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.     

In vitro activity of sparfloxacin compared with those of five other quinolones.

The in vitro activity of sparfloxacin, a new difluorinated quinolone, was evaluated against 857 gram-positive and gram-negative clinical isolates and compared with those of ciprofloxacin, norfloxacin, ofloxacin, fleroxacin, and lomefloxacin. The MIC of sparfloxacin for 90% of the members of the family Enterobacteriaceae tested was 0.5 microgram/ml (range, 0.06 to 4.0 micrograms/ml); only for members of the genera Serratia, Citrobacter, and Providencia were MICs above 1 microgram/ml. Some 90% of Pseudomonas aeruginosa isolates were inhibited by 8 micrograms of the drug per ml. The MICs for 90% of Staphylococcus spp. and Enterococcus faecalis were 0.12 and 2 micrograms/ml, respectively. All (100%) Streptococcus pneumoniae strains were inhibited by 0.5 microgram/ml. The inoculum size had little effect on either the MIC or the MBC of sparfloxacin. An increase in the magnesium concentration from 1.1 to 8.4 mM increased the MIC between 2 and 10 times, depending on the genus tested. Sparfloxacin was less active at pH 5. The antibacterial activity of sparfloxacin against gram-positive bacteria was generally higher than those of the quinolones with which it was compared; against Streptococcus pneumoniae, sparfloxacin was four- and eightfold more active than ofloxacin and ciprofloxacin, respectively. The activity of sparfloxacin against gram-negative rods was generally comparable to that of ciprofloxacin except against Enterobacter and Acinetobacter spp., Pseudomonas cepacia, Xanthomonas maltophilia, and Alcaligenes and Flavobacterium spp., against which sparfloxacin was the most active quinolone.     

In vitro activity and beta-lactamase stability of a new difluoro oxacephem, 6315-S.

6315-S, a novel difluoromethyl thioacetamido oxacephem, had in vitro activity comparable to that of cefotaxime and moxalactam against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Klebsiella oxytoca, Citrobacter diversus, Salmonella spp., and Shigella spp., inhibiting 90% at less than or equal to 0.25 microgram/ml. It inhibited piperacillin- and cefoperazone-resistant isolates in these species. 6315-S did not inhibit cefotaxime- or moxalactam-resistant Citrobacter freundii, Enterobacter aerogenes, or Enterobacter cloacae (MICs for 90% of the strains tested were greater than or equal to 16 micrograms/ml). Proteus vulgaris resistant to cefotaxime was inhibited. Pseudomonas species and Acinetobacter species were resistant (MICs greater than 64 micrograms/ml). MICs for 90% of the Staphylococcus aureus and S. epidermidis isolates were 4 micrograms/ml. 6315-S was highly active against anaerobic species of Clostridium, Fusobacterium, Bacteroides, and peptostreptococci and was superior to other agents against these organisms. 6315-S was not hydrolyzed by the major plasmid and chromosomal beta-lactamases, but it induced chromosomal beta-lactamases in Enterobacter cloacae and Pseudomonas aeruginosa.     

In vitro activity of U-76,252 (CS-807), a new oral cephalosporin.

U-76,252 is the prodrug of U-76,253. MICs of U-76,253 were 0.015 to 0.06 microgram/ml for greater than or equal to 90% of the strains of Streptococcus spp., Haemophilus influenzae, and Proteus mirabilis; 0.25 to 1 microgram/ml for Branhamella catarrhalis, Escherichia coli, Klebsiella spp., and Citrobacter diversus; 1 to 8 micrograms/ml for Staphylococcus spp.; and 2 to greater than 16 micrograms/ml for other members of the family Enterobacteriaceae and Aeromonas hydrophila; for 72% of the latter group, MICs were less than or equal to 4 micrograms/ml. MICs for Pseudomonas aeruginosa and Enterococcus faecalis were greater than 16 micrograms/ml.     

In vitro activity and beta-lactamase stability of a new carbapenem, SM-7338.

