[Candida albicans: the relationship between morphotypes and in-vitro adhesivity to the oral mucosa cells of HIV-positive and AIDS patients. I]. / Candida albicans: relazione tra morfotipi e adesività in vitro a cellule della mucosa orale di pazienti HIV-positivi e con AIDS. Parte I.

BACKGROUND: The significant frequency of oropharyngeal candidiasis due to C. albicans in HIV-infected and AIDS patients and the undoubted differences in pathogenicity among strains, lead us to study whether a possible correlation exists between the phenotypic characteristics of the fungal strain and the blastospores adhesivity to the human buccal epithelial cells. METHODS: From 203 oro-pharyngeal swabs of HIV-infected patients, 133 C. albicans were identified among 159 yeast strains. Analytical strains delineation below the species level was made by the morphotyping method, assigning a morphotype code of three digits, each of which being expressive of one colonial fringe characteristic. To study the possible blastospores adhesivity differences, we have isolated 10 strains of C. albicans, chose according to the more significant colonial morphologies; they were mixed with oral epithelial cells obtained by scraping of 36 HIV-positive patients and 2 volunteer donors HIV-negative at the rate cells/blastospores of 1:20. Suspensions were filtered, fixed and examined by optical microscope (MO) for counting the number of blastospores adhering to 100 epithelial cells and the number of cells with adhering blastospores. RESULTS: The index obtained by comparing the two qualitative analysis was higher for these isolates producing a rough or very coarse lateral fringes. CONCLUSIONS: This finding suggests that these strains may possess the highest adhesive properties, in fact the index decreases progressively to reach lower values for the strain not producing fringe.

[Candida albicans morphotypes and in vitro adhesivity to cells of the human oral mucosa in HIV-positive and AIDS patients after exposure of blastospores to fluconazole. II]. / Morfotipi di Candida albicans e adesività in vitro a cellule della mucosa orale di pazienti HIV-positivi e con AIDS dopo esposizione delle blastospore al fluconazolo. Parte II.

BACKGROUND: Oro-pharyngeal candidosis is a frequently initial clinical manifestation of HIV infection and the adhesive properties of Candida spp. represent a very important pathogenicity factor. METHODS: In this study the adhesivity rate of Candida albicans to the oral epithelial cells of 33 HIV-positive patients and 12 healthy volunteers, have been assessed before and after the exposure of blastospores to inhibitory concentrations of fluconazole, in relation to 11 morphotypes obtained from 13 C. albicans strains. RESULTS: Results can be summarized as follows: 1) the number of blastospores adhering to the HIV-positive donor' cells is higher than that of blastospores adhering to the healthy donors' cells (rate is 2.7:1); 2) blastospores from strains producing rough or very coarse fringes show adhesive properties higher than those of strains with different morphology; 3) in the group of HIV-positive patients the adhesivity inhibition of blastospores from strains producing rough or very coarse fringes was higher (38.3%) than that of strains with different morphology (33.8%); 4) overall, adhesivity inhibition due to exposure to fluconazole is higher for epithelial cells from healthy donors. CONCLUSIONS: These results can suggest the validity of an antimycotic pretreatment of persons at risk of oro-pharyngeal candidiasis.

Morphotypes of Candida albicans and their associations with underlying diseases and source of samples.

The morphotyping method was applied to differentiate a series of 276 Candida albicans strains recovered from hospitalized patients, by using a three-digit code based on the characteristics of the fringe outgrowth. By this scheme 32 different morphotypes were identified. An 86% reproducibility was achieved. The aim of this study was to investigate whether significant correlations exist between the morphotypes and: i) some underlying diseases of the patients, ii) the anatomical sources of the samples. The most striking associations were observed between fringeless strains and non-neoplastic diseases of the respiratory tract, and again between continuous filamentous fringe with parallel outgrowth and AIDS. With a significantly high frequency, samples from the genitourinary tract had a very coarse fringe texture.

Susceptibility of Helicobacter pylori and pharmacokinetic properties in mice of new 5-nitroimidazole derivatives devoid of mutagenic activity in the Ames test.

