Comparative in vitro activity of cefodizime and other antibiotics against pathogens recently isolated in Italy.

In the present study we tested the susceptibility to cefodizime on 1,985 selected nosocomial pathogens isolated in five laboratories. Moreover, we evaluated the epidemiology of the resistance of the tested strains to cefodizime and to other antibiotics clinically available in Italy. The susceptibility to cefodizime was determined with both MIC (microdilution method) and the agar diffusion method (Kirby-Bauer). The Kirby-Bauer method was used to compare the antibiotics. Cefodizime was equivalent in activity to ceftazidime and ceftriaxone and was more active than piperacillin and amoxicillin + clavulanic acid. The activity of gentamicin (where tested) was generally comparable to that of cefodizime; ciprofloxacin had lower percentages of resistance against some species of Enterobacteriaceae and staphylococci.

Production of cytokines by alveolar and peritoneal macrophages stimulated by Aspergillus fumigatus conidia or hyphae.

Aspergillus fumigatus is an opportunistic pathogen responsible for severe, invasive infections in neutropenic hosts. Lung clearance of A. fumigatus conidia seems to be mediated by phagocytic cells and oxygen radicals. It is not known if cytokines or nitrogen radicals are also involved. We tested for the production of TNF alpha, IL-1 and nitric oxide (NO) after stimulation of mouse macrophages with the fungus. We found that both cytokines, but not NO, were produced in a dose-dependent manner during the first 24 h of culture. Except for a faster kinetic, no appreciable differences were seen between alveolar and peritoneal macrophages. Furthermore, both hyphae and conidia, either alive or killed, were capable of inducing cytokines production. However, among different Aspergillus spp. only A. fumigatus and A. flavus seemed to induce significant amount of TNF alpha and IL-1, whereas A. terreus and A. niger were less effective. In no case could we detect production of NO. Finally, macrophages from dexamethasone-treated mice failed to produce cytokines in response to A. fumigatus conidia. These results indicate that in normal hosts inflammatory cytokines contribute to the natural response against Aspergillus infections and suggest that the impairment of cytokine production, in immunodepressed patients, may favour the growth and spread of the fungus.

Open, controlled, randomized study on the efficacy and safety of cefodizime single daily dose versus two daily doses and versus ceftriaxone single daily dose in patients with acute purulent bronchitis and acute purulent exacerbation of chronic bronchitis.

Two hundred and thirty-eight in-patients with signs and symptoms of acute purulent bronchitis or purulent exacerbation of chronic bronchitis at stage 1 and 2 of Anthonisen's classification were enrolled in 11 Centers and randomly assigned to one of the following 3 treatment groups: group A, cefodizime 1 g i.m. qD; group B, cefodizime 1 g i.m. BID; group C, ceftriaxone 1 g i.m. qD. Bacteriological results after treatment were satisfactory in 64 patients (91.4%) of group A, 64 (92.8%) of group B and 74 (94.9%) of group C. Global clinical results after treatment showed satisfactory efficacy in 57 patients (79.2%) of group A, 59 (85.5%) of group B and 63 (80.8%) of group C. There was no statistically significant difference in improvement in single symptoms, global bacteriological or clinical results between the 3 groups. Mild adverse events occurred in only 3 patients (one per group).

Outer membrane permeability of Serratia marcescens to meropenem and imipenem.

The penetration rates of meropenem and imipenem through the outer membrane (OM) of Serratia marcescens was evaluated by the method of Zimmermann and Rosselet. To this aim, two strains of the specie were transformed with the pMON-01 plasmid DNA that carries the bla S gene from Xanthomonas maltophilia encoding for the L-1 beta-lactamase. The permeability of the transformants to cephaloridine was not affected by the presence of the plasmid. Imipenem was shown to penetrate the OM of the transformants at a rate 4- to 5-fold higher than that of meropenem and close to that of cephaloridine. Meropenem appeared more active than imipenem in inhibiting the targets as inferred from the calculated concentrations of antibiotic in the cell periplasm in the presence of MIC. The calculation of the target access index (TAI) indicated that a 20- to 50-fold decrease in permeability or increase in beta-lactamase activity would be required to significantly increase the MICs of imipenem or meropenem for these strains.

