamase stability of FK482, a new oral cephalosporin.

FK482 is an oral aminothiazolyl hydroxyimino cephalosporin with a C-3 vinyl group. Its activity was compared with those of cephalexin, cefuroxime, cefixime, and amoxicillin-clavulanate. FK482 inhibited 90% of Staphylococcus aureus isolates at 1 micrograms/ml and 90% of Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus pneumoniae isolates at less than or equal to 0.012 micrograms/ml, superior to cephalexin and cefuroxime and similar to cefixime. It did not inhibit oxacillin-resistant S. aureus. FK482 inhibited 90% of Enterococcus faecalis isolates at 8 micrograms/ml. Although 90% of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Salmonella species, and Shigella species isolates were inhibited by less than or equal to 2 micrograms/ml, FK482 was less active than cefixime against Citrobacter, Enterobacter, Morganella, Serratia, and Providencia species, with MICs for many isolates of greater than 8 micrograms/ml. FK482 inhibited Haemophilus influenzae and Neisseria gonorrhoeae at concentrations comparable to that of cefixime and superior to those of cephalexin and cfaclor. Bacteroides and Pseudomonas species were resistant. FK482 was not hydrolyzed by the TEM-1 and TEM-2 beta-lactamases but was hydrolyzed by TEM-3 and the Proteus vulgaris enzyme. It had a high affinity for chromosomal beta-lactamases.

Activity of A-56268 compared with that of erythromycin and other oral agents against aerobic and anaerobic bacteria.

A-56268 was compared with erythromycin, roxithromycin (RU 28965), and perorally administered antimicrobial agents. Its in vitro activity was similar to that of erythromycin and slightly greater than that of roxithromycin, with beta-hemolytic streptococci and Streptococcus pneumoniae inhibited by less than 2 micrograms of A-56268 per ml (50% inhibited by 0.06 microgram/ml). Streptococcus pyogenes, S. agalactiae, S. Pneumoniae, and S. faecalis resistant to erythromycin were resistant to A-56268, and 4 micrograms/ml inhibited 90% of Haemophilus influenzae isolates.

In vitro activity of temafloxacin, a new difluoro quinolone antimicrobial agent.

Temafloxacin, a new difluoro quinolone, inhibited the majority ofEnterobacteriaceae at ⩽ 1µg/ml. It was 4–8-fold less active than ciprofloxacin and 2-fold less active than ofloxacin. Cefotaxime and imipenem-resistant isolates such asEnterobacter cloacae, Citrobacter freundii, Pseudomonas aeruginosa, andAcinetobacter spp. were inhibited. Temafloxacin inhibitedNeisseria, Branhamella, andHaemophilus species at < 0.25µg/ml. Methicillin-susceptible and methicillin-resistantStaphylococcus aureus, Staphylococcus epidermidis andClostridium spp. were inhibited at concentrations less or equal to that of ciprofloxacin and ofloxacin.

Comparative in vitro activity of a new fluorinated 4-quinolone, T-3262 (A-60969).

The in vitro activity of a new quinolone, T-3262 [A-60969; DL-7-(3-amino-1-pyrrolidinyl)-1-(2,4-difluorophenyl)-6-fluoro-1-, 4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid monohydrate], was compared with those of ciprofloxacin, ofloxacin, ceftazidime, imipenem, and gentamicin. T-3262 inhibited 90% of isolates of the family Enterobacteriaceae at a concentration of less than or equal to 0.25 micrograms/ml. It was two to four times more active than ofloxacin and similarly or slightly less active than ciprofloxacin. Ninety percent of isolates of Pseudomonas aeruginosa were inhibited at 0.5 micrograms/ml. It was 4- to 8-fold more active than ciprofloxacin and 8- to 16-fold more active than ofloxacin against Pseudomonas cepacia and Pseudomonas maltophilia, which were resistant to imipenem and gentamicin. Most Haemophilus influenzae, Neisseria gonorrhoeae, and Branhamella catarrhalis isolates were inhibited at concentrations of less than or equal to 0.008 micrograms/ml. The MIC for 90% of the Staphylococcus aureus isolates, including methicillin-resistant S. aureus, was 0.12 micrograms/ml; that for Staphylococcus epidermidis was 0.5 micrograms/ml, as was that for Enterococcus faecalis. It inhibited 90% of Bacteroides fragilis isolates at 2 micrograms/ml, considerably more active than ciprofloxacin and ofloxacin. The frequency of spontaneous point mutational resistance was less than 10(-10) for members of the family Enterobacteriaceae and Pseudomonas spp. Resistant strains could be selected by repeated subculture. Similar to other quinolones, its activity could be affected by culture conditions. T-3262 showed a postantibiotic suppressive effect on Escherichia coli, P. aeruginosa, and S. aureus.

Comparative in vitro activity of the new oral macrolide azithromycin

The in vitro activity of the new oral macrolide azithromycin was compared with that of erythromycin against gram-positive and gram-negative aerobic and anaerobic bacteria. Ninety percent of hemolytic streptococci groups A and B, andStreptococcus pneumoniae were inhibited by 0.5 µg/ml. Activity of azithromycin was similar to that of erythromycin; erythromycin-resistant staphylococci and streptococci were not inhibited. Azithromycin was more active than erythromycin againstHaemophilus influenzae (MIC90 1 µg/ml) andNeisseria gonorrhoeae. It inhibitedCampylobacter spp. andPasteurella multocida, and had an MIC50 of 8 µg/ml forEscherichia coli, Salmonella spp.,Shigella spp. andYersinia enterocolitica compared to an erythromycin value of > 64 µg/ml.