SM-7338, a new carbapenem, inhibited most members of the family Enterobacteriaceae at MICs of 0.015 to 0.25 microgram/ml, including Klebsiella oxytoca, Citrobacter freundii, Enterobacter cloacae, and Proteus vulgaris isolates resistant to cefotaxime, ceftazidime, piperacillin, and gentamicin. It was two- to eightfold more active than imipenem, but it inhibited Pseudomonas aeruginosa at 1 to 8 micrograms/ml, which was comparable to the activity of imipenem. Haemophilus, Neisseria, and Branhamella species were inhibited by less than or equal to 0.25 microgram/ml, which was superior to the activity of imipenem. SM-7338 inhibited Staphylococcus aureus and coagulase-negative staphylococci at 0.25 microgram/ml, but for methicillin-resistant isolates MICs were 4 to 16 micrograms/ml. Group A, B, and C streptococci and Streptococcus pneumoniae were inhibited by less than or equal to 0.03 microgram/ml. Bacteroides species, including clindamycin-resistant isolates, were inhibited by 0.25 microgram/ml. There was no major inoculum size effect, and the MBCs were within a dilution of the MICs. SM-7338 was more active than imipenem at an acid pH under anaerobic conditions. Plasmid beta-lactamases of TEM-1, TEM-2, TEM-3, TEM-5, SHV-1, SHV-2, PSE-1, PSE-2, PSE-3, OXA-2, OXA-3, OXA-4, OXA-5, and OXA-7; Staphylococcus aureus enzymes; and the chromosomal beta-lactamases P-99 and K-1; Morganella species; and Proteus vulgaris did not hydrolyze SM-7338. The repeated transfer of organisms increased the MICs of SM-7338, as it did the MICs of imipenem.     

In vitro activity of an oral iminomethoxy aminothiazolyl cephalosporin, R-3746.

The in vitro activity of R-3746, an iminomethoxy aminothiazolyl cephalosporin with a CH2OCH3 moiety at position 3, was compared with those of other antibiotics. R-3746 inhibited the majority of hemolytic streptococci (groups A, B, C, F, and G) and Streptococcus pneumoniae at less than 0.06 micrograms/ml, which was comparable to the activity of amoxicillin, 2- to 8-fold more active than cefixime, and 16- to 64-fold more active than cefaclor and cephalexin. Ninety percent of beta-lactamase-producing Haemophilus influenzae and Neisseria gonorrhoeae were inhibited at a concentration 0.25 micrograms/ml, but it was less active against Branhamella spp. It did not inhibit (MIC, greater than 16 micrograms/ml) enterococci, viridans group streptococci, or methicillin-resistant staphylococci. The MICs of R-3746 for 90% of strains tested for Escherichia coli; Klebsiella pneumoniae; Citrobacter diversus; Proteus mirabilis; and Salmonella, Shigella, and Yersinia spp. were less than or equal to 1 micrograms/ml. It was two- to eightfold less active than cefixime but was markedly superior to cefaclor, cephalexin, amoxicillin-clavulanate, and trimethoprimsulfamethoxazole. R-3746 inhibited 50% of Enterobacter cloacae, Enterobacter aerogenes, Citrobacter freundii, Morganella spp., Providencia spp., Proteus vulgaris, and Serratia marcescens at less than or equal to 8 micrograms/ml. Pseudomonas spp. were resistant. Fifty percent of Clostridium spp. were inhibited by 0.5 micrograms/ml, but MICs for Bacteroides spp. were greater than 128 micrograms/ml. R-3746 was not appreciably hydrolyzed by most chromosomal and plasmid-mediated beta-lactamases.     

In vitro activity of cefquinome, a new cephalosporin, compared with other cephalosporin antibiotics.

