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1.  In vitro activity of SCE-2787, a new cephalosporin with potent activity against Pseudomonas aeruginosa and members of the family Enterobacteriaceae. 
Antimicrobial Agents and Chemotherapy  1994;38(12):2896-2901.
The in vitro activity of SCE-2787, 7-[(Z)-2-(5-amino-1,2,4-thiadiazol-3- yl)-2-methoxyiminoacetamido]-3-(1-imidazo[1,2-b]pyridazinium)methy l-3- cephem-4-carboxylate, was compared with those of ceftazidime, ceftriaxone, and imipenem against recent clinical isolates. SCE-2787 inhibited 50% of tested isolates of the family Enterobacteriaceae at < or = 0.25 micrograms/ml. SCE-2787 was equally active as or more active than ceftazidime and ceftriaxone against members of the Enterobacteriaceae, with the exception of Proteus vulgaris. The MIC of SCE-2787 at which 90% of the isolates of Pseudomonas aeruginosa were inhibited was 2 micrograms/ml, two- to fourfold lower than those of imipenem and ceftazidime, respectively. SCE-2787, like ceftazidime and imipenem, did not inhibit the majority of strains of Pseudomonas cepacia and Xanthomonas maltophilia. SCE-2787 inhibited beta-hemolytic streptococci at < or = 0.12 micrograms/ml, but it did not inhibit Enterococcus faecalis, Listeria monocytogenes, or the anaerobic species tested. Methicillin-resistant staphylococci required SCE-2787 MICs of > or = 16 micrograms/ml, whereas methicillin-susceptible staphylococci were inhibited by 2 micrograms/ml. No difference between the MICs and MBCs was noted, except for P. aeruginosa, for which there was a fourfold difference. SCE-2787 was active over a pH range of 6 to 8. The inoculum size of 10(5) to 10(7) CFU caused only a twofold change in the MIC for Escherichia coli and Staphylococcus aureus but a 4- to 16-fold change in Enterobacter cloacae and P. aeruginosa. beta-Lactamases from Bush groups 1, 2a, and 2b did not hydrolyze SCE-2787. There was significant hydrolysis of SCE-2787 by the beta-lactamases designated 2b', i.e., TEM-3, TEM-5, TEM-7, and TEM-9, and by the group 2d beta-lactamases. SCE-2787 had poor affinity for group 1 and group 2b enzymes and constitutively produced chromosomal beta-lactamases such as P-99 of Enterobacter cloacae and plasmid-mediated TEM-1 of E. coli. SCE-2787 has in vitro activity comparable to that of current parenteral cephalosporin and is more active against P. aeruginosa and S. aureus.
PMCID: PMC188303  PMID: 7695279
2.  In vitro activity of the new fluoroquinolone CP-99,219. 
Antimicrobial Agents and Chemotherapy  1994;38(11):2615-2622.
The in vitro activity of the new fluoroquinolone CP-99,219 [7-(3-azabicyclo[3.1.0]hexyl)naphthyridone] was compared with those of four other quinolones against 541 gram-negative, 283 gram-positive, and 70 anaerobic bacterial isolates. CP-99,219 inhibited 90% of many isolates in the family Enterobacteriaceae at a concentration of < or = 0.25 micrograms/ml (range, < 0.008 to 1 microgram/ml), an activity comparable to those of tosufloxacin and sparfloxacin and two times greater than that of temafloxacin. Ninety percent of the Proteus vulgaris, Providencia rettgeri, Providencia stuartii, and Serratia marcescens isolates were inhibited by 0.5 to 2 micrograms of CP-99,219 per ml. CP-99,219 inhibited 90% of the Pseudomonas aeruginosa and Haemophilus influenzae isolates at 1 and 0.015 micrograms/ml, respectively. The compound inhibited methicillin-susceptible Staphylococcus aureus at 0.06 micrograms/ml, whereas a ciprofloxacin concentration of 1 microgram/ml was required to inhibit these organisms. CP-99,219 inhibited 90% of methicillin-resistant S. aureus isolates at a concentration of < or = 4 micrograms/ml, while ciprofloxacin and temafloxacin had MICs against these isolates of > 16 micrograms/ml. Streptococci were inhibited by < or = 0.25 micrograms/ml, an activity comparable to that of tosufloxacin. CP-99,219 was eight times more active than ciprofloxacin against Streptococcus pneumoniae. Bacteroides species were inhibited by CP-99,219 at a concentration of 2 micrograms/ml, whereas inhibition of these species required 4- and 16-microgram/ml concentrations of tosufloxacin and ciprofloxacin, respectively. The MBCs of CP-99,219 ranged from two to four times the MICs, and inoculum size had a minimal effect on MIC. CP-99,219 was active against P. aeruginosa at pH 5.5, with only a fourfold increase in MIC compared with values obtained at pH 7.5. The addition of up to 9 mM Mg(2+) increased the MIC range from 0.03 to 0.06 microgram/ml to 0.12 to 0.5 microgram/ml. In view of its excellent in vitro activity against both gram-positive and gram-negative bacteria, CP-99,219 merits further study to determine it's clinical pharmacologic properties and potential for therapeutic use.
