Synergy of caspofungin with human polymorphonuclear granulocytes for killing Candida albicans.

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 microg/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.

In vitro activities of fluconazole and voriconazole against clinical isolates of Candida spp. determined by disk diffusion testing in Turin, Italy.

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.

In vitro fluconazole susceptibility of 1565 clinical isolates of Candida species evaluated by the disk diffusion method performed using NCCLS M44-A guidelines.

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.

Influence of thiamphenicol on the primary functions of human polymorphonuclear leucocytes against Streptococcus pyogenes.

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.

Immunomodulating effect of antimicrobial agents on cytokine production by human polymorphonuclear neutrophils.

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.

Synergistic effect of erythromycin on polymorphonuclear cell antibacterial activity against erythromycin-resistant phenotypes of Streptococcus pyogenes.

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.

Non-dermatophyte moulds as skin and nail foot mycosis agents: Phoma herbarum, Chaetomium globosum and Microascus cinereus.

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.

Schizophyllum commune: an unusual of agent bronchopneumonia in an immunocompromised patient.

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).

Effect of dialysis membrane biocompatibility on polymorphonuclear granulocyte activity in dialysis patients.

BACKGROUND: Among patients with defects of the phagocytic component of the immune system, chronic haemodialysis patients are highly susceptible to microbial infections characterized by high morbidity/mortality, related to an impairment of the phagocytic response. Therefore the potential influence of dialysis membrane biocompatibility on the activity of polymorphonuclear (PMN) granulocytes from dialysis patients was investigated in this study. METHODS: Nineteen patients in haemodialysis were included in the protocol and divided into two groups: a control group (7 patients) and a study group (12 patients). The study group patients were treated for subsequent periods of 1 month with different dialysis membranes: low flux excebrane E membrane (CL-E), low flux polysulfone (PS). The control group patients were treated with a low flux modified cellulose membrane (SMC) for the entire observation period. The aetiology of end-stage renal disease included glomerulonephritis, nephroangiosclerosis and interstitial nephropathy. Following each period of treatment, clinical and haematological parameters were evaluated; phagocytosis and microbicidal activity of PMNs from uraemic patients against Klebsiella pneumoniae, the pathogen which can pose severe problems in immune depressed patients, were investigated in parallel. RESULTS: The data evidence that both clinical and haematological parameters remained unchanged during the study period and no differences were found among treatments. On the contrary, the PMN activity varied according to the type of the membrane. In fact, the use of both PS and CL-E, in contrast to SMC, resulted in a PMN functionality similar to that observed in healthy subjects. CONCLUSIONS: These results provide evidence that the depressed PMN activities in dialysis patients may be influenced by membrane biocompatibility in such a way to be totally restored.

Contribution of imaging to the evaluation of pyomyositis.

PURPOSE: To analyse the fundamental features of each imaging modality with the aim of defining their contribution to the diagnosis of pyomyositis. MATERIALS AND METHODS: We retrospectively reviewed 10 observations collected between 1997 and 2004, 5 of paravertebral muscles and 5 of the muscles of the limbs. Imaging was carried out with US (8/10 observations) and/or CT (9/10 observations), and/or MRI (6/10 observations). The pathogen was isolated in 6/10 observations. RESULTS: The imaging criteria for the detection and characterization of pyomyositis are based on three pathological phases: an invasive phase characterized by inflammatory oedema, a suppurative phase characterised by abscess development, and a late phase featuring the distant spread of the infection. Based on these interpretation criteria, pyomyositis was correctly diagnosed with US in 5/8 observations, with CT in 9/9 observations and with MR in 5/6 observations. Four false-negative cases were found. CONCLUSIONS: Since the clinical symptoms of pyomyositis are often insidious and delayed, an integrated imaging approach may be very useful for diagnosing this condition.