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Biomedical subjects

F Caselli

Publications and source records attributed to F Caselli.

13 recordsLinked to original sources

Antiseptic compounds still active against bacterial strains isolated from surgical wound infections despite increasing antibiotic resistance.

The in vitro activities of povidone iodine, potassium peroxymonosulfate, and dimethyldidecylammonium chloride were investigated against 379 nosocomial isolates of Staphylococcus aureus and Pseudomonas aeruginosa responsible for surgical wound infections in patients operated on between July 1995 and June 2001. Overall, the isolates were inhibited by the antiseptics at concentrations below those used routinely. In spite of increasing resistance to the various antibiotics used to treat surgical wound infections, no significant variation in the susceptibility to antiseptics was demonstrated during this 6-year study.

Anti-Infective Agents, Local↗

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↗

Activity of the new antifungal triazole, posaconazole, against Cryptococcus neoformans.

The new antifungal derivative posaconazole was tested against three clinical isolates of Cryptococcus neoformans var. neoformans using a broth microdilution procedure performed according to the guidelines established by the NCCLS. Posaconazole MICs were 0.125, 0.25 and 1.0 mg/L for isolates 491, 2337 and 486, respectively. To investigate the in vivo activity of this new compound, we established an experimental model of systemic cryptococcosis in CD1 mice by iv injection of cells of each strain of C. neoformans. Low (3 mg/kg/day) and high (10 mg/kg/day) doses of posaconazole were compared with amphotericin B given at 0.3 mg/kg/day for 10 consecutive days. Survival studies showed that all treatment regimens were effective in prolonging the survival of mice infected with C. neoformans 486 (P < 0.001). Only posaconazole at 10 mg/kg and amphotericin B were effective in prolonging the survival in mice infected with C. neoformans 2337 (P from <0.01 to <0.001), while neither agent was effective in mice infected with C. neoformans 491. Tissue burden experiments performed 24 h after the end of therapy revealed that posaconazole at 10 mg/kg was effective at reducing the fungal burden in both lung and brain tissues of all three strains of C. neoformans. In particular, for C. neoformans 491 and 2337 posaconazole was superior to amphotericin B at reducing the fungal burden in the brain (P < 0.05). The efficacy of posaconazole was also confirmed by determining the capsular antigen serum levels of treated mice versus untreated mice. Our study underlines the excellent activity of posaconazole against this pathogenic yeast.

Animals↗

Interactions of posaconazole and flucytosine against Cryptococcus neoformans.

A checkerboard methodology, based on standardized methods proposed by the National Committee for Clinical Laboratory Standards for broth microdilution antifungal susceptibility testing, was applied to study the in vitro interactions of flucytosine (FC) and posaconazole (SCH 56592) (FC-SCH) against 15 isolates of Cryptococcus neoformans. Synergy, defined as a fractional inhibitory concentration (FIC) index of <0.50, was observed for 33% of the isolates tested. When synergy was not achieved, there was still a decrease in the MIC of one or both drugs when they were used in combination. Antagonism, defined as a FIC of >4.0, was not observed. The in vitro efficacy of combined therapy was confirmed by quantitative determination of the CFU of C. neoformans 486, an isolate against which the FC-SCH association yielded a synergistic interaction. To investigate the potential beneficial effects of this combination therapy in vivo, we established two experimental murine models of cryptococcosis by intracranial or intravenous injection of cells of C. neoformans 486. At 1 day postinfection, the mice were randomized into different treatment groups. One group each received each drug alone, and one group received the drugs in combination. While combination therapy was not found to be significantly more effective than each single drug in terms of survival, tissue burden experiments confirmed the potentiation of antifungal activity with the combination. Our study demonstrates that SCH and FC combined are significantly more active than either drug alone against C. neoformans in vitro as well in vivo. These findings suggest that this therapeutic approach could be useful in the treatment of cryptococcal infections.

Animals↗

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↗

Experimental induction of fluconazole resistance in Candida tropicalis ATCC 750.

