Shalom Z. Hirschman

Severe Acquired Immunodeficiency in Male Homosexuals, Manifested by Chronic Perianal Ulcerative Herpes Simplex Lesions

Four homosexual men presented with gradually enlarging perianal ulcers, from which herpes simplex virus was cultured. Each patient had a prolonged course characterized by eight loss, fever, and evidence of infection by other opportunistic microorganisms including cytomegalovirus, Pneumocystis carinii, and Candida albicans. Three patients died; Kaposis sarcoma developed in the fourth. All were found to have depressed cell-mediated immunity, as evidenced by skin anergy, lymphopenia, and poor or absent responses to plant lectins and antigens in vitro. Natural-killer-cell activity directed against target cells infected with herpes simplex virus was depressed in all patients. The absence of a history of recurrent infections or of histologic evidence of lymphoproliferative or other neoplastic diseases suggests that the immune defects were acquired.

Bloodstream infections in the elderly.

PURPOSEnBacteremia in the elderly is associated with a different clinical course and a higher mortality rate when compared with that in younger age groups. In order to examine these issues in the aged, we reviewed the clinical course and factors involved in the outcome of 100 episodes of bloodstream infections in patients over 65 years of age.nnnPATIENTS AND METHODSnThe hospital records of all patients over 65 years of age at The Mount Sinai Hospital with a positive blood culture result during the period October 1984 to October 1986 were reviewed. Place of residence before hospital admission, site of acquisition of infection, source of bloodstream infection, and microorganism were analyzed. Antimicrobial therapy was defined as appropriate if initial therapy included one agent to which the isolate was sensitive, or inappropriate if the isolate was resistant. The following factors affecting survival were analyzed: age, sex, underlying diseases, clinical parameters on admission, white blood cell count, mental status, source of infection, microorganism isolated, antibiotic toxicity, and appropriate versus inappropriate antibiotic therapy.nnnRESULTSnMost patients were female (63 percent), were febrile (90 percent), had an altered mental status (52 percent), and had a neutrophilic response (61 percent). Eighty-three percent of patients were admitted from the community (home), 14 percent were from long-term-care facilities, and 3 percent were transferred from other hospitals. Fifty percent of infections were nosocomial, and 44 percent were community (home and nursing home)-acquired. Gram-negative organisms accounted for 60 percent of isolates, with Escherichia coli (22 percent) and Klebsiella species (11 percent) predominating; 30 percent were gram-positive organisms, with Staphylococcus aureus (13 percent) and Streptococcus faecalis (10 percent) the most common. The overall survival was 60 percent; the survival rate was 65.8 percent for community-acquired (home) bacteremia, 75 percent for nursing home-acquired bacteremia, and 52.8 percent for hospital-acquired bacteremia. Survival for gram-negative isolates was 65 percent, versus 51.7 percent for gram-positive isolates. Survival was greatest in patients whose source of bacteremia was either the genitourinary tract (70 percent) or an intravascular device (78 percent) and poorest in patients with lower respiratory tract source (42 percent); all three patients with endocarditis died. Increased survival was observed in patients treated with appropriate antimicrobial agents regardless of age, source of infection, or bloodstream isolates.(ABSTRACT TRUNCATED AT 400 WORDS)

Coxsackie virus myopericarditis. A microbiological and clinical review.

Abstract Coxsackie viruses belong to a large group of viruses called picornaviruses. This group of viruses contains a ribonucleic acid (RNA) core; the nucleocapsid has cubic symmetry; the virion has no envelope; and infectivity is resistant to lipid solvents such as ether and chloroform. Coxsackie viruses are divided into two groups based on their pathogenicity in suckling mice; group A contains 24 types and group B 6 types. Numerous reports of Coxsackie virus B outbreaks involving adults have established the considerable importance of these viruses as a cause of acute pericarditis and myocarditis. The diagnosis is based on viral isolation and serologic techniques. Coxsackie virus heart disease usually is observed during epidemics Involving several diseases including Bornholm disease or cardlorespiratory tract syndromes. The treatment of acute myopericarditis is mainly supportive.

Crossover study of the pharmacokinetics of ceftriaxone administered intravenously or intramuscularly to healthy volunteers.

The pharmacokinetics of ceftriaxone were investigated in six healthy adults. One-gram doses were administered either intramuscularly or intravenously in a crossover design study. Mean peak ceftriaxone concentrations in plasma of 79.2 and 123.2 micrograms/ml were achieved with intramuscular injection and intravenous infusion, respectively, with plasma half-lives of 5.4 and 5.8 h. The urinary recovery of ceftriaxone in the first 24 h was 37% after intravenous infusion and 25% after intramuscular injection.

Biliary concentrations of piperacillin in patients undergoing cholecystectomy.

