A case-control, prospective, open-label, clinical trial to evaluate efficacy and safety of a combined zidovudine/Thymus Humoral Factor Gamma-2 (THF) therapy in HIV-infected subjects was conducted in 13 patients. Twenty-six patients were included as controls receiving only zidovudine. The two groups of patients were matched according to sex, age, CDC stage of HIV infection, number of CD4+ T cells and type of previous opportunistic infections (if any) and all patients and controls were naive for antiretroviral therapy at the moment they entered the trial. The observation period was protracted up to 47 months (mean 28 +/- 13 months). No significant difference was observed between the two groups as far as surrogate markers of HIV disease progression are concerned. However, patients receiving zidovudine and THF showed a lower number of opportunistic complications. Only one patient in this group progressed to manifest AIDS while 9 of 18 controls presented disease progression. Four patients died in the case group, all of them were CDC stage IV at admission, and 15 of 26 died in the control group (all CDC stage IV at admission, and four patients who presented disease progression during the study period). Survival time was increased in the case group. The exact immunological effect of thymus hormones in HIV infection has still to be elucidated, but a possible therapeutic role of these agents is foreseeable.

The antimicrobial activity of imipenem was tested in an in-vitro model mimicking human serum pharmacokinetics after either 1000 mg im once daily or 500 mg im twice daily. Six recent clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae and Salmonella group B were used as test strains. Our results suggest that a single daily dose of imipenem 1000 mg im exerts an antibacterial action comparable to that obtained with two divided doses of 500 mg.

The postantibiotic effect (PAE), sub-MIC effect (SME), and postantibiotic sub-MIC effect (PASME) of imipenem on Pseudomonas aeruginosa were investigated with an in vitro dynamic model reproducing in vivo elimination kinetics of the antibiotic. The PASMEs were constantly longer than the corresponding SMEs, but differences between them were not statistically significant. Both PASMEs and SMEs were initially bactericidal and were significantly longer than PAEs. The mean values of both PASMEs and SMEs were over 12 h. SMEs appear to be more relevant for the bacterial growth kinetics than PAEs.Dosage schedules for antibiotic therapy are generally based on the assumption that drug concentrations must be maintained above the MIC. However, it has been shown that discontinuous therapy is as effective as continuous therapy, even if the concentrations in serum fall below the MIC (24). A lag phase before the regrowth of bacteria previously challenged with antibiotics has been demonstrated and named the postantibiotic effect (PAE) (2,14). This phenomenon is thought to be a possible explanation for the success of intermittent-dosing regimens (2).The PAE has been demonstrated for various antibioticbacterium combinations (1,8,9,22). However, the PAE is a highly artificial parameter, as in vivo, a suprainhibitory concentration of a drug will always be followed by subinhibitory concentrations (sub-MICs).Subinhibitory antibiotic concentrations may have different effects on bacteria previously exposed to suprainhibitory concentrations and on unexposed bacteria (18)(19)(20). In most of the investigated combinations with I8-lactam antibiotics, the postantibiotic sub-MIC effect (PASME) was significantly longer than the sub-MIC effect (SME).The aim of this study was to investigate the occurrence of the PASME and SME of imipenem on The bacteria, in the exponential growth phase, were then exposed to five times the MIC of the antibiotic for 1.5 h at 37°C. The exposed strains were washed three times for 5 min each time at 1,400 x g to eliminate the antibiotic and were then resuspended in fresh medium. Controls, unexposed to the antibiotic, were treated similarly. Exposed cultures and controls were either diluted or left undiluted and inoculated into the dynamic model (see below) to obtain a final concentration of approximately 5 x 105 CFU/ml.Samples were withdrawn at 0 (before and after dilution), 1, 2, 4, 7, 10, 13, 16, and 20 h and, if necessary, diluted with phosphate-buffered saline. Samples were seeded on Iso-Sensitest agar plates and incubated for 20 h, and CFU were counted. CFU were counted only for plates with 10 to 500 colonies. All experiments were performed in triplicate.The PAE was defined according to the previously described formula (2) PAE = T -C, where T is the time required for the viable counts of the antibiotic-exposed cultures to increase by 1 log1o above the counts observed immediately after the seeding of the system and C is the corresponding time for the unexposed cultures.Determination of the effects of sub-MICs. Th...