Effect of cefodizime and ceftriaxone on phagocytic function in patients with severe infections

Abstract

Thirty patients with severe bacterial infections were treated with 50 mg of cefodizime per kg of body weight once daily or 50 mg of ceftriaxone per kg once daily for 10 ؎ 3 days. The effect of cefodizime and ceftriaxone on the phagocytic capacity and generation of reactive oxygen intermediates after phagocytosis by granulocytes was assessed prior to, during, and after therapy. Flow cytometry was used to study phagocytic capacity by measuring the uptake of fluorescein-labeled bacteria. The generation of reactive oxygen intermediates after phagocytosis was estimated by the quantification of the intracellular conversion of dihydrorhodamine 123 to rhodamine 123. Prior to therapy, patients in both groups exhibited a decreased capacity to phagocytize Escherichia coli and subsequently to generate reactive oxygen intermediates. Granulocyte function increased after the initiation of therapy and normalized within 7 days for the ceftriaxone-treated patients and within 3 days for the cefodizime group (P < 0.05). In the cefodizime group, an enhancement of phagocytic capacity was observed 14 days after the initiation of therapy (P < 0.05). Prior to therapy, phagocytic capacity was significantly correlated with the generation of reactive oxygen products (r ‫؍‬ 0.674 and P < 0.005).

Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or "Immuno-Fairy Tales"?

“…Ethical (and economic) problems, the good "classical" antibacterial activity of this drug, and the unclarified mechanism of action and cellular targets have made it difficult to establish satisfactory protocols to illustrate the advantages of such an IRM antibiotic. In the study by Wenisch et al (410), phagocyte function recovered significantly earlier in a group of 15 infected patients receiving cefodizime than in a comparable group treated with ceftriaxone, but the only apparent clinical advantage was earlier defervescence in the cefodizime-treated group. No reports are available on the consequences of prophylactic administration of cefodizime in patients at risk of infections.…”

“…Restoration of phagocytic microbicidal function could lead to accelerated clinical improvement or better coverage of potential superinfections. Cefodizime, a broad-spectrum cephalosporin, has been proposed as such a biological response modifier antibiotic (195,324,410). It is even possible that quinolones may be active in immunocompromised individuals not only through their bactericidal potency but also through immunoenhancing effects (57,85).…”

Oxidative burst measurement in patients treated with cytostatics: influence of G-CSF and role as a prognostic factor

“…The oxidative burst can be altered, enhanced, or decreased by a number of substances and medical drugs such as antibiotics [36,54,55], nitric oxide [14], amphotericin B, lipid emulsions [29], and anesthetics [12,17]. It has been found that the oxidative burst is impaired during sepsis [13,32,47,53].…”

WBC count and functional changes induced by co-administration of clofazimine and clarithromycin, in single and multiple doses, in Wistar rats

“…In studies that used FACS to evaluate the effects of antimicrobial treatments on neutrophilic burst oxidative activity and phagocytosis (Wenisch et al, 1995;Wenisch et al, 1996), no changes in ROS production were observed in patients who used clarithromycin. In a different study, an increase in neutrophilic oxidative burst activity was observed (Shirai et al, 1995).…”

“…Although a number of studies have investigated the role of these two drugs over the modulation of inflammatory responses, including the production of reactive oxygen species (ROS) by phagocytes (Umeki, 1993;Lemke, 1995;Shirai et al, 1995;Wenisch et al, 1995;Wenisch et al, 1996;Abdelghaffar et al, 1997;Kadota et al, 1998;Kadir et al, 2000;Abdelghaffar et al, 2002;Jain et al, 2002;Sugihara et al, 2003;Tamaoki et al, 2004;Ishida et al, 2007;Yano et al, 2011), none have evaluated the effects of co-administration of the two drugs.…”