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Biomedical subjects

L D Sabath

Publications and source records attributed to L D Sabath.

At least 55 records · Page 3Linked to original sources

Susceptibility of "enterobacteria" to aminoglycoside antibiotics: comparisons with tetracyclines, polymyxins, chloramphenicol, and spectinomycin.

Strains of enterobacteria, including common, aerobic, pathogenic gram-negative bacilli, and enterococci were tested for susceptibility to 11 aminoglycoside antibiotics by a twofold agar-dilution method with an inocula replicator. For comparison, similar tests were done with seven tetracycline analogues, two polymyxins, chloramphenicol, and spectinomycin. Tobramycin compared favorably with the more active aminoglycosides, with some exceptions related to individual strains of species. The tetracyclines and chloramphenicol were generally less active than the more active aminoglycosides. The polymyxins were as active or more active against most species of gram-negative rods but were essentially inactive against Proteus, Providencia, and many strains of Enterobacter.

Acinetobacter↗

Susceptibility of "enterobacteria" to penicillins, cephalosporins, lincomycins, erythromycin, and rifampin.

Agar dilution tests for susceptibility of gram-negative rods and enterococci were done with a number of penicillins, cephalosporins, lincomycin analogues, erythromycin, and rifampin. Many in the first three categories were investigational drugs. All were generally less active than aminoglycoside and tetracycline antibiotics against gram-negative rods and more active against enterococci. Cephalosporins as a group were more active than penicillins against Klebsiella pneumoniae and Escherichia coli and less active enterococci. Both groups were equally active against Enterobacter, Proteus, and Providencia but inactive against most strains of Serratia and all strains of Pseudomonas; however, ticarcillin, carbenicillin, and BL-1654 were active against most strains of Pseudomonas. Penicillins and cephalosporins were more active against Proteus mirabilis than against indole-positive Proteus. Lincomycins had little or no activity against gram-negative rods but were moderately active against enterococci. Erythromycin was more active than the lincomycins, but rifampin was much more active than either of these types of drug. Of the penicillins, ticarcillin, carbenicillin, and BL-P1654 were the most active against gram-negative rods, whereas BL-P1654, amoxicillin, and ampicillin were the most active against enterococci. The penicillinase-resistant penicillins, cyclacillin, and penicillin V were essentially inactive against gram-negative rods. Of the cephalosporins tested, cephanone and cefamandole were the most active against most gram-negative rods, whereas cephaloridine and cephacetrile were the most active against enterococci. The least active of the cephalosporins against most species were cephradine, cephalexin, and cephapirin, but cefoxitin was the least active against enterococci.

Acinetobacter↗

Susceptibility of recently isolated bacteria to amikacin in vitro: comparisons with four other aminoglycoside antibiotics.

In vitro tests for susceptibility to amikacin and to four other aminoglycoside antibiotics were carried out with strains of many bacterial species by use of an agar dilution method and an inocula replicator. In general, amikacin was as active as or more active against most of the organims than kanamycin, neomycin, and streptomycin; in particular, amikacin was active against strains resistant to one or more of these three antibiotics. Amikacin was more active than gentamicin against strains of Nocardia asteroides and Providencia stuartii and also against gentamicin-resistant strains of some other gram-negative bacilli, notably Serratia marcescens. However, gentamicin was more active than amikacin against most of the other gram-positive and gram-negative bacteria that were tested. In comparative tests of four media, minimal inhibitory concentrations MICs) were greater in tests with Mueller-Hinton agar, and generally somewhat lower in those with heart infusion agar, than in tests with trypticase soy agar and nutrient agar. Inocula of a 1:1,000 dilution of culture generally gave MICs lower than those obtained with undiluted cultures; the differences were small with enterococci, but they were greater with amikacin than with gentamicin in tests on strains of Klebsiella pneumoniae. These findings generally confirm those previously reported by others.

Amikacin↗

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.

Aminoglycosides↗

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 mug/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.

Aminoglycosides↗

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.

Anti-Bacterial Agents↗

Extracellular and bacterial factors influencing staphylococcal phagocytosis and killing by human polymorphonuclear leukocytes.