PMCID: PMC188251  PMID: 7872757
3.  In vitro activity and beta-lactamase stability of FK-037, a parenteral cephalosporin. 
The in vitro activity of FK-037, 5-amino-2-[[(6R, 7R)-7-[[(Z)-2-(2-amino-4-thiazolyl)-2- methoxyimino) acetyl] amino]-2-carboxy-8-oxo-5-thia-1- azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-1-(2-hydroxyethyl)-1H-pyrazoli um hydroxide, inner salt, sulfate (1:1), a new parenteral cephem, was compared with those of cefepime, ceftazidime, imipenem, and ciprofloxacin. FK-037 inhibited methicillin-susceptible staphylocci at < or = 4 micrograms/ml. Of 98 isolates of homogenous methicillin-resistant Staphylococcus aureus, 55 (56.1%) were inhibited by 8 micrograms of FK-037 per ml, compared to 3.1% for cefepime. Imipenem was the most active beta-lactam tested against staphylococci. The MIC of FK-037 for 90% of the strains tested (MIC90) was 0.06 micrograms/ml for hemolytic streptococci, Streptococcus pneumoniae, viridans group streptococci, and Streptococcus bovis. The MIC90 for many of the members of the family Enterobacteriaceae was 1 microgram/ml, similar to that of cefepime and lower than those of ceftazidime and imipenem. The MIC90 for Klebsiella pneumoniae and Enterobacter cloacae was 8 micrograms/ml, similar to that for cefepime, but all isolates were inhibited by 2 micrograms of imipenem per ml. K. pneumoniae isolates with cefotaxime and ceftazidime MICs of > 32 micrograms/ml with Bush type 2b' beta-lactamases were inhibited by 4 micrograms of FK-037 per ml. E. cloacae, Citrobacter freundii, and S. aureus stably resistant to FK-037 could be selected by repeated transfer in the presence of FK-037. The FK-037 MIC90 for Pseudomonas aeruginosa was 4 microgram/ml, compared to 32 microgram/ml for cefepime and ceftazidime and 8 microgram/ml for imipenem. Xanthomonas maltophilia, Pseudomonas cepacia, Acinetobacter anitratus, and Bacteroides species were resistant to FK-037 (MIC, more than or equal 32 microgram/ml). MBCs were identical to or within twofold of the MICs except for a 32-fold greater MBC for P. aeruginosa. Inoculum size and acid environment did not lower the activity of FK-037. FK-037 was not appreciably hydrolyzed by Bush group 1, 2a, 2b, and 2e beta-lactamases but was hydrolyzed by 2b' and 2d enzymes at rates comparable to that of ceftazidime. Nonetheless, FK-037 inhibited bacteria possessing TEM-3, -5, and -7 and SHV -5 at less than or equal 8 microgram/ml. Overall, FK-037 has lower MICs against staphylococci and P. aeruginosa than the currently available iminomethoxy aminothiazolyl cephalosporins and has activity against members of the family Enterobacteriaceae comparable to that of cefepime.
