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D Arzeni

Publications and source records attributed to D Arzeni.

At least 19 recordsLinked to original sources

Epidemiology of onychomycosis and paronychia in the area of ANCONA (ITALY) over a period of 5 years.

We retrospectively evaluated the epidemiology of onychomycosis and/or paronychia in 172 patients attending the Clinic of Dermatology and Venereology over a 5 year period. Although yeast isolates, belonging to the Candida species, represented the most frequent etiologic agents of these infections, an increasing prevalence of fungal infections due to emerging fungal pathogens (EFP) was noted throughout this time period. In particular, EFP as causative agents of these infections increased from 0 to 28.4% from 1998 to 2002.

Adult↗

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.

Adult↗

Electrophoretic karyotyping and antifungal susceptibility patterns of Candida parapsilosis clinical isolates causing deep and superficial fungal infections.

Forty-six isolates of Candida parapsilosis, each from a single patient, were collected from July 1993 through March 1999 at the University of Ancona Hospitals and Clinics. Twenty-eight strains were isolated from superficial lesioned sites, including skin, nails and other sources while 18 strains were isolated from blood. The isolates were typed by electrophoretic karyotyping (EK) and tested for their susceptibility to fluconazole (FLC), itraconazole (ITC), flucytosine (5-FC), and amphotericin B (AMB). Our data confirmed that EK is a useful technique for DNA typing of isolates of Candida parapsilosis and showed that the source of isolation is not associated with a given DNA type. Although strains belonging to this species of Candida are susceptible to the most common antifungals, including the triazoles, the degree of ITC susceptibility was dose dependent (MIC ranging from 0.25-0.5 microgram/ml) for 98% of the isolates.

Antifungal Agents↗

In vitro activity of posaconazole against clinical isolates of dermatophytes.

A broth macrodilution method following the recommendations established by the National Committee for Clinical Laboratory Standards was used to compare the in vitro activity of posaconazole (PCZ) with that of itraconazole (ITC) against 30 clinical isolates of dermatophytes belonging to six different species. In terms of MICs, PCZ showed an activity equal to that of ITC. MICs of PCZ at which 50% (MIC(50)) and 90% (MIC(90)) of the isolates were inhibited were 0.5 and > 4.0 microg/ml, respectively. The MIC(50) and MIC(90) of ITC were 1.0 and > 4.0 microg/ml, respectively. However, PCZ showed a more potent fungicidal activity than that of ITC against isolates belonging to the genus Microsporum (P = 0.03). PCZ merits further investigation as a potentially useful agent for treatment of dermatophytosis.

Antifungal Agents↗

In vitro activities of the new antifungal triazole SCH 56592 against common and emerging yeast pathogens.

A broth microdilution method performed in accordance with the National Committee for Clinical Laboratory Standards guidelines was used to compare the in vitro activity of the new antifungal triazole SCH 56592 (SCH) to that of fluconazole (FLC), itraconazole (ITC), and ketoconazole (KETO) against 257 clinical yeast isolates. They included 220 isolates belonging to 12 different species of Candida, 15 isolates each of Cryptococcus neoformans and Saccharomyces cerevisiae, and seven isolates of Rhodotorula rubra. The MICs of SCH at which 50% (MIC(50)) and 90% (MIC(90)) of the isolates were inhibited were 0.06 and 2.0 microg/ml, respectively. In general, SCH was considerably more active than FLC (MIC(50) and MIC(90) of 1.0 and 64 microg/ml, respectively) and slightly more active than either ITC (MIC(50) and MIC(90) of 0.25 and 2.0 microg/ml, respectively) and KETO (MIC(50) and MIC(90) of 0.125 and 4.0 microg/ml, respectively). Our in vitro data suggest that SCH has significant potential for clinical development.

Antifungal Agents↗

Interactions between triazoles and amphotericin B against Cryptococcus neoformans.

