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G Scalise

Publications and source records attributed to G Scalise.

At least 73 records · Page 4Linked to original sources

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↗

In-vitro activity of cationic peptides alone and in combination with clinically used antimicrobial agents against Pseudomonas aeruginosa.

The in-vitro activity of cecropin P1, indolicidin, magainin II, nisin and ranalexin alone and in combination with nine clinically used antimicrobial agents was investigated against a control strain, Pseudomonas aeruginosa ATCC 27853 and 40 clinical isolates of P. aeruginosa. Antimicrobial activities were measured by MIC, MBC and viable count. In the combination study, the clinically used antibiotics were used at concentrations close to their mean serum level in humans in order to establish the clinical relevance of the results. To select peptide-resistant mutants, P. aeruginosa ATCC 27853 was treated with consecutive cycles of exposure to each peptide at 1 x MIC. The peptides had a varied range of inhibitory values: all isolates were more susceptible to cecropin P1, while ranalexin showed the lowest activity. Nevertheless, synergy was observed when the peptides were combined with polymyxin E and clarithromycin. Consecutive exposures to each peptide at 1 x MIC resulted in the selection of stable resistant mutants. Cationic peptides might be valuable as new antimicrobial agents. Our findings show that they are effective against P. aeruginosa, and that their activity is enhanced when they are combined with clinically used antimicrobial agents, particularly with polymyxin E and clarithromycin.

Anti-Bacterial Agents↗

In-vitro activity of rifabutin and albendazole singly and in combination with other clinically used antimicrobial agents against Pneumocystis carinii.

The in-vitro activity of rifabutin and albendazole alone and in combination with clarithromycin, etoposide, minocycline and pyrimethamine was investigated against four clinical isolates of Pneumocystis carinii. The susceptibility tests were performed by inoculation of the isolates on to cell monolayers and by determining the parasite count after 72 h incubation at 37 degrees C. The culture medium was supplemented with serial dilutions of each agent. Albendazole tested alone was more active than rifabutin. Albendazole suppressed the growth of cysts and trophozoites by >50% at 4 mg/L. Rifabutin, at the same concentration, produced about 40% reduction in the mean cyst and trophozoite counts. Albendazole (4 mg/L) combined with etoposide 4 mg/L showed the highest anti-P. carinii activity, with a decrease of 86.3% and 90.1% in cyst and trophozoite counts, respectively. The greatest synergic interaction was detected when rifabutin (4 mg/L) was combined with clarithromycin (4 mg/L). Our study suggests that clinically used antimicrobial agents may be effective in inhibiting P. carinii growth in vitro and that, above all, some of these agents possess a positive interaction upon combination with other clinically used compounds. These findings may be useful in the establishment of a prophylaxis regimen for multiple opportunistic pathogens.

Albendazole↗

In vitro activities of polycationic peptides alone and in combination with clinically used antimicrobial agents against Rhodococcus equi.

The in vitro activities of magainin II, nisin, and ranalexin alone and in combination with other antimicrobial agents against six clinical isolates of Rhodococcus equi were investigated by MIC and time-kill studies. All isolates were more susceptible to nisin. A positive interaction was observed when the peptides were combined with ampicillin, ceftriaxone, rifabutin, rifampin, azithromycin, clarithromycin, and vancomycin.

Anti-Bacterial Agents↗

Unusual clinical presentation of infection due to Flavimonas oryzihabitans.

Six cases of Flavimonas oryzihabitans infection are presented, four of which were community-acquired pneumonia and two of which were nosocomially acquired bacteremia. All four cases of pneumonia occurred in immunosuppressed hosts, three of whom were HIV-positive individuals and one of whom was a young man affected by chronic myeloid leukemia. Flavimonas oryzihabitans is recognized with increasing frequency as a cause of opportunistic infection, but the present cases of community-acquired pneumonia due to this organism are believed to be the first four reported in the English literature. The findings emphasize that Flavimonas oryzihabitans should be included in the list of pathogens that cause community-acquired infections in the immunocompromised host.

