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Biomedical subjects

L D Sabath

Publications and source records attributed to L D Sabath.

At least 37 records · Page 2Linked to original sources
PubMed1978

Staphylococcus aureus endocarditis. Combined therapy with vancomycin and rifampin.

Two children with persistent bacteremia and endocarditis due to Staphylococcus aureus failed to respond to vancomycin therapy, even though serum levels greatly exceeded the inhibitory concentrations. The Staphylococcus from one patient was resistant to methicillin; the other patient had a penicillin hypersensitivity. There was a wide disparity between the minimum inhibitory and the minimum bactericidal concentrations of vancomycin. Striking clinical and laboratory evidence of improvement was demonstrated with the addition of rifampin therapy.

Blood↗
PubMed1978

In vitro activity of cephalosporins against methicillin-resistant, coagulase-negative staphylococci.

The in vitro activity of five cephalosporins, gentamicin, and vancomycin was determined against 41 clinical isolates of methicillin-resistant, coagulase-negative staphylococci. Results obtained with disk diffusion and agar dilution methods failed to show complete cross-resistance between methicillin and four of the five cephalosporins despite the use of a high-salt medium and a large inoculum. Thirty-six (88%) of the 41 isolates were sensitive to cephalothin by a standardized disk diffusion method, whereas 23 isolates (56%) were sensitive to cephalothin with use of an agar dilution method and a large inoculum. Of these 23 isolates, only 11 (47%) were both inhibited and killed by less than or equal to 6.25 microgram of cephalothin/ml. The inhibitory and bactericidal activity of gentamicin was greater than that of vancomycin and cephalothin. These results suggest that the disk diffusion technique has limitations in determining the in vitro activity of cephalosporins against methicillin-resistant, coagulase-negative staphylococci and that cephalothin exhibits poor bactericidal activity against these same isolates.

Cephalosporins↗
PubMed1978

Use of a heavy inoculum in the in vitro evaluation of the anti-staphylococcal activity of 19 cephalosporins.

The in vitro activity of 19 cephalosporins against 105 clinical isolates of Staphylococcus aureus and S. epidermidis was determined by using a heavy inoculum, i.e., 10(8) to 10(9) organisms per ml, to maximally challenge the antibiotics. The anti-staphylococcal activities of cephaloridine and 87/312 were consistently decreased by the use of a heavy inoculum when compared with the activity obtained with two less-concentrated inocula. The activity of most of the other compounds was also decreased with the use of a heavy inoculum, but this was observed only with selected isolates. Cephapirin, cephalothin, and cefazaflur were the most active drugs against the methicillin-susceptible isolates. Cephaloridine, cefamandole, cefazaflur, and 87/312 had substantial activity against methicillin-resistant staphylococci even with heavy inocula. With the exception of cefaclor against S. aureus, the orally absorbed cephalosporins were generally one-half to one-sixteenth as active as the parenterally administered cephalosporins. The median minimal inhibitory concentrations of five of the 12 parenteral cephalosporins were lower with the methicillin-susceptible S. aureus than with the methicillin-susceptible S. epidermidis strains.

Bacteriological Techniques↗
PubMed1978

Cell wall composition and associated properties of methicillin-resistant Staphylococcus aureus strains.

Methicillin-resistant (MR) Staphylococcus aureus strains have previously been reported to be deficient in surface negative charge; this has been correlated with methicillin resistance and ascribed to a deficiency of teichoic acid at the cell surface (A. W. Hill and A. M. James, Microbios 6:157-167, 1972). Teichoic acid was present in walls of MR organisms as revealed by appreciable phosphate levels and detection of ribitol residues. Phosphate levels in walls from five MR strains (0.54 to 0.77 mumol/mg of wall) were lower than in three unrelated methicillin-sensitive (MS) strains (0.86 to 1.0 mumol/mg of wall). However, two MS strains derived from two of the MR strains had wall phosphate levels very similar to those of the MR strains. No evidence for unusual wall polymers was found. Simple deficiency of wall teichoic acid does not result in methicillin resistance since an independently isolated teichoic acid-deficient strain (0.1 mumol of phosphate per mg of wall) was not methicillin resistant. In studies of biological properties possibly related to wall teichoic acid, it was discovered that walls isolated from MR organisms grown in the presence of methicillin autolyzed more rapidly than those isolated from organisms grown in the absence of the drug. Since methicillin resistance is enhanced by NaCl and suppressed by ethylenediaminetetraacetate, the effects of these compounds on autolysis of isolated walls were studied. NaCl (1.0 M) and ethylenediaminetetraacetate (1.0 mM) inhibited the autolysis of walls isolated from MR and MS strains. An MR strain bound phage 47, 52A, and 3A only slightly less well than their respective propagating strains.

