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Biomedical subjects

J Fierer

Publications and source records attributed to J Fierer.

At least 91 records · Page 5Linked to original sources

Invasive Salmonella dublin infections associated with drinking raw milk.

Salmonella dublin is a serotype of Salmonella that is host-adapted to cattle and rarely infects people. In one year (1980-1981) we diagnosed five cases of salmonellosis due to S dublin at the Veterans Administration Medical Center, San Diego. Four patients had positive blood cultures and one died. A sixth patient, diagnosed in 1978, had a mycotic aortic aneurysm but survived. Compared with nine patients who had Salmonella infections due to other serotypes, the S dublin patients were older, had a greater number of underlying chronic illnesses and were more seriously ill with their infections. Four of the six S dublin cases occurred in association with drinking "certified" raw milk from a commercial dairy.Two microbiologic features of S dublin strains circulating in San Diego were distinctive. They failed to ferment arabinose and could not be grown in a minimal medium using citrate as the sole carbon source. Chronically ill elderly patients should be cautioned against drinking raw milk, an increasingly popular "health food."

Adult↗

Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli.

In an effort to decrease deaths from gram-negative bacteremia and endotoxin shock, we treated bacteremic patients with human antiserum to endotoxin (lipopolysaccharide) core. Antiserum was prepared by vaccinating healthy men with heat-killed Escherichia coli J5; this mutant lacks lipopolysaccharide oligosaccharide side chains, so that the core, which is nearly identical to that of most other gram-negative bacteria, is exposed for antibody formation. In a randomized controlled trial, patients were given either J5 antiserum or preimmune control serum intravenously, near the onset of illness. The number of deaths in the bacteremic patients was 42 of 109 (39 per cent) in controls and 23 of 103 (22 per cent) in recipients of J5 antiserum (P = 0.011). In those with profound shock, mortality was 30 of 39 (77 per cent) in controls and 18 of 41 (44 per cent) in recipients of J5 antiserum (P = 0.003). We conclude that human antiserum to the lipopolysaccharide core can substantially reduce deaths from gram-negative bacteremia.

Adolescent↗

Ketoconazole for treatment of disseminated coccidioidomycosis.

Of 29 selected patients with disseminated coccidioidomycosis, 27 were treated for at least 6 months with ketoconazole, 200 to 600 mg/d. Two patients had progression of coccidioidal disease shortly after starting ketoconazole, and one developed meningitis. Seven of eight patients with synovitis had prompt improvement in symptoms, but four either had recurrent synovial thickening without recoverable Coccidioides immitis or could not remain free of symptoms off the drug. The response of osteomyelitis to ketoconazole was hard to assess; three of eight cases clearly improved and none progressed. Abscess or sinus formation clearly improved in eight of patients; five remained free of disease after the drug was discontinued. Skin lesions improved in six of nine; three lesions remain healed off the drug. Ketoconazole is absorbed readily after oral ingestion and has little toxicity. In the dosages used, it seems to suppress but not eradicate C. immitis. The drug may be able to stabilize the infection while cell-mediated immunity is restored.

Adult↗

An outbreak of Providencia stuartii urinary tract infections. Patients with condom catheters are a reservoir of the bacteria.

We investigated an outbreak of multiple antibiotic-resistant Providencia stuartii urinary tract infections that occurred on a neurology ward. Only patients who had been catheterized became infected. However, approximately 10% of patients with condom catheter urinary drainage systems were colonized, ie, P stuartii was present on their skin and in the urine drainage bags but not in fresh-voided urine. Patient urinals were also contaminated. The outbreak was terminated by segregating infected and colonized patients from other patients who required either external or indwelling urinary catheters and by stopping the practice of exchanging urinals among patients.

California↗

Effects of rifampin on biliary lipids in humans.

Because the action of rifampin induces hepatic microsomal enzymes, a study was carried out in four patients to determine whether this drug alters the composition of biliary lipids. Several different measurements were made while patients were both on and off rifampin therapy for various infective processes. These measurements included multiple determinations of lipid composition of gallbladder bile, the relative proportions f individual bile acids, and kinetics of cholic acid and chenodeoxycholic acid. In all four patients, the saturation of gallbladder bile increased during rifampin treatment, and the bile consistently became supersaturated. The relative portions of chenodeoxycholic acid and cholic acid were essentially unchanged by treatment, but total synthesis of bile acids increased in three tested patients with rifampin therapy. These results indicate that rifampin increases saturation of bile with cholesterol, but this increase is not due to a reduction in bile acid production.

Adult↗

Hepatitis B virus exposure of hospital staff.

A patient admitted to a general medical ward for evaluation of jaundice was transferred to an intensive care unit when he developed a hemorrhagic diathesis and hepatic encephalopathy. Fifteen days elapsed before it was recognized that the patient was infected with hepatitis B virus (HBV), during which time the staff took no precautions other than routine hand washing. On subsequent evaluation of risk, it was decided that administration of an immunoglobulin preparation was not indicated despite the patient's massive contamination of his immediate environment. Of 89 persons heavily, casually, or indirectly exposed, none developed clinical illness within six months following contact. A nurse, first tested 30 days after contact, was persistently hepatitis B surface antigen-positive, but results of testing for antibody to core antigen demonstrated she was a long-term carrier. Among 61 susceptible staff members tested serially, none had serologic evidence of HBV infection. Thus, not all HBV-infected patients are highly contagious. Nonetheless, procedures to prevent such unprotected exposures are needed.

Aged↗

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↗

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↗

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↗

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↗

Bacteremia in the pathogenesis of retrograde E. coli pyelonephritis in the rat.

Female rats deprived of water overnight, and then given 1.0 ml of E coli 0111:B4 via the urethra, developed pyelonephritis. A nearly absolute association was found between the occurrence of bacteremia after the transurethral infusion and the development of pyelonephritis. An identical lesion was produced by a combination of forniceal damage and intravenous injection of E coli. The kidney damaged by reflux was shown to be more susceptible to hematogenous pyelonephritis than the obstructed kidney and the distribution of the infection was due to localization of bacteria in the damaged fornix but not to the route of infection. The induction of retrograde E coli pyelonephritis in the rat required a tear in the pelvic epithelium creating pyelovenous communications, and the resultant bacteremia produced pyelonephritis. The incidence of ureteral reflux and the volume of inoculum that refluxed to the renal pelvis was shown radiologically to be a function of bladder distensibility, which is reduced by withholding water for a few hours. In this system, retrograde E coli pyelonephritis developed from a combination of two factors: (1) reflux-induced damage to the renal pelvis so that E coli are introduced into the kidney and (2) hematogenous infection of the damaged kidney.

Animals↗