The in vitro activity of cefquinome, a new aminothiazolyl cephalosporin with a C-3 bicyclic pyridinium group, was compared with ceftazidime, cefpirome, and cefepime. Cefquinome inhibited members of the Enterobacteriaceae at less than or equal to 0.5 microgram/ml for Escherichia coli, Klebsiella pneumoniae, K. oxytoca, Citrobacter diversus, Salmonella Shigella, Proteus mirabilis, Morganella, and Providencia. Although most Citrobacter freundii and Enterobacter cloacae were inhibited by less than 2 micrograms/ml, some strains resistant to ceftazidime were resistant, [minimum inhibitory concentration (MIC) greater than 16 micrograms/ml]. Serratia marcescens were inhibited by less than 1 microgram/ml and Pseudomonas aeruginosa by 8 micrograms/ml similar to the activity of cefepime. The majority of Haemophilus influenzae and Neisseria gonorrhoeae were inhibited by less than 0.25 microgram/ml. Most enterococci had cefquinome MICs of 4-8 micrograms/ml. Cefquinome was extremely active against group-A streptococci and Streptococcus pneumoniae with MICs less than 0.12 microgram/ml. 90% of methicillin-susceptible Staphylococcus aureus 90% were inhibited by 2 micrograms/ml. Overall, the in vitro activity of cefquinome was comparable with aminothiazolyl cephalosporins. It inhibited some Enterobacter and Citrobacter freundii resistant to ceftazidime as did cefpirome and cefepime. Cefquinome was not destroyed by the common plasmid beta-lactamases TEM-1, TEM-2, SHV-1, or by the chromosomal beta-lactamases of Klebsiella, Branhamella, and Pseudomonas, but it was hydrolyzed by TEM-3, TEM-5, and TEM-9. Its activity was not adversely decreased in different medium or protein, and minimum bactericidal concentrations (MBCs) for most species except for Enterobacter were within a dilution of MICs.     

Tigemonam, an oral monobactam.

Tigemonam is an orally administered monobactam. At less than or equal to 1 microgram/ml it inhibited the majority of strains of Escherichia coli, Klebsiella spp., Enterobacter aerogenes, Citrobacter diversus, Proteus spp., Providencia spp., Aeromonas hydrophila, Salmonella spp., Shigella spp., Serratia marcescens, and Yersinia enterocolitica. At less than or equal to 0.25 microgram/ml it inhibited Haemophilus spp., Neisseria spp., and Branhamella catarrhalis. It did not inhibit Pseudomonas spp. or Acinetobacter spp. Tigemonam was more active than cephalexin and amoxicillin-clavulanate and inhibited many members of the family Enterobacteriaceae resistant to trimethoprim-sulfamethoxazole and gentamicin. Some Enterobacter cloacae and Citrobacter freundii strains resistant to aminothiazole iminomethoxy cephalosporins and aztreonam were resistant to tigemonam. The MIC for 90% of hemolytic streptococci of groups A, B, and C and for Streptococcus pneumoniae was 16 micrograms/ml, but the MIC for 90% of enterococci, Listeria spp., Bacteroides spp., and viridans group streptococci was greater than 64 micrograms/ml. Tigemonam was not hydrolyzed by the common plasmid beta-lactamases such as TEM-1 and SHV-1 or by the chromosomal beta-lactamases of Enterobacter, Morganella, Pseudomonas, and Bacteroides spp. Tigemonam inhibited beta-lactamases of E. cloacae and Pseudomonas aeruginosa but did not induce beta-lactamases. The growth medium had a minimal effect on the in vitro activity of tigemonam, and there was a close agreement between the MICs and MBCs.     

In vitro activity of CI-934 compared with ciprofloxacin, enoxacin, norfloxacin, and vancomycin

The in vitro activity of the quinolone CI-934 was compared with ciprofloxacin, norfloxacin, enoxacin, and vancomycin against 607 Gram-positive and -negative isolates. CI-934 inhibited 90% of the Enterobacteriaceae, Aeromonas hydrophila, and Acinetobacter spp. at 1 microgram/ml. Decreased activity was observed against Pseudomonas aeruginosa. Pseudomonas maltophilia, and other Pseudomonas spp. with CI-934 MIC90 greater than or equal to 8 micrograms/ml. CI-934 activity against Gram-positive organisms exceeded vancomycin and the other quinolones. MIC90 for Streptococcus faecalis, Listeria monocytogenes, and Corynebacterium spp. were less than or equal to 2 micrograms/ml. CI-934 was equally effective against oxacillin-susceptible and -resistant staphylococci with MIC90 of 0.5 micrograms/ml.     

In-vitro activity of enoxacin (CL-919), a new quinoline derivative, compared with that of other antimicrobial agents

The in-vitro activity of enoxacin (CI-919), a new synthetic quinoline derivative was compared with that of three other quinolines ofloxacin, norfloxacin and nalidixic acid. In addition beta-lactams and gentamicin were also included when appropriate. The MICs of enoxacin for 90% of Escherichia coli, Klebsiella spp., Enterobacter spp., Proteus spp., Providencia stuartii, Pseudomonas aeruginosa and Staphylococcus aureus were less than 4 mg/l, for Haemophilus influenzae less than 0.25 mg/l and Neisseria gonorrhoeae less than 0.03 mg/l. Bacteroides fragilis and streptococci (including Streptococcus pneumoniae) were less susceptible, MIC90 16 mg/l. Against many of the common Enterobacteriaceae enoxacin displayed a similar degree of activity as gentamicin. Gentamicin-resistant strains of common bacterial pathogens were susceptible to enoxacin as were methicillin-resistant Staph. aureus. The protein binding of enoxacin (concentration 5 mg/l) was 18%.     

