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In order to highlight the potential erythromycin immunomodulatory properties related to different antibiotic resistance patterns in Streptococcus spp., we evaluated the influence of the macrolide on the PMNs primary functions against erythromycin-susceptible (Ery-S) and erythromycin-resistant (Ery-R) S. pyogenes strains. A total of 438 S. pyogenes were isolated over the period 2005–2007. On the basis of the triple disk testing, 345 out of 438 S. pyogenes isolates were Ery-S and 93 were Ery-R; among the resistant strains, 65 displayed the cMLSB phenotype, 23 had the M phenotype and 5 had iMLSB phenotype. Concerning antibacterial activity of PMNs, our results showed that erythromycin did not modify bacterial uptake, but significantly increased the phagocyte intracellular killing, compared with controls, for both Ery-S and Ery-R strains. Consequently, this report underlines that in immunocompetent hosts the dichotomy between the in vitro resistance and clinical trial data for antimicrobial agents should be thoroughly re-evaluated.

We report a case of bronchopneumonia due to Schizophyllum commune in an immunocompromised patient. While this fungus rarely causes disease in humans, it has been reported in association with several clinical entities and lung disorders. A 59-year-old white man with a gastric carcinoma was admitted to S. Giovanni Battista Hospital (Turin, Italy). Three days after the admission, he developed a bronchopneumonia, which was diagnosed through the use of X-ray and showed an abnormal infiltrative shadow. Samples of bronchial aspirate were collected for laboratory microbiological investigation. Direct microscopic examination of these specimens revealed the presence of numerous septate, hyaline hyphae and rare clamp connections. Sabouraud Dextrose Agar and Columbia agar plus 5% blood media inoculated with portions of the same specimens yielded, after 4-5 days of incubation at 25 degrees C and 37 degrees C, a cottony white mould. The fungus was identified on the basis of its macroscopic and microscopic morphology. The macroscopic examination of the colony showed raised, curved, fan-shaped and shell-like basidiocarps. The microscope examination revealed the presence of hyaline, septate hyphae with clamp connections and short, thin spicules. The fungal isolate was identified as S. commune. The patient was cured after therapy with intravenous fluconazole (600 mg twice daily for over six weeks).

Aims: The in vitro activity of some essential oils (EO) (thyme red, fennel, clove, pine, sage, lemon balm and lavender) against clinical and environmental fungal strains was determined. Methods and Results: The minimal inhibitory concentrations were determined by a microdilution method in RPMI 1640 and by a vapour contact assay. The composition of oils was analysed by gas chromatography (GC) and GC/mass spectrometry. The results indicated that the oils antifungal activity depended on the experimental assay used. The inhibiting effects of EO in vapour phase were generally higher than those in liquid state. According to both methods thyme red and clove were found to be the oils with the widest spectrum of activity against all fungi tested. Conclusions: Despite the differences between the two methods, our results demonstrate that some EO are very active on dermatophytes and dematiaceous fungi. However, more data will be necessary to confirm this good in vitro efficacy. Significance and Impact of the Study: This study could identify candidates of EO for developing alternative methods to control environmental and clinically undesirable filamentous fungi.

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.

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.

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.

The influence of caspofungin on polymorphonuclear leukocyte (PMN) phagocytosis and intracellular killing of Candida albicans was investigated. Caspofungin, at all of the concentrations tested (2, 3.2, and 8 μg/ml), significantly increased intracellular killing by PMNs through its direct action on both yeast cells and PMNs, indicating the potential ability of caspofungin to synergize with phagocytes for candidal killing. Caspofungin may therefore constitute an effective therapeutic option for the treatment of invasive fungal infections, including those refractory to conventional treatment with azole agents.