The interaction of amphotericin B (AmB) and azole antifungal agents in the treatment of fungal infections is still a controversial issue. A checkerboard titration broth microdilution-based method that adhered to the recommendations of the National Committee for Clinical Laboratory Standards was applied to study the in vitro interactions of AmB with fluconazole (FLC), itraconazole (ITC), and the new investigational triazole SCH 56592 (SCH) against 15 clinical isolates of Cryptococcus neoformans. Synergy, defined as a fractional inhibitory concentration (FIC) index of < or =0.50, was observed for 7% of the isolates in studies of the interactions of both FLC-AmB and ITC-AmB and for 33% of the isolates in studies of the SCH-AmB interactions; additivism (FICs, >0.50 to 1.0) was observed for 67, 73, and 53% of the isolates in studies of the FLC-AmB, ITC-AmB, and SCH-AmB interactions, respectively; indifference (FICs, >1.0 to < or =2.0) was observed for 26, 20, and 14% of the isolates in studies of the FLC-AmB, ITC-AmB, and SCH-AmB interactions, respectively. Antagonism (FIC >2.0) was not observed. When synergy was not achieved, there was still a decrease, although not as dramatic, in the MIC of one or both drugs when they were used in combination. To investigate the effects of FLC-AmB combination therapy in vivo, we established an experimental model of systemic cryptococcosis in BALB/c mice by intravenous injection of cells of C. neoformans 2337, a clinical isolate belonging to serotype D against which the combination of FLC and AmB yielded an additive interaction in vitro. Both survival and tissue burden studies showed that combination therapy was more effective than FLC alone and that combination therapy was at least as effective as AmB given as a single drug. On the other hand, when cells of C. neoformans 2337 were grown in FLC-containing medium, a pronounced increase in resistance to subsequent exposures to AmB was observed. In particular, killing experiments conducted with nonreplicating cells showed that preexposure to FLC abolished the fungicidal activity of the polyene. However, this apparent antagonism was not observed in vivo. Rather, when the two drugs were used sequentially for the treatment of systemic murine cryptococcosis, a reciprocal potentiation was often observed. Our study shows that (i) the combination of triazoles and AmB is significantly more active than either drug alone against C. neoformans in vitro and (ii) the concomitant or sequential use of FLC and AmB for the treatment of systemic murine cryptococcosis results in a positive interaction.

Amphotericin B↗

Electrophoretic karyotyping and triazole susceptibility of Candida glabrata clinical isolates.

A series of 35 strains of Candida glabrata isolated from 29 subjects (5 AIDS patients and 24 HIV-seronegative individuals) were typed by electrophoretic karyotyping and tested for their susceptibilities to both fluconazole and itraconazole. Almost every individual harboured his/her own specific isolate (DNA type). Neither the source of isolation nor the patient's HIV status was associated with a given DNA type. Recurrences were generally due to the persistence of the same DNA type over time. Only 9% of the isolates showed reduced susceptibility to fluconazole (MIC > or = 8.0 microg/ml), while 43% of the isolates showed reduced susceptibility to itraconazole (MIC > or = 0.25 microg/ml) (P = 0.02). These data show that electrophoretic karyotyping is a useful technique for DNA typing of isolates of Candida glabrata. Care must be taken prior to initiation of antifungal therapy with either of these drugs.

Antifungal Agents↗

Infection due to Absidia corymbifera in a patient with a massive crush trauma of the foot.

We report the case of a patient with a massive crushing trauma of the right foot who developed a local infection due to Absidia corymbifera. Systemic and local antifungal therapy with ketoconazole associated with hyperbaric oxygen therapy (HBO) yielded a rapid clinical and microbiological resolution. Controlled clinical studies are warranted to further elucidate the potential utility of HBO/antifungal combination therapy.

Absidia↗

In-vitro interactions of itraconazole with flucytosine against clinical isolates of Cryptococcus neoformans.

