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Biomedical subjects

A M Cuffini

Publications and source records attributed to A M Cuffini.

At least 37 records · Page 2Linked to original sources

Effect of ceftriaxone on the phagocytosis and intracellular killing of Staphylococcus aureus by human macrophages.

The efficacy of an antimicrobial agent in the treatment of infections depends upon the interactions of bacteria, antibiotic and phagocytes. The influence of ceftriaxone on the phagocytic and bactericidal activity of human macrophages in vitro and ex vivo was investigated. At concentrations one-half the minimum inhibitory concentration (1/2 x MIC) the antibiotic caused in vitro a significant enhancement of phagocytosis and a reduction in the survival of intracellular Staphylococcus aureus. The distinction between any effect of ceftriaxone on the staphylococci and the macrophages was made by exposure of each of them to the antibiotic before they were incubated together. The results suggest that ceftriaxone may have a direct positive action on macrophages, possibly by interfering with the cellular membrane functions and hence enhancing engulfment of bacteria. The ex vivo data seem to corroborate this hypothesis.

Animals↗

Effect of rufloxacin upon non-specific immune defences: in-vitro, ex-vivo and in-vivo results.

This study investigated in-vitro, ex-vivo and in-vivo the immunomodulatory effects of rufloxacin. 0.5 MIC of rufloxacin significantly enhanced human macrophage phagocytosis and increased intracellular killing of Klebsiella pneumoniae in vitro. Pre-incubation of K. pneumoniae with rufloxacin made the bacteria more susceptible to both phagocytosis and intracellular killing by human macrophages than control organisms. Following pre-exposure of macrophages to 0.5 MIC of rufloxacin, there was a significant increase in the intracellular killing of K. pneumoniae compared with the controls, indicating the ability of rufloxacin to cross biological membranes and to remain active within phagocytes. Ex-vivo experiments show that iv administration of rufloxacin in mice lead to an increase in both phagocytic and microbicidal intracellular activity by phagocytes. In-vivo models of experimental infections showed that prophylactic administration of rufloxacin increased the survival of mice after challenge with Candida albicans.

Animals↗

Enhanced Staphylococcus aureus susceptibility to immunodefences induced by sub-inhibitory and bactericidal concentrations of imipenem.

Recent evidence suggests that the selection of an antibiotic for the treatment of infection should take into account not only the drug's antimicrobial activity but also the way in which it interacts with host defence mechanisms, since this may influence the response to infection. In this study we have investigated the effects of imipenem on the activities of human macrophages against Staphylococcus aureus. Bacterial susceptibility to phagocytosis and intracellular killing were determined after S. aureus and macrophages were incubated both simultaneously with sub-inhibitory and bactericidal concentrations of imipenem and following pre-exposure of the organisms and the macrophages individually to the same concentrations of imipenem. At both concentrations and under both circumstances, imipenem potentiated the phagocytic and microbicidal activities of the macrophages.

Blood Bactericidal Activity↗

The entry of meropenem into human macrophages and its immunomodulating activity.

The uptake of meropenem by human macrophages and its consequences upon subsequent phagocytosis and killing of intracellular staphylococci has been studied. The cellular to extracellular concentration ratios (C/E) of meropenem were always high (range 3-12) at extracellular concentrations ranging from 0.125 to 1 mg/L. The uptake was not energy-dependent, being similar when viable and formalin-killed cells were used and was influenced neither by environmental temperature nor by the addition of a metabolic inhibitor. Meropenem at half the MIC caused a significant enhancement of phagocytosis and a reduction in the survival of intracellular Staphylococcus aureus. Pre-exposure of either staphylococci or macrophages to sub-MIC concentrations of meropenem led to an increase in uptake of bacteria and intracellular bactericidal activity by macrophages.

Adjuvants, Immunologic↗

Pefloxacin and immunity: cellular uptake, potentiation of macrophage phagocytosis and intracellular bioactivity for Klebsiella pneumoniae.

Antibiotic potentiation of host defence mechanisms may be of potential clinical importance in the outcome of infections. Therefore the effect of pefloxacin upon the interaction of in vitro of human macrophages with Klebsiella pneumoniae, by assays of antibiotic cellular uptake, bacterial phagocytosis and intracellular killing, was examined. The results indicated that pefloxacin was well concentrated by phagocytes at all the concentrations tested. The uptake proceeded rapidly and was not affected either by cell viability or physiological environmental temperature. Synergistic phagocytosis and intracellular killing of K. pneumoniae was observed in the presence of macrophages and subinhibitory concentrations (one-half MIC) of pefloxacin. Pretreatment of bacteria with pefloxacin led to an increase in both bacterial uptake and microbicidal activity of phagocytes. Exposure of the macrophages to pefloxacin did not affect any phagocyte functions.

Humans↗

Cefonicid potentiation of human macrophage activity.

This study was undertaken to evaluate the in vitro effects of cefonicid on phagocyte functions such as phagocytosis and intracellular killing of phagocytosed bacteria. At concentrations of half the MIC cefonicid caused human macrophages to ingest and kill Klebsiella pneumoniae at a greater rate than did drug-free macrophages. Bacteria pretreated with subinhibitory concentrations of cefonicid became more susceptible to the phagocytic and bactericidal activity of macrophages than untreated microorganisms. Sub-MIC cefonicid pretreatment of macrophages did not reduce phagocytosis and killing, confirming the inability of beta-lactam antibiotics to cross biological membranes.

Cefonicid↗

Adhesion of Proteus mirabilis and Proteus vulgaris to uroepithelial cells following exposure to various antimicrobial agents.