AIDS-Related Opportunistic Infections↗

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↗

In-vitro activity of lytic peptides, inhibitors of ion transport systems and ionophorous antibiotics against Pneumocystis carinii.

The in-vitro activity of two vertebrate lytic peptides, two ion transport system inhibitors and two polyether ionophores was investigated against four clinical isolates of Pneumocystis carinii recovered from bronchoalveolar lavages of AIDS patients. The susceptibility tests were performed by inoculating the isolates on to cell monolayers and determining the parasite count after 72 h incubation at 37 degrees C. The culture medium was supplemented with Dulbecco's modified Eagle's medium containing serial dilutions of cecropin P1, magainin II, benzamil, 5-(Nmethyl-Nisobutyl)amiloride (MIBA), lasalocid and nigericin. The two vertebrate lytic peptides showed high activity against trophozoites and cysts. At a concentration of 66.77 mg/L, cecropin P1 produced a 93.3% and 98.1% reduction in cyst and trophozoite counts, respectively, while magainin II at a concentration of 49.33 mg/L produced a 90.6% and 98.7% reduction in cyst and trophozoite counts, respectively. The IC50s of benzamil and MIBA were observed at the highest concentrations tested, 35.62 and 29.98 mg/L, respectively. However, 90% inhibition was not achieved. Lasalocid and nigericin at 0.05 mg/L gave inhibition comparable to that observed with the highest tested concentrations of cecropin P1 and magainin II, but significant injury to the cell monolayer was also observed when nigericin was tested at this concentration. Lasalocid 0.05 mg/L produced a reduction of 91.3% and 92.0% in cyst and trophozoite counts, respectively. Our results suggest that lytic peptides and lasalocid may be effective in inhibiting P. carinii growth at concentrations which are not toxic for the cell monolayer.

AIDS-Related Opportunistic Infections↗

In-vitro activity of lytic peptides alone and in combination with macrolides and inhibitors of dihydrofolate reductase against Pneumocystis carinii.

The in-vitro activity of cecropin P1, magainin II, indolicidin and ranalexin alone and in combination with macrolides and dihydrofolate reductase inhibitors (DHFRs) was investigated against six clinical isolates of Pneumocystis carinii. The susceptibility tests were performed by inoculation of the isolates on to cell monolayers and determining the parasite count after 72 h incubation at 37 degrees C. The culture medium was supplemented with serial dilutions of each agent. The four peptides suppressed the growth of cysts and trophozoites by > or = 50% at 20 microM and 2 microM, respectively, with the exception of indolicidin (cysts: IC50, 20 microM; trophozoites: IC50, 20 microM). The IC90 values of all peptides for either cysts or trophozoites were observed at a concentration of 20 microM. Our data showed that the activity of lytic peptides remained virtually unchanged when they were tested either alone or in combination with macrolides and DHFRs, with the exception of ranalexin: a cysts/trophozoites reduction in the range 77.3-85.1% was observed when ranalexin 2 microM was combined with 4 mg/L of macrolides. Our study suggests that lytic peptides may be effective in inhibiting the growth of P. carinii in vitro. In addition some of these compounds seem to have an effective interaction with hydrophobic antibiotics.

Anti-Bacterial Agents↗

Cyclosporiasis in a traveler returning from South America.

Cyclospora is a coccidian, previously referred to as a cyanobacterium-like body, with an epidemiology similar to that of Cryptosporidium parvum. In recent years, several studies have shown that Cyclospora is not a rare opportunistic pathogen but rather is the cause of common, worldwide intestinal infections in healthy adults and children. Previous reports of diarrhea resulting from Cyclospora sp. have been linked to travelers and immunocompromised patients. The species has a worldwide distribution. Although Cyclospora infection has been reported from Southeast Asia, Papua New Guinea, Indonesia, India, Pakistan, Nepal, the Middle East, North Africa, the United Kingdom, the Caribbean, the United States, Central America, and South America, the true prevalence of this parasite in any population is unknown. The parasite is associated with prolonged self-limiting and relapsing watery diarrhea, anorexia, fatigue, and sometimes myalgia. Fever is infrequent.