Treatment failures can occur in AIDS patients infected with Cryptococcus neoformans, despite aggressive antifungal therapy. Combination regimens with additive or synergic drugs could provide additional options for treating cryptococcosis. We studied the effects of itraconazole combined with flucytosine against 16 strains of C. neoformans var. neoformans. Combination therapy revealed different results for the various strains, including synergy (fractional inhibitory concentration (FIC) index 0.5, 63% of the interactions), addition (FIC >0.5 to 1.0, 31% of the interactions) and indifference (FIC >1.0 to <2.0, 6% of the interactions). Antagonism (FIC >2.0) was not observed. The efficacy of combination therapy was confirmed by quantitative cfu and killing curve assays. In particular, killing curves conducted in replicating cells showed that the addition of itraconazole prevented the development of flucytosine-resistant mutants of C. neoformans. These data show that the combination of itraconazole and flucytosine is significantly more active than either drug alone against C. neoformans in vitro.

Antifungal Agents↗

In vitro activity of five antifungal agents against clinical isolates of Saccharomyces cerevisiae.

We evaluated the in vitro activity of fluconazole, itraconazole, ketoconazole, 5-fluorocytosine and amphotericin B against 30 clinical isolates of Saccharomyces cerevisiae by a broth microdilution method, following the NCCLS recommendation. Testing was performed either in RPMI-1640 or yeast nitrogen base (YNB). YNB supported the growth of all isolates tested, while results in RPMI-1640 were not obtained for six isolates (20%). The MIC of all three azoles in YNB were one or two dilutions higher than those obtained in RPMI-1640 (P=0.0001 for fluconazole and itraconazole, P=0.03 for ketoconazole). Elevated MICs were observed for all three azoles, while all the isolates were susceptible to 5-fluorocytosine and amphotericin B. All MIC values were confirmed by spectrophotometric reading. Six strains of S. cerevisiae isolated from the faeces and consecutive blood cultures from an AIDS patient over a 7-month period were typed by electrophoretic karyotyping (EK). EK showed the maintenance of the same karyotype over time suggesting that the faecal isolate changed from a colonizing to infection-causing strain. The relative resistance of S. cerevisiae to azole drugs as well as its ability to cause widespread infections may promote the emergence of this species as a pathogen in immunosuppressed patients.

AIDS-Related Opportunistic Infections↗

In-vitro interaction of terbinafine with amphotericin B, fluconazole and itraconazole against clinical isolates of Candida albicans.

A chequerboard titration broth microdilution method, performed according to the recommendations of the National Committee for Clinical Laboratory Standards, was applied to study the in-vitro interaction of terbinafine with amphotericin B, fluconazole and itraconazole against 30 strains of Candida albicans isolated from the oral cavities of AIDS patients. MICs were determined spectrophotometrically at 490 nm and read at either 24 h or 48 h. The end-point was defined as the drug concentration resulting in > or = 90% inhibition of growth relative to control growth. Synergy, defined as a fractional inhibitory concentration (FIC) index of < or = 0.50, was observed in 93% (28 of 30) of terbinafine-amphotericin B interactions, in 47% (14 of 30) of terbinafine-fluconazole interactions and in 43% (13 of 30) of terbinafine-itraconazole interactions; antagonism (FIC > 2.0) was not observed. Where synergy was not achieved, there was still a decrease, although not as dramatic, in the MIC of one or both drugs when used in combination. Reading the MICs on day 2 did not significantly affect the mode of interaction of terbinafine-triazoles, while for terbinafine-amphotericin B the proportion of synergic interactions dropped from 93% (28 of 30) to 30% (nine of 30; P = 0.0001). Antagonism was not observed for any drug combination even at 48 h. Minimum fungicidal concentrations (MFCs) of all drugs alone and in combination were determined against five isolates. Neither terbinafine nor the two triazoles showed fungicidal activity when tested alone or in combination. The fungicidal activity of amphotericin B was slightly enhanced when combined with terbinafine, there being a decrease of two-fold dilutions in the amphotericin B MFCs against all five isolates tested. Thus terbinafine enhances the activities of amphotericin B and triazoles against C. albicans in vitro. Clearly, clinical studies are warranted to elucidate further the potential utility of these combination therapies.

Amphotericin B↗

Fluconazole susceptibility and strain variation of Candida albicans isolates from HIV-infected patients with oropharyngeal candidosis.