In vitro activity and beta-lactamase stability of LJC 10,627.

The in vitro activity of LJC 10,627, a new carbapenem, was compared with those of imipenem, cefotaxime, ceftazidime, and gentamicin. LJC 10,627 inhibited 90% of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Hafnia alvei, Citrobacter freundii, Citrobacter diversus, Proteus mirabilis, Morganella morganii, Proteus rettgeri, Serratia marcescens, Pseudomonas cepacia, salmonellae, shigellae, aeromonas, and yersiniae at less than or equal to 2 micrograms/ml. Haemophilus influenzae was inhibited by 0.5 microgram/ml, and moraxellae were inhibited by 0.12 microgram/ml. LJC 10,627 was twofold more active than imipenem against aerobic gram-negative organisms and inhibited ceftazidime-, cefotaxime-, and gentamicin-resistant members of the genera Klebsiella, Enterobacter, Citrobacter, and Serratia at less than or equal to 2 micrograms/ml. Xanthomonas maltophilia strains were resistant to the drug. Imipenem was two- to fourfold more active than LJC 10,627 against Staphylococcus aureus and Staphylococcus epidermidis. LJC 10,627 did not inhibit most methicillin-resistant Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis strains. LJC 10,627 inhibited Streptococcus pyogenes and Streptococcus pneumoniae at 0.06 and 0.12 microgram/ml, respectively. Bacteroides fragilis and other Bacteroides spp. were inhibited by 0.5 microgram of LJC 10,627 per ml. Serum (50%) did not affect the MICs. LJC 10,627 was not hydrolyzed by plasmid-mediated beta-lactamases of Bush types 2b, 2b', TEM-1, TEM-2, TEM-3, TEM-5, TEM-7, TEM-9, and SHV-1; the chromosomal beta-lactamases of Bush type 1; P-99; a Morganella enzyme; or a Citrobacter freundii enzyme. The Bush type 2c and 2d enzymes OXA-1, OXA-2, PSE-1, PSE-2, and PSE-4 did not hydrolyze LJC 10,627, nor did the beta-lactamases of Staphylococcus aureus, Moraxella spp., Bacteroides fragilis, and Proteus vulgaris. The beta-lactamase of Xanthomonas hydrolyzed LJC 10,627, albeit at approximately one-third the rate that imipenem was hydrolyzed.     

In vitro antibacterial activity and beta-lactamase stability of E-0702, a new cephalosporin

The in vitro activity of E-0702 was compared with the in vitro activity of cefotaxime, ceftazidime, moxalactam, and aztreonam against 600 gram-positive and gram-negative aerobic and anaerobic isolates. E-0702 had a minimal inhibitory concentration for 50% of isolates (MIC50) of 25 micrograms for Staphylococcus aureus, 50 micrograms for Staphylococcus epidermidis, and 1.6 to 3.1 micrograms for streptococci, with Streptococcus faecalis resistant. E-0702 had MIC50s against Escherichia coli, Klebsiella pneumoniae, and Enterobacter aerogenes comparable to those of cefotaxime, ceftazidime, moxalactam, and aztreonam, but MIC90S were higher than those of the other agents. It was as active as the other agents against Proteus mirabilis, Salmonella spp., and Shigella spp., but was four- to eightfold less active against Citrobacter freundii, Enterobacter cloacae, Providencia spp., Morganella spp., and Proteus vulgaris, with isolates in each species resistant. Activity against Bacteroides fragilis was fourfold less than that of cefoxitin. E-0702 was hydrolyzed by plasmid beta-lactamases and was only a weak inhibitor of plasmid and chromosomal beta-lactamases. There was an inoculum effect for E. cloacae, Serratia spp., Morganella spp., and Pseudomonas spp.     