PMCID: PMC187708  PMID: 8460925
4.  In vitro activity of MC-352, a new 16-membered macrolide. 
The in vitro activity of MC-352, 3,4'-dideoxy-5-O-mycaminosyltylonolide, was compared with those of erythromycin, clarithromycin, and rokitamycin. The MC-352 MIC90 (MIC for 90% of isolates) for erythromycin-susceptible Staphylococcus aureus and Staphylococcus epidermidis was less than or equal to 1 microgram/ml, similar to those of the other agents. The MC-352 MIC50 for erythromycin-resistant S. aureus was 2 micrograms/ml, similar to that of rokitamycin. The MC-352 MIC90 (0.12 micrograms/ml) for Streptococcus pyogenes was similar to those of erythromycin and clarithromycin and superior to that of rokitamycin, and the MC-352 MIC90 for group B, C, and G streptococci was 0.25 microgram/ml. MC-352 and clarithromycin had an MIC90 of 0.12 microgram/ml for Streptococcus pneumoniae. Erythromycin-susceptible Enterococcus faecalis was inhibited by MC-352 at 1 microgram/ml, but the MIC for constitutively erythromycin-resistant isolates was greater than 16 micrograms/ml. Legionella pneumophila was inhibited by less than or equal to 0.25 microgram/ml. MC-352 was the most active agent against Bacteroides fragilis, with an MIC90 of 8 micrograms/ml, and was more active than the other agents against Haemophilus influenzae, with an MIC90 of 4 micrograms/ml. Moraxella spp. were inhibited by MC-352 at less than or equal to 0.25 microgram/ml. The MIC90 for Escherichia coli, Klebsiella pneumoniae, and Salmonella, Shigella, Yersinia, Enterobacter, Citrobacter, and Serratia spp. was greater than or equal to 32 micrograms/ml. MC-352 was bactericidal for S. pyogenes and S. pneumoniae, and its activity was not altered by human serum.
PMCID: PMC192033  PMID: 1416853
5.  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.
PMCID: PMC191596  PMID: 1510436
6.  In vitro activity and susceptibility to hydrolysis of S-1006. 
The in vitro activity of S-1006, the active component of a new orally absorbed cephalosporin, S-1108, inhibited 90% of Staphylococcus aureus isolates at less than or equal to 2 micrograms/ml, 90% of group A, B, C, F, and G streptococci and Streptococcus pneumoniae isolates at less than or equal to 0.12 microgram/ml, and all Haemophilus influenzae isolates at less than or equal to 0.06 microgram/ml. Although 50% of the members of the family Enterobacteriaceae were inhibited by less than or equal to 2 micrograms of S-1006 per ml, Enterobacter spp. and Citrobacter freundii resistant to ceftriaxone were resistant to S-1006. The MICs of S-1006 for approximately 20% of Providencia, Proteus vulgaris, and Serratia isolates were 4 micrograms/ml. S-1006 was hydrolyzed by the plasmid TEM-3, TEM-5, PSE-1, and PSE-4 beta-lactamases and by the chromosomal beta-lactamase of Enterobacter and Morganella spp. and P. vulgaris.
PMCID: PMC190343  PMID: 1416835
7.  In vitro activity of OPC-17116. 
The in vitro activity of OPC-17116, a new C-5 methyl fluoroquinolone, was compared with the activities of other fluoroquinolones. OPC-17116 inhibited 50% of the members of the family Enterobacteriaceae tested and 90% of Haemophilus influenzae, Neisseria species, and Moraxella catarrhalis isolates at less than or equal to 0.25 microgram/ml. At less than or equal to 2 micrograms/ml, 90% of the Enterobacteriaceae were inhibited, which was comparable to or better than the activities of fleroxacin, ofloxacin, and lomefloxacin but less than the activity of ciprofloxacin. OPC-17116 inhibited 90% of the staphylococci tested at less than or equal to 0.25 micrograms/ml, but it did not inhibit methicillin-resistant, ciprofloxacin-resistant Staphylococcus aureus or Staphylococcus epidermidis. Group A, B, C, F, and G streptococci and Streptococcus pneumoniae were inhibited by less than or equal to 0.5 microgram/ml, being four-fold more active than ciprofloxacin and ofloxacin. Tosufloxacin was the most active agent tested against gram-positive cocci. OPC-17116 inhibited Bacteroides fragilis at 4 micrograms/ml. There was a minimal effect of inoculum size on MIC, and the MBCs were within 1 dilution of the MICs. The activity of OPC-17116 was decreased at pH 6 and in the presence of high Mg2+ concentrations, but it was unaffected by human serum. OPC-17116 showed a postantibiotic effect against Pseudomonas aeruginosa and Staphylococcus aureus similar to the postantibiotic effects reported for other fluoroquinolones. The frequency of spontaneous single-step resistance was low (less than 10(-9)), but repeated passage of organisms in the presence of OPC-17116 resulted in the selection of resistant isolates.
