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Among third-generation cephalosporins, cefodizime (CFDZ) has shown to modulate many functions of the host defense system against infections. The aim of the present study was to assess the in vitro CFDZ-dependent modulation of interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha) and IL-8 release from lipopolysaccharide (LPS)-stimulated human peripheral mononuclear cells (MNCs). Two other third-generation cephalosporins: ceftriaxone (CFX) and ceftazidime (CFT), were also tested under the same experimental conditions. At concentrations ranging from 200 to 50 micrograms/ml, CFDZ significantly decreased TNF-alpha and IL-6 release from maximally (LPS 1 microgram/ml) stimulated MNCs (42% inhibition of TNF-alpha release with 100 micrograms/ml of CFDZ). On the other hand, CFDZ revealed a marked stimulatory effect on IL-8 release (200 micrograms/ml of CFDZ induced 51.5% enhancement of IL-8 release). On the contrary, both CFX and CFT failed to exert any significant effect on TNF-alpha, IL-6 or IL-8 release.

The immunological and clinical effects of two oral treatment schedules of RU 41740 (standard for 3 months vs. long-term for 6 months) were assessed in 40 patients with chronic bronchitis by a controlled, double-blind, randomized trial. Both treatments significantly improved phagocytosis index of both neutrophils and monocytes, and the phagocytosis frequency and the candidacidal activity of neutrophils, showing the maximum stimulation at the end of the third course of treatment. Both treatment schedules reduced the number and the duration of infectious exacerbations of chronic bronchitis with respect to those observed in the corresponding period of the previous year. However, no significant difference between standard and long-term treatment with RU 41740 was found with respect to the immunological and clinical effect and tolerability.

The intracellular activity of flurithromycin, erythromycin, roxithromycin and miocamycin against susceptible clinical isolates of Staphylococcus aureus, phagocytosed by human monocytes, was investigated. Intracellular bioactivity was studied in a 24-hour assay, using experimental conditions which allowed the intracellular growth of bacteria. A colony counting method was used to differentiate between intracellular bacteriostatic and bactericidal activity of antibiotics. Moreover, the effect of macrolides against extracellular staphylococci was assessed. All agents showed higher intracellular than extracellular activity against staphylococci. At low concentration (0.1 mg/l) they had intracellular bacteriostatic activity. At concentrations higher than the minimal inhibitory ones (1 and 5 mg/l), miocamycin only still produced a bacteriostatic effect while flurithromycin, erythromycin and roxithromycin also showed intracellular bactericidal activity.

Studies with cefodizime in animals have shown that this new aminothiazolyl cephalosporin, possessing a broad antibacterial spectrum, positively influences a number of immunological parameters. In most investigations in which different dosage regimens were compared, a bell-shaped dose-response relationship was determined, i.e. activity after higher doses returned to near-baseline levels. This finding is typical of most immunomodulating agents. On this basis, the results obtained in healthy subjects were reviewed. Studies for investigating the biological response modifying (BRM) properties of cefodizime have been conducted in this population with either 2 g once daily i.v. or — in the majority — with 2 × 2 g/day i.v. After seven days of treatment with 1 × 2 g daily, no relevant changes could be demonstrated in healthy subjects, whereas there was an increase in monocyte and granulocyte chemotaxis in a parallel group of patients with multiple myeloma. In contrast, treatment with 2 × 2 g daily induced higher lymphocyte responsiveness and significantly increased nonspecific phagocytosis of both neutrophils and monocytes. The experience in healthy volunteers clearly demonstrates that the latter dose, usually the highest required for antibiotic treatment with cefodizime, is still located on the upward slope of the dose-response curve of positive BRM effects.

An apparently healthy boy was suffering from recurrent Aspergillus infections. No classical conditions of immunodeficiency were found. Studies on the patient's phagocytic system revealed neutrophils and monocytes to function normally except in Aspergillus killing (microbicidal activity for bacteria and Candida was normal). Aspergillus killing mechanisms may be complex and peculiarly selective, possibly involving both oxygen-dependent and independent mechanisms.

Some data exist showing that rifampicin can reduce or abolish the tuberculin reaction in guinea pigs infected with tubercle bacilli [1] as well as the development both of immediate and delayedhypersensitivity reactions in rabbits inoculated with bovine serum albumin [2]. In addition some authors showed that rifampicin could interfere in the blastic transformation of lymphocytes [3, 4] and in the metabolism of some mammalian cells [5]. We sought to determine whether or not rifampicin could directly influence the phenomena of delayed hypersensitivity both in vitro and in vivo (independent of its antimycobacterial activity).

Repeated transfers of strains of Escherichia coli and Staphylococcus aureus in medium containing subminimal inhibitory concentrations (sub-MICs) of gentamicin caused a moderate increase in the minimal inhibitory concentration of gentamicin. At the end of such transfers, E. coli K12 produced aminoglycoside phosphotransferase(3')-I [APH(3')], AND E. coli R112, which carries the plasmid-coded enzyme APH(3')-I, also produced the acetylating enzyme aminoglycoside acetyltransferase(2') [AAC(2')]. E. coli R148, which produces aminoglycoside phosphotransferase(3')-II [APH(3')-II], did not change its output of enzymes. Repeated transfers to media containing increasing concentrations of gentamicin resulted in the development of complete resistance to all aminoglycosides without the concurrent development of any demonstrable new enzyme activity. With repeated transfers in drug-free medium, a complete reversal to susceptibility to gentamicin, but not to other aminoglycosides, was obtained for strains that had previously been transferred in sub-MICs of gentamicin, whereas strains that had been transferred in increasing concentrations of gentamicin did not revert to their original sensitivity to aminoglycosides despite repeated transfers in drug-free medium.