Piperacillin is a new semisynthetic, expanded-spectrum penicillin with marked activity against Pseudomonas aeruginosa. The biliary excretion of piperacillin was studied in patients undergoing cholecystectomy. Concentrations of piperacillin in common duct bile at 35 to 90 min postinfusion of 1-g doses ranged from 31 to 920 micrograms/ml, with a mean (+/- standard deviation) of 467 +/- 363 micrograms/ml. Gallbladder piperacillin levels at 30 to 75 min postinfusion ranged from 2.2 to 80 micrograms/ml, with a mean of 27 +/- 31 micrograms/ml. No correlation occurred with peak serum level of antibiotic, creatinine, bilirubin, or alkaline phosphatase. Significant amounts of piperacillin were excreted via the biliary system.

Comparative study of piperacillin, ticarcillin, and carbenicillin pharmacokinetics.

Piperacillin, ticarcillin, and carbenicillin were administered intravenously to 10 healthy volunteers in a three-way, crossover study. The pharmacokinetics of the three drugs were in general quite similar. The peak serum concentration of piperacillin achieved at the end of a 30-min intravenous infusion was 63.5 +/- 27.6 microgram/ml. During the first 8 h, 67.5% of the dose of piperacillin was excreted in the urine, and the urinary concentration was extremely high. All three penicillins had high volumes of distribution. The serum half-life of the beta elimination phase of carbenicillin was lower than that of either piperacillin or ticarcillin. The volunteers experienced no adverse reactions from the administration of the drugs.

Pharmacokinetics of piperacillin in patients with moderate renal failure and in patients undergoing hemodialysis.

The pharmacokinetics of piperacillin administered intravenously were studied in five patients with stable mild to moderate renal impairment and in five patients undergoing hemodialysis. Patients with stable renal failure given 1 g of piperacillin intravenously had peak serum concentrations within 30 min ranging from 78 to 280 micrograms/ml. The mean serum half-life was 3.57 +/- 1.36 h; the mean apparent volume of distribution was 28.6 +/- 13.5 liters/100 kg; and the plasma clearance was 4.10 +/- 1.46 liters/h per 1.73 m2. Neither serum half-life nor clearance correlated with serum creatinine, implying significant nonrenal elimination. Patients undergoing hemodialysis had peak serum concentrations within 30 min of 66 to 138 micrograms/ml after 1 g of piperacillin infused intravenously. During hemodialysis, the serum half-life was 3.6 +/- 2.5 h; the mean apparent volume of distribution was 26.7 +/- 16.7 liters/100 kg; and the plasma clearance was 3.28 +/- 0.76 layers/h per 1.73 m2. Mean hemodialysis clearance was 0.484 +/- 0.282 liters/h per 1.73 m2, and only 10.0 +/- 5.3% of the total dose could be recovered in the dialysate.

Pharmacokinetic Study of Netilmicin

Netilmicin at a dose of 2 mg/kg was infused intravenously into 10 healthy volunteers. A peak serum concentration of 16.56 μg/ml was obtained at the end of the infusion. Thirty-nine percent of the infused dose was excreted in the urine during the first 8 h after infusion. The pharmacokinetic parameters of netilmicin were derived by analyzing the elimination data according to a two-compartment model.

Pharmacokinetics of cefoperazone in ambulatory elderly volunteers compared with young adults.

Two groups of 10 healthy ambulatory subjects, i.e., a group of 10 persons less than or equal to 30 years of age (mean age, 27.6 years) and a group of 10 persons greater than or equal to 65 years of age (mean age, 70 years), were randomized in a single-trial crossover design to receive 1 and 2 g of cefoperazone with a 1-week washout between doses. The elderly subjects had both decreased estimated creatinine clearances and decreased albumin concentrations in serum. Cefoperazone concentrations in serum of elderly persons were significantly higher at each interval from 30 min to 6 h for the 2-g dose. Compared with that in younger persons, the total clearance in elderly subjects was significantly lower for both the 1- and 2-g doses, the renal clearance was significantly lower for the 2-g dose, and the area under the curve was significantly higher for the 2-g dose in the elderly persons. The half-life at beta phase was higher in the elderly persons at both the 1- and 2-g doses but not significantly so. Changes in total clearance and area under the curve and higher levels in serum in the elderly persons suggest a longer duration of antimicrobial activity in this age group.

Comparison of Activity of Sisomicin and Gentamicin in Mouse Protection Tests with Gram-Negative Bacilli

The efficacy of sisomicin and gentamicin was compared in mouse protection studies against strains of Escherichia coli, Klebsiella sp., Enterobacter aerogenes, Serratia marcescens, Proteus mirabilis, and Pseudomonas aeruginosa. There was no significant difference in mortality of the mice in any of the protocol groups when five different dosages of sisomicin and gentamicin given by three separate schedules were compared for each bacterial inoculum in each antibiotic protocol. The mean protective dose values of sisomicin were at least one-half those of gentamicin for each protocol against Pseudomonas aeruginosa.