Clare Wilcox

Effect of Inoculum and of Beta-Lactamase on the Anti-Staphylococcal Activity of Thirteen Penicillins and Cephalosporins

Because there are few persuasive data for selecting one semisynthetic penicillin or cephalosporin over another for treatment of serious staphylococcal infections, 118 recent clinical isolates of Staphylococcus aureus were studied to determine to what extent the presence of β-lactamase affected the relative anti-staphylococcal activity of six penicillins and seven cephalosporins. In addition, the effect of inoculum was studied for its possible effect on the anti-staphylococcal activity of the 13 β-lactam antibiotics. By all criteria, methicillin and nafcillin were clearly more resistant to both the inoculum effect and the production of staphylococcal β-lactamase, whereas benzylpenicillin and cephaloridine (especially benzyl-penicillin) were the most susceptible to these effects. Cephazolin was clearly more susceptible to staphylococcal β-lactamase and heavy inocula than the other cephalosporins (with the exception of cephaloridine), whereas cephalothin was the most resistant cephalosporin to these factors. The minimal inhibitory concentration for benzylpenicillin for tests with undiluted inoculum, compared to results with inoculum diluted 10−4, differed by a factor up to 16,384, whereas with methicillin and nafcillin the differences were rarely more than twofold. Ratios for the other 10 antibiotics fell between these extremes. These results suggest that methicillin or nafcillin is most stable to staphylococcal β-lactamase, and that benzylpenicillin and cephaloridine are the most susceptible.

Comparative studies of antibacterial activity in vitro and absorption and excretion of lincomycin and clinimycin.

The antibacterial spectrum of clinimycin (7-chloro-7-deoxy-lincomycin) and that of lincomycin were found to be identical. Both were highly active against recent isolates of Staphylococcus aurcus, pneumococci and streptococci other than enterococci, but clinimycin was 8 to 16 times more active than lincomycin against S. aurcus and pneumococci. Neither drug was highly active against Ncisseria meningitidis, N. gonorrhocac, or Hemophilus influenzac and both were essentially inactive against the commonly encountered pathogenic gram-negative rods. Strains of Staph. aurcus resistant to erythromycin were as sensitive to both lincomycin antibiotics as were erythromycin-resistant strains. Both appear to be bactericidal against most strains of S. aurcus. Peak levels of clinimycin in serum were at least twice as high as those of lincomycin. Absorption of clinimycin was slightly delayed but not decreased by ingestion with food, which markedly decreased the absorption of lincomycin; the levels of the former remained higher for eight hours at which time all subjects still had significant serum levels of clinimycin. Bioactivity appeared in the urine in higher concentrations and more rapidly following clinimycin than after lincomycin. About one-eighth of the doses of clinimycin given either fasting or immediately after a meal were recovered as active drug in the urine in 24 hours, as compared with 9.3 and 2.6% of the fasting and postprandial doses, respectively, of lincomycin. Side effects were limited to mild gastrointestinal symptoms which were similar with both drugs.

Susceptibility of Staphylococcus aureus and Staphylococcus epidermidis to 65 Antibiotics

The susceptibilities of 36 recent isolates of Staphylococcus aureus and 35 recent isolates of Staphylococcus epidermidis were determined against each of 65 antimicrobial agents and against two of them in combination. Rifampin was the most active of all the agents tested against both S. aureus and S. epidermidis. Among the penicillins, cloxacillin, dicloxacillin, and nafcillin were most active, although benzylpenicillin and phenoxymethyl penicillin were more active against susceptible strains. Cephaloridine was the most active of the cephalosporins, and sisomicin was the most active aminoglycoside. Minocycline was more active than the other tetracycline analogues tested. Among the macrolide-lincomycin compounds in clinical use, clindamycin was more active, and lincomycin was less active than erythromycin. The synergy of trimethoprim-sulfamethoxazole was more striking against S. aureus than against S. epidermidis. The median minimal inhibitory concentrations of the penicillins, cephalosporins, and aminoglycosides were lower against S. aureus, whereas the minimal inhibitory concentrations of the tetracyclines were lower against S. epidermidis.

Absorption and Excretion of Four Penicillins: Penicillin G, Penicillin V, Phenethicillin and Phenylmercaptomethyl Penicillin.

THE first of the semisynthetic penicillins to be prepared and exploited for clinical use after the isolation of pure 6-aminopenicillanic acid from penicillin fermentations1 is the potassium salt of...

