Improved phagocyte response by co-amoxiclav in renal transplant recipients.

BACKGROUND: Infectious diseases are a major source of morbidity and mortality for immunosuppressed transplant recipients and the antimicrobial chemotherapy can be often less effective in these individuals, because the contribution of underlying host defenses is absent. METHODS: The influence of co-amoxiclav on the functions of polymorphonuclear granulocytes (PMNs) from renal transplant recipients were investigated. RESULTS: PMNs from renal transplant recipients showed a diminished phagocytic activity with reduced phagocytosis and bactericidal activity against intracellular Klebsiella pneumoniae, compared to that seen with PMNs from healthy subjects. Co-amoxiclav significantly elicited the functions of PMNs from uremic patients, resulting in an increased percentage of ingested klebsiellae and in a higher bactericidal effect (98-99%), compared with the drug-free control system. When PMNs were collected from renal transplant recipients treated with co-amoxiclav a significant high increase in both phagocytosis and killing activity were detected, showing the co-amoxiclav capability of "restoring" even in vivo the depressed primary functions of PMNs. CONCLUSIONS: The interesting beneficial properties of co-amoxiclav, which result in restoring the phagocyte-dependent response in renal transplant patients both in vitro and in vivo, may make this drug more suitable for the treatment of infections in patients with defects of phagocyte functions.

Enhanced effects of amoxycillin/clavulanic acid compared with amoxycillin and clavulanic acid alone on the susceptibility to immunodefenses of a penicillin-resistant strain of Streptococcus pneumoniae.

The recent increase in the incidence of infections due to Streptococcus pneumoniae resistant to penicillin and other antibiotics, often associated with considerable morbidity and mortality, has been recognized as an alarming problem. From the recent medical literature data it emerges that among beta-lactam antibiotics used as an empiric treatment for infections caused by S. pneumoniae, amoxycillin and amoxycillin/clavulanic acid are the most active oral antibiotics and may be considered as a first-line therapeutic agent for the treatment of these infections. Since the therapeutic result of the treatment of an infection is determined by the combined effect of the antimicrobials and host defenses, we investigated the effect of amoxycillin, with and without clavulanic acid, upon the in vitro interaction between human polymorphonuclear leukocytes (PMNs) and a penicillin-resistant strain of S. pneumoniae. Amoxycillin significantly inhibited the streptococcal uptake by PMNs referred to the control system. Clavulanic acid did not have any significant effect upon the interaction PMNs-S. pneumoniae. The addition of amoxycillin/clavulanic acid to phagocytes and streptococci resulted in a synergystic potentiation of the activity of both drugs upon the PMN functions towards S. pneumoniae in such a manner that the bacteria became more susceptible to either the phagocytosis or the microbicidal activities of phagocytes. These effects came in addition to the intrinsic, excellent antimicrobial properties of this drug combination. Although the clinical significance of the observed enhanced effects of amoxycillin/clavulanate are far from elucidated, the possibility exists that they may play a contributory role, especially in patients with impaired host defense.

Cellular uptake and intraphagocytic activity of the new fluoroquinolone AF 3013 against Klebsiella pneumoniae.

The entry of an antibiotic into phagocytes is a prerequisite for its intracellular bioactivity against susceptible facultative or obligatory intracellular microorganisms. AF 3013 is a new fluoroquinolone, and its uptake into and elimination from mouse peritoneal macrophages, together with its effects on phagocytic and antimicrobial mechanisms against Klebsiella pneumoniae, were investigated. AF 3013 efficiently penetrated into phagocytic cells at all concentrations tested. The uptake proceeded rapidly and was energy independent, since it was not affected by cell viability, environmental temperature or the addition of a metabolic inhibitor. Therefore, a possible passive transmembrane diffusion mechanism might be proposed. The elution of AF 3013 from macrophages occurred relatively slowly; in fact, 60 min after the removal of extracellular AF 3013, nearly 40% of the drug still remained in the phagocytes. Exposure to 1 MIC of AF 3013 significantly enhanced macrophages phagocytosis and increased intracellular bactericidal activity against K. pneumoniae. Following preexposure of macrophages to 1 MIC of AF 3013, there was a significant increase in both phagocytosis and killing, compared with the controls, indicating the ability of AF 3013 to interact with biological membranes and remain active within phagocytes. Preexposure of Klebsiella to AF 3013 made the bacteria more susceptible to the bactericidal mechanisms of macrophages than untreated organisms.

Population exposure to electromagnetic fields generated by radio base stations: evaluation of the urban background by using provisional model and instrumental measurements.

Electromagnetic radiation, which is used by broadcasting and mobile telephone systems to transmit information, permeates the city environment. In order to properly evaluate population exposure to electromagnetic fields, knowledge of their intensity and spectral components is necessary. In this study the results of radiofrequency field monitoring carried out in Torino, a large town located in the north-west of Italy are shown: the variation of the electromagnetic field strength is evaluated as a function of the height from the ground, the location in the urban area and the frequency. separating the contributions of the different sources (broadcasting antennas and radio base stations for mobile phones). Furthermore, the contribution of the radio base stations is theoretically evaluated, adding the emissions off all installations situated in Torino and examining the field strength maps calculated, considering the orography, for different heights. The theoretical values are also compared with those measured in the frequency range of mobile telephony emissions.

Tanning lamps ultraviolet emissions and compliance with technical standards.