PMCID: PMC190337  PMID: 1329620
8.  Activity of mersacidin, a novel peptide, compared with that of vancomycin, teicoplanin, and daptomycin. 
Mersacidin, a new peptide antibiotic, was four- to eightfold less active (MIC for 90% of isolates, 8 micrograms/ml) than vancomycin, teicoplanin, or daptomycin against Staphylococcus aureus. Coagulase-negative staphylococci were inhibited by 8 micrograms/ml, and the MICs of mersacidin for hemolytic streptococci and Streptococcus pneumoniae were 4 to 8 micrograms/ml. The mersacidin MICs for anaerobic organisms were as follows: Clostridium perfringens, 4 micrograms/ml; Propionibacterium acnes, 8 micrograms/ml; peptococci, 1 microgram/ml; and peptostreptococci, 8 micrograms/ml. Mersacidin had no activity against members of the family Enterobacteriaceae, Neisseria and Haemophilus species, or Pseudomonas aeruginosa. The size of the inoculum, the pH of the assay (5.5 to 7.5), the type of medium, and the anaerobic conditions had minimal effects on the MICs and MBCs of mersacidin. Overall, mersacidin proved less active than available glycopeptides and peptolides.
PMCID: PMC245145  PMID: 1649577
9.  In vitro activity of sparfloxacin. 
Sparfloxacin, a new fluoroquinolone, inhibited the majority of members of the family Enterobacteriaceae at less than or equal to 1 microgram/ml. It was less active than ciprofloxacin but more active than ofloxacin. Against Pseudomonas aeruginosa, it was less active than ciprofloxacin but twofold more active than ofloxacin. It inhibited Staphylococcus aureus and most Streptococcus pneumoniae and Streptococcus pyogenes isolates at 0.25 micrograms/ml, whereas ciprofloxacin and ofloxacin inhibited these isolates at 2 micrograms/ml. Bacteroides fragilis was inhibited by less than or equal to 2 micrograms/ml. Sparfloxacin was less active at an acidic pH and in the presence of Mg2+. Resistance to sparfloxacin was produced by repeated exposure, although the frequency of single-step mutants was less than 10(-9).
PMCID: PMC245051  PMID: 2039209
10.  In vitro activity and beta-lactamase stability of GR69153, a new long-acting cephalosporin. 
GR69153, a new parenteral cephalosporin, inhibited 90% of Escherichia coli, Klebsiella oxytoca, Proteus mirabilis, Citrobacter diversus, shigellae, and salmonellae at less than 0.25 micrograms/ml (MIC90). It had activity comparable to those of ceftazidime, cefpirome, cefepime, and E-1040. Against cephalosporinase-producing Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens, MICs ranged from 0.12 to greater than 32 micrograms/ml, and cefpirome and cefepime were the most active agents against these species. Pseudomonas aeruginosa was highly susceptible to GR69153, and for this organism the MIC90 was less than or equal to 2 micrograms/ml, which was similar to the E-1040 MIC90, but most Pseudomonas cepacia and Xanthomonas maltophilia isolates were resistant. GR69153 inhibited Haemophilus influenzae and Moraxella branhamella at less than or equal to 0.5 micrograms/ml. For Staphylococcus aureus GR69153 MICs were similar to those of ceftazidime and E-1040. Enterococci and listeriae were resistant to GR69153, but Streptococcus pyogenes and Streptococcus pneumoniae were inhibited by 0.5 micrograms/ml. The activity of GR69153 was not affected by serum. GR69153 was not inactivated by the beta-lactamases of Staphylococcus aureus, TEM-1, TEM-2, SHV-1, and BRO-1, but it was hydrolyzed by TEM-3, TEM-9, and morganellae. GR69153 had overall activity comparable to those of commercially available parenteral cephalosporins or those found in clinical investigations. It is more active against bacteroides than most available aminothiazolyl parenteral cephalosporins are. GR69153 is hydrolyzed by the new plasmid beta-lactamases, and thus, its primary value may be related to its pharmacological properties.