The effect of subinhibitory concentrations of netilmicin, ceftriaxone, cefotaxime, aztreonam and piperacillin on the adherence of Proteus species to uroepithelial cells was examined. Bacterial adhesion to human uroepithelial cells, measured microscopically, was affected by all five antibiotics but to different extents. The most effective was netilmicin. There was a correlation between the decreased rate of bacterial attachment and morphological changes in the drug-exposed bacteria.

Anti-Bacterial Agents↗

Effect of bacampicillin and ampicillin on the phagocytic, microbicidal functions of human macrophages.

During acute bacterial infections, antibiotics only assist the phagocytic system in eradicating the invading organism. In this regard, the effect of ampicillin and its prodrug bacampicillin on the phagocytosis and killing of Staphylococcus aureus by human macrophages was compared. Bacterial phagocytosis was enhanced after pre-incubation of staphylococci with bacampicillin. At a concentration of half the MIC bacampicillin showed a much more impressive killing capacity on macrophage-ingested live bacteria than did ampicillin, under all the experimental conditions tested.

Ampicillin↗

New imidazole derivates: in-vitro activity on dermatophytes.

The in-vitro activities of two new miconazole and econazole salts (sulfosalicylic acid formulation) against 98 clinical isolates of dermatophytes were evaluated, in comparison to those of miconazole, miconazole nitrate, econazole and econazole nitrate. Miconazole sulfosalicylate and econazole sulfosalicylate exhibited good activity towards all the dermatophytes tested, although econazole and its derivatives were more efficacious than miconazole and its salts. The new imidazoles were equally effective in inhibiting the fungal growth with respect to miconazole, miconazole nitrate, econazole and econazole nitrate.

Antifungal Agents↗

Teicoplanin and its influence on Staphylococcus aureus ultrastructure.

Teicoplanin, a glycopeptide antibiotic chemically related to the vancomycin-ristocetin group of antibiotics, has been shown to be active against gram-positive bacteria. Binding of teicoplanin by actively growing bacteria leads to morphological damage to the cell surface in staphylococci, as largely shown by transmission and scanning microscopy results.

Anti-Bacterial Agents↗

Interactions of antibiotics with phagocytes in vitro.

The goal of antimicrobial therapy is to eliminate invading bacteria both in the extracellular and intracellular environment. Thus, recent work has focused on the ability of various antibiotics to enter phagocytic cells and kill intracellular pathogens, since bacteria which survive within phagocytes may often produce prolonged or recurrent infections. In the last ten years the antibiotic modulation of phagocytic cell functions has become the subject of our major investigational activity. Taking into account that entry of antibiotics into phagocytes is necessary for activity against intracellular organisms, we examined the uptake of 11 radiolabelled antibiotics by macrophages. Penicillins and cephalosporins were taken up poorly by phagocytes. Teicoplanin was efficiently concentrated by macrophages, achieving intracellular concentrations higher than those in the surrounding extracellular medium. Roxithromycin was more markedly accumulated within phagocytes than was erythromycin, depending upon an active transport mechanism. Antitubercular drugs were concentrated approximately twofold in the macrophages. Besides, since antibiotics that act on phagocytosed bacteria have clinical advantages, we evaluated the direct action of the above mentioned drugs on the macrophage, by determining their interference with its functions or their potentiation of both phagocytosis and killing of bacteria.

Anti-Bacterial Agents↗

In vitro antifungal activities of new imidazole salts towards dermatophytes.

The in vitro activities of two new miconazole and econazole salts with the sulphosalicylic acid against 71 clinical isolates of dermatophytes were evaluated in comparison with those of miconazole, miconazole nitrate, econazole and econazole nitrate. Miconazole sulphosalicylate and econazole sulphosalicylate were equally effective in inhibiting the fungal growth compared with miconazole, econazole, and their nitrates.

Arthrodermataceae↗

Cellular uptake, and intracellular bactericidal activity of teicoplanin in human macrophages.

The effects of teicoplanin on human macrophage functions were evaluated by assays of antibiotic uptake, bacterial phagocytosis and intracellular killing. The results indicated that teicoplanin was efficiently concentrated by both resident and stimulated phagocytes, achieving intracellular concentrations higher than those in the surrounding extracellular medium. Comparison of the degree of antibiotic penetration into dead, resident and stimulated macrophages seemed to suggest that transfer across the macrophage membrane was of a passive nature, and was not related to the metabolic state of the cells. At concentrations of half its MIC for the bacteria, teicoplanin caused macrophages to ingest and kill Staphylococcus aureus at a greater rate than did macrophages without drug. Phagocytes harvested from mice receiving intravenous teicoplanin showed greater phagocytic activity than those from control mice, suggesting that potentiation of host defences can occur in vivo.

Animals↗

Comparative effects of roxithromycin and erythromycin on cellular immune functions in vitro. 1. Uptake of 3H-macrolides by human macrophages.

The degree of penetration of roxithromycin in human macrophages was evaluated and compared with that of erythromycin. The results indicated that both macrolides at concentrations of 2, 10 and 20 micrograms/ml were concentrated by macrophages, even if roxithromycin was consistently and significantly more accumulated than erythromycin. Comparison of the degree of penetration of the two drugs into dead, resident and stimulated phagocytes indicated that the process of transfer through the macrophage wall was of an active nature, related to the metabolic state of the cells. Analysis of the binding of the two macrolides to intracellular proteins showed that more binding sites were available for erythromycin than for roxithromycin.

Analysis of Variance↗

Comparative effects of roxithromycin and erythromycin on cellular immune functions in vitro. 3. Killing of intracellular Staphylococcus aureus by human macrophages.

The in vitro effect of roxithromycin on the bactericidal activity of human macrophages was compared with that of erythromycin. At a concentration of half the MIC roxithromycin showed a much more impressive killing capacity on macrophage-ingested live Staphylococcus aureus than did erythromycin, under all the experimental conditions used.

Erythromycin↗