In vitro activity of fluconazole, voriconazole and caspofungin against clinical yeast isolates.

Predicting the clinical outcome of a systemic mycosis is often a difficult task, especially when microbiological resistance is one of the factors contributing to therapeutic failure. Some of these factors are host-related--e.g. immune state, site and severity of infection, poor compliance to therapy--while others are associated with the drug's characteristics--e.g. dosage, type of compound (fungistatic/fungicidal), pharmacokinetic properties and drug-drug interactions. In the last few years, clinicians have been confronted with the problem of selecting the most appropriate antifungal therapy for systemic infections and have highlighted the need for a reliable method to assay the in vitro susceptibility of yeasts and molds to different antifungal agents, which would allow them to institute a tailored therapy. Using the CLSI micromethod--the reference method for clinically relevant yeast testing--we assayed 70 clinical yeast isolates ( Candida spp., collected from patients with systemic mycosis) for susceptibility against fluconazole, voriconazole and caspofungin. Data obtained from our in vitro susceptibility assays revealed good activity of azoles against the majority of Candida spp. In particular, 88.6% of the assayed isolates were susceptible to fluconazole, with minimum inhibitory concentrations (MICs) ranging from =0.125 microg/mL to 8 microg/mL; 97.1% of the isolates were susceptible to voriconazole, with MICs ranging from 0.008 microg/mL to 1 microg/mL; regarding caspofungin 72.9% of the isolates had MICs ranging from 0.25 microg/mL to 1 microg/mL.

Identification of Candida dubliniensis among oral yeast isolates from an Italian population of human immunodeficiency virus-infected (HIV+) subjects.

Candida dubliniensis, an emerging oral pathogen, phenotypically resembles Candida albicans so closely that it is easily misidentified as such. The aim of the present study was to evaluate the usefulness of two phenotypic methods, growth at 45 degrees C and 2,3,5-triphenyltetrazolium chloride (TTC) reduction, for confirming presumptive identification of C. dubliniensis and C. albicans by colony color on CHROMagar Candida (CAC) medium. A combination of these methods was used to establish the prevalence of oral C. dubliniensis in an Italian population of 45 human immunodeficiency virus (HIV)-infected subjects. Twenty-two samples (48.9%) were positive for yeasts on CAC medium producing a total of 37 fungal isolates. The colony color and 45 degrees C growth ability test correctly identified all C. dubliniensis and C. albicans isolates (5/37, 13.5%, and 16/37, 43.2%, respectively), while assessment of TTC reduction misidentified one C. albicans isolate. The isolation rate of C. dubliniensis was 11.1% (5/45 patients). All of the C. dubliniensis isolates were highly susceptible to fluconazole (MIC = 0.5 microg/ml). The combination of CAC medium screening with growth at 45 degrees C and TTC reduction tests may represent a simple, reliable and inexpensive identification protocol for C. dubliniensis.

Genotyping and antifungal susceptibility of human subgingival Candida albicans isolates.

Subgingival colonization by Candida albicans has been described in human immunodeficiency virus (HIV)-infected individuals, but subgingival isolates have scarcely been characterized, particularly with respect to genotype and antifungal susceptibility. A series of 29 subgingival strains of C. albicans isolated from nine HIV-infected individuals was typed by electrophoretic karyotyping and tested for susceptibility to fluconazole, itraconazole, the new investigational triazole posaconazole and amphotericin B. DNA typing showed genetic heterogeneity within subgingival isolates, as almost every individual harbored his/her own specific isolate. Genetic identity was usually demonstrated within oral and subgingival isolates simultaneously collected from the same individual, but a number of DNA types were found to be unique to subgingival strains. These findings suggest that colonization is not just the result of Candida spreading from oral surfaces, and that subgingivally adapted strains could be involved. All isolates were susceptible to all the triazole drugs tested and amphotericin B. Additional studies on subgingival Candida colonization and further characterization of subgingival isolates are now required to clarify the role of Candida as opportunistic periodontal pathogen.

Fluconazole susceptibility of Italian Candida dubliniensis clinical isolates determined by reference and simplified tests.

