Combined action of fluconazole and PMNs from uremic patients in clearing intracellular Candida albicans.
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Adult↗
Biomedical subjects
N A Carlone
Publications and source records attributed to N A Carlone.
Clarithromycin mediated the expression of polymorphonuclear granulocyte response against streptococcus pneumoniae strains with different patterns of susceptibility and resistance to penicillin and clarithromycin.
There is an urgent need for antibiotics that can be used in the therapy of infections caused by penicillin-resistant Streptococcus pneumoniae, the incidence of which is often associated with considerable morbidity and mortality. Antibiotics that can interact positively with the immune response and that also possess microbicidal properties might significantly contribute to improving the outcome of S. pneumoniae infections. Therefore, in the present study we investigated the effect of clarithromycin, an extended spectrum macrolide currently used in the treatment of respiratory tract infections, on the in vitro interaction between human polymorphonuclear granulocytes (PMN) and three strains of S. pneumoniae with different susceptibility or resistance patterns to both penicillin and clarithromycin. At a concentration of one-half the minimal inhibitory concentration (MIC), clarithromycin significantly enhanced human PMN functions, particularly intracellular bactericidal activity, against all the S. pneumoniae strains, including resistant ones. This finding may help to explain clarithromycin activity in vivo despite apparent resistance in vitro. Preexposure of PMNs to one-half the MIC of clarithromycin had no effect on either phagocytosis or intracellular killing, ruling out a direct antibiotic action on PMNs. Preexposure of streptococci to clarithromycin increased the susceptibility of S. pneumoniae to the bactericidal mechanisms of human PMNs compared with untreated bacteria, indicating that this macrolide may partly reduce bacterial virulence via changes in S. pneumoniae.
Anti-Bacterial Agents↗
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.
Amoxicillin-Potassium Clavulanate Combination↗
Impact of co-amoxiclav on polymorphonuclear granulocytes from chronic hemodialysis patients.
Phagocyte-dependent host defenses are frequently impaired in maintenance hemodialysis patients who show an increased susceptibility to infections. In these individuals, the course of infections can be more aggressive than in normal hosts, and the antibiotic of choice should have a high antimicrobial effect without impairing host defenses. Hence, in uremic patients, the antibiotic enhancement of phagocyte functions may be of potential clinical importance in the outcome of bacterial infections. Because we demonstrated previously that co-amoxiclav had beneficial properties that result in enhancement of the microbicidal functions of human polymorphonuclear cells (PMNs) from healthy subjects, we investigated the influence of this combination on the activities of PMNs from chronic hemodialysis patients against Klebsiella pneumoniae, a human pathogen that can pose severe problems in patients whose immunity is impaired. PMNs from chronic dialysis patients showed a diminished in vitro phagocytic efficiency with a reduced phagocytosis and bactericidal activity towards intracellular K. pneumoniae compared with that seen in PMNs from healthy subjects. When co-amoxiclav was added to PMNs from chronic hemodialysis patients, it was able to restore the depressed primary functions of PMNs, resulting in a significant high increase in both phagocytosis or killing activity. A similar pattern was detected with PMNs collected from hemodialysis patients treated with co-amoxiclav. The results of the present study provide evidence that co-amoxiclav is able to induce stimulation of depressed phagocytic response of PMNs from patients on chronic hemodialysis, restoring their primary functions both in vitro and in vivo.
Administration, Oral↗
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.
Animals↗
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.
Amoxicillin-Potassium Clavulanate Combination↗
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.
Animals↗
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.
Anti-Bacterial Agents↗
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.
Adult↗
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.
Anti-Bacterial Agents↗
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.
Amoxicillin↗
Potential effects of amoxycillin/clavulanic acid and ticarcillin/clavulanic acid on human granulocyte activity: a comparative study.