To evaluate the synergistic activity of erythromycin and human polymorphonuclear cells (PMNs) on the binomial erythromycin-resistant (ERY(R)) Streptococcus pyogenes/host, the phagocytic and bactericidal activities of PMNs against ERY(R) streptococcal strains (cMLS(B), M, and iMLS(B) A, B and C phenotypes) were assessed in the presence of the macrolide. The results showed that when erythromycin, PMNs and streptococci [both erythromycin-sensitive (ERY(S)) and ERY(R)] were simultaneously present in the culture medium, PMN phagocytic activity was similar to that of drug-free controls. In contrast, the results emphasised a significant high increase in intracellular killing by PMNs in the presence of erythromycin not only for ERY(S) streptococci but also for ERY(R)S. pyogenes with high (cMLS(B), iMLS(B) A and iMLS(B) B phenotypes) and moderate (M and iMLS(B) C phenotypes) erythromycin resistance compared with controls without drug. From literature data it emerged that, even if intracellularly concentrated, erythromycin is relatively inactive because of its instability. The results indicate that the enhanced intra-PMN streptococcal killing detected is mainly attributable to PMN bactericidal systems that synergise with intracellular erythromycin in eradicating ERY(R)S. pyogenes strains (both with high and moderate resistance). These data confirm that the antibiotic resistance detected in vitro does not always imply a failure of antimicrobial treatment.

The aim of this study was to evaluate the in vitro antibiotic susceptibility of respiratory pathogens recently isolated in Italy to commonly used antibiotics including cefditoren. Six clinical microbiological laboratories collected, between January and September 2009, a total of 2,510 respiratory pathogens from subjects with community-acquired respiratory tract infections (CARTI). Ceftditoren, out of all the beta-lactams studied, had the lowest MIC(90 )against 965 strains of Streptococcus pneumoniae examined, followed by cefotaxime and ceftriaxone (2% resistance in penicillin-resistant S. pneumoniae (PRSP)). Against 470 Haemophilus influenzae , independently of their production of beta-lactamases or ampicillin resistance, cefditoren was the oral cephalosporin with the best in vitro activity, comparable to that of the injectable cephalosporins and levofloxacin. Higher MIC(90)s were found for the macrolides (4 - 16 mg/l) and cefaclor (4 - 32 mg/l). As was foreseeable, Streptococcus pyogenes (225 strains) was uniformly sensitive to all the beta-lactam antibiotics, but the elevated MIC(90 )values reduced (75%) susceptibility of this pathogen to macrolides. Beta-lactamase-negative Moraxella catarrhalis (100 strains) had reduced susceptibility only to the macrolides, while the 250 beta-lactamase-producing strains also had reduced susceptibility to cefuroxime. Levofloxacin showed the lowest MIC(50)/MIC(90 )values in the producing strains, whereas cefditoren, cefotaxime and ceftriaxone in the non-producers. As regards the enterobacteriaceae, cefditoren and levofloxacin had the lowest MIC(90)s against Klebsiella pneumoniae. Cefditoren and the third-generation injectable cephalosporins had the lowest MIC(90)s against Escherichia coli (100% susceptibility) while levofloxacin was less active (86% susceptibility).In conclusion, cefditoren's wide spectrum and high intrinsic activity, as well as its capacity to overcome most of the resistance that has become consolidated in some classes of antibiotics widely used as empiric therapy for CARTI, allows us to suggest that cefditoren might be included in the european guidelines as one of the first-choice antibiotics in the treatment of CARTI.

The increased prevalence of dermatomycoses along with the wide range of organisms now recognized as potential pathogens needs accurate laboratory isolation and identification of the aetiological agents. In this report three cases of foot dermatomycoses due to filamentous fungi commonly present in the environment with ubiquitous distribution are described in immunocompetent subjects. Skin and nail samples were collected, suspended in 20% KOH solution, examined under a light microscope and cultured in Mycobiotic agar and Sabouraud dextrose agar containing chloramphenicol to detect fungal growth. Phoma herbarum, Chaetomium globosum, and Microascus cinereus were isolated and identified.

The in vitro activities of fluconazole and voriconazole against 1,024 clinical isolates of Candida spp. were determined by the agar disk diffusion test using the Clinical and Laboratory Standards Institute (CLSI) M44-A guidelines. The results of this investigation demonstrated the broad-spectrum in vitro activity of voriconazole, relative to that of fluconazole, against yeasts tested, in particular fluconazole-resistant isolates, such as Candida krusei that showed high susceptibility to voriconazole. The situation in Turin, Italy, is quite similar to that of the rest of Italy, reflecting the worldwide trend.