The minimum inhibitory concentrations of metronidazole and four new 5-nitroimidazole derivatives (EU 11100, EU 11102, EU 11103, EU 11104), obtained by the reaction of 1-methyl-5-nitroimidazolyl-2-carboxyaldehyde and terbutyl-phenol, were determined against 25 clinical isolates of Helicobacter pylori. Three of them (EU 11100, EU 11103, EU 11104) exhibited an antibacterial activity higher than that of metronidazole. The last one, the molecule EU 11102, was less active than metronidazole. In mice, after a single equimolar oral administration, the molecules EU 11100 and 11103 were poorly absorbed and poorly excreted in urine. The molecular EU 11104 was well adsorbed and its urinary recovery was slightly lower than that of metronidazole. The substance EU 11102 was not demonstrable in blood and urine. In the Salmonella/microsome mutagenicity test only the molecule EU 11100 showed an increase of mutation frequency in S. typhimurium TA 100.

[Bone marrow cryptococcosis as the first manifestation of AIDS]. / Criptococcosi midollare quale prima espressione di AIDS.

Bone marrow cryptococcosis as initial sign of AIDS. The Authors describe a case of bone marrow cryptococcosis in a patient, female aged 27, in which a toluene-induced aplastic anemia was suspected. The mycosis was at first extracerebral and represented the initial manifestation of unexpected AIDS. The Authors discute the symptomatology and the clinical findings leading to the diagnosis and remark the main point of bone marrow evaluation as aid in diagnosing the infective pathology.

Listeria monocytogenes infections: the organism, its pathogenicity and antimicrobial drugs susceptibility.

L. monocytogenes can induce serious, life-threatening infections. Multiple clinical manifestations of the disease include neonatal and perinatal listeriosis, infections in adult immunocompromised patients as well as in normal hosts, with the CNS as the more frequent site involved. Many outbreaks are believed to be food-borne in origin, but there can be other means of transmission. The susceptibility of L. monocytogenes to different antimicrobial drugs is reviewed. Many drugs that are highly effective in vitro show only a moderate activity in vivo, due either to their poor ability to enter the phagocytes and destroy the engulfed bacteria, as with the beta-lactams, ampicillin and amoxicillin, or to their bacteriostatic rather than bactericidal activity, as with the fluoroquinolones, or their affinity for a serum glycoprotein, as with the macrolide antibiotics. The bacterial killing appears to be enhanced by some synergistic drug associations, the best therapeutic results being achieved by trimethoprim-cotrimoxazole and ampicillin plus gentamicin. Other more recent antimicrobial drugs and drug combinations are still under clinical evaluation.

Antibacterial, antimycotic and trichomonicidal activity of a new nitroimidazole (EU 11100).

The antimicrobial profile of a new nitroimidazole derivative (5-nitro-1-methyl-imidazolyl-2-hydroxy-3 terbutylphenyl carbinol) has been studied. The in vitro activity of the new molecule has been evaluated against both aerobic and anaerobic bacteria, Trichomonas vaginalis, and mycetes, under suitable experimental conditions. The new compound was compared with ampicillin against aerobic bacteria; with metronidazole against anaerobic bacteria, lactobacilli and T. vaginalis; with nistatin and econazole against candida and with econazole and bifonazole against filamentous fungi. The new nitroimidazole derivative has been shown to be moderately active against some anaerobic bacteria belonging to both the Gram-positive and Gram-negative groups. Its inhibitory activity against T. vaginalis was similar to that of metronidazole.

Activity of two benzofuran-imidazoles, IM/B/4-62 and IM/B/4-66, against experimental infections with Candida albicans and Trichophyton mentagrophytes.

The therapeutic activity of two new benzofuran-imidazoles, IM/B/4-62 and IM/B/4-66, formulated as 1% cream, has been evaluated against Candida albicans and Trichophyton mentagrophytes by inducing experimental vaginal candidosis in female rats and dermatophytosis in female guinea pigs. Results of the treatment were compared with those obtained by the same therapeutic regimen carried out with bifonazole. IM/B/4-66 proved to possess superior antimycotic activity to that of IM/B/4-62 and similar to that of bifonazole in both infections. Nmaley vaginal candidosis was cured in all the treated in animals at 6 days post-inoculation and skin lesions were healed in 9 of 10 animals at 15 days after infection, with negative cultures from all the infected sites.

Antifungal activity of two benzofuran-imidazoles in different experimental conditions.

