Carol Garner

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.

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.

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.

Disk Diffusion and Serial Dilution Tests of Susceptibility of Some Pathogenic Gram-Negative Bacilli and Enterococci to Carbenicillin and Ampicillin

Tests for susceptibility to ampicillin and carbenicillin were performed with 35 strains each of Klebsiella, Enterobacter, Serratia, and Proteus, 71 strains of Pseudomonas aeruginosa, and 68 strains of enterococci by serial dilution and disk-diffusion tests employing 10−3 dilutions of overnight cultures as inocula for both. Commercial 10-μg ampicillin and 50- and 100-μg carbenicillin disks, and freshly prepared 10-, 50-, and 75-μg ampicillin and 10- and 50-μg carbenicillin disks were used. Results were displayed as cumulative distribution curves for both minimal inhibitory concentrations and zone diameters, and as scattergrams for correlating them. Differences in susceptibility to the two antibiotics were small for Klebsiella, Enterobacter, and Serratia and large for the others. The freshly prepared and commercial disks of the same content gave comparable zones. There was good correlation of zone diameter with each disk and the minimal inhibitory concentration. Among the ampicillin disks tested, none was useful for Pseudomonas; with the other species, the 10-μg disk, as well as those with higher ampicillin content, could discriminate susceptible from resistant strains. However, only the 75-μg disk selected some Klebsiella strains susceptible to high concentrations. The 50- and 100-μg carbenicillin disks were equally discriminating for most strains, but the higher concentration was more selective for Klebsiella. The 10-μg carbenicillin disk was as effective as the 50- and 100-μg disks for discriminating among Enterobacter, Serratia, Pseudomonas, and Proteus, but not for Klebsiella or enterococci. The 10−3 inoculum gave zone sizes considerably larger than those reported by other workers who used the standard Kirby-Bauer method.

Synergistic Action of Ampicillin and Erythromycin Against Nocardia asteroides: Effect of Time of Incubation

Ampicillin and erythromycin were shown to act synergistically in vitro against the majority of strains of Nocardia asteroides tested. With these strains, the minimal inhibiting concentration (MIC) of each drug when combined was reduced 4- to more than 512-fold as compared with the MIC of each antibiotic acting individually against the same strains. The combined action against other strains was at least additive, and occasionally indifferent, but antagonism was not observed. The duration of incubation greatly influenced the MIC of erythromycin but had less effect on the action of ampicillin. Synergistic action was still demonstrable, although less frequently, when the period of incubation was increased from 48 to 72 h.