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Biomedical subjects

L L Pelletier

Publications and source records attributed to L L Pelletier.

At least 19 recordsLinked to original sources

Enhanced hepatotoxicity of acetaminophen in the alcoholic patient. Two case reports and a review of the literature.

We report 2 fatal cases of the acetaminophen-alcohol syndrome and review 51 reported cases in the medical literature. The MEDLINE database from January 1966 to December 1995 and bibliographies of selected articles were used to obtain the case reports. Inclusion criteria were a clear history of alcohol use, a history of acetaminophen use and/or an elevated serum acetaminophen level, peak aspartate aminotransferase (AST) greater than 800 U/L, and exclusion of other causes of hepatotoxicity by negative hepatitis serologies and/or a liver biopsy showing typical findings of acetaminophen toxicity. Demographic characteristics, clinical features, treatment, and outcome were extracted from reports meeting inclusion criteria and our own 2 cases. This syndrome affected relatively young, frequently healthy patients. Acetaminophen was invariably taken for nonsuicidal intent. The mortality rate was 32%. A typical laboratory picture was defined, characterized by an extraordinarily high AST level. Treatment with N-acetylcysteine was not effective due to delayed presentation and diagnosis. Patients who use alcohol and health care providers should be educated about this potentially fatal syndrome. Prevention is the key to reducing its occurrence.

Acetaminophen↗

Review of the experience with cefprozil for the treatment of lower respiratory tract infections.

A regimen of cefprozil (500 mg twice daily), a new oral cephalosporin with a broad in vitro spectrum of antimicrobial activity, was compared to standard regimens of cefaclor (500 mg three times daily), cefuroxime axetil (500 mg twice daily), or amoxicillin/clavulanate (500 mg/125 mg three times daily) for the treatment of lower respiratory tract infections (mainly bronchitis and acute exacerbations of chronic bronchitis) in adults in three open-label, randomized trials. In the first trial, in which bacterial pathogens were isolated in initial cultures for only one-third of the patients, 90% of the pathogens were susceptible to cefprozil. A satisfactory clinical response was noted for 84% of the evaluable patients who received cefprozil versus 79% of those who received cefaclor for treatment of lower respiratory tract infections; rates of bacteriologic efficacy were 82% and 78%, respectively. In the second study rates of satisfactory clinical response were 96% with cefprozil and 83% with cefuroxime axetil (P less than .03) for treatment of bronchitis; the respective bacteriologic response rates were 100% and 92%. In the third trial, clinical efficacy was 91% for cefprozil and 87% for amoxicillin/clavulanate for treatment of bronchitis; bacteriologic efficacy was 95% and 96%, respectively. Tolerability and safety profiles were comparable, except that there was a higher rate of diarrhea among patients who received amoxicillin/clavulanate (P = .03).

Acute Disease↗

Oxacillin, cephalothin, and vancomycin tube macrodilution MBC result reproducibility and equivalence to MIC results for methicillin-susceptible and reputedly tolerant Staphylococcus aureus isolates.

Measurement of antimicrobial killing endpoints of Staphylococcus aureus isolates in tube macrodilution MBC testing has been difficult because of multiple technical factors. A total of 41 fresh clinical isolates and 23 reputedly oxacillin-tolerant strains were examined by a modification of the Taylor MBC method. Oxacillin, cephalothin, and vancomycin MBCs were equal to MICs for most strains and were seldom more than fourfold greater than the corresponding MICs after a 48-h incubation. Oxacillin MBC result reproducibility for S. aureus ATCC 25923 and clinical isolates was better than that of cephalothin and vancomycin, and reproducibility improved after a 48-h incubation. Measurement of the percentage of the initial inoculum remaining after 24 and 48 h of incubation for the strains for which the MBCs were highest confirmed improved killing over a wide range of antimicrobial concentrations after a 48-h incubation. Since S. aureus MBC testing is expensive, is subject to error, and almost always gives results equal to the MIC, we suggest that MBC testing is an experimental reference laboratory test that should not be done by clinical microbiology laboratories. Antimicrobial selection should be based on reproducible and standardized MIC tests.

Anti-Bacterial Agents↗

Chronic strongyloidiasis in Vietnam veterans.

Chronic Strongyloides stercoralis infections can produce intermittent urticarial skin eruptions and gastrointestinal discomfort for years. Three cases of symptomatic infection acquired by United States military personnel in Vietnam are presented as examples of chronic parasitic disease unrecognized by physicians despite clear histories of geographic exposure, classic creeping skin eruptions, and eosinophilia. More attention needs to be paid to the possible long-term sequela from military service in tropical climates by both military and civilian physicians.

Adult↗

Hospital usage of parenteral antimicrobial agents: a gradated utilization review and cost containment program.

Forty percent to 60% of antimicrobial agents administered in hospitals without effective antimicrobial review and control programs are not needed. Excessive use of antimicrobial agents in the hospital promotes colonization of patients with resistant organisms, needlessly exposes them to the risk of an adverse drug reaction, and increases the cost of care. A gradated antimicrobial utilization review program is presented that determines hospital usage, develops guidelines for appropriate cost-effective drug administration, provides several options for implementation, and monitors outcome so that measures can be modified for specific situations. The techniques used are basic epidemiologic measures currently used to assess hospital infections.

Anti-Bacterial Agents↗

Urinary tract infections with antibiotic resistant organisms in catheterized nursing home patients.

