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Biomedical subjects

L D Sabath

Publications and source records attributed to L D Sabath.

At least 19 recordsLinked to original sources

Therapeutic and epidemiologic recommendations to reduce the spread of type-I beta-lactamase resistance.

The objectives of this United States Consensus Panel meeting were to evaluate the effectiveness of current surveillance systems for the detection of bacterial resistance as well as to formulate recommendations that can assist hospitals in determining actions that should be taken when a resistance problem is detected. These recommendations may be particularly helpful in controlling the emergence and spread of type-I beta-lactamase resistance. Numerous case reports of antimicrobial resistance among Enterobacter species, Pseudomonas aeruginosa, and other Gram-negative nosocomial pathogens known to produce type-I beta-lactamases have appeared in the literature since the introduction of the newer "third-generation" cephalosporins. The widespread use of these newer antimicrobial agents, often selected as standard therapy for serious hospital-acquired infections, has been associated with a corresponding increase in resistance to them. The failure of hospitalwide surveillance methods to describe the scope of this problem, especially among the most critically ill patients, may have resulted in a false sense of security among some infectious disease specialists and clinicians prescribing these antimicrobials as empiric therapy. High-level resistance in individual hospital units may be masked in hospitalwide antibiograms. A variety of conclusions and recommendations were formulated based on the collective experiences of the Consensus Panel members. Microbiology laboratories must make it a high priority to identify markers that will assist in rapidly identifying resistant organisms. Cooperative efforts are needed among users of commercial and automated microbiology test instruments to standardize results and to improve quality control, thereby making the data more directly comparable between laboratories.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents

Endocarditis caused by coagulase-negative staphylococci.

Sixteen patients with coagulase-negative staphylococcal endocarditis were treated at the University of Minnesota Hospitals between January 1970 and September 1977. In six patients, endocarditis developed after prosthetic valve surgery; among the other ten patients (the medical group), eight had known antecedent valvular disease. The skin was thought to be the source of infection in eight patients, suggesting that prompt treatment of skin infections and avoidance of injections in patients with valvular disease are important measures in the prevention of this disease. Patients with prosthetic valve endocarditis were infected with antibiotic-resistant organisms and had a higher mortality than those in the medical group (83% versus 20%). Bacterial isolates from three patients with prosthetic valve endocarditis were resistant to methicillin, and two of these three isolates also were resistant to cephalothin by quantitative susceptibility testing. The only patient with prosthetic valve endocarditis to survive was operated upon early in the course of his illness. These observation, coupled with the high mortality in this series and in others, has prompted us to advocate early surgery in prosthetic valve endocarditis.

Adolescent

Antibiotic sensitivity and synergism of 'penicillin-tolerant' Staphylococcus aureus.

15 Staphylococcus aureus strains were isolated from 15 patients with staphylococcal bacteremia. Eight of these strains were shown to be tolerant for cloxacillin. Cloxacillin-tolerant strains were also tolerant for most of the cephalosporins tested except for cephapirin. Strains were not tolerant for clindamycin and gentamicin. Penicillin-tolerant staphylococci showed a high degree of synergism between gentamicin and cloxacillin or cephalothin and gentamicin.

Anti-Bacterial Agents

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

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

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

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

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

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

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

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

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