PMCID: PMC244988  PMID: 2024959
11.  In vitro activity of dirithromycin (LY 237216) compared with activities of other macrolide antibiotics. 
Dirithromycin inhibited Streptococcus pyogenes, Streptococcus pneumoniae, and other hemolytic streptococci at concentrations of less than or equal to 0.03 to 0.12 micrograms/ml, with 90% inhibition at 0.12 micrograms/ml, which is comparable to results using erythromycin. Group A streptococci, listeriae, and enterococci resistant to erythromycin were resistant to dirithromycin. Erythromycin-susceptible staphylococci were inhibited by 0.5 micrograms/ml, but for erythromycin-resistant isolates MICs were greater than or equal to 8 micrograms/ml. For Haemophilus influenzae, MICs were greater than or equal to 8 micrograms/ml, two- to fourfold greater than for erythromycin. The activity of dirithromycin against staphylococci and streptococci was not decreased by the addition of human serum.
PMCID: PMC171944  PMID: 2126695
12.  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.
PMCID: PMC171554  PMID: 2327765
13.  In vitro activity of dactimicin, a novel pseudodisaccharide aminoglycoside, compared with activities of other aminoglycosides. 
Antimicrobial Agents and Chemotherapy  1989;33(11):1998-2003.
The in vitro activity of dactimicin, a new pseudodisaccharide aminoglycoside which possesses a formimidoyl group, was compared with those of gentamicin, tobramycin, and amikacin against 500 isolates. Dactimicin inhibited 90% of isolates from the family Enterobacteriaceae at a concentration of less than or equal to 4 micrograms/ml. It was more active than amikacin against Klebsiella pneumoniae, Serratia marcescens, Citrobacter diversus, Enterobacter agglomerans, Yersinia species, and Salmonella species, with an MIC for 90% of the strains (MIC90) of less than or equal to 4 micrograms/ml. The MIC90s for the Pseudomonas aeruginosa isolates were greater than 128 micrograms/ml. Dactimicin did not inhibit most methicillin-resistant Staphylococcus aureus isolates and coagulase-negative staphylococci but had an MIC50 (MIC for 50% of strains tested) of 2 micrograms/ml against methicillin-susceptible S. aureus isolates and coagulase-negative staphylococci. Dactimicin in combination with piperacillin acted synergistically against 75% of Escherichia coli, K. pneumoniae, S. marcescens, and S. aureus isolates. It exhibited an excellent postantibiotic suppressive effect on E. coli. Dactimicin was active against organisms possessing aminoglycoside-modifying enzymes including AAC(2')-b, AAC(3)-III, -IV, and -V, and AAC(6')-Ia, -Ib, Ic, -II, and -IV but was not active against isolates which contained AAC(3)-I and the bifunctional APH(2")-AAC(6')-I. Its lack of activity against P. aeruginosa appeared to be permeability related since in the presence of EDTA P. aeruginosa was susceptible, as were mutant isolates resistant because of permeability barriers.
PMCID: PMC172802  PMID: 2514625
14.  Comparative in vitro activity and beta-lactamase stability of FK482, a new oral cephalosporin. 
Antimicrobial Agents and Chemotherapy  1989;33(10):1795-1800.
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.