Extracellular and bacterial factors that influence the phagocytosis and killing of staphylococci by human polymorphonuclear leukocytes have been studied. Staphylococcus epidermidis strains were, in general, more rapidly phagocytized than were S. aureus strains. However, two strains of S. epidermidis had a very slow rate of ingestion. Although the rate of phagocytosis of S. aureus Wood 46 was greater than that of S. aureus 502A, the Wood 46 strain was more difficult to kill. Serum was essential for phagocytosis of both S. aureus and S. epidermidis. The opsonic titer of pooled serum was similar for S. aureus and S. epidermidis. In normal pooled serum, heat-labile factors were more important for effective phagocytosis than they were in immune serum. Although a saturation point for ingestion was reached, the percentage of ingested bacteria that remained alive within the leukocyte remained relatively fixed. Heat-killed and live staphylococci were igested in a similar fashion. The rate of phagocytosis was greatly reduced at 41 degrees C.

Blood Bactericidal Activity↗

Current status of treatment of pneumonia.

Proper treatment of pneumonia is dependent upon a correct diagnosis. Pneumonia may be due to infectious agents, allergic phenomena, or chemical causes. Treatment regimens are outlined for the various types of pneumonia--pneumococcal, staphylococcal, fungal, and pneumonia due to gram-negative and anaerobic gram-negative bacilli, to Blastomyces dermatitidis, and to the parasite Pneumocystis carinii. In discussing current concepts of treatment, several well-known methods are emphasized, as well as newer developments, knowledge of which is essential for optimal treatment of pneumonia.

Ampicillin↗

Parenteral clindamycin phosphate: pharmacology with normal and abnormal liver function and effect on nasal staphylococci.

Parenteral clindamycin was evaluated in 41 patients with a variety of infections. The four major findings were as follows. (i) Five hours after the intravenous administration of 600 mg of clindamycin, the mean serum concentration in patients with "moderate to severe" hepatic dysfunction was 24.3 mug/ml, and in those with normal liver function it was 8.3 mug/ml (P < 0.02). This suggests that the dose of clindamycin might be modified in patients with liver disease. (ii) There was a positive association between the 5-h serum clindamycin level and the degree of elevation of the serum glutamic oxaloacetic transaminase. (iii) No significant side effects were observed. Of 24 patients with preexisting hepatic dysfunction, 5 showed deterioration and 5 showed improvement of liver function during therapy. (iv) Whereas all pre-treatment isolates of Staphylococcus epidermidis from the anterior nares were susceptible to clindamycin, 6 of 9 post-treatment isolates were resistant, most probably due to selection of resistant organisms.

Adolescent↗

Laboratory evaluation of a rapid, automatic susceptibility testing system: report of a collaborative study.

Seven laboratories participated in a collaborative study to evaluate the Autobac 1 system. Results obtained with this assay system were compared to those obtained by the standardized Bauer-Kirby disk diffusion test, and each of these two methods was compared to the agar dilution technique. Comparison of the Autobac 1 and the disk diffusion results from the seven laboratories showed an overall average of 91.5% interpretive agreement with the 17 antimicrobial agents tested. The distribution in the levels of Autobac 1/disk diffusion agreement was such that with 13 antimicrobial drugs agreement was 90% or higher; with three, between 85 and 90%; and with one, 77% (nitrofurantoin). Comparison of the Autobac 1 and disk diffusion tests with the International Collaborative Study agar dilution test showed that both methods gave levels of agreement with the International Collaborative Study agar dilution technique that were generally high and equivalent. The average overall agreement between the agar dilution test and each of the other two methods was approximately 90%. Disagreements that did occur tended to involve organisms that were drug susceptible by the Autobac 1 system but intermediate or resistant by the other two methods. This was in part due to the narrow intermediate interpretive zone of the Autobac 1 test. In reproducibility studies with the Autobac 1 and disk diffusion methods, no significant differences were observed between the interpretive reproducibility of the two methods.

Anti-Bacterial Agents↗

Rapid semiquantitative testing of antibiotic susceptibility: use of a multicell disk elution system.

Semiquantitative data regarding antibiotic susceptibility of bacteria were obtained by measuring the growth of bacteria in several different compartments ("cells") of a plastic module. Each compartment contained an inoculum of the organism and various concentrations of antibiotics in broth, achieved by elution of antibiotic from paper disks placed into the individual cells. Growth of the organisms was measured using an automated monitor to detect the scattering of light. Susceptibility of 300 strains of gram-negative bacilli to multiple concentrations of nine antibiotics was determined by this disk elution system, and the results (expressed in terms of four clinical susceptibility groupings) were compared with those obtained by a quantitative agar dilution method. Results obtained by the two methods agreed completely in 78% of the 2,700 determinations. In evaluating whether individual strains would be susceptible to systemic therapy or not, results obtained by the two systems agreed in all except 149 of the tests. Results of testing by the disk elution method were available on the same day that testing was begun. A system of this type may prove useful, for it provides information of a semiquantitative nature and decreases the time between isolation of a bacterial pathogen and availability of susceptibility data to the clinician.