Amino Acids↗
PubMed1978

Tissue penetration of antibiotics; an overview.

The recent development of several techniques has made it possible to more adequately study the tissue penetration of various antibiotics. The major technical advances making this possible have been various assay systems permitting measurement of antibiotics in very small amounts of fluid or tissue. In addition, various tissue cages and the use of skin blisters has been a popular means for testing antibiotic penetration into extra-cellular fluid.

Anti-Bacterial Agents↗
PubMed1978

Bacterial persistence in vivo: resistance or tolerance to antibiotics.

The in vivo persistence of bacteria in spite of "adequate" therapy may be due to a variety of causes or factors. The most "obvious" cause is the presence of drug resistant strains, missed in conventional testing because of heterogeneity of resistance, special test requirements or emergence during treatment. A second large group of causes is due to atypical forms, whereas a third cause is due to tolerance. A fourth group of causes may be termed invironmental factors, and this includes drug inactivation, bioconversion or antagonism, often a result of the infection itself.

Animals↗
PubMed1978

Atrio-ventricular shuntinfections and endocarditis due to Staphylococcus epidermidis.

Two groups of patients (with endocarditis and with atrioventricular shunt infections due to Staphylococcus epidermidis) are presented together with analysis of the causative agents by bio- and phage-typing. Additionally phagocytic function of polymorphonuclear leukocytes of selected patients was investigated but no decreased phagocytic function was found. A possible way of treatment is discussed.

Cardiac Surgical Procedures↗
PubMed1977

A new type of penicillin resistance of Staphylococcus aureus.

Penicillin--"tolerant" Staphylococcus aureus strains are resistant to the lethal action of penicillins, but are inhibited by normal (low) concentrations. They are deficient in autolytic enzyme activity which appears to be necessary for bacteriolysis and the lethal action of penicillins. This "deficiency" is caused by a large excess of an inhibitor of autolysin. Seven such tolerant strains have been isolated from blood, bone, or sputum of patients who responded poorly to penicillin treatment of endocarditis, osteomyelitis, or staphylococcal pneumonia. These isolates were of different phage-types, and most showed cross-tolerance to the killing action of cephalosporins or vancomycin, antibiotics to which they were sensitive (inhibited). They were killed at normal rates by gentamicin, cycloserine, and rifampicin. Population analysis indicated that the proportion of tolerant organisms within a resistant strain is 7% or less; their ability to inhibit autolytic activity within their own and neighbouring cells appears to account for the net decreased autolytic activity of the entire strain; 44% of the bacteraemic strains studied showed penicillin tolerance. Tolerance is thus a common, clinically important form of penicillin resistance, that differs from previously described forms of pencillin resistance, that due to beta-lactamase, and that due to "intrinsic" (e.g., methicillin resistance) mechanisms.

Adult↗
PubMed1977

Abnormal neutrophil chemotaxis and T-lymphocyte function in staphylococcal scalded skin syndrome in an adult patient.

Staphylococcal scalded skin syndrome, a disease rarely reported in adults, developed in a 38-year-old male while on steroid therapy for chronic active hepatitis. Studies of immunologic parameters important in staphylococcal host defense revealed normal opsonic activity and phagocytic function but marked defects in neutrophil chemotaxis and T-lymphocyte function. Compromised host defense appears to play a significant role in the pathogenesis of the syndrome in adults.

Adult↗
PubMed1977

Comparative in vitro activity of piribenicillin, ticarcillin, and carbenicillin against Pseudomonas aeruginosa.

Pirbenicillin, a semisynthetic penicillin, showed greater in vitro activity against 68 recent isolates of Pseudomonas aeruginosa than did ticarcillin or carbenicillin. The median minimum inhibitory concentration of each of these three compounds, respectively, was 3.1, 12.5, and 25 mug/ml when a 10(-4) dilution of an overnight culture (about 10(5) colony-forming units [CFU]/ml) was used as inoculum, but these differences were less striking when larger inocula were used: at 10(7) CFU/ml these values were 6.25, 12.5, and 50 mug/ml, and at 10(8) to 10(9) CFU/ml these values were 50, 50, and 100 mug/ml. All three compounds showed greater inhibitory activity at pH 6 than at pH 8. This pH effect was greatest with pirbenicillin, for 6.25 mug of pirbenicillin per ml inhibited 7, 11, and 57% of the strains at pH 6, 7, and 8, respectively; these values were 4, 4, and 11% with ticarcillin and 0, 0, and 7% with carbenicillin. At sufficient inhibitory concentrations, the rates of bacterial killing of the three compounds were similar. The observed differences in anti-pseudomonad activity were not due to differences in stability to pseudomonad beta-lactamases, but all three compounds were more stable than were cefazolin, cephaloridine, and benzylpenicillin.