In vitro activity of Ro 23-9424, a dual-action cephalosporin, compared with activities of other antibiotics.

The in vitro activity of Ro 23-9424, which is desacetyl-cefotaxime linked to fleroxacin, was compared with the activities of cefotaxime, desacetyl-cefotaxime, fleroxacin, ofloxacin, and ciprofloxacin. It inhibited the majority of members of the family Enterobacteriaceae, except for some Serratia marcescens, Citrobacter freundii, and Enterobacter cloacae strains, at less than or equal to 0.25 microgram/ml and had an MIC for 90% of strains tested (MIC90) of 8 micrograms/ml against Pseudomonas aeruginosa. Most group A, B, C, and G streptococci and Streptococcus pneumoniae were inhibited at less than or equal to 0.25 microgram/ml. Ninety percent of the staphylococci were inhibited at less than or equal to 4 micrograms/ml, except for some methicillin-resistant Staphylococcus aureus isolates. The MIC90S of Ro 23-9424 for Enterococcus faecalis and Listeria monocytogenes were greater than or equal to 16 micrograms/ml. Ninety percent of Clostridium perfringens isolates were inhibited by less than or equal to 2 micrograms/ml, whereas Bacteroides fragilis had an MIC90 of 32 micrograms/ml. There was a minimal inoculum size effect. The MICs and MBCs were either identical or within a twofold dilution. The MICs of Ro 23-9424 for Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Enterobacter cloacae, Citrobacter freundii, Pseudomonas aeruginosa, and Staphylococcus aureus increased 16- to 128-fold after 2 weeks of transfer in the presence of Ro 23-9424, showing that the presence of two agents does not prevent resistance.     

In vitro activity of a catechol-substituted cephalosporin, GR69153.

The in vitro activity of GR69153, a new catechol-substituted cephalosporin, was compared with those of ceftazidime, imipenem, meropenem, and ceftriaxone against 604 recent clinical isolates and other strains with known mechanisms of resistance. The MICs of GR69153 for 90% of the members of the family Enterobacteriaceae tested were less than 0.5 micrograms/ml, with the exceptions of those for Serratia spp. (4 micrograms/ml), Citrobacter spp. (2 micrograms/ml), and Enterobacter spp. (8 micrograms/ml). Ninety percent of Pseudomonas aeruginosa isolates were susceptible to less than or equal to 1 microgram of GR69153 per ml. With the exception of methicillin-resistant strains, 90% of Staphylococcus aureus isolates were susceptible to less than or equal to 2 micrograms/ml, and GR69153 was four- to eightfold more active than ceftazidime and ceftriaxone against these strains. Isolates of Haemophilus influenzae, Branhamella catarrhalis, Neisseria spp., and Streptococcus pneumoniae (penicillin susceptible) were highly susceptible (MIC for 90% of the strains, less than or equal to 0.12 micrograms/ml). GR69153 was stable to hydrolysis by the TEM-1 and TEM-5, SHV-1 and SHV-2, and K1 beta-lactamases, but some susceptibility to hydrolysis by the TEM-3, TEM-9, and P99 enzymes was observed. The protein-binding activity of GR69153 was 74.5 to 66.8%, depending on the concentration, and serum had little effect upon activity.     

The in-vitro activity of CI-934 compared with that of other new 4-quinolones and nalidixic acid

The in-vitro activity of CI-934, a new 4-quinolone compound, was compared with that of the other new 4-quinolones, enoxacin and ciprofloxacin, and also with that of nalidixic acid. CI-934 was more active than any of the other 4-quinolones tested against Gram-positive aerobic organisms including Staphylococcus aureus (MICs 0.06-0.25 mg/l), beta-haemolytic streptococci (MICs 0.12-0.5 mg/l), Streptococcus pneumoniae (MICs 0.25-0.5 ml/l), viridans streptococci (MICs 0.06-0.5 mg/l) and most enterococci (MICs 0.12-0.5 mg/l), although some ampicillin-resistant isolates of Str. faecium were slightly less susceptible (MICs 2 mg/l). All three of the newer 4-quinolones tested were highly active against Enterobacteriaceae, Aeromonas sp., Haemophilus influenzae and Neisseria gonorrhoeae (MICs mostly less than 1 mg/l). The other Gram-negative aerobes tested were in general somewhat less susceptible, although for Acinetobacter and Pseudomonas aeruginosa MICs seldom exceeded 8 mg/l. CI-934 was more active than enoxacin against Gardnerella vaginalis (MICs 1-8 mg/l) although it was a little less active than ciprofloxacin. Bacteroides species (including about half of the fragilis group) were susceptible to CI-934 (MICs mostly 1-8 mg/l): ciprofloxacin had similar activity but enoxacin was less active. Other anaerobes tested were mostly highly susceptible to CI-934 (MICs 1 mg/l or less) but were somewhat less susceptible to enoxacin and ciprofloxacin.     