In this work the compliance of tanning lamps with technical standards EN 60335-2-27 'Household and similar electrical appliances-Safety. Part 2: Particular requirements for appliances for skin exposure to ultraviolet and infrared radiation' was analysed. Results of this analysis showed that none of the examined technical documentation produced by the lamps manufacturers is fully compliant with the standard technique. Furthermore data reported in the same manuals, such as effective radiant exposure or irradiance, would indicate that these sources may be the cause of undue exposure to ultraviolet (UV) radiation. For this reason a measurement campaign on UV lamps used in tanning salons was organised. The first results of these measurements seem to confirm the doubts raised from the analysis of the lamp manuals: the use of a tanning lamp can lead to UV radiation exposure levels higher than reference maximum values recommended by EN 60335-2-27.

Sub-MICs of sanfetrinem promote the interaction of human polymorphonuclear granulocytes with a multiply resistant strain of Klebsiella pneumoniae.

The effect of sanfetrinem, a member of a new class of antibiotics, upon the in-vitro interaction between human polymorphonuclear granulocytes (PMNs) and a multiply resistant strain of Klebsiella pneumoniae was investigated. Sub-MICs of sanfetrinem significantly enhanced PMN phagocytosis and greatly reduced the survival of intracellular bacteria compared with antibiotic-free systems. The distinction between any effect of sanfetrinem on the klebsiellae and the phagocytes was made by exposing each of them to the drug before they were incubated together. The results indicate that sanfetrinem may have a direct positive action either on K. pneumoniae or on human granulocytes.

Entry of sanfetrinem into human polymorphonuclear granulocytes and its cell-associated activity against intracellular, penicillin-resistant Streptococcus pneumoniae.

The entry of antibiotics into phagocytes is necessary for activity against intracellular pathogens. The ability of sanfetrinem, the first member of a new class of antibiotics, to penetrate human polymorphonuclear granulocytes and its consequences upon subsequent phagocytosis and killing of ingested penicillin-resistant Streptococcus pneumoniae have been evaluated. Sanfetrinem penetrated into human polymorphonuclear leukocytes (PMNs) at all concentrations tested, with cellular concentration/extracellular concentration ratios of 6.6 to 5.03 and 4.21 when sanfetrinem was used at 0.25 to 0.5 and 1 microgram/ml, respectively, within 30 min of incubation. The uptake was complete within 5 min and was not energy dependent, since it was not affected by cell viability, environmental temperature, or the addition of a metabolic inhibitor. At a concentration of one-half the MIC, sanfetrinem significantly enhanced human PMN phagocytosis and increased intracellular bactericidal activity against penicillin-resistant S. pneumoniae. Following preexposure of PMNs to a concentration of one-half the MIC of sanfetrinem, there was a significant increase in both phagocytosis and killing compared with that for the controls, indicating the ability of sanfetrinem to interact with biological membranes and remain active within PMNs. Preexposure of streptococci to sanfetrinem made penicillin-resistant S. pneumoniae more susceptible to the bactericidal mechanisms of human PMNs than untreated organisms.

Co-amoxiclav affects cytokine production by human polymorphonuclear cells.

Some antimicrobial agents have been reported to modify the host immune responses both in vivo and in vitro. As we demonstrated previously that co-amoxiclav had beneficial properties which result in enhancement of the microbicidal functions of human poly-morphonuclear cell (PMNs), we investigated the modulatory effect of this combination on cytokine production by human PMNs in vitro. The addition of co-amoxiclav elicited the production by lipopolysaccharide (LPS)-stimulated PMNs of substantial amounts of some cytokines, namely IL-8 and IL-1beta, after the addition of Klebsiella pneumoniae. These cytokine levels were higher than those obtained by PMNs incubated in culture medium only, without co-amoxiclav.

Cefonicid 'restores' the depressed activities of polymorphonuclear cells from chronic haemodialysis patients and renal transplant recipients in vitro.

BACKGROUND: Chronic haemodialysis patients and renal transplant recipients are highly susceptible to infection characterized by high morbidity and mortality and related to an impairment of the phagocytic response. SUBJECTS AND METHODS: In order to elucidate how cefonicid, a cephalosporin with a broad spectrum of activity and once-daily dosage, influences this phagocytic response, the effects of the drug upon the functions of human PMNs from both healthy individuals and immunocompromised patients were investigated. RESULTS: In vitro, PMNs from haemodialysed patients and renal transplant recipients showed a diminished phagocytic efficiency with reduced phagocytosis and bactericidal activity towards intracellular Klebsiella pneumoniae when compared with that seen in PMNs from healthy subjects. Cefonicid significantly affected the activity of PMNs from healthy volunteers, resulting in either an increased percentage of ingested klebsiellae or a reduced intracellular bacterial load when compared with the control, drug-free system. When cefonicid was added to PMNs from uraemic patients a pattern similar to that observed with phagocytes from healthy subjects was detected: the antibiotic was able to 'restore' the depressed primary functions of PMNs, resulting in a significant increase in both phagocytosis and killing activity. CONCLUSIONS: Cefonicid, with its several immunoproperties observed in this study, possesses interesting beneficial properties which make it suitable for the treatment of infections in patients with impaired components of the immune system.

Influence of a new fluoroquinolone, AF3013 (the active metabolite of prulifloxacin), on macrophage functions against Klebsiella pneumoniae: an in vitro comparison with pefloxacin.

The efficacy of an antibiotic in the treatment of bacterial infections depends upon the interaction of bacterium, drug and phagocytes. In this study we have investigated the influence of AF3013, a new fluoroquinolone, on the activities of mouse peritoneal macrophages against Klebsiella pneumoniae, in comparison with the influence of pefloxacin. Bacterial susceptibility to phagocytosis and intracellular killing were determined after klebsiellae and macrophages had been incubated simultaneously with inhibitory concentrations of both AF3013 and pefloxacin and following pre-exposure of the microorganisms and the macrophages individually to the same concentrations of each drug. Under the experimental conditions used, both AF3013 and pefloxacin potentiated the phagocytic and microbicidal activities of the macrophages, although different mechanisms may be involved.