Candida tropicalis is less commonly isolated from clinical specimens than Candida albicans. Unlike C. albicans, which can be occasionally found as a commensal, C. tropicalis is almost always associated with the development of fungal infections. In addition, C. tropicalis has been reported to be resistant to fluconazole (FLC). To analyze the development of FLC resistance in C. tropicalis, an FLC-susceptible strain (ATCC 750) (MIC = 1.0 microg/ml) was cultured in liquid medium containing increasing FLC concentrations from 8.0 to 128 microg/ml. The strain developed variable degrees of FLC resistance which paralleled the concentrations of FLC used in the medium. The highest MICs of FLC were 16, 256, and 512 microg/ml for strains grown in medium with 8.0, 32, and 128 microg of FLC per ml, respectively. Development of resistance was rapid and could be observed already after a single subculture in azole-containing medium. The resistant strains were cross-resistant to itraconazole (MIC > 1.0 microg/ml) and terbinafine (MIC > 512 microg/ml) but not to amphotericin B. Isolates grown in FLC at concentrations of 8.0 and 32 microg/ml reverted to low MICs (1.0 microg/ml) after 12 and 11 passages in FLC-free medium, respectively. The MIC for one isolate grown in FLC (128 microg/ml) (128 R) reverted to 16 microg/ml but remained stable over 60 passages in FLC-free medium. Azole-resistant isolates revealed upregulation of two different multidrug efflux transporter genes: the major facilitators gene MDR1 and the ATP-binding cassette transporter CDR1. The development of FLC resistance in vitro correlated well with the results obtained in an experimental model of disseminated candidiasis. While FLC given at 10 mg/kg of body weight/day was effective in reducing the fungal burden of mice infected with the parent strain, the same dosing regimen was ineffective in mice infected with strain 128 R. Finally, the acquisition of in vitro FLC resistance in strain 128 R was related to a loss of virulence. The results of our study elucidate important characteristics and potential mechanisms of FLC resistance in C. tropicalis.

Animals↗

In vitro susceptibility tests for cationic peptides: comparison of broth microdilution methods for bacteria that grow aerobically.

The in vitro susceptibilities of 90 clinical isolates of gram-positive and gram-negative aerobic bacteria to six cationic peptides, buforin II, cecropin P1, indolicidin, magainin II, nisin, and ranalexin, were evaluated by two broth microdilution methods. The first method was performed according to the procedures outlined by the National Committee for Clinical Laboratory Standards for bacteria that grow aerobically, while the second was performed according to the procedures recently proposed by the R. E. W. Hancock laboratory for testing antimicrobial peptides. Overall, the first method produced MICs two- and fourfold higher than the second method.

Anti-Bacterial 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↗

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 polycationic peptides against Cryptosporidium parvum, Pneumocystis carinii and yeast clinical isolates.

The in-vitro activity of magainin II, indolicidin and ranalexin against 14 clinical isolates of eukaryotic microorganisms was evaluated. Antifungal susceptibility testing was performed by broth microdilution, and activity against Pneumocystis carinii and Cryptosporidium parvum was determined by inoculation on to cell monolayers. For yeasts, peptide MICs and MFCs ranged from 6.25 to > 50 mg/L. Ranalexin showed the highest activity against Candida spp., while magainin II demonstrated greatest anticryptococcal activity. The peptides suppressed the growth of P. carinii by > or = 50% and > or = 90% at 5 and 50 microM, respectively, with the exception of indolicidin. Ranalexin, the most effective compound against C. parvum, suppressed its growth by > or = 40% at 50 microM.

Animals↗

Variations of skin temperature in patients with craniofacial pain. A thermographic evaluation.

Thermography of craniofacial region was taken in 33 patients with different types of craniofacial pain. In 26 patients (78%) a thermal asymmetry was found which corresponded to the painful area in 19 patients (57%). It can be concluded that temperature alterations in different areas of the face are common in such patients and are probably the consequence of functional alterations of the sympathetic system.

Adolescent↗