In vitro activities of PD 117,596 and reference antibiotics against 448 clinical bacterial strains.

The in vitro activity of PD 117,596, a new fluoroquinolone antibiotic, was tested against 448 bacterial isolates (15 genera) by agar dilution (inoculum, 10(4) CFU per spot). The activity of PD 117,596 was compared with that of 15 antibiotics against 327 gram-negative strains and with that of 8 other antibiotics against 121 gram-positive strains. PD 117,596 demonstrated the best activity against Klebsiella spp., Enterobacter spp., Acinetobacter spp., Serratia marcescens, and Branhamella catarrhalis (MICs for 90% of the isolates [MIC90S], 0.008 to 0.25 microgram/ml). PD 117,596 (MIC90, 0.25 microgram/ml) was at least twofold more active than ciprofloxacin against Pseudomonas aeruginosa and Pseudomonas spp. PD 117,596 and ciprofloxacin were similar in activity against Escherichia coli, Proteus mirabilis, Haemophilus influenzae, H. parainfluenzae, Neisseria gonorrhoeae, Legionella pneumophila, and Campylobacter jejuni (MIC90, 0.002 to 0.125 microgram/ml). PD 117,596 was more active than ciprofloxacin against streptococcal groups A, B, C, and G, S. pneumoniae, and enterococci (MIC90S, 0.06 to 0.125 microgram/ml). Against Staphylococcus aureus, including methicillin-resistant isolates, PD 117,596 (MIC90S, 0.03 to 0.06 microgram/ml) was 4- to 16-fold more active than ciprofloxacin and was most active against Corynebacterium spp. PD 117,596 appears to be the most active fluoroquinolone to date, with excellent activity against gram-positive bacteria and enhanced activity against gram-negative aerobic-facultative bacteria.     

In vitro activities of quinolones against enterococci resistant to penicillin-aminoglycoside synergy.

The MICs and MBCs of CI-934, ciprofloxacin, difloxacin (A-56619), A-56620, norfloxacin, enoxacin, amifloxacin, and coumermycin were determined for 43 clinical isolates of Enterococcus faecalis known to be resistant to penicillin-aminoglycoside synergy. Results were compared with those obtained for 37 synergy-susceptible E. faecalis and 22 Enterococcus faecium strains. Although no substantial differences in quinolone activities were observed between synergy-resistant and -susceptible E. faecalis strains, CI-934 and ciprofloxacin were the drugs that demonstrated the greatest bactericidal activity against both types of E. faecalis. The MBCs of the other quinolones were generally within a single twofold dilution of the MICs, but their antienterococcal activity did not approach that of CI-934 or ciprofloxacin. The MBCs for 90% of the isolates of CI-934 for synergy-resistant and -susceptible E. faecalis strains were 1 and less than or equal to 0.5 microgram/ml, respectively. The ciprofloxacin MBC for 90% of the E. faecalis strains tested was 1 microgram/ml. For E. faecium isolates the CI-934 and ciprofloxacin MBCs for 90% of the isolates were 8 and 4 micrograms/ml, respectively. Time-kill assays performed with synergy-susceptible enterococcal strains showed that the bactericidal activities of both CI-934 and ciprofloxacin were less than those of the penicillin-aminoglycoside combinations tested. However, against synergy-resistant isolates the activities of these two quinolones were comparable with and sometimes greater than those of penicillin-aminoglycoside combinations.     

In vitro activity of LY264826 compared to other glycopeptides and daptomycin.