Antibiotic susceptibility of gram-negative bacilli isolated from blood cultures: Results of tests with 35 agents and strains from 169 patients at Boston City Hospital during 1972

Abstract Gram-negative bacilli of several of the more common species grown from the blood of 169 patients hospitalized at Boston City Hospital during 1972 were tested with 32 antibiotics and with trimethoprim and sulfamethoxazole, alone and in combination. More than half of the agents are currently under clinical trial for efficacy and safety. Chemically related antibiotics were shown to differ in varying degrees in their activity against the different species, and even against different strains of the same species. The size of the inoculum affected the activity of the agents differently, depending on the antibiotic, the species and even the strain. Polymyxin B was generally the most active antibiotic against most species, but it was essentially inactive against Proteus mirabilis and Serratia marcescens. Trimethoprim alone, and particularly when combined with sulfamethoxazole, was even more active against most species, but it was essentially inactive against Pseudomonas aeruginosa.

Susceptibility of Beta-Hemolytic Streptococci to 65 Antibacterial Agents

Tests for susceptibility of 29 group A, 4 group C, and 2 group G strains of beta-hemolytic streptococci to 63 antibiotics and to trimethoprim and sulfamethoxazole, singly and combined in a ratio of 1:16, were carried out in vitro. All strains tested were moderately or highly susceptible to all the antibiotics used except those belonging to the aminoglycoside and polymyxin groups. A few were also resistant to the tetracyclines and to sulfamethoxazole alone. Comparisons with results obtained in previous years indicate that, except for the tetracyclines and sulfonamides, there has been no change in the susceptibility of beta-hemolytic streptococci to the most important and useful antibiotics, particularly penicillin.

Susceptibility of Pneumococci and Haemophilus influenzae to Antibacterial Agents

Strains of Diplococcus pneumoniae and Haemophilus influenzae were tested for susceptibility to numerous antibiotics by a twofold agar dilution method using an inocula replicator. Undiluted, fully grown broth cultures were used as inocula for both species, and cultures of pneumococci diluted 1:1,000 were also tested. The antibiotics included most of those in common use in the United States as well as some chemical modifications recently approved and others that are under investigation. The most striking aspect of the results was the marked susceptibility of the pneumococci to all the antibiotics tested except the polymyxins and most of the aminoglycoside antibiotics, although some new aminoglycosides were active in quite low concentrations. Some of the strains of pneumococci were of decreased susceptibility to penicillin G (minimal inhibitory concentrations, 0.2 to 0.4 μg/ml), but none were tetracycline resistant, although such strains had been reported previously from this laboratory. The strains of H. influenzae, which were all serologically nontypable, exhibited different patterns of susceptibility to the groups of antibiotics and to the individual chemically related ones. None of these strains (isolated early in 1972) were ampicillin resistant. The most active agents against H. influenzae were: carbenicillin and ampicillin, analogues related to each of them, rifampin, chloramphenicol, and the polymyxins. However, the tetracycline analogues other than tetracycline, some aminoglycosides, notably tobramycin, kanamycin, gentamicin, and verdamicin, erythromycin, and some new lincomycin analogues were also active in low concentrations. Trimethoprim alone was highly active, and in combination with sulfamethoxazole it was even more active and synergistic against strains of both D. pneumoniae and H. influenzae.

Treatment of Pneumococcal Pneumonia with Penicillin

ALTHOUGH the sulfonamide drugs are highly effective in the treatment of the pneumococcal pneumonias, serious problems sometimes arise in their administration. In patients with underlying cardiac or...

Synergy of Mecillinam (FL1060) with Penicillins and Cephalosporins Against Proteus and Klebsiella, with Observations on Combinations with Other Antibiotics and Against Other Bacterial Species

Thirty-five strains each of Klebsiella and Proteus were tested for susceptibility to mecillinam alone and in combination with ampicillin, carbenicillin, cephalothin, and cefazolin. Antibiotics were considered to be synergistic when there was a ≥fourfold reduction in minimum inhibiting concentration of both antibiotics in the combination as compared with that of each antibiotic alone. Synergy of mecillinam with ampicillin, carbenicillin, cephalothin, and cefazolin was demonstrated against 2, 3, 7, and 8 of the 35 strains of Klebsiella and against 14, 14, 19, and 24 of the 35 strains of Proteus, respectively. Synergy against the isolates of Proteus was related to species, whereas against Klebsiella it was related to susceptibility of the isolates to mecillinam. Tests of combinations of mecillinam with other antibiotics on the same and different species indicated that synergy was related to the antibiotic, the species, and the strains of organisms tested.

Cross Resistance to Antibiotics Effect of Exposures of Bacteria to Carbomycin or Erythromycin in Vitro

Summary and Conclusions The antibacterial spectrum of carbomycin parallels very closely that of erythromycin. Both of these new antibiotics are highly active against gram-positive and gram-negative cocci, moderately active against strains of Haemophilus and are essentially inactive against coliform and enteric bacilli. Against susceptible bacterial strains erythromycin is usually from 4 to 16 times more active than carbomycin, weight for weight. Repeated subcultures of staphylococci and of certain strains of streptococci in the presence of increasing concentrations of either one of these antibiotics result in fairly rapid and marked increases in resistance not only to the antibiotic to which it was exposed but to the other agent as well.