Candida dubliniensis ia an opportunistic pathogen mainly associated with oral candidiasis in human immunodeficiency virus (HIV)-infected individuals. We recently recovered the first Italian clinical isolates of C. dubliniensis from the oral cavities of seven HIV-seropositive subjects. The in vitro susceptibility to fluconazole (FLCZ) of these isolates was determined according to the National Committee for Clinical Laboratory Standards (NCCLS) M27-A broth microdilution method for yeasts. All seven isolates of C. dubliniensis were susceptible to FLCZ (MICs < or =0.5 microg/ml). Results of this reference method were compared to those obtained with simplified tests, more adapted to routine evaluation in hospital laboratories. Fungitest and Sensititre YeastOne colorimetric microplate-based methods have been evaluated. The agar disk diffusion method has also been tested on two different media: RPMI 1640-2% glucose and High Resolution-2% glucose-0.5 microg/ml methylene blue. All of the simplified methods tested were able to correctly identify FLCZ-susceptibility of this group of Italian C. dubliniensis isolates.

Effect of antimicrobial mouthrinses on the in vitro adhesion of Candida albicans to human buccal epithelial cells.

Adhesion to epithelial cells is a critical step in successful oral colonization and infection by Candida albicans. Therefore, three mouthrinse products, containing chlorhexidine 0.2% (CHX), cetylpyridinium chloride 0.05% (CPC) or triclosan 0.045% (TRN), were compared for their effects on the in vitro adhesion of C. albicans to human buccal epithelial cells (BEC). Candidal adhesion appeared to be significantly reduced by oral rinsing with the CHX-containing mouthrinse (P<0.0001). In vivo exposure of BEC to the CPC mouthrinse also inhibited adhesion of C. albicans (P<0.0001). Both CHX and CPC products suppressed adhesion to the same extent (P>0.01). On the other hand, the TRN mouthrinse did not significantly affect epithelial adhesion of C. albicans (P>0.01). These findings suggest that mouthrinses containing CHX or CPC could be of value in the control of candidal colonization and infection. Clinical trials are warranted on the effectiveness of these products in reducing oral Candida carriage.

Effect of dietary carbohydrates on the in vitro epithelial adhesion of Candida albicans, Candida tropicalis, and Candida krusei.

Adhesion to epithelial surfaces is considered as a critical step in the pathogenesis of oral candidosis. Therefore, the effects of the most commonly consumed dietary carbohydrates on the adhesion of Candida albicans, Candida tropicalis, and Candida krusei to monolayered HeLa cells were investigated. Adherence of C. albicans and C. tropicalis appeared significantly promoted by incubation in defined medium containing a high concentration (500 mM) of fructose, glucose, maltose, and sucrose (p < 0.001). C. albicans organisms grown in sucrose elicited maximal increase in adhesion, whereas adhesion of C. tropicalis and C. krusei was enhanced to the greatest extent when cultured in glucose. Maltose and fructose also promoted adherence of C. albicans and C. tropicalis (p < 0.001), but to a lesser extent than sucrose and glucose. On the other hand, sorbitol-grown yeasts demonstrated a marginal increase in adhesion (p > 0.01). Xylitol only significantly reduced adherence of C. albicans (p < 0.001). These results suggest that the frequent consumption of carbohydrates, such as sucrose, glucose, maltose, or fructose, might represent a risk factor for oral candidosis. The limitation of their consumption by substituting xylitol or sorbitol could be of value in the control of oral Candida colonization and infection.

In vitro activities of antimicrobial agents against Candida species.

OBJECTIVE: Antimicrobial mouthrinses may represent a valid alternative to topical antifungal agents. However, the action of antimicrobials could be affected by the different ingredients incorporated into mouthrinse products. The purpose of the present study was to investigate the in vitro antifungal and fungicidal activities of antimicrobials alone. STUDY DESIGN: A broth macrodilution method was used to determine the minimum inhibitory concentration of 4 antimicrobial agents against Candida species. Minimum fungicidal concentration was also determined. RESULTS: All antimicrobials showed antifungal activity against all tested organisms, but cetylpyridinium chloride received significantly lower minimum inhibitory concentrations (P < .005). Cetylpyridinium chloride also showed a greater fungicidal activity than chlorhexidine digluconate and hexetidine (P< .005), whereas sanguinarine chloride appeared to be less fungicidal against most of the isolates tested. CONCLUSIONS: These findings suggest that cetylpyridinium chloride may be used as a topical antifungal agent. Clinical trials are now required to assess its value in the management of oral candidosis.