The frequency of erythromycin resistance in Streptococcus pneumoniae isolates from human specimens, in different Piemonte Region hospitals between 2005-2007, has been studied. Erythromycin-susceptible isolates were 137/198 and erythromycin-resistant 61/198.Among resistant S. pneumoniae isolates 26/61 belonged to constitutive resistance phenotype, 26/61 to M phenotype and 9/61 to inducible resistance phenotype.

Antimicrobial agents and polymorphonuclear cells (PMNs) have the potential to interact in such a way that improve the therapy for infectious diseases. In immunocompromised patients highly susceptible to microbial infections with high morbidity and mortality, several metabolic and functional alterations in PMNs, mostly related to microbicidal activity, are observed. Therefore, the antibiotic of choice should have a good antimicrobial effect without impairing host defences. The aim of this study is to evaluate in vitro effects of sub-inhibiting fosfomycin tromethamine (FT) concentrations on the primary functions of PMNs from healthy subjects and immunocompromised patients (haemodialysed and renal transplant recipients), against an ESBL-producing Escherichia coli, the most common aetiological agent in urinary tract infections (UTIs). FT is considered a first line drug in the eradication of UTIs due to its appropriate antimicrobial spectrum, oral bioavailability and minimal risk of microbial resistance. Our results provide evidence that FT is able to induce enhancement of the depressed phagocytic response of PMNs from patients on chronic haemodialysis and from renal transplant recipients, restoring their primary functions in vitro against ESBL-producing E. coll All these data permit the conclusion that uremic-infected patients might additionally benefit from the immunomodulating properties of FT.

Aims: This study compared the in vitro activity of telithromycin with that of azithromycin against 438 Streptococcus pyogenes and 198 Streptococcus pneumoniae, isolated over the period 2005–2007 from specimens of different human origin obtained in three Piemonte Region’s hospitals. Methods and Results: The determination of antimicrobial activity was evaluated by the microdilution broth method and the erythromycin-resistant (Ery-R) phenotypes by the triple-disc test. Exactly 78·8% of S. pyogenes and 69·2% of S. pneumoniae were erythromycin-susceptible (Ery-S). Concerning S. pyogenes, telithromycin was active against M and inducible MLSB, subtype-C, phenotypes but not against constitutive MLSB strains. Telithromycin acted well against all S. pneumoniae, irrespective of their mechanism of macrolide-resistance. On the contrary, the Ery-R isolates, both S. pyogenes and S. pneumoniae, were resistant to azithromycin. Conclusions: Our results indicate that macrolide resistance in streptococci still persist in northwest Italy (21·2% of S. pyogenes and 30·8% of S. pneumoniae) and that telithromycin is confirmed as being extremely active even against recent clinical Ery-R streptococcal isolates. Significance and Impact of the Study: The present study emphasizes that an active surveillance of the phenotype distribution and antibacterial resistance in streptococci is essential in guiding the effective use of empirical treatment option for streptococcal infections, also at regional level.

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.

This report documents tinea pedis and tinea unguium in a 7-year-old child. In all cultures Trichophyton rubrum was present. As tinea pedis and tinea unguium affect adults more often than children, they might be overlooked and misdiagnosed in the latter.

There is an increased incidence of the morbidity and mortality associated with fungal infections caused by resistant fungi in various groups of patients; therefore the monitoring of their susceptibility to antifungal agents to be necessary for optimizing clinical therapeutic treatment. The susceptibility profiles of recent clinical yeasts and yeast-like fungi isolated from Turin’s Hospitals to current antifungal drugs are here reported. Candida albicans was the most frequently isolated species (40%), followed by C. glabrata (22%).A high rate of susceptibility to all antifungal agents tested was observed and low evidence of resistance was found.