Anti-Bacterial Agents↗

Sequence effect on ampicillin blood levels noted in an amoxicillin, ampicillin, and epicillin triple crossover study.

Amoxicillin, ampicillin, and epicillin (500 mg of each) were given orally to fasting men and women in a triple crossover study. Peak serum concentrations were significantly higher for amoxicillin than for ampicillin and significantly lowest for epicillin. The concentrations of antibiotics in serum were comparable in men and women. Total urine recovery was highest for amoxicillin (56.7%) and lowest for epicillin (27.5%), and higher in men than in women for each of the three antibiotics. Saliva, sweat, and tears contained only very small amounts of amoxicillin and, rarely, ampicillin or epicillin. A significant (P < 0.02) sequence effect was noted in that peak serum concentrations of ampicillin were higher (6.4 mug/ml) if epicillin had been taken the previous week than when ampicillin was taken first (2.7 mug/ml).

Adult↗

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 beta-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 beta-lactam antibiotics. By all criteria, methicillin and nafcillin were clearly more resistant to both the inoculum effect and the production of staphylococcal beta-lactamase, whereas benzylpenicillin and cephaloridine (especially benzyl-penicillin) were the most susceptible to these effects. Cephazolin was clearly more susceptible to staphylococcal beta-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 beta-lactamase, and that benzylpenicillin and cephaloridine are the most susceptible.

Amidohydrolases↗

Antagonism of the antibacterial action of some penicillins by other penicillins and cephalosporins.

There are many examples of two penicillins acting synergistically, usually by one competitively inhibiting beta-lactamase, thus protecting the other from inactivation. There are few reports on penicillins antagonizing each other. Eight strains of three genera (Proteus, Escherichia, Pseudomonas) isolated at Boston City Hospital or Institut Pasteur, Paris, showed antagonism of carbenicillin or ampicillin by cephaloridine, cloxacillin, or 6-aminopenicillanic acid. Broth dilution tests showed that with seven of the eight strains the minimum inhibiting concentration (MIC) of the more active antibiotic was increased by 800-6,400% by low concentrations (often one-tenth the MIC) of the antagonist, whereas higher concentrations of "antagonist" were not as antagonistic, This suggested that two or more receptor sites of action for penicillins were present; the antagonist thus blocks the antibacterial action at the more sensitive site but acts additively with the antagonized antibiotic at the less sensitive site. The possibility that the mechanism of antagonism was induction of inactivating enzymes (beta-lactamase, penicillin acylase) was studied in two strains(one Escherichia coli and one Proteus rettgeri), and two antagonists were studied in detail. With E. coli cephaloridine was a poorer inducer of beta-lactamase than were the antagonized antibiotic and 6-aminopenicillanic acid. From these organisms, the good inducers of a beta-lactamase that acted on benzylpenicillin did not induce enzymes that inactivated carbenicillin. Thus, the mechanism of antagonism was not due to beta-lactamase induction.

Ampicillin↗

Decrease in ribosomal density of Proteus mirabilis exposed to subinhibitory concentrations of ampicillin or cephalothin.

The finding of reduced ribosomal densities at lower concentrations than those required to stop growth or cause visible defects in the cell wall is in contrast to the current view that the initial lesion produced by penicillins or cephalosporins is a defect in murein synthesis (11). This reduction in ribosomal density could be a primary or secondary effect and might be due to a decreased rate of growth, which has been shown to be associated with a lower ribosome frequency (12, 13) or to less stable ribosomes which disintegrated either spontaneously or as a result of the fixation procedures. The possibility that the decrease in ribosomal frequency was due to dilution (influx of liquid through a defective cell wall and/or cytoplasmic membrane, or efflux of ribosomes) remains, but no gross defect in cell wall was seen in more than 50 sections of cells showing reductions in ribosomal frequency. These findings suggest that an effect on ribosomes may antecede an effect on the cell wall.

Ampicillin↗