Adult↗

In vitro activities of membrane-active peptides against gram-positive and gram-negative aerobic bacteria.

Four peptides, cecropin P1, magainin II, indolicidin, and ranalexin, were evaluated against 202 clinical isolates of gram-positive and gram-negative aerobic bacteria by a microbroth dilution method. The gram-negative isolates were more susceptible to cecropin P1. Ranalexin was the most active compound against the gram-positive strains. The bactericidal activity of each peptide was equivalent to, or 1 dilution above, the MIC. In conclusion, the four peptides exhibited different in vitro activities and rapid time-dependent killing.

Anti-Bacterial Agents↗

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↗

Standardization of antifungal susceptibility testing and clinical relevance.

Standardization of antifungal susceptibility testing became essential to overcome the problem of interlaboratory variability and to determine the clinical relevance of in vitro data. This evolving process began for the yeasts and consequently broth macrodilution and microdilution methods (NCCLS M27 document) have been developed. These tests may not be useful for testing all organism-drug combinations or be the most convenient techniques for routine use in the clinical laboratory. Different alternatives to the NCCLS methods are currently under investigation. The identification of standard guidelines for antifungal susceptibility testing has reduced interlaboratory variability and further progress has been achieved with the determination of tentative interpretive breakpoints for certain drug-yeast combinations. However, these breakpoints are not adequate for interpretations of MICs for fungi-drug combinations beyond the setting for which they were determined. The NCCLS Subcommittee has also generated data for proposed testing guidelines for the moulds.

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↗

Epidemiologic features of intestinal parasitic infections in Italian mental institutions.

To determine the prevalence of intestinal parasitic infections in the residents of four Italian psychiatric institutions, we examined the stool specimens collected in triplicate from 238 residents, enrolled between May 1995 and May 1996. Besides, physician and staff nurses provided data about each resident by standardized questionnaires. Parasites were detected in the fecal samples from 128 patients (53.8%). However, in the stool specimens from 106 residents only non-pathogenic protozoa were found (82.8%). Trichuris trichiura ova, Giardia lamblia cysts and trophozoites, Cryptosporidium parvum oocysts, and Balantidium coli cysts were found in the fecal samples from 22 residents (9.2%). B. hominis was the most prevalent parasite. It was detected in the fecal specimens from 97 residents (40.8%). The so-called nonpathogenic amebae were detected in the fecal specimens from 65 residents, though, at the same time, there was no evidence of Entamoeba histolytica infection. Twelve residents (5.0%) showed intestinal colonization by nonpathogenic flagellates. All the subjects with T. trichiura infection were housed in the facility of Ancona. Parasites were found in fecal samples from all the 11 residents with behavioural aberrations, but only three of those suffering from intestinal pathogen infection associated to diarrhea. Statistical analyses revealed that the presence of pathogenic parasites in fecal specimens was significantly associated with diarrhea, nausea, vomiting, abdominal pain, fever, behavioural aberrations and nonpathogenic protozoa (p < 0.01), but did not demonstrate any other significant associations between these parasites and the other variables, such as pruritus, mucus or blood in the stools and presence of fecal leukocytes. On the other hand, the presence of nonpathogenic protozoa was significantly related to aberrations such as pica, geophagia, phytophagy, coprophagy, coprophilia and pathogenic parasites (p < 0.01). Data analyses revealed that both pathogenic and nonpathogenic parasites were significantly more common in institutionalized patients than in controls. The rare presence of clinical signs and symptoms in colonized patients represents an important public health problem, since the presence of asymptomatic carriers among residents with low hygienic conditions, raises concern of transmission of parasitic infections to professional staff and other residents. Since the eradication of parasitic colonization in residential facilities is hard to reach, an effective prevention is the only measure to deal with this public health problem.

Adult↗