Intestinal colonization by lactobacilli is suggested to be a prerequisite to normal mucosal immune functions. An inadequate level of lactobacilli may be involved in appearance of allergic disease of which, infantile colic, is often considered an early clinical manifestation. The aim of the study is to evaluate intestinal lactobacilli in breast-fed infants with infantile colic and healthy infants. Fifty-six breast-fed infants, aged 15-60 days were enrolled in the study and divided into two groups: colicky (30 cases) and healthy (26 cases) according to Wessel's criteria. Stool samples were collected, diluted and cultured on selective media. The colonies were counted, reported as colony forming unit (cfu) per gram of faeces and identified by biochemical methods. Different colonization patterns of lactobacilli were found among colicky and healthy infants. Lactobacillus brevis (4.34 x 10 8 cfu/g) and L. lactis lactis (2.51 x 10 7 cfu/g) were found only in colicky infants while L. acidophilus (2.41 x 10 7 cfu/g) was found only in healthy infants. Lactobacillus brevis and L. lactis lactis might be involved in the pathogenesis of infantile colic increasing meteorism and abdominal distension. Further studies are required to understand how the observed differences may be involved in the pathogenesis of this common disorder.

We determined the in vitro activity of fluconazole against 1565 clinical Candida spp. isolates collected from different specimens of non-AIDS outpatients and inpatients in 3 different regions of Italy. Susceptibility testing was performed by agar disk diffusion using the NCCLS document M44-A guidelines. Candida albicans was the most frequently isolated yeast (68%) followed by C. glabrata (15%), C. tropicalis (5%), C. parapsilosis (5%), and C. krusei (5%). Other yeasts represented 4% of all isolates. Of the 1565 isolates tested, 1449 (92.6%) were susceptible (S) to fluconazole, 43 (2.7%) were susceptible dose-dependent (S-DD) and 73 (4.7%) were resistant (R). Almost all (98.2%) of the C. albicans isolates were classified as S or S-DD. Despite its widespread use, fluconazole displayed good activity against the isolates we tested, and the disk diffusion method was confirmed as a reliable approach to the evaluation of in vitro susceptibility of yeasts to this antimycotic agent.

It has been previously demonstrated that some antimicrobial agents enhance activities of human polymorphonuclear neutrophils (PMNs). The effect on the release of cytokines in an inflammatory context from PMNs by these antibiotics was evaluated. We studied the effect of the release of some cytokines by human PMNs RT-PCR analysis on a clinical strain of Klebsiella pneumoniae by comparing the effect with that observed in the presence of co-amoxiclav, sanfetrinem, clarithromycin, prulifloxacin and tobramycin. All the drugs tested were capable of modulating PMN synthesis in vitro of pro-inflammatory cytokines IL-8, IL-1beta, TNF-alpha and IL-6, but not that of anti-inflammatory cytokine IL-10. The degree of their stimulatory or inhibitory potency varied with the cytokine examined.

Current antibiotic therapy encourages the use of antibiotics that may potentiate the host's immune defences. We therefore investigated the effect of thiamphenicol (TAP), the active principle of thiamphenicol glycinate acetylcysteinate (TGA), on human granulocyte functions, mainly phagocytosis and intracellular killing of Streptococcus pyogenes. Our findings support the use of thiamphenicol in the treatment of respiratory tract infections caused by S. pyogenes as it acts directly against the pathogen as well as in cooperation with PMNs by eliciting their intracellular killing.

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.

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 μg/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.

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.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.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.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.

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.

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.

Clinical experience has shown that the efficacy of antibiotic therapy depends not only on the direct effect exerted by the antibiotic on a given microorganism (expressed in terms of the minimum inhibitory or minimum bactericidal concentration) but also on the functional activity of the immune system of the host. The literature reports evidence suggesting that many antimicrobial drugs can modulate host defenses in various ways. It thus follows that a possible influence (both negative and positive) of antibiotics on phagocyte functions should always be tested, especially when antibiotics are given for the treatment or prophylaxis of infections in immunocompromised patients. In these cases it would be logical to employ drugs enhancing rather than depressing host defenses.

