A double-blind study was designed to test the hypothesis that local side-effects during i. v. administration of erythromycin lactobionate depend on the drug concentration and that they can therefore be minimized by dissolving erythromycin in a larger infusion volume. Forty healthy students were assigned in a randomized sequence to four 30 min infusions: 120 and 250 ml of erythromycin lactobionate (1 g in 0.9% NaCl) and 120 and 250 ml of placebo (0.9% NaCl). An unexpectedly high incidence (95% and 80% for the infusion volumes of 120 and 250 ml, respectively) of severe systemic side-effects was observed during the first 79 infusions. Because all of these systemic side-effects were associated with the infusion of erythromycin, the study was terminated at this point. Side-effects included abdominal cramps, nausea, vomiting, dizziness and profuse sweating. The postulated positive effect of lower erythromycin concentrations in the infusion on local side-effects (pain at the infusion site, erythema) was marginal (63% vs. 45%). Compared to the systemic side-effects, the problem of local tolerance is less important. In young adults, 30 min infusions of 1 g erythromycin lactobionate are associated with a high incidence of systemic side-effects which may be due to an age-dependent effect of the drug on smooth muscle.

Adult↗

PubMedDate not supplied

Susceptibility and tolerance of beta-lactamase-producing, methicillin-sensitive strains of Staphylococcus aureus towards seven broad-spectrum penicillins.

The activity of penicillin G, ampicillin, carbenicillin, ticarcillin, azlocillin, mezlocillin and piperacillin against 102 beta-lactamase-producing, methicillin-sensitive strains of Staphylococcus aureus was determined by agar dilution (method A) and broth microdilution (method B) techniques. By NCCLS breakpoint criteria, 4% of the strains were "sensitive" to penicillin and ampicillin, and almost 100% were "sensitive" to the other drugs when method A was used. Results with method B were only significantly lower as far as the cumulative percentage of strains "sensitive" to azlocillin, mezlocillin and piperacillin was concerned (63-71%). Bactericidal effects at "sensitive" levels were observed in 0-2% (penicillin, ampicillin), 31-35% (carbenicillin, ticarcillin) and 10-14% (azlocillin, mezlocillin, piperacillin). While differences in MIC and MBC levels ranged from 0 to 8 dilution steps, tolerance (a greater than 32-fold difference) was seen in at least 9-22% of all strains (depending on the drug tested); experimental limitations, however, excluded a determination of tolerance in all our strains. In a semi-quantitative nitrocefin assay, "strong" beta-lactamase production was correlated to high MIC and/or MBC levels.

Drug Tolerance↗

PubMedDate not supplied

Ciprofloxacin-induced hematuria.

We used ciprofloxacin, a quinolone-derivative, to treat a lung infection due to Pseudomonas aeruginosa in an adult cystic fibrosis patient. On three different occasions the use of ciprofloxacin was associated with the development of an asymptomatic hematuria with red blood cell casts. The mechanism responsible for this hematuria is presently unknown, but clinicians should be aware of this potential adverse effect of ciprofloxacin.

Adult↗

PubMedDate not supplied

Low-dose zidovudine in combination with either acyclovir or lymphoblastoid interferon-alpha in asymptomatic HIV-infected patients: a pilot study.

The antiretroviral activity, tolerance and toxicity of two different antiviral drug combinations were assessed and compared in a randomized, crossover pilot study in 16 HIV-1 p24 antigenaemic subjects with asymptomatic HIV infection. Oral zidovudine 250 mg twice daily was combined with either oral acyclovir 800 mg twice daily or lymphoblastoid interferon-alpha 1.5 x 10(6) IU administered subcutaneously three times weekly. The 12-week treatment period was followed by a 4-week washout period and a further 12-week crossover phase. During the entire treatment period a decline in p24 antigen was observed in all patients. No significant differences were found between the two treatment regimens. No patient showed clinical progression of HIV infection. Three patients were withdrawn from the study, one due to serious anaemia and two due to severe clinical adverse events. Long-term efficacy and tolerance data in asymptomatic HIV-infected patients with these regimens would be valuable.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Variability of serum concentrations of trimethoprim and sulfamethoxazole during high dose therapy.

Serum kinetics of trimethoprim and sulfamethoxazole were studied in 23 patients during oral and i.v. treatment of Pneumocystis carinii pneumonia. Daily doses of 15-22 mg/kg trimethoprim and 75-110 mg/kg sulfamethoxazole were given every 6 h. Despite administration of a loading dose of twice the regular dose, serum trough concentrations continuously rose from 12 h to 96 h by 63% for trimethoprim and 102% for sulfamethoxazole. After 4-6 days mean trough concentrations of trimethoprim and sulfamethoxazole were 7.7 +/- 3.0 and 198 +/- 74 mg/l, with individual values of < 4.6 and < 103 mg/l in two patients and > 11.4 and > 307 mg/l in two others. Patients treated orally or i.v. had similar serum levels. However, large interindividual variability was observed despite weight-specific dosing. Administration of a loading dose did not prevent accumulation of serum levels of trimethoprim and sulfamethoxazole over several days of treatment.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

Phase I/II vaccination study of recombinant peptide F46 corresponding to the HIV-1 transmembrane protein coupled with 2.4 dinitrophenyl (DNP) Ficoll.

In order to evaluate tolerance, toxicity, and in vivo antigenicity, 29 HIV-1-infected patients (eight with ARC and 21 with AIDS) were vaccinated with a synthetic peptide derived from the gp41 transmembrane protein of the HIV-1. This peptide had been coupled with 2.4 dinitrophenyl-Ficoll (F46), a T-cell independent adjuvant. The patients received a single intradeltoid injection of either 0.1 or 0.3 mg of F46. Five of the individuals with AIDS were boostered, four of them twice. Anti-F46 antibody titers were measured before vaccination, and on days 7, 14, 21, 28, 90, 180 and 270 after vaccination. Anti-F46 titers rose at least twofold over prestudy values in 10/21 individuals with AIDS and in 1/8 individuals with ARC at least once during the observation period. The overall response, however, consisted of only weak antibody production that was independent of the dose or patient characteristics. No signs of toxicity or of clinical progression related to the vaccination were observed in this phase I/II trial of a T-cell independent therapeutic vaccine.

AIDS Vaccines↗

PubMedDate not supplied

Comparative multiple-dose pharmacokinetics of cefotaxime, moxalactam, and ceftazidime.

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Biotransformation↗