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The combination of sulbactam (S) plus ampicillin (A) extends the activity of ampicillin (Amp) against beta-lactamase producing strains. This combination is therefore useful in many clinical situations including LRTI. A clinical trial was carried out to evaluate the clinical and bacteriological efficacy of S-Amp in LRTI in comparison with Amp alone. Concerning clinical outcome the results were satisfactory in 83.3% of cases for S-Amp group and 82.3% of cases for Amp group. Pathogen eradication was achieved in 87.5% and 70.5% of cases respectively for the S-Amp and Amp group.

This review summarizes the experience gained on interactions between antimicrobial agents and some reactions of the host defense system (adherence, chemotaxis, phagocytosis, microbicidal activity of leukocytes, complement system, antibody production, cell-mediated immunity) and attempts a critical evaluation. The data collected from the literature are often conflicting and there seem to be differences of behavior among derivatives belonging to the same family of antibiotics. Therefore it is quite difficult to draw a correct conclusion from these data. So far it has not been possible to understand the impact that the interference of antibiotics in natural and immunologic reactions of the host defense has on the outcome of chemotherapy, mainly in patients with some degree of immunodepression. In this instance, in fact, the interference with certain immunologic reactions could influence the therapeutic activity of specific antibiotics that are endowed with inhibitory activity. However, so far no controlled study or clear demonstration has shown that antibiotics with different activity on the immunologic reactions can have different efficacy in immunodepressed patients.

We studied the effects of rifamycin SV, rifampicin and rifapentine on human phagocyte functions. Rifamycins inhibited in vitro neutrophil chemotaxis in the range of their therapeutic levels, and they significantly affected the survival of a rifamycin-sensitive strain of Staphylococcus aureus inside human monocytes. Both effects were related to the intraphagocytic penetration of these antibiotics. For the ex vivo studies, 600 mg of rifampicin were orally administered to five subjects with defective S. aureus killing. A significant reduction of neutrophil chemotaxis and increased activity against S. aureus were shown 150 and 210 min after administration of the drug.

The interference of teicoplanin with certain phagocyte activities was investigated in comparison with that of vancomycin. Neither teicoplanin nor vancomycin interfered with chemotaxis, adherence, phagocytosis or nitroblue tetrazolium reduction of human neutrophils. Teicoplanin, but not vancomycin, enhanced intracellular killing by neutrophils from normal donors and from a patient with chronic granulomatous disease. Human monocytes in the absence of fresh human serum did not significantly kill Staphylococcus aureus but when pre-treated with teicoplanin 90% of phagocytozed bacteria were killed during 4 h incubation.

Roxithromycin sputum and serum concentrations after administration of therapeutic doses (150 mg in a single dose) were evaluated in six patients. Blood samples and pooled sputum samples were collected at corresponding time intervals up to 24 h after drug administration. Roxithromycin sputum levels were found to be almost always above serum concentrations, the highest sputum levels being 5.85 +/- 2.5 micrograms/ml in the interval ranging from 2 to 4 h after drug administration. Due to its antibacterial spectrum and favourable pharmacokinetic properties, roxithromycin, like other macrolide antibiotics, seems to be particularly indicated in the treatment of respiratory tract infections.

Bacitracin and neomycin have been used for a long time for local intestinal antisepsis or decontamination, due to their scarce or nonexistent intestinal absorption. The aim of the present study was to determine the activity of bacitracin and neomycin against recent clinical isolates of aerobic and anaerobic microorganisms and to verify their capacity to have a synergistic effect and to prevent the emergence of bacterial resistance when in combination. The results showed that the activity of either antibiotic against recent clinical isolates (even if resistant to cephalosporins and aminoglycosides) is similar to that originally displayed at the time introduction in therapy. Generally the combination of the two antibiotics showed a synergistic or additive effect and prevented the selection of resistant strains.

Staphylococcus aureus, which has exceptional ability to cause disease in man, has responded to the introductions of antimicrobial agents by the selection and emergence of antibiotic-resistant strains. There have been cyclical changes in the prevalence of these strains in nosocomial infections. Other Gram-positive species that give rise to concern, for related reasons, are Staph. epidermidis and other coagulase-negative staphylococci, Streptococcus faecalis and the JK group of corynebacteria. These problems are discussed to provide a background for the contributions that follow.

The aim of this study was to examine the in vitro activity of erythromycin, josamycin, flurithromycin, miocamycin and roxithromycin on some leukocyte functional parameters. All tested macrolides did not interfere with the frequency and index of phagocytosis, nitroblue tetrazolium reduction to formazan deposits and candidacidal activity of human polymorphonuclear leukocytes (p greater than 0.05). Among macrolide antibiotics, only flurithromycin significantly inhibited neutrophil chemotaxis at a high concentration (greater than or equal to 50 micrograms/ml). All macrolides, at 10 and 50 micrograms/ml, reduced the survival of a susceptible strain of Staphylococcus aureus ingested by human monocytes.