LY264826 a new naturally occurring glycopeptide inhibited 90% of methicillin-susceptible and -resistant Staphylococcus aureus at 1 micrograms/ml. LY264826 had similar activity against methicillin-susceptible and -resistant coagulase-negative staphylococci. The LY264826 MIC90 for Streptococcus pyogenes was 0.25 microgram/ml, twofold more active than vancomycin and twofold less active than teicoplanin. LY264826 was eightfold more active than vancomycin and twofold more active than teicoplanin against enterococci. LY264826 inhibited Streptococcus pneumoniae at 0.25 microgram/ml and Listeria monocytogenes at 0.5 microgram/ml. Clostridium were inhibited by less than or equal to 0.25 microgram/ml of LY264826 and peptococci, peptostreptococci, and Fusobacterium were inhibited by less than 0.5 microgram/ml. Bacteroides species were LY284826 -resistant as were all Enterobacteriaceae, Flavobacterium, and Neisseria spp. Minimum bactericidal and inhibitory concentrations (MBCs and MICs) were within a dilution for S. aureus, S. pyogenes, and S. pneumoniae, but greater than or equal to 32-fold greater for enterococci.     

The comparative activity of fleroxacin, three other quinolones and eight unrelated antimicrobial agents.

The in vitro activity of fleroxacin, a new trifluorinated quinolone was evaluated against 432 bacterial isolates. Fleroxacin was 1- to 2-fold less active than ciprofloxacin and at least as active as ofloxacin and lomefloxacin against most members of the family Enterobacteriaceae. The MICs of fleroxacin for 90% of strains tested (MIC90) were < or = 0.25 micrograms/ml against all isolates of Enterobacteriaceae except Citrobacter freundii (MIC90, 4 micrograms/ml) and Serratia marcescens (MIC90, 2 micrograms/ml). Fleroxacin was as active as ciprofloxacin, ofloxacin and lomefloxacin against Pseudomonas spp, (MIC90 for all quinolones tested were > 8 micrograms/ml). Acinetobacter and Haemophilus influenzae were very susceptible to fleroxacin; however fleroxacin was 1-fold less active than lomefloxacin against Acinetobacter and at least 1-fold less active than ciprofloxacin or ofloxacin against H. influenzae. Methicillin-susceptible and -resistant strains of Staphylococcus epidermidis and methicillin-susceptible strains of S. aureus were very susceptible to fleroxacin, with an MIC90 < or = 1 microgram/ml (range 0.5-1 microgram/ml). Methicillin-resistant S. aureus and Staphylococcus spp. other than aureus and epidermidis were not susceptible to fleroxacin (MIC90 > 8 micrograms/ml). In addition, fleroxacin as well as ciprofloxacin, ofloxacin and lomefloxacin were inactive against Enterococcus spp. (MIC90 > 8 micrograms/ml). Streptococcus pneumoniae and S. pyogenes were resistant to both fleroxacin and lomefloxacin but were very susceptible to ciprofloxacin and ofloxacin. These results suggest that fleroxacin represents a valid therapeutic option in the treatment of infections caused by most Enterobacteriaceae and some species of staphylococcus.     

In vitro activity of HRE 664, a penem antibiotic

HRE 664, a new penem antibiotic, inhibited 90% of Escherichia coli, Klebsiella, Citrobacter diversus, Proteus mirabilis, Proteus vulgaris, Salmonella, Shigella, Providencia, Aeromonas, and Morganella at less than or equal to 2 micrograms/ml but was considerably less active than cefotaxime, ceftazidime, and imipenem. It did not inhibit Pseudomonas aeruginosa (MIC greater than 128 micrograms/ml). HRE 664 inhibited Enterobacter spp., Citrobacter freundii, and Serratia marcescens at 1-8 micrograms/ml, two- to fourfold higher MICs than imipenem. HRE 664 inhibited methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis at less than or equal to 0.12 micrograms/ml, but methicillin-resistant S. aureus and S. epidermidis were resistant. Group A, C, and G streptococci and Streptococcus pneumoniae were inhibited by 0.06 micrograms/ml. Bacteroides and Clostridium species were inhibited by 0.25 micrograms/ml comparable to imipenem. HRE 664 was not hydrolyzed by beta-lactamases TEM-1, TEM-2, TEM-3, TEM-5, SHV-1, PSE-1, PSE-4, OXA-2, OXA-3, K-1, P99, Morganella, P. vulgaris, and S. aureus PC-1 but was hydrolyzed by the beta-lactamase of Xanthomonas maltophilia.