Barbara M. LeBlanc

In vitro studies of 1-oxacephalosporin (LY 127935), a new beta-lactam antibiotic.

LY 127935 exhibited potent, broad-spectrum activity in vitro against 573 clinical isolates of bacteria. At concentrations below 6.25 iLg/ml, it inhibited the majority of isolates of all organisms except Pseudomonas aeruginosa, and was active even against organisms which usually exhibit resistance such as Serratia marcescens and Enterobacter spp. A rise in inoculum from 105 to 107 cells per ml significantly reduced the activity of this drug. LY 127935 was more active than cephalothin, cefamandole, or cefoxitin against the Enterobacteriaceae. Gram-negative bacillary infections are a major cause of morbidity and mortality among hospitalized patients. The search for new antibiotics and derivatives with broad-spectrum activity against major pathogens is of great importance, especially since the widespread use of currently available antibiotics at times has been associated with the emergence of resistant isolates. LY 127935, C20H18N6O9SNa2, is a new, semisynthetic beta-lactam antibiotic which is the first of a new class of f8-lactam antibiotics reported to have exceptional biological properties, including activity against multiply-resistant pathogens and aminoglycoside-resistant strains (2). Because of its broad-spectrum activity against most organisms causing infection in the compromised host, we determined the activity of LY 127935 against organisms isolated from cancer patients hospitalized at this institution and compared its activity with that of cefamandole, cefoxitin, cephalothin, tobramycin, carbenicillin, mezlocillin, and piperacillin. Susceptibility tests were performed simultaneously in duplicate on 425 clinical isolates of gram-negative bacilli and 148 clinical isolates of gram-positive cocci by a microbroth dilution method in minimum inhibitory concentration (MIC) plates (Cook Laboratory Products, Division of Dynatech Laboratories, Inc.). Organisms included 100 isolates of Escherichia coli, 75 isolates of Enterobacter spp., 100 isolates of Klebsiella pneumoniae, 28 isolates of Proteus mirabilis, 15 isolates of indole-positive Proteus spp., 117 isolates of P. aeruginosa, 32 isolates of S. marcescens, 45 isolates of Streptococcus pyogenes, 16 isolates of Streptococcus pneumoniae, 37 isolates of Staphylococcus aureus resistant to penicillin G, and 47 isolates of S. aureus susceptible to penicillin G. Materials and methods were the same as in previous studies (5) except that plates were prepared and inoculated by a Dynatech MIC-2000 System (Cooke Laboratory Products, Division Dynatech Laboratories, Inc.). Plates were frozen at -35°C and thawed before inoculation. Enterobacter cloacae ATCC 13047, E. coli ATCC 25922, K. pneumoniae ATCC 27736, Proteus vulgaris ATCC 6380, P. aeruginosa ATCC 27853, and S. aureus ATCC 25923 were included as control organisms. LY 127935, cefamandole, cephalothin, and tobramycin were supplied by Eli Lilly and Co., Indianapolis, Ind. Cefoxitin was supplied by Merck, Sharp and Dohme Research Laboratories, Rahway, N.J. Mezlocillin was supplied by Delbay Research Corp., Florham, N.J. Piperacillin was supplied by Lederle Laboratories, Pearl River, N.Y. Carbenicillin was supplied by Beecham Laboratories, Bristol, Tenn. The activity of LY 127935 against gram-negative bacilli and gram-positive cocci is summarized in Table 1. A concentration of 6.25 ug/ml inhibited the majority of isolates of all organisms except P. aeruginosa. A concentration of 25 jig/ ml inhibited only 47% of these isolates. The concentration of LY 127935 required for bactericidal activity against 100% of isolates was the same as the MIC for Enterobacter spp. and indole-positive Proteus spp. A twofold-higher concentration than the MIC was required for bactericidal activity against E. coli, and a fourfold-higher concentration than the MIC for K. pneumoniae and S. marcescens (Table 1). A substantial difference was observed between the MICs and minimum bactericidal concentrations (MBCs) for P. mirabilis and P. aeruginosa. LY 127935 was inhibitory against 100% of isolates of P. mirabilis at a concentration of 1.56 ILg/ml, but it was bactericidal against only 50% at this concentration. It was inhibitory against 67% of isolates of P. aeruginosa at a concentration of 50 ,ug/ml, but it was bactericidal against only 27% at this same concentration. The effect of inoculum size on the activity of LY 127935 against 10 isolates each of E. coli, K.