Long-term use of indwelling urinary catheters in nursing home (NH) patients is a potential cause of significantly morbidity. We retrospectively studied 10 NH patients with chronic indwelling urinary catheters. Sixty-four percent of all 84 antibiotic courses prescribed were for bacteriuria alone without clinical infection. Seventy percent of 63 antibiotic courses were followed by bacteriuria with organisms resistant to the antibiotic administered. Bacteria isolated from NH patients often displayed greater resistance to specific antibiotics than those isolated from hospitalized patients. Four of the 20 urinary tract infections were associated with bacteremia. Three episodes of bacteremia were with highly-resistant organisms and one was fatal. Use of urinary catheters and inappropriate use of antibiotics in NH patients results in urinary tract colonization and infection with resistant bacteria and is an important cause of morbidity and mortality.

Aged↗

Lack of reproducibility of macrodilution MBCs for Staphylococcus aureus.

MBCs of methicillin, oxacillin, penicillin G, cephalothin, vancomycin, and gentamicin were determined by a standard broth macrodilution technique for 101 clinical isolates of methicillin-susceptible Staphylococcus aureus. Increased killing (more than 99.9%) was observed after 48 versus 24 h of incubation for many strains, and cross tolerance to antimicrobial bactericidal activity (less than 99.9% killing) was frequently observed among antimicrobial agents. However, these in vitro measurements of bactericidal activity against S. aureus were not reproducible.

Anti-Bacterial Agents↗

Chronic strongyloidiasis in World War II Far East ex-prisoners of war.

Fifty-two of 142 (37%) American ex-prisoners of war that worked on the Burma-Thailand Railroad during World War II were found to have previously unrecognized symptomatic Strongyloides stercoralis infections. A characteristic urticarial creeping skin eruption on the abdomen, buttocks and thighs occurred in 92%. Infection was also associated with pruritus ani, abdominal pain, indigestion, heartburn, and diarrhea. Demonstration of larvae in ether-formalin stool concentrates in these chronic low density infections required 5 hours of microscopy per case to detect 90% of positive cases. Therapy with thiabendazole resulted in a clinical cure in 93% and a microscopic cure in 100%; but was associated with frequent side effects. Chronic strongyloidiasis should be considered in veterans of Far East conflicts and in others with intimate soil contact in rural Strongyloides stercoralis-endemic areas who present with recurrent creeping skin eruption, abdominal pain, and eosinophilia.

Aged↗

Virulent gentamicin-induced small colony variants of Staphylococcus aureus.

Stable nonhemolytic small colony variants were isolated in pure culture from nine of 30 Staphylococcus aureus clinical strains after incubation of log10 7.0 cfu for 48 hr in MH broth containing 1.0 microgram/ml gentamicin. The variants resembled Staphylococcus epidermidis on blood agar, but they were positive for tube coagulase and thermostable nuclease at 24 hr and fermented mannitol slowly. The infectivity and virulence of four variants were compared to four parent S. aureus and three S. epidermidis strains in a rabbit model of endocarditis. Log10 5.0 cfu of the variant S. aureus, parent S. aureus, or S. epidermidis strains were injected intravenously into rabbits with intracardiac catheters. Quantitative culture of vegetations demonstrated endocardial infection in 47 of 49 (96%) animals injected with S. aureus variants, 44 of 44 injected with S. aureus parent strains, and four of 21 (19%) S. epidermidis-injected animals. The mortality rate in untreated animals within 4 days was five of 49 (10%) for variant S. aureus, 33 of 44 (75%) for parent S. aureus, and 0 of 21 for S. epidermidis. Small colony variants of S. aureus may be mistaken for S. epidermidis, but the variants are significantly more infective than S. epidermidis and are more likely to cause endocarditis. Gentamicin-induced S. aureus small colony variants are as infective but less virulent than their parent S. aureus strains.

Animals↗

Chemotherapy of experimental streptococcal endocarditis. V. Effect of duration of infection and retained intracardiac catheter on response to treatment.

The dynamics of infection and response to penicillin G (P) or combined P plus streptomycin (S) therapy were studied in a rabbit model of penicillin-sensitive Streptococcus sanguis endocarditis. Increased delay between infection and initiation of treatment required longer duration of therapy to effect a cure. Irrespective of the interval between infection and onset of therapy, P combined with S regularly eliminated streptococci from endocardial vegetations more rapidly than P alone, both in the presence and absence of an intracardiac catheter--although the difference in response was more marked with the catheter present. The combination of P and S consistently showed superior in vivo bactericidal activity compared to P alone in established S. sanguis endocarditis.

Animals↗

Chemotherapy of experimental streptococcal endocarditis. IV. Further observations on prophylaxis.

The ability of antibiotics to prevent Streptococcus sanguis endocarditis was tested in rabbits. Only vancomycin or a combination of penicillin G plus streptomycin always prevented infection when administered as a single dose. A loading dose of 30 mg/kg of phenoxymethyl penicillin (penicillin V) followed by additional 7.5 mg/kg doses for 48 h proved to be the only successful prophylactic program that could be given orally to man. Cefazolin alone or with streptomycin in multiple doses was also an effective alternative to penicillin or penicillin derivatives. Erythromycin uniformly failed to protect animals from bacterial endocarditis but showed greater prophylactic efficacy when a low inoculum of streptococci was used.

Ampicillin↗

Chemotherapy of experimental streptococcal endocarditis. II. Synergism between penicillin and streptomycin against penicillin-sensitive streptococci.

Bacterial endocarditis was produced by intravenous injection of Streptococcus viridans into rabbits with preexisting sterile endocardial vegetations. After 6 h had elapsed, bacteria in the vegetations could not be eradicated by brief treatment with antimicrobials to which the streptococci were sensitive. However, when treatment with penicillin was continued for 4 days, the animals were cured. The 6-h infection therefore offered a model in which treatments could be conveniently compared over a short period. Synergism was demonstrated between penicillin and streptomycin in endocarditis due to a fully penicillin-sensitive streptococcus, a point which had not been previously proved in vivo. The clinical implications are discussed.

Animals↗