PMCID: PMC172757  PMID: 2589845
15.  In vitro activity of ME1228, a new parenteral cephalosporin. 
ME1228 is a new cephalosporin with an iminocarboxymethyl moiety on the acyl side chain and a novel pyridiniumthiomethyl group at position 3 of the bicyclic ring. Its activity was compared with those of ceftazidime, imipenem, piperacillin, and gentamicin. ME1228 inhibited most members of the family Enterobacteriaceae, except for some Enterobacter spp. and Citrobacter freundii, at less than or equal to 0.25 micrograms/ml, and it inhibited gentamicin- and piperacillin-resistant isolates. It had MICs for Pseudomonas aeruginosa between 1 and 32 micrograms/ml, comparable to those of ceftazidime, and it inhibited piperacillin- and gentamicin-resistant isolates. Most group A, B, C, and G streptococci and Streptococcus pneumoniae were inhibited by less than or equal to 0.25 micrograms/ml. Enterococci and listeriae were resistant (MICs, 64 to 128 micrograms/ml). The MICs for staphylococci were 4 to 8 micrograms/ml, and methicillin-resistant Staphylococcus aureus was resistant. There was a minimal inoculum effect and no effect of the medium. ME1228 was not hydrolyzed by TEM-1, TEM-2, SHV-1, and S. aureus plasmid beta-lactamases and was stable against hydrolysis by Richmond-Sykes type 1a, 1c, 1d, and IV chromosomal beta-lactamases. It was hydrolyzed by TEM-3 and Xanthomonas maltophilia beta-lactamases. Overall, ME1228 had activity comparable or superior to that of ceftazidime.
PMCID: PMC172637  PMID: 2802554
16.  In vitro activity of S-ofloxacin. 
S-Ofloxacin, the optically active form of ofloxacin, was twice as active as the S,R mixture of ofloxacin against members of the family Enterobacteriaceae, Pseudomonas aeruginosa, and gram-positive species. Of the Enterobacteriaceae, 90% were inhibited by less than or equal to 1 microgram/ml and 90% of Staphylococcus aureus and Streptococcus pyogenes isolates were inhibited by 0.5 microgram/ml. Bacteroides fragilis was inhibited by 4 micrograms/ml. Organisms resistant to ofloxacin were resistant to S-ofloxacin. Like ofloxacin activity, the activity of S-ofloxacin was reduced by Mg2+ and by acid pH. Spontaneous mutational resistance to S-ofloxacin was similar to that to ofloxacin.
PMCID: PMC176070  PMID: 2506805
17.  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
PMCID: PMC176058  PMID: 2675753
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.
PMCID: PMC176054  PMID: 2789493
Antimicrobial Agents and Chemotherapy  1988;32(11):1666-1675.
The in vitro activity of E-1040 [(6R,7R)-3-[(4-carbamoyl-1-quinuclidinio)methyl]-7-[2-(5-amino-1,2 ,4- thiadiazol-3-yl)-(Z)-2-methoxyiminoacetoamido]-8-oxo-5-thia- 1- azabicyclo(4,2,0)oct-2-ene-2-carboxylate], a novel cephalosporin, was compared with that of ceftazidime, cefpirome, cefepime, imipenem, and gentamicin. E-1040 inhibited 50% of members of the family Enterobacteriaceae, Pseudomonas aeruginosa, and Haemophilus and Neisseria species at less than or equal to 0.25 microgram/ml, and the MIC for 90% of strains tested ranged from 0.06 to 2 micrograms/ml. It was two- to fourfold more active than ceftazidime and similar in activity to cefepime and cefpirome. It inhibited Enterobacter, Citrobacter, Serratia, and Morganella species that were resistant to ceftazidime. E-1040 inhibited imipenem-, piperacillin-, aztreonam-, and tobramycin-resistant P. aeruginosa. It was less active against Xanthomonas maltophilia and P. cepacia but inhibited other Pseudomonas species. The activity of E-1040 against staphylococci and hemolytic streptococci was similar to that of ceftazidime, but E-1040 was less active than cefepime and cefpirome. It did not inhibit Bacteroides spp. There was no inoculum effect or medium effect, and MBCs were within a dilution of MICs. Plasmid beta-lactamases TEM-1, TEM-2, TEM-3 (CTX-1), SHV-1, Staphylococcus aureus, PSE, and CARB did not hydrolyze E-1040. Chromosomal beta-lactamases P99 and K-1 did not hydrolyze E-1040; E-1040 had poor affinity for these enzymes, with a Ki of greater than 100 microM.
PMCID: PMC175949  PMID: 3150915
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.