[Microbiological aspects of antibiotics with immunomodulating action]. / Aspetti microbiologici degli antibiotici ad azione immunomodulante.

Through the introduction of a 7-mercapto-1,3-thiazole chain at position 3' of the dihydrothiazine ring, cefodizime, which is structurally similar to cefotaxime, has acquired a number of remarkable immunomodulatory properties while retaining a potent antimicrobial spectrum of activity. Cefodizime penetrates in fact readily through the bacterial cell wall and interacts with its molecular targets in such a way that at high concentrations cell death and lysis are rapidly induced. Its spectrum of action encompasses the Enterobacteria, Neisseriae, Haemophilus, Moraxella catarrhalis, methicillin-susceptible staphylococci and streptococci, with pneumococci included. Cefodizime is devoid of useful potency against Pseudomonas, Acinetobacter and enterococci. Given the wide occurrence of strains synthesizing beta-lactamases in several primary pathogens of community-acquired and nosocomial infections, the complete stability of cefodizime towards the most prevalent of these hydrolytic enzymes (TEM-1, TEM-2, SHV-1, BRO-1 and the staphylococcal penicillinases) seems reassuring. Only a few chromosomally-coded and extended spectrum beta-lactamases produced by gram-negative microorganisms inactivate the new cephalosporin. Since the distribution of pathogens carrying these enzymes depends on the local trends of antibacterial consumption and cannot be easily predicted, a large multicenter study in Italy has recently assessed the antibacterial potency of cefodizime, in comparison with suitable drugs, on 1985 selected nosocomial strains. In this survey cefodizime was more effective in vitro than amoxicillin-clavulanate, gentamicin and piperacillin while being substantially similar in the rates of eradication of gram-negative and gram-positive organisms to other third generation cephalosporins like ceftazidime and ceftriaxone.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of fluoroquinolones on the in-vitro proliferation of myeloid precursor cells.

The effects of three fluoroquinolones (ofloxacin, pefloxacin and rufloxacin) on the in-vitro proliferation of murine myeloid cells were studied. Their activity was compared with that of nalidixic acid and novobiocin. Therapeutic concentrations of quinolones do not affect the physiological course of myelopoiesis. Only very high concentrations of drug (greater than 70 mg/l) affect bone marrow cell growth producing a dose-dependent inhibition. Because quinolones are active on topoisomerase II from eukaryotic cells they can modulate mammalian cell growth.

[Bactericidal and potent antiadhesive activity of sulbenicillin]. / Studio dell'attivita battericida di sulbenicillina e del suo potere antiaderente.

Sulbenicillin, a wide broad spectrum penicillin, is active against a lot of gram positive and gram negative bacteria. The AA. studied the activity of this molecule against urinary infections causing germs, by evaluating two parameters: his antiadhesive capability and the Killing curves, in comparison with mezlocillin and piperacillin. An inhibition in adhesive capability of test-germs, due to sulbenicillin was obtained. Furthermore, resulting Killing curves showed more rapidity in action for sulbenicillin than for the two others molecules, versus resistant germs, like P. aeruginosa and S. faecalis.

In-vitro antibacterial activity of Sch 25393, a fluorinated analogue of thiamphenicol.

The in-vitro antibacterial activity of a fluorinated analogue of thiamphenicol, Sch 25393, has been evaluated in comparison with chloramphenicol and thiamphenicol. The substitution of an hydroxyl group at position 3 and of two atoms of chlorine with fluorine in the acyl side-chain improves remarkably the antibacterial activity of the compound against strains resistant to chloramphenicol and thiamphenicol because of the production of acetyltransferases, but not against strains resistant because of non-enzymatic mechanisms of resistance. Although itself resistant to the enzymatic inactivation, Sch 25393 is unable to inhibit the acetylation of chloramphenicol and thiamphenicol.