[Clinical study of residual function and recurrence in patients undergoing partial thyroidectomy for euthyroid nodular goiter]. / Studio clinico della funzione residua e delle recidive in pazienti operati di tiroidectomia parziale per struma nodulare eutiroideo.

The different surgical options for the treatment of non toxic nodular goiter led the Authors to study the residual thyroid function following conservative surgery (subtotal thyroidectomy, lobectomy and enucleation). Follow-up showed an overall recurrence rate of 49%, with a higher rate after lobectomy and enucleation than after subtotal thyroidectomy. On the other hand, subclinical hypothyroidism was higher in patients who underwent subtotal thyroidectomy. No significative correlation was found between high plasmatic levels of TSH and recurrences.

In vitro antifungal properties of mouthrinses containing antimicrobial agents.

The purpose of this study was to investigate the in vitro antifungal properties of seven commercial mouthrinses containing antimicrobial agents. These included cetylpyridinium chloride (CPC), chlorhexidine digluconate (CHX), hexetidine (HEX), sanguinarine (SNG), and triclosan (TRN). The minimum fungicidal concentration (MFC) against six species of yeasts was determined by a broth macrodilution method. The kill-time of mouthrinses at half the concentration of the commercial formulations was also determined. MFCs were achieved with each mouthrinse, except the SNG-containing mouthrinse, against all the organisms being tested. However, the CPC-containing mouthrinse appeared more active than the other products (P < 0.001). There were no significant differences in MFC values among CHX mouthrinse products, once adjusted for initial concentration differences (P = 0.1). Kill-times of mouthrinses containing either CHX or CPC were less than or equal to 180 seconds with all the species of yeasts, and no significant differences were found among these products (P = 0.18). On the other hand, mouthrinses containing either TRN or HEX did not show a lethal effect on Candida albicans, Candida parapsilosis, or Candida guilliermondii. No kill-times were achieved with the SNG-containing mouthrinse. These results suggest that mouthrinses containing antimicrobial agents might represent an appropriate alternative to conventional antifungal drugs in the management of oral candidiasis. However, the effectiveness of antimicrobial mouthrinses as antifungal agents needs to be evaluated in further clinical trials.

[Approach to male breast cancer. Our experience]. / L'approccio al cancro della mammella maschile. Nostra esperienza.

Male breast cancer is a rare neoplasia and represents only 1% of all forms of breast cancer. The etiopathogenesis of breast carcinoma is still unknown in both males and females, but an altered hormonal metabolism may play a role in its genesis. The prognosis of breast cancer is slightly worse in males, especially in cases with axillary lymph node metastases. The paper discusses the therapy administered to 8 patients with male breast cancer who were treated by the authors between January 1983 and April 1990.

[Esophageal leiomyoma: ultrasonographic endoscopic diagnosis]. / Leiomioma dell'esofago: diagnosi ecoendoscopica.

Leiomyoma is the most frequent benign neoplasia of the esophagus. It is generally diagnosed, accidentally during a radiologic examination (filling defect with clear and regular margins) or endoscopically (sessile, hemispheric, covered by pink mucosa). Recently, to the above conventional exams, endoscopic ultrasonography has been added allowing to identify the single layers of the esophageal wall, thus furnishing useful informations on the morpho-structural characteristics of the leiomyoma. From October '94 to May '96, at the Endoscopy Service of the Institute of Oncology of the University of Messina, 12 patients, 8 males and 4 females, ranging from 39 to 69 years of age (median age 55.4) underwent EUS for suspect leiomyoma. An Olympus EU-M20 echoendoscope was used with a radial scan transducer of 12 Mhz. In 8 patients the leiomyoma was located in the III mid-esophagus, while in 4 patients the III inferior portion was interested. The Authors observed lesions ranging in size from 0.5 to 2.5 cm. In their experience, a suspect of leiomyoma represents a good indication for an endoscopic ultrasonography, which shows high sensitivity and specificity.

