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Biomedical subjects

J Fierer

Publications and source records attributed to J Fierer.

7 recordsLinked to original sources
PubMed1979

Lethal effect of complement and lysozyme on polymyxin-treated, serum-resistant gram-negative bacilli.

When genetically serum-resistant Escherichia coli, Klebsiella pneumoniae, and Citrobacter freundii, but not Pseudomonas aeruginosa or Proteus mirabilis, were exposed to polymyxin B, they became susceptible to the bactericidal action of normal human and rabbit sera. In constrast, beta-lactam and aminoglycoside antibiotics did not render any serum-resistant bacteria serum-sensitive. Synergy between polymyxin B and the serum bactericidal system could be demonstrated by the addition of polymyxin B to bacteria in vitro, as well as to bacilli in serum from rabbits injected with the antibiotic. Polymyxin B-treated bacteria were killed by normal, lysozyme-depleted, C2-deficient, and hypogammaglobulinemic sera, but not by heated or C6-deficient sera. These findings indicate that polymyxin B-treated bacteria can be killed via the alternative complement pathway. However, C3 and C3b were detected on the surface of serum-resistant E. coli, regardless of whether the bacteria had been treated with polymyxin B. This observation suggests that a change in susceptibility to the alternative complement pathway was not the only explanation for the acquired serum sensitivity. Polymyxin B may also affect a step in the complement sequence beyond the activation of C3, a step that is apparently blocked in serum-resistant gram-negative bacteria.

Animals↗
PubMed1979

Deficient serum bactericidal activity against Escherichia coli in patients with cirrhosis of the liver.

The serum bactericidal activity (SBA) of cirrhotic patients was compared with that of normal individuals using the release of (51)Cr from radiolabeled Escherichia coli as the assay method. 80% (22/27) of patients were found to have deficient SBA against at least one of three smooth, serum-sensitive test strains of E. coli. Cirrhotic patients were found to have normal levels of serum lysozyme. Although some patients were mildly hypocomplementemic, this abnormality did not correlate with the presence of a bactericidal defect. Bactericidal antibody in normal and cirrhotics' sera was limited to the immunoglobulin (Ig)M class. Purified IgM from patients with deficient SBA against E. coli 0111 had lower concentrations of bactericidal antibody for that E. coli than did IgM from normal sera; the calculated bactericidal activity of total serum IgM was also lower. The bactericidal defect in cirrhotic serum could be completely corrected by either human antiserum to the homologous strain of E. coli or by purified, normal human IgM. However, because higher concentrations of IgM were required to restore normal SBA to a cirrhotic's serum than to agammaglobulinemic serum, there may be an inhibitor of bactericidal antibody in addition to a deficiency of bactericidal IgM antibody to E. coli in the serum of patients with cirrhosis. The bactericidal activity of the alternative complement pathway was also assessed. Sera from cirrhotic patients had no deficit in SBA attributable to the alternative complement pathway. In fact, in some, the activity of the alternative complement pathway was supernormal, compensating in part for the deficit in IgM-mediated SBA.

Antibodies, Bacterial↗
PubMed1978

Nitrate reduction: new method for testing the antibiotic susceptibility of Haemophilus influenzae.

We have developed a new micro-broth-dilution assay for determining the antimicrobial susceptibility of Haemophilus influenzae. This assay is based on the ability of viable H. influenzae to reduce nitrates to nitrites. Bacterial viability is detected by a positive nitrite reaction rather than visible turbidity. The nitrate reduction assay was compared with a standard microassay using 51 isolates of H. influenzae and six beta-lactam antibiotics. Although there was good agreement between the two methods, the nitrate reduction assay was more sensitive in detecting viable bacteria, and so established a more accurate estimate of the minimal inhibitory concentration. The nitrate reduction assay offered the additional advantage that it could be used to determine the minimal bactericidal concentration without having to subculture the broth. Ampicillin, penicillin, and cefamandole were equally effective in vitro against susceptible strains (minimal inhibitory concentrations, 0.125 to 0.5 mug/ml), whereas all three antibiotics were ineffective against two beta-lactamase-producing strains. Using the nitrate reduction assay, resistance to cefamandole was detectable with inoculum sizes ranging from 10(4) to 10(6) colony-forming units per ml, while the turbidity assay detected resistance only with the largest inoculum.

Anti-Bacterial Agents↗
PubMed1978

Activation of the alternate complement pathway in Staph. aureus infective endocarditis and its relationship to thrombocytopenia, coagulation abnormalities, and acute glomerulonephritis.

Twenty-four patients with infective endocarditis (IE) are described, fourteen with Staph. aureus and ten with other organisms. Despite the acute nature of the infection, ten of the fourteen with Staph. aureus IE were hypocomplementaemic; six of these ten had normal levels of C4 associated with low C3 levels, suggesting activation of the alternate complement pathway. Factor B (C3PA) was also low in three of these six cases. In the ten patients with non-Staph. IE, three had hypocomplementaemia with low levels of C4, C3, and Factor B, probably due to C1 (classical pathway) activation with feedback activation of the alternate pathway. In addition, thrombocytopenia was noted in nine of the twenty-four patients and was associated with hypocomplementaemia; the degree of renal insufficiency noted in these patients also correlated with hypocomplementaemia. In Staph. aureus IE thrombocytopenia and hypocomplementaemia, occurring early in the course of the disease, may be due to a non-immune interaction of Staph. cell wall products (Protein A) with immunoglobulin, complement components, and thrombocytes.

Acute Disease↗
PubMedDate not supplied

The fetid foot: lower-extremity infections in patients with diabetes mellitus.

Infections of the lower extremities in patients with diabetes mellitus have been attributed to Staphylococcus aureus and other facultatively anaerobic bacteria. However, a review of 30 consecutive diabetics who required surgery for lower-extremity infections revealed that 17 had mixed infections due to both obligate and facultative anaerobes; only six had infections due to S. aureus. Mixed infections often had characteristics of anaerobic suppuration and responded poorly to therapy. Patients with mixed infections required more operations than did those with staphylococcal infections, and their surgical wounds healed more slowly. Seven patients had infections with mixed enteric bacteria (neither anaerobes nor S. aureus), and their response to therapy was intermediate between that of the patients with mixed anaerobic infections and those with staphylococcal infections. Nine additional patients with mixed anaerobic infections were treated with cefoxitin; three required amputations at a level above the ankle, but six patients improved and required only limited surgery that preserved foot function. Bacteroides fragilis was the anaerobe isolated most often. Cefoxitin (less than or equal to 20 micrograms/ml) inhibited all of the anaerobes isolated from the nine patients and 97% of an additional 135 consecutive clinical isolates of B. fragilis; 98% of 54 strains of Bacteroides oralis and all of 34 strains of Bacteroides melaninogenicus were also inhibited. These in vitro results and the results of our clinical study show that cefoxitin is a promising antibiotic for therapy of foot infections due to a mixed flora of anaerobes in diabetics.

Aged↗
PubMedDate not supplied

Coccidioidomycosis of the extensor tenosynovium of the wrist. A case report.

A 59-year-old man had isolated coccidioidomycosis infestation of the tenosynovium of the wrist extensor tendons resistent to surgical and amphotericin chemotherapy. Some improvement has been noted on Miconazole chemothearapy, but neither the long term side effects nor clinical results are known.

Amphotericin B↗