Comparative in vitro activity of the new difluoro-quinolone temafloxacin (A-62254) against bacterial isolates from cancer patients

The in vitro activity of temafloxacin, a new difluoro quinolone agent, against 725 bacterial isolates representing 32 species was evaluated in comparison with that of ciprofloxacin. Temafloxacin inhibited the majority ofEnterobacteriaceae isolates at a concentration of≤0.5 µg/ml. It was also extremely active againstAcinetobacter spp. andAeromonas hydrophila. Its activity was 2–8fold less than that of ciprofloxacin against most gram-negative isolates. Methicillin-susceptible and methicillin-resistantStaphylococcus aureus, coagulase-negativeStaphylococcus spp.,Streptococcus spp.,Listeria monocytogenes, Bacillus spp. and group JK corynebacteria were inhibited at concentrations equal to that of ciprofloxacin.

Thienamycin: New Beta-Lactam Antibiotic with Potent Broad-Spectrum Activity

Thienamycin, a new beta-lactam antibiotic, exhibited potent, broad-spectrum activity in vitro against gram-negative bacilli and gram-positive cocci, including many isolates resistant to currently available antibiotics. All isolates were inhibited at concentrations less than or equal to 25 μg/ml, with the exception of 12% of isolates of Enterobacter spp. and 3% of isolates of Serratia marcescens. Its activity decreased with an increase in inoculum concentration of from 105 to 107 cells per ml.

In Vitro Studies of Netilmicin, a New Aminoglycoside Antibiotic

Netilmicin, a semisynthetic derivative of sisomicin, was tested in vitro against 600 clinical bacterial isolates. At a concentration of 1.56 μg/ml, over 90% of gram-negative bacilli were inhibited. Netilmicin was substantially more active against isolates of Serratia marcescens and Enterobacter spp. than gentamicin, sisomicin, tobramycin, or amikacin. Isolates of Staphylococcus aureus (both penicillin G susceptible and resistant) were quite susceptible to netilmicin. Most isolates of Klebsiella spp. and Serratia spp. and some of the isolates of Pseudomonas aeruginosa that were resistant to gentamicin proved to be susceptible to netilmicin.

BL-S786 (Ceforanide), a New Parenteral Cephalosporin: In Vitro Studies

BL-S786 (ceforanide) is a new cephalosporin which showed broad-spectrum activity in vitro against 453 clinical isolates. At a concentration of 3.12 μg/ml, it inhibited greater than 75% of isolates of Escherichia coli, Klebsiella spp., Proteus mirabilis, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. Essentially no activity was observed against isolates of Serratia marcescens, and only minimal activity was observed against Enterobacter spp. Its activity was directly related to the size of the inoculum. The minimal bactericidal concentrations were similar to the minimal inhibitory concentrations for isolates of all organisms except S. aureus and S. pyogenes. The minimal bactericidal concentrations were considerably higher than the minimal inhibitory concentrations for these organisms.

A comparative in vitro study of thienamycin

SummaryThein vitro activity of thienamycin was compared to that of other antibiotics against a large panel of bacteria obtained in blood cultures from cancer patients. This compound was the most active against gram-positive cocci and also proved to be extremely active against the gram-negative bacteria. It was also very active against multi-resistant gram-negative bacilli. Because of its broad spectrum of activity includingPseudomonas spp., thienamycin deserves clinical testing in the future.ZusammenfassungDieIn-vitro-Aktivität von Thienamycin gegenüber einem breiten Spektrum von aus Blutkulturen von Karzinomkranken isolierten Bakterien wurde mit derjenigen anderer Antibiotika verglichen. Die Substanz war am wirksamsten gegenüber grampositiven Kokken und erwies sich auch als äußerst wirksam gegenüber gramnegativen Bakterien. Ebenso wies sie hohe Aktivität gegenüber mehrfachresistenten gramnegativen Bazillen auf. Wegen seines hohen Wirkspektrums, das auchPseudomonas spp. einschließt, verdient Thienamycin, in Zukunft klinisch geprüft zu werden.

Comparative in vitro activity of the two new 4-quinolones S-25930 and S-25932 against gram-positive bacteria isolated from cancer patients

The in vitro activity of S-25930 and S-25932, two new quinolone antimicrobial agents, against 306 gram-positive organisms representing 12 bacterial species, was evaluated and compared with the activity of ciprofloxacin, difloxacin, enoxacin, amifloxacin and A-56620. Both agents were active against staphylococcal species (including methicillin-resistant and coagulase-negative isolates),Bacillus spp. and group JK diphtheroids. They were less active against streptococcal species andListeria monocytogenes. Their activity against most isolates was superior to that of amifloxacin, enoxacin and difloxacin and similar to that of ciprofloxacin and A-56620.