C. Bersani

Evaluation of Systemic Host Defense Mechanisms in Chronic Bronchitis

Seventy-six chronic bronchitis patients were studied in order to determine the possible presence of disorders in their systemic defense mechanisms. No significant difference in lymphocyte subsets, in serum immunoglobulin and complement component (C3 and C4) levels was found in chronic bronchitis patients compared to normal adult controls. Skin tests for delayed hypersensitivity revealed a high frequency (39%) of hypoergic patients (with 1-2 positive reactions) in comparison to normal subjects. Altered values of many functional properties of both neutrophils and monocytes were demonstrated. The percentage of patients with intermediate (between 1 and 2 SD below the mean of controls) and defective (lower than 1.96 SD) values of chemotaxis, phagocytosis index and Candida killing was about 50%. Phagocytosis frequency and nitroblue tetrazolium reduction frequency were less frequently impaired.

In vitro and ex vivo Enhancement of Nonspecific Phagocytosis by Cefodizime

The in vitro and ex vivo effects of cefodizime on some functional activities of both human neutrophils and monocytes were studied. In vitro experiments were performed with antibiotic concentrations ranging from 1 to 200 micrograms/ml. For the ex vivo study, 7 adult healthy controls were treated intravenously with 4 g/day of cefodizime for 6 days. We found that the drug modulated phagocytosis frequency and index when nonopsonized zymosan and heat-killed Candida albicans were used as phagocytic challenge both in vitro (from 25 micrograms/ml) and ex vivo 12 h after the last administration of cefodizime. No effect on the other phagocyte functional parameters was shown. The in vitro enhancement of nonspecific phagocytosis was demonstrated both in the presence of cefodizime and when phagocytes and particles were separately incubated with the drug.

Double-Blind Trial RU 41740 vs. Placebo: Immunological and Clinical Effects in a Group of Patients with Chronic Bronchitis

A double-blind trail was performed to investigate the effects of RU 41740, a glycoprotein extract from Klebsiella pneumoniae, on host defenses and its efficacy in reducing the number of exacerbation in 29 evaluable patients with chronic bronchitis, out of 36 patients who entered the study. The drug enhanced the phagocytosis indexes of both polymorphonuclear and mononuclear phagocytes. Increased candidacidal activity of monocytes was also observed. These effects, already detectable after one course of therapy and during the entire period of treatment, were no longer detectable when tested 6 months after the end of treatment. A significantly (p less than 0.05) larger number of patients in the treated group than in the placebo group had no exacerbations during drug administration (0-3 months). Moreover, patients treated with RU 41740 had significantly fewer and shorter episodes of acute exacerbation. The positive decreases in these two parameters persisted throughout the follow-up.

In vitro Activity of Teichomycin against Isolates of Gram-Positive Bacteria

The in vitro activity of teichomycin has been evaluated against 189 clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis and group D streptococci. Teichomycin was as active as vancomycin, a chemically related antibiotic, on staphylococci and inhibited the in vitro growth of methicillin-resistant strains at the same concentration necessary to inhibit the sensitive ones. Against group D streptococci teichomycin was about three times more active than vancomycin (MIC50 = 0.125 mg/l, MIC90 = 0.4 mg/l). MBC:MIC ratios of both drugs against staphylococci were comparable, but teichomycin had higher bactericidal activity against group D streptococci, as shown also by killing curves. The activity of teichomycin was not significantly affected by variation of pH, even if the maximum activity was achieved at neutral pH, or by different methods of MIC evaluation. The antibiotic seemed more active when tested with a low inoculum (10(3)-10(5)/ml): a two- to threefold increase in MIC was observed at an inoculum of 10(7)/ml. A reduction of the in vitro activity could be shown when Penassay broth was used as culture medium.

The effect of teicoplanin on leukocytic activity and intraleukocytic micro-organisms

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.

In Vitro and Ex Vivo Effect of Cefodizime on Phagocytosis

Among the newer cephalosporins, cefodizime, an α-methoxy-imino-2-thiazolyl derivative, has been reported to display direct and indirect effect on some components of the host defense system against infection [3–7]. The aim of our research was to study the in vitro and ex vivo direct effect of cefodizime on human mononuclear and polymorphonuclear phagocytes in order to better understand the mechanism of its immunomodulating properties.

Phagocytes and their pharmacological modulation in chronic bronchitis

Altered values of many functional properties of both peripheral phagocytes (neutrophils and monocytes) and alveolar macrophages were demonstrated in patients with chronic bronchitis. Out of this population 16 patients with defective phagocytosis index were included in an open randomized trial to investigate the effect of RU41740, a glycoprotein extract of K1. pneumoniae, on this phagocytic function and its efficacy in reducing the number of exacerbations. A relationship between the restoration of the immunological parameter and the clinical improvement was demonstrated. This effect suggests that phagocytosis can play a role in protecting patients with chronic bronchitis from infectious exacerbations.