Over a 16 month period we conducted a prospective study in a cohort of 45 HIV-positive patients to detect the development of resistance to fluconazole and to analyse the epidemiology of oropharyngeal candidosis (OPC). Each episode was treated with fluconazole 100 mg/day po for 10 days. All yeast isolates were tested for their in-vitro susceptibility to fluconazole. Multiple strains of Candida albicans simultaneously isolated from a given patient were typed by electrophoretic karyotyping. Overall, 106 episodes of OPC were diagnosed among the 45 patients: 18/45 patients (40%) had only one episode, 11/45 (24%) had two episodes, and the remaining 16/45 (36%) had three or more episodes (range 3-7). Cure (complete resolution of signs and symptoms and negative post-treatment cultures) and improvement (complete resolution of signs and symptoms but positive post-treatment cultures) were observed in 30/106 (28%) and 69/106 (65%) episodes of OPC, respectively. Failure (absence of improvement or exacerbation of signs and symptoms) was observed in seven episodes (7%) from four patients. In two of these four patients a significant and progressive increase in fluconazole MICs was observed: from 0.25 to 16 mg/L in one patient, and from < or = 0.125 to 32 mg/L in the second one. Tests on multiple colonies from individual isolation plates showed that it was not unusual to obtain different fluconazole MICs, indicating that, in order to avoid misleading results, one should perform in-vitro susceptibility testing by using a multiple colony inoculum rather than an inoculum made from a single colony. A total of 213 strains of C. albicans isolated from seven patients who suffered from four or more episodes of OPC through the course of the study were typed by electrophoretic karyotyping. Five individuals (71%) were infected with yeasts with only one DNA type, while the other two patients showed the presence of two or three different DNA types. The simultaneous presence of multiple types was found only in one of the seven subjects. Our data confirm the efficacy of fluconazole 100 mg/day for the treatment of OPC in HIV patients. Isolation of fluconazole-resistant strains of C. albicans with this regimen is rare. The vast majority of HIV patients are infected with a unique strain of C. albicans throughout each episode of infection. A minority of patients, however, can harbour strains of C. albicans with variable patterns of fluconazole susceptibility simultaneously.

AIDS-Related Opportunistic Infections↗

Comparison of three methods for testing azole susceptibilities of Candida albicans strains isolated sequentially from oral cavities of AIDS patients.

Three susceptibility testing procedures were compared to determine fluconazole, itraconazole, and ketoconazole MICs against 47 Candida albicans strains isolated sequentially from the oral cavities of five AIDS patients undergoing azole therapy. They included the broth microdilution method (BM), performed according to the National Committee for Clinical Laboratory Standards' tentative standard, the agar dilution method (AD), and the Etest; the latter two tests were performed both in Casitone agar (AD-Cas and Etest-Cas) and in RPMI (AD-RPMI and Etest-RPMI). Twenty-four- and 48-h MICs obtained by AD and Etest were compared with 48-h MICs obtained by BM. The MICs of all the azoles determined by BM were usually lower than those obtained by the other methods, mainly due to different reading criteria. In order to assess the most appropriate way of evaluating the agreement of MICs obtained by different methods with those produced by the proposed reference method (BM), we used the mean differences calculated according to Bland and Altman's method. Comparison of fluconazole MICs obtained by BM and AD-Cas yielded a mean difference of 3, and the percentages of agreement within +/-2 dilutions were 98 and 100% at 24 and 48 h, respectively. For ketoconazole and itraconazole MICs, lower mean differences were noted, and agreement ranged from 96 to 100%. Agreement between the AD-RPMI and BM results was poor for all azoles, and an increase in MICs was always observed between the 1st- and 2nd-day readings. Similarly, Etest-Cas gave better agreement with BM than did Etest-RPMI for all the azoles. BM, AD-Cas, and Etest-Cas each demonstrated a progressive increase in fluconazole MICs against strains isolated sequentially from a given patient, in accordance with the decreased clinical response to fluconazole.

AIDS-Related Opportunistic Infections↗

In vitro activity of terbinafine against clinical isolates of dermatophytes.