PMCID: PMC172250  PMID: 3260766
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.
PMCID: PMC172249  PMID: 3293524
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.
PMCID: PMC172248  PMID: 3164987
The antibacterial activities of DuP 105 and DuP 721, new oxazolidinone antimicrobial agents, were compared with those of beta-lactams and glycopeptides. Ninety percent of Staphylococcus aureus and Staphylococcus epidermidis isolates, including methicillin-resistant isolates, were inhibited by 4 micrograms of DuP 105 and 1 microgram of DuP 721 per ml. DuP 721 inhibited hemolytic streptococcus groups A, B, C, F, and G at a concentration of less than or equal to 1 microgram/ml, and it inhibited viridans group streptococci at a concentration of 2 micrograms/ml. Both agents inhibited Listeria monocytogenes, Corynebacterium group JK species, anaerobic cocci, and Clostridium spp. including Clostridium difficile. They did not inhibit members of the family Enterobacteriaceae or Pseudomonas aeruginosa, but the MIC for 90% of Bacteroides fragilis isolates was 8 micrograms of DuP 721 per ml.
PMCID: PMC172224  PMID: 3377467
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.
PMCID: PMC172104  PMID: 3279906
The in vitro activity of CGP 31608, a new penem, against aerobic and anaerobic organisms was evaluated and compared with those of other beta-lactams. CGP 31608 inhibited Escherichia coli, Klebsiella pneumoniae, K. oxytoca, Proteus mirabilis, Citrobacter diversus, and Salmonella, Shigella, Aeromonas, and Yersinia spp. with MICs for 50% of the strains (MIC50s) of 2 to 4 micrograms/ml and MIC90s of 4 micrograms/ml, compared with cefotaxime, ceftazidime, aztreonam, and imipenem MICs of less than 0.25 microgram/ml. MIC90s were 8 micrograms/ml for Enterobacter species and C. freundii, for which other agents had MICs of 32 micrograms/ml, except imipenem, which had equal activity. The MIC90 for Proteus vulgaris, Morganella morganii, Providencia stuartii, and Providencia rettgeri was 8 micrograms/ml, compared with less than 2 micrograms/ml shown by the other agents. Acinetobacter species resistant to other agents except imipenem were inhibited by 4 micrograms/ml, as were Pseudomonas aeruginosa, including piperacillin-, ceftazidime-, and gentamicin-resistant isolates. The MIC for P. cepacia, P. fluorescens, and P. acidovorans was less than or equal to 8 micrograms/ml, but that for P. maltophilia was greater than or equal to 128 micrograms/ml. Hemolytic streptococci A, B, C, G, and F were inhibited by less than 1 micrograms/ml, but the MIC for Streptococcus faecalis was greater than or equal to 32 micrograms/ml. MICs for Staphylococcus aureus methicillin-susceptible and -resistant strains were less than or equal to 1 microgram/ml, as were those for methicillin-susceptible and -resistant S. epidermidis. Bacteroides fragilis and Clostridium species and Fusobacterium spp. were inhibited by less than or equal to 4 micrograms/ml. CGP 31608 was not hydrolyzed by plasmid beta-lactamases TEM-1, TEM-2, SHV-1, PSE-1, OXA-2, PSE-4, or by S. aureus. Chromosomal beta-lactamases of type Ia in Enterobacter cloacae P99 and Morganella morganii, Ic in P. vulgaris, K-1 in K. oxytoca, and Id in P. aeruginosa also did not hydrolyze CGP 31608. It inhibited TEM-1, but the 50% inhibitory concentration was 14.2 micrograms/ml compared with 0.15 micrograms/ml for the P99 enzyme. CGP 31608 induced beta-lactamases in P. aeruginosa, E. cloacae, C. freundii and Providencia rettgeri, but there was no increase in MICs for the isolates and it did not select strains derepressed for beta-lactamase production. Synergy of CGP 31608 and gentamicin was found against 90% P. aeruginosa, 60% Enterobacter cloacae, and 50% Serratia marcescens strains. No synergy was found with rifampin. A postantibiotic effect was found against E. coli.
PMCID: PMC174777  PMID: 3496845

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