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Biomedical subjects

S M Finegold

Publications and source records attributed to S M Finegold.

At least 19 recordsLinked to original sources

Erythromycin for anaerobic pleuropulmonary and soft-tissue infections.

Erythromycin has been reported to be active in vitro against most anaerobic bacteria. We found it effective in treating 14 of 17 patients with mild to moderately severe anaerobic or mixed aerobic/anaerobic pleuropulmonary of soft-tissue infections when adjunctive measures (eg, drainage, débridement, and the use of additional antibiotics to treat important aerobic pathogens) were employed. Erythromycin offers a reasonable therapeutic alternative to penicillin in the treatment of a penicillin-allergic patient who has a mild or moderately severe anaerobic or mixed aerobic/anaerobic infection not involving Bacteroides fragilis or fusobacteria.

Aerobiosis

Transformation of 4-androsten-3,17-dione by growing cultures and cell extracts of Clostridium paraputrificum.

Growing cultures of Clostridium paraputrificum transformed 4-androsten-3,17-dione to 3 alpha-hydroxy-5 beta-androstan-17-one in a sequential manner with 5 beta-androstan-3,17-dione as an intermediate. The addition of 1.5 mM menadione to log-phase cultures which had formed 5 beta-androstan-3,17-dione resulted in a partial reoxidation of this steroid to 4-androsten-3,17-dione. However, this treatment also resulted in transient inhibition of culture growth. Resumption of growth was accompanied by complete reduction of 4-androsten-3,17-dione to 5 beta-androstan-3,17-dione. Cell extracts of C. paraputrificum were capable of carrying out these reductive transformations in the absence of added cofactors. However, Sephadex G-25 treated extracts required NADH or NADPH for these reactions. A flavin nucleotide, either FAD (plus NADH or NADPH) or FMN (plus NADH) was highly stimulatory for 4-androsten-3,17-dione reduction to 5 beta-androstan-3,17-dione. NADH was the preferred reduced pyridine nucleotide for reduction of the C4-C5 double bond, while time-course measurements suggested that NADPH was the preferred donor for reduction of the 3-keto group.

Androstanes

Bacteriology of chronic otitis media.

Tympanocentesis was performed in 50 patients with chronic otitis media; pus was cultured aerobically and anaerobically. Only aerobes were isolated from 21 patients (42%), three patients had only anaerobes (Peptococcus sp), and 25 patients (50%) had both aerobes and anaerobes. Only one specimen had no growth. There were 68 aerobic isolates. Pseudomonas aeruginosa was recovered in 36 patients (72%); other aerobes commonly recovered included Proteus sp and Staphylococcus aureus. There were 48 anaerobes isolated. Anaerobic Gram-positive cocci were isolated in 24 instances (21 Peptococcus sp and three Peptostreptococcus sp). Sixteen Bacteroides sp were recovered, including seven B fragilis group and six B melaninogenicus.

Adult

Bacteriology and therapy of lung abscess in children.

The bacteriology and clinical findings of ten pediatric patients with lung abscess are presented. Bacteriologic data were based on percutaneous transtracheal aspiration obtained before initiation of antimicrobial therapy. Anaerobic bacteria were present in all ten patients; in nine they were mixed with aerobic bacteria. The most frequent isolates were Peptostreptococcus (8), Peptococcus (5), Bacteroides melaninogenicus (6), and Bacteroides fragilis (3). The aerobic isolates most frequently recovered were alpha-hemolytic streptococci (5), group A beta-hemolytic streptococci (4), and Escherichia coli and Klebsiella pneumoniae (4 each). Virtually all abscesses were located in dependent pulmonary segments. Antimicrobial therapy was guided by the bacteriologic findings and was successful in all instances.

Adolescent

Diarrhea and colitis associated with antimicrobial therapy in man and animals.

Antimicrobial agent-induced ileocecitis of laboratory animals and colitis of man share common features. The significance of a newly described toxin in these two entities, the apparent source of the toxin (Clostridium difficile) and characteristics of the toxin are reviewed. Methods of toxin detection, isolation and rapid identification of C. difficile, and possible modes of therapy for antimicrobial agent-associated colitis of man are discussed.

Animals

Susceptibility of isolates of Bacteroides to the bactericidal activity of normal human serum.

Seventy-one strains of species from the Bacteroides fragilis group, including 46 isolates of B. fragilis, were tested for susceptibility to the bactericidal effect of serum from healthy subjects. Twenty-seven (38%) of the isolates were killed by serum. Isolates from feces were significantly more sensitive to serum than were isolates from patients with clinical infections. Killing of bacteria required heat-labile serum components and was an exponential function of serum concentration. Among the various species tested, B. fragilis was clearly the most resistant to bactericidal activity of serum. These observations may be important to the understanding of infections caused by the B. fragilis group, which contains the anaerobes of greatest clinical importance.

Bacteroides fragilis

Bacteriology of rattlesnake venom and implications for therapy.

Although the incidence of infection secondary to the bites of venomous snakes remains unknown, the routine use of prophylactic antimicrobial therapy is advocated. In this study, the venom from 15 rattlesnakes was cultured, and 58 aerobic and 28 anaerobic strains of bacteria were isolated. The most common species isolated were Pseudomonas aeruginosa, Proteus species, coagulase-negative staphylocci, and Clostridium species. Bacteroides fragilis was also recovered. When the fang sheaths of four additional rattlesnakes were retracted and the fangs of these snakes decontaminated, 50% of the samples of venom had no bacterial growth (P = 0.035). Until a clinical study is performed, the use of antimicrobial therapy that reflects that complex oral flora of rattlesnakes is still recommended in most cases of envenomization.