Post-antibiotic effect of the new streptogramin RP 59500

The post-antibiotic effect (PAE) of RP 59500, a new streptogramin antibiotic, was determined forStaphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Streptococcus pneumoniae, andStreptococcus pyogenes. A 30 min exposure ofStaphylococcus aureus to 5 µg/ml of RP 59500 produced a PAE of 1.9–6.9 h, and a 60 min exposure of 2.5 µg/ml produced a PAE of 3.2–8 h. A 30 min exposure of 5 µg/ml of RP 59500 of coagulase-negative staphylococci produced a PAE of 2.5–7.5 h. PAEs of constitutively erythromycin-resistant staphylococcal isolates were shorter than were the PAEs of highly susceptible isolates. A 30 min exposure to 5 µg/ml of RP 59500 produced a PAE of 7.5–9.5 h forStreptococcus pneumoniae and a PAE of >18 h forStreptococcus pyogenes. RP 59500 produced a longer PAE withStaphylococcus aureus than did vancomycin, oxacillin or erythromycin. These results suggest that RP 59500 may be administered less frequently than would be suggested by its half-life.

Comparative in vitro activity of a new quinolone, AM-1091.

The in vitro activity of a new quinolone, AM-1091 [7-(3-amino-1-pyrrolidinyl)-8-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro- 4-oxo- 3-quinoline carboxylic acid hydrochloride], was compared with those of ciprofloxacin, ofloxacin, beta-lactams, and gentamicin. AM-1091 inhibited 90% of the isolates of the family Enterobacteriaceae at less than or equal to 0.12 micrograms/ml. For many species AM-1091 was 2-fold more active than ciprofloxacin and 2- to 32-fold more active than ofloxacin. It inhibited Enterobacter, Citrobacter, and Klebsiella species resistant to ceftazidime and gentamicin. Ninety percent of Pseudomonas aeruginosa isolates were inhibited by 0.5 micrograms/ml, so for this species AM-1091 was twofold less active than ciprofloxacin. AM-1091 was more active against Pseudomonas cepacia and Xanthomonas maltophilia, inhibiting isolates resistant to imipenem and gentamicin. Most Haemophilus influenzae, Neisseria gonorrhoeae, Neisseria meningitidis, and Branhamella catarrhalis isolates were inhibited by less than or equal to 0.06 micrograms/ml. The MICs for 90% of Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis isolates were 0.06, 0.06, and 2 micrograms/ml, respectively. AM-1091 inhibited hemolytic streptococci and Streptococcus pneumoniae at 0.25 micrograms/ml and was more active than ciprofloxacin or ofloxacin against gram-positive species. AM-1091 inhibited 90% of the Bacteroides species at 0.5 micrograms/ml. The frequency of spontaneous resistance was less than 10(-10) for most organisms, but resistant strains could be selected by repeated subculturing. Although AM-1091 had lower in vitro activity at pH 5.5 and in the presence of high concentrations of Mg2+, it still inhibited most organisms at </= 0.5 micrograms/ml under these conditions. AM-1091 rapidly killed Escherichia coli and P. aeruginosa and had a prolonged postantibiotic suppressive effect on these bacteria.

In vitro antimicrobial activity of the new antibiotic vermisporin

The antimicrobial activity of vermisporin, a new antibiotic produced by fermentation of the fungusOphiobolus vermisporis, was tested in vitro. Vermisporin inhibited 90 % ofBacteroides fragilis and otherBacteroides spp. at 1 µg/ml (range 0.25–1 µg/ml).Clostridium perfringens were inhibited by 1 µg/ml (range 0.25–2 µg/ml). Vermisporin inhibited 90 % ofStaphylococcus aureus, including methicillin-resistantStaphylococcus aureus, at 0.5 µg/ml (range 0.12–0.5 µg/ml). Vermisporin MICs for group A, B, C, F and G streptococci were < 1 µg/ml when tested in Haemophilus Test Medium but ≥ 8 µg/ml in the presence of blood. Vermisporin MICs forEnterobacteriaceae, Pseudomonas aeruginosa andHaemophilus influenzae exceeded 64 µg/ml. Inhibited organisms had MBCs 16- to 32-fold above the MICs.

In vitro activity of the new glycopeptide decaplanin

The activity of decaplanin, a new glycopeptide, was compared to that of vancomycin, teicoplanin and daptomycin. Decaplanin was two- to four-fold less active than vancomycin, teicoplanin and daptomycin againstStaphylococcus aureus andStaphylococcus epidermidis, with an MIC90 of 2 µg/ml for methicillin-susceptible and 4 µg/ml for methicillin-resistant isolates. Decaplanin had activity similar to that of vancomycin againstStreptococcus pyogenes, Streptococcus agalactiae, group C and G streptococci, with an MIC90 of 0.12 µg/ml. It was less active than the other agents against the viridans group streptococci (MIC90 4 µg/ml). The activity of decaplanin against enterococci (MIC90 4 µg/ml) was similar to that of vancomycin.Clostridium spp. were inhibited by 0.5 µg/ml, peptostreptococci and peptococci by 0.25 µg/ml. Decaplanin was active from pH 5.5 to 7.5. Inoculum size had a minimal effect on MICs, and increased concentrations of Ca2+ and Mg2+ and 50 % serum did not alter MICs or MBCs.