The efficacy of an antimicrobial agent in the therapy of infection depends upon the interaction of bacteria, antibiotic and phagocytes. The influence of both ticarcillin/clavulanic acid and amoxycillin/clavulanic acid on the phagocytic and bactericidal activity of human PMNs in vitro was investigated. The results show that clavulanic acid, with its beta-lactamase inhibitory properties, potentiated the efficacy of both ticarcillin and amoxycillin, resulting in a significantly increased susceptibility of a beta-lactamase producing strain of Klebsiella pneumoniae to phagocytic and microbicidal activities of human PMNs. Overall, amoxycillin/clavulanic acid showed greater enhancement of the killing of K. pneumoniae by human PMNs.
Amoxicillin↗
Interaction of Candida albicans, macrophages and fluconazole: in vitro and ex vivo observations.
In recent years, medical interest in evaluating the interaction among mycetes, phagocytes, and antimycotic drugs has increased notably due to higher incidences of fungal infections in immunocompromised subjects and to the long-term therapy they require. In this study the in vitro and ex vivo interaction of fluconazole, at plasma concentrations, with mouse macrophages was evaluated in the presence of different inocula of Candida albicans. The results showed that fluconazole did not interfere negatively with phagocyte functions; conversely, according to different experimental conditions, it was able to increase both phagocytosis and intracellular killing of candida, probably exerting its action on the yeast rather than on the phagocyte. A higher enhancement of macrophage functions was observed in vitro when the drug was present in the medium with macrophages and candida in a 1:1 ratio.
Animals↗
Potentiation of human polymorphonuclear leukocyte phagocytosis and intracellular bactericidal activity by amoxycillin/clavulanic acid.
The use of broad spectrum beta-lactamase inhibitors in association with beta-lactam agents provides one strategy to overcome the enzymatic resistance. Clavulanic acid is a potent inhibitor of a wide range of bacterial beta-lactamases and its potentiating effect on amoxycillin has been established both in vitro and in clinical trials. Since the efficacy of an antimicrobial agent in the therapy of infections depends on the interaction of bacteria, antibiotic and phagocytes, we investigated the effect of amoxycillin/clavulanic acid on the in vitro interaction between human polymorphonuclear cells (PMNs) and beta-lactamase producing strains of Klebsiella pneumoniae and Staphylococcus aureus. Clavulanic acid did not have any significant influence upon the PMN phagocytosis and killing against intracellular bacteria. Interestingly, the presence of the suicide inhibitor, with its beta-lactamase inhibitory properties, potentiated the activity of amoxycillin against the beta-lactamase producing strains of K. pneumoniae and S. aureus in such a manner that bacteria became significantly more susceptible to either phagocytosis or microbicidal activities of human phagocytes, compared to both the control and amoxycillin systems.
Amoxicillin↗
The antibacterial activity of amoxycillin/clavulanic acid against Staphylococcus aureus ingested by human granulocytes.
The effect of amoxycillin, and amoxycillin/clavulanic acid on the in vitro interaction between human polymorphonuclear cells and a beta-lactamase producing strain of Staphylococcus aureus was investigated. Amoxycillin alone, at half the MIC, significantly inhibited the bacterial uptake by polymorphonuclear (PMN) cells compared with the control; as a consequence the killing of intracellular staphylococci was higher. Clavulanic acid did not have any significant effect upon the activities of phagocytes. The combination amoxycillin/clavulanic acid possesses beneficial properties which result in enhancement of both phagocytosis and microbicidal activity of PMN cells against the beta-lactamase producing strain of S. aureus. A synergic effect between drugs and serum activity was noted.
Amoxicillin↗
Effect of ticarcillin and ticarcillin/clavulanic acid on the in-vitro activity of human granulocytes against beta-lactamase-producing Klebsiella pneumoniae.
Clavulanic acid is an effective inhibitor of a broad range of clinically important beta-lactamases and its combination with some beta-lactam antibiotics such as ticarcillin has been shown to extend the inhibition spectrum of the beta-lactams. The activity of ticarcillin, both alone and in combination with clavulanic acid, upon PMN phagocytosis and bactericidal activity towards Klebsiella pneumoniae was investigated. The results indicate that a combination of ticarcillin with clavulanic acid is more active than ticarcillin alone against a beta-lactamase-producing strain of K. pneumoniae, and hence may significantly increase the bacterial vulnerability to phagocyte functions.
Clavulanic Acid↗
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↗