[Sedation in endoscopic diagnosis: rationale of the use of specific benzodiazepine antagonists]. / Sedazione in diagnostica endoscopica: rationale d'uso degli antagonisti specifici delle benzodiazepine.

The aim of this study was to evaluate the best clinical use of Flumazenil, a specific antagonist of benzodiazepines, during endoscopic exams. Two-hundred patients were studied: 120 were treated with Flumazenil and 80 with placebo. The patients were prepared for the endoscopic exam with local anaesthesia and i.v. Diazepam administration. Controls performed at the end of the exam and at 5, 30, 120 e 240 minutes from the administration of Flumazenil and placebo, allowed to evaluate the state of awakeness, the level of conscience and the capacity of time-space orientation. Significantly statistical differences between the two groups were obtained at 5, 30 and 120 minutes after Flumazenil administration, while both groups had retrograde amnesia. The drug was well tolerated and there were no undesiderable side effects or reactions. The Authors therefore affirm that Flumazenil, in virtue of its competitive action toward benzodiazepine receptors, interrupts sedation with immediate awakening and improvement of the state of consciousness. Such drug, thus, permits the Day Hospital performance of endoscopic procedures which otherwise would require hospitalization, at the same time allowing the surgeon to use benzodiazepines at doses more adequate for surgical necessities.

[Gynecomastia: diagnosis and therapy update]. / La ginecomastia: attualità diagnostiche e terapeutiche.

The Authors report their experience in the management of gynaecomastia. Physiologic, pathologic and iatrogenic causes of the lesion, as well as possible interfering mechanisms, and diagnostic protocol are examined. When there is no spontaneous regression or when the precipitating factors are eliminated surgery is the therapeutical choice, also because it helps in resolving the related psychological problems affecting these patients.

[Derivatives of phenoxyacetamide and antimycotic activity]. / Derivati della fenossiacetammide ad attività antimicotica.

Novel N-(3-methyl-4-R-isoxazol-5-yl)-2-R1-4-R2-phenoxyacetamides and N-(3-methyl-4-R-isoxazol-5-yl)-2-(2-R1-4-R2-phenoxyacetamido) benzamides were prepared and tested against Candida albicans and Cryptococcus neoformans. The results of the antimicrobial assay showed that the presence of two amidic groups usually enhances antimycotic activity.

Urogenital inflammations: aetiology, diagnosis and their correlation with varicocele and male infertility.

The urogenital inflammations may be considered as "apparatus pathology". We analyze only inflammatory diseases of the prostate gland, because it may be extensible to the entire male genital apparatus. Among aethiological agents of infections an important role belongs to Chlamydia and Mycoplasma; we describe various methods for diagnosis of the Chlamydia and Mycoplasma infections. When objective clinical findings are poor or absent (such in prostatosis and prostatodynia) the transrectal ultrasonography demonstrates characteristic pictures useful for diagnosis and follow-up. Our clinical data and anatomo-pathological remarks suggest a real correlation between varicocele and genital inflammations (26%). This association doesn't represent the only cause of infertility, but frequently reduces the probability of male fertility.

[N-pyrazolyl-2-nitrobenzamides with antifungal activity]. / N-pirazolil-2-nitrobenzammidi ad attività antifungina.

Novel N-pyrazolyl-2-nitrobenzamides variously substituted on the pyrazole nucleus were prepared. The products obtained together with some other N-substituted 2-nitrobenzamides were tested for their antifungal activity against Cryptococcus neoformans and Candida albicans. The results of the antimicrobial assay showed different behaviours of the organisms used with regard to the derivatives tested.

[Novel N-pyrazolylsalicylamides with antifungal activity]. / Nuove N-pirazolilsalicilammidi ad attività antifungina.

A number of new N-pyrazolylsalicylamides were prepared by fusion of phenyl salicylate and aminopyrazoles. The condensation reaction is influenced by the substitution at the C-4 position of the aminopyrazole. All the substances obtained were tested for antifungal activity against Cryptococcus neoformans and Candida albicans. It was found that their fungitoxicity is dependent on the structural feature.