A multicenter study aimed at assessing the in vitro activity of sulbactam/ampicillin against a wide range of bacterial pathogens was performed using 2,209 clinical strains, all recently collected from inpatients in seven Italian centers and preliminarily screened as being ampicillin-resistant and beta-lactamase producers. In comparative disk diffusion trials using 8 large-spectrum antimicrobials, the percentage of resistance to sulbactam/ampicillin in staphylococci was similar to the percentage of resistance to netilmicin and lower than to the other antibiotics; with gram-negative bacteria, only netilmicin, ofloxacin, and, less consistently, cefotetan showed lower incidences of resistance. The minimal inhibitory concentrations (MICs) of ampicillin alone and sulbactam/ampicillin together were determined using the agar dilution method. The Enterobacteriaceae strains which shifted to ampicillin susceptibility in the presence of sulbactam averaged 68%, but values significantly above or below average were observed in some genera of this family. The percentage of strains which the presence of sulbactam rendered ampicillin-susceptible in vitro reached 97% in Haemophilus strains and 100% in branhamellae and gonococci. High percentages were also recorded in staphylococci, with a peak of 100% in oxacillin-susceptible Staphylococcus aureus strains. In general, center-to-center differences were relatively limited.

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.

The effect of ceftazidime on the phagocytic and bactericidal activity of human macrophages was investigated. At concentrations of half the MIC the antibiotic caused macrophages to ingest and kill Staphylococcus aureus and Pseudomonas aeruginosa at a higher level than did macrophages without drug. Bacteria pretreated with ceftazidime became more sensitive to the bactericidal activity of macrophage lysozyme. Macrophages taken from mice receiving intravenous ceftazidime showed greater phagocytic activity than those from control mice.

Scanning and transmission electron microscopy showed that a ceiling quantity (1.56 mcg) of antifungal antibiotic Pyrrolnitrin caused heavy damage to dermathophyteMicrosporon audouinii Gruby CBS 313-54in vitro. Suitable preparation technique made it clear that the changes involved consisted of hyphal collapse on the edge of the culture, with loss of euplasmic organelles identity and cell autolysis. The cell wall, however, was apparently undamaged. These findings fit in with the suggestion that the mode of action of the antibiotic leads to generalised lipoproteic membranes damage. They must, however, be considered as representing the result of the terminal phase of cell distress.

Allergic rhinitis is known to be one of the most common chronic diseases in the industrialized world. According to the concept that allergic rhinitis patients generally suffer from an immune deficit, in order to stimulate specifically or aspecifically their immune system, immunomodulating agents from various sources, such as synthetic compounds, tissue extracts or a mixture of bacterial extracts, have been used. The aim of the present trial is to evaluate the efficacy of the treatment with an immunostimulating vaccine consisting of a polyvalent mechanical bacterial lysate (PMBL) in the prophylaxis of allergic rhinitis and subsequently to analyze its in vivo effects on immune responses. 41 allergic rhinitis patients were enrolled: 26 patients were randomly assigned to the group for PMBL sublingual treatment and 15 others to the group for placebo treatment. For all 26 patients blood samples were drawn just before (T0) and after 3 months of PMBL treatment (T3) to evaluate plasma IgE levels (total and allergen-specific) and the cytokine production involved in the allergic response (IL-4, IFN-γ). The results of our study indicate that PMBL is effective in vivo in the reduction or in the elimination of the symptoms in rhinitis subjects during the treatment period in comparison to a non-immunostimulating treatment. A significant and clinically relevant improvement was found in 61.5%, a stationary clinical response was registered in 38.4% and no negative side effects associated with the medication or worsening were recorded. At the end of a 3-month follow up period the clinical picture remained the same as that observed at T3. PMBL treatment did not affect the serum IgE levels (either total or allergen-specific) and did not induce significant changes in IFN-γ concentration. In contrast, PMBL therapy may be accompanied, in some patients, by a potential immunomodulating activity by decreasing IL-4 cytokine expression.

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.

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.

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.