Alcaligenes

New markers for Eubacterium lentum.

Of 37 strains of Eubacterium lentum and phenotypically similar organisms, 26 (70%) synthesized a corticoid 21-dehydroxylase and/or a 3 alpha-hydroxysteroid dehydrogenase. It appeared that the corticoid 3 alpha-hydroxysteroid dehydrogenase was identical to the bile acid 3 alpha-hydroxysteroid dehydrogenase. Steroid-metabolizing enzymes were found both in E. lentum and in phenotypically similar organisms. E. lentum is characterized by nitrate reduction and enhanced growth in the presence of arginine. Many phenotypically similar organisms possess either one or the other of the two markers. In contrast, using the steroid-metabolizing enzymes as markers, a "steroid-active" and a "steroid-inactive" group were established with minimal overlapping of metabolic characteristics. Synthesis of the steroid enzymes was positively correlated with production of gas from H2O2 and formation of H2S. A simple method for the detection of corticoid 21-dehydroxylase and 3 alpha-hydroxysteroid dehydrogenase, one or both of which were present in 92% of the steroid-active group, is described.

3-Hydroxysteroid Dehydrogenases

Purification and characterization of Clostridium difficile toxin.

Recent evidence indicates that toxigenic Clostridium difficile strains are a major cause of antimicrobial-associated ileocecitis in laboratory animals and pseudomembranous colitis in humans. C. difficile ATCC 9689 was cultivated in a synthetic medium to which 3% ultrafiltrated proteose peptone was added. Purification of the toxin from broth filtrate was accomplished through ultrafiltration (100,000 nominal-molecular-weight-limit membrane), precipitation with 75% (NH4)2SO4, and chromatographic separation using Bio-Gel A 5m followed by ion-exchange chromatography on a diethylaminoethyl-Sephadex A-25 column. The purified toxin displayed only one band on polyacrylamide gel electrophoresis, and approximately 170 pg was cytopathic for human amnion cells. The isolated toxin was neutralized by Clostridium sordelli antitoxin, heat labile (56 degrees C for 30 min), and inactivated at pH 4 and 9; it had an isoelectric point of 5.0, increased vascular permeability in rabbits, and caused ileocecitis in hamsters when injected intracecally. Treatment of the toxin with trypsin, chymotrypsin, pronase, amylase, or ethylmercurithiosalicylate caused inactivation, whereas lipase had no effect. By gel filtration, its molecular weight was estimated as 530,000. Upon reduction and denaturation, the toxin dissociated into 185,000- and 50,000-molecular-weight components, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Extensive dissociation yielded only the 50,000-molecular-weight component. The toxin appears to be protoplasmic and is released into the surrounding environment upon autolysis of the cells. Attempts to correlate specific enzymatic activity with the toxin have been unsuccessful. These studies will help delineate the role of C. difficile toxin in antimicrobial-associated colitis and diarrhea.

Bacterial Toxins

Rapid presumptive bacteriological diagnosis of Legionnaires disease.

A simple, relatively rapid silver impregnation stain has been found to stain Legionella pneumophila effectively in paraffin-embedded tissue sections while permitting visualization of histological detail. It may also be used to stain the organism in body fluids. The stain is not specific and thus must be confirmed by direct fluorescent-antibody technique or culture, but, in the absence of other bacilli demonstrable by Gram or other stain, visualization of typical bacillary forms in a patient with illness compatible with Legionnaires disease provides strong presumptive evidence supporting this diagnosis.

Bacteria

Use of a semiselective medium to culture Legionella pneumophila from contaminated lung specimens.

Legionella pneumophila was successfully isolated, using a semiselective medium, from two of three lung specimens heavily contaminated with other organisms. This medium is composed of charcoal yeast extract agar, supplemented with vancomycin and polymyxin B. L. pneumophila was observed at 8 days on plates containing less than or equal to 40 units of polymyxin B and less than or equal to 1 microgram of vancomycin per ml.

Bacteria

Selective and differential medium for isolation of Clostridium difficile.

Clostridium difficile is a recognized cause of pseudomembranous (antimicrobial agent-associated) colitis and may be one of the causes of antimicrobial agent-induced diarrhea. A selective and differential agar medium that contains cycloserine, cefoxitin, fructose, and egg yolk (CCFA) was developed to facilitate the isolation of C. difficile from fecal specimens. Quantitative cultures of 16 stock strains of C. difficile on this medium (and on a medium containing cycloserine, fructose, and egg yolk) yielded counts equivalent to those obtained on blood agar; other media selective for clostridia, including Clostrisel agar, reinforced clostridial agar plus 0.2% para-cresol, and egg yolk-neomycin agar (the latter was inoculated with cultures subjected to prior heat shocking), were also tested and found to be inhibitory to the growth of C. difficile. Of 28 fecal or colostomy effluent specimens cultured on the above media, 14 yielded C. difficile. CCFA was found to be the most sensitive and selective of these media for the recovery of C. difficile. Colonies of C. difficile growing on CCFA had distinctive morphological and fluorescent properties which were sufficient for presumptive identification. CCFA should provide a rapid method for the screening of fecal specimens from patients with antimicrobial agent-associated diarrhea or colitis for C. difficile.

Animals