Carbenicillin↗
PubMed1977

Effect of protein A on staphylococcal opsonization.

To study the effect of wall protein A on bacterial opsonization, phagocytosis of 10 strains of Staphylococcus aureus with high and low protein A contents was measured. Those strains that contained the highest concentrations of protein A were phagocytized by human neutrophils at a slower rate than strains with little or no protein A when normal human serum and purified immunoglobulin G (IgG) were used as opsonic sources. When IgG-deficient serum was used as an source, however, protein A-rich strains were phagocytized more rapidly than protein A-deficient strains. Extracellular (purified) protein A decrease the opsonic activity of all sera tested including IgG-deficient serum. It is proposed that when IgG is not present in the opsonic medium, cell wall protein A is capable of activating complement at the bacterial surface and thereby opsonization is promoted.

Bacterial Proteins↗
PubMed1977

Opsonic requirements for staphylococcal phagocytosis. Heterogeneity among strains.

Efficient phagocytosis of staphylococci by human neutrophilis is dependent on bacterial opsonization by serum factors. These factors include specific antibodies as well as components of the classical and alternative complement systems. In this study the opsonic requirements of three strains of S. aureus and three strains of S. epidermidis were investigated by incubating [3H]thymidine-labelled bacteria in sera with different opsonic activities and measuring rates of phagocytosis by human neutrophils. Opsonization of S. aureus Cowan I and 502 A depended primarily on activation of the classical complement pathway. Effective opsonization occurred in the absence of immunoglobulin but not in the absence of complement. A protein A deficient mutant of S. aureus Cowan I was poorly opsonized in the absence of IgG, however. S. aureus Wood 46 and two strains of S. epidermidis were opsonized primarily through the alternative complement pathway and depended on the presence of serum IgG. A third S. epidermidis strain was efficiently opsonized in heat-inactivated serum without complement activity. Thus, a heterogeneity of opsonic requirements was found among staphylococcal strains. It is proposed that cell wall protein A may be an important determinant of this heterogeneity.

Complement C2↗
PubMed1976

Erythromycin and clindamycin absorption and elimination in pregnant women.

Thirty-nine pregnant women admitted for therapeutic abortions during early or mid pregnancy were given erythromycin estolate, erythromycin base, or clindamycin hydrochloride orally in single or multiple doses. Peak serum levels of clindamycin were 3.4 to 9.0 mug/ml following a single dose of 450 mg, whereas peak serum levels of erythromycin were 0.29 to 7.2 mug/ml following 500 mg in a single dose. The individual variability of serum concentrations of erythromycin was greater than that reported in normal men and nonpregnant women, whereas the serum levels of clindamycin were rather uniform, and similar to what has been reported in nonpregnant individuals. Following multiple doses of each antibiotic, high serum levels were obtained in virtually all subjects, and urine levels were also higher. Following single doses the mean urinary recovery was 2% for erythromycin and 16.8% for clindamycin.

Abortion, Therapeutic↗
PubMed1976

The assay of antimicrobial compounds.

The earliest antibiotic assays evolved from attempts to qualitatively demonstrate antimicrobial activity in biological fluids. The need for rapid, selective, accurate assays of antibiotics present in blood arises from the fact that many potentially toxic, commonly used antibiotics have narrow toxic: therapeutic ratios; no single dosage regimen can insure adequate therapeutic levels that are not toxic, because of individual variation in excretory patterns and in susceptibility of infecting bacteria. This need for rapid quantitative information about the serum antibiotic concentration can be met by agar diffusion assays, enzymatic assay, or radioimmunoassay. Other assay techniques less commonly used to meet this clinical need are both dilution assay, turbidimetric assay, potentiometric assay, and chemical assay. Details for one agar diffusion assay are presented, as well as principles and references for other techniques.

Anti-Bacterial Agents↗