A broth macrodilution method following the recommendations established by the National Committee for Clinical Laboratory Standards was employed for testing terbinafine against 20 clinical isolates of dermatophytes belonging to seven species. The minimal inhibitory concentrations resulting in either 80% or 100% inhibition of growth, compared to growth in drug-free control tubes, ranged from </=0.03 to 0.25 g ml-1 and from </=0.03 to 2.0 g ml-1, respectively. Terbinafine was shown to be fungicidal at a concentration of </=1.0 microg ml-1 for 19 isolates. No differences in susceptibilities were found between strains isolated from HIV-positive and -negative individuals.

Antifungal Agents↗

Genotypic identification of sequential Candida albicans isolates from AIDS patients by polymerase chain reaction techniques.

Random amplification of polymorphic DNA and inter-repeat polymerase chain reaction (IR-PCR) were compared with restriction fragment length polymorphism (RFLP) analysis as methods for DNA typing of Candida albicans. Forty-seven strains of Candida albicans isolated from the oral cavities of five AIDS patients undergoing fluconazole therapy were analyzed. There was an excellent correspondence between the DNA types obtained by both PCR-based techniques and by RFLP. With the exception of one patient who was infected with three DNA types of Candida albicans during a five-year observation period, the patients each harboured only one major strain, which became progressively less susceptible to fluconazole. Each DNA type was unique to a patient. The data suggest that these typing methods are suitable for investigating the epidemiology of oropharyngeal candidiasis in this patient group.

AIDS-Related Opportunistic Infections↗

Prevalence and antifungal susceptibility of vaginal yeasts in outpatients attending a gynecological center in Ancona, Italy.

Between February 1993 and May 1994 we studied the prevalence of fungal vulvovaginitis among women attending the Obstetric and Gynecology Clinic of the University of Ancona. Out of the 222 patients, 18 (8.2%) women had symptomatic vaginitis and 24 (10.8%) were carriers. Candida albicans was the species most frequently isolated (44.2%), followed by Torulopsis glabrata (28%) and Saccharomyces cerevisiae (16.2%), from symptomatic and carrier patients. The activity of acid proteinase was determined for C. albicans isolated from both symptomatic and carrier patients. All 13 carriers showed low activity for aspartyl proteinase (score 1+), while 5 of 6 symptomatic patients showed higher activity (score 2+), with a significant difference (p = 0.026). In general, isolates of T. glabrata and S. cerevisiae were less susceptible in vitro to fluconazole than isolates of C. albicans. We did not find any differences in fluconazole MIC results among the C. albicans strains isolated from symptomatic and carrier patients. On the other hand, the fluconazole MICs of T. glabrata and S. cerevisiae isolates showed statistically significant differences between symptomatic and carrier patients (p = 0.009 and p = 0.000, respectively). The differences in proteinase secretion between the isolates from symptomatic and carrier patients suggest a correlation between proteinase production and vaginal candidiasis caused by C. albicans. Torulopsis glabrata, however, was found to be the most common causative agent of vaginitis (7 out 19 episodes), followed by C. albicans (6 out of 19 episodes). Due to the varying patterns of antifungal susceptibility, mainly to fluconazole for the yeast isolates considered in this study, an in vitro susceptibility testing program might be useful for monitoring the outcome of this infection.

Adult↗

Comparison of broth dilution and semisolid agar dilution for in vitro susceptibility testing of Cryptococcus neoformans.

We compared the in vitro activity of amphotericin B, flucytosine, itraconazole, fluconazole, ketoconazole and miconazole against 18 strains of Cryptococcus neoformans by using two methods: microbroth dilution and semisolid agar dilution. By both of the methods minimum inhibitory concentrations (MICs) showed a wide range for all antifungal agents but not for amphotericin B. Statistically significant differences between the two methods were observed only with amphotericin B and flucytosine, p = 0.048 and p = 0.045 respectively. Our study suggests that azole susceptibility testing for C. neoformans may be performed by the broth microdilution as well as the semisolid agar test. The choice of the method when testing amphotericin B and flucytosine is more problematic.

Amphotericin B↗