A number of experiments was performed in order to analyze the in vitro activity of two new benzofuran-imidazoles, IM/B/4-62 and IM/B/4-66. Studies included the determination of minimum inhibitory concentrations (MICs) on three culture media, at different pH values and at different inoculum sizes. Furthermore, the killing activity and induced resistance were determined. In all the experiments econazole, clotrimazole and bifonazole were the reference compounds. The best MIC values of the two new imidazoles were observed on modified Sabouraud's medium, at neutral pH and an inoculum size of 10(4) cells/ml. The two substances showed killing activity and no resistance was observed. On the whole, the more favorable results were obtained with the compound IM/B/4-66.

Microbiological patterns of four new imidazole derivatives.

The authors present an in vitro experimental study concerning the microbiological properties of four imidazole derivatives, with a piperazine group between two benzene rings. Seventy strains of Gram-positive and Gram-negative bacteria, 30 of yeasts, 14 of filamentous fungi and 10 strains of Trichomonas vaginalis were tested. The new compounds revealed a good inhibitory activity against Gram-positive bacteria, yeasts and dermatophytes. These results compare well with those obtained with the other known imidazoles. Moreover any mutagenic activity is absent.

[Pathology of the internal organs and central nervous system in acquired immunodeficiency syndrome (with special reference to opportunistic infections)]. / La patologia degli organi interni e del sistema nervoso centrale nella sindrome da immunodeficienza acquisita (con particolare riferimento alle infezioni opportunistiche).

Extracerebral and cerebral pathology in AIDS (with particular emphasis on the opportunistic infections). The Authors present the extracerebral pathology of 27 cases of AIDS observed at the Department of Pathology of Milan and the cerebral pathology of 80 cases of AIDS collected by three Institutes (Department of Pathology of Milan, Department of Pathology of Rimini and Department of Neuropathology of Münster) with particular emphasis on the pathology of the opportunistic infections. In the adults' group, the most frequent infections are the protozoan ones (T. gondii) followed with equal incidence by the viral and fungal diseases. In the pediatric group the viral diseases are the most frequently seen. Almost all of the adults show multiple infections in the same organ or in different organs. Diffuse lesions with heavy pathologic fields were observed also without tissue reaction. As to cerebral pathology AIDS' patients with opportunistic infections show focal symptoms, whereas the so called "subacute microglial encephalitis" generally appears as a demential syndrome. In cases with progressive multifocal leukoencephalopathy JC virus was always found and in one case also SV 40 - and BK virus. The diffuse demyelinization in some cases of HIV-Encephalopathy is aspecific. In HIV-positive newborns with cerebral signs, the lesions are characterized by oedema, spongiosis and microcalcifications of the basal ganglia; these are aspecific lesions which can be found in toxic and infectious encephalopathies.

Cerebral listeriosis in adults. Three cases report.

The Authors describe three autoptic cases of meningoencephalitis in adults due to an emerging pathogen, the Gram-positive bacillus Listeria monocytogenes. Only one of these was an immunosuppressed patient (recurrent carcinoma of the larynx and bladder papillomas), while no severe cause of debilitation was detected in the other two cases, excluding colonic diverticulosis in both. The post-mortem examination revealed leptomeningitis and encephalitis. Lympho-monocytic tissue reaction with perivascular cuffing was present in all the cases. The etiologic agent, L. monocytogenes, was identified by cultures from clinical or autoptic specimens.

Treatment of experimental cystitis in the rat with a single dose of fosfomycin trometamol.

The therapeutic effectiveness of a single oral dose (60 and 200 mg/kg body weight) of fosfomycin trometamol (FT), norfloxacin, trimethoprim sulfamethoxazole (Bactrim) and pipemidic acid against experimental cystitis in the rat were compared. Infections were produced with clinical isolates of Klebsiella pneumoniae, Proteus mirabilis and Escherichia coli in a total of 135 Sprague-Dawley albino rats. Oral treatment with all four drugs consistently lowered the numbers of CFU in bladder tissue, especially E. coli and P. mirabilis. Fosfomycin trometamol appeared to be as effective as norfloxacin for treatment of E. coli cystitis even thoughs its minimal inhibitory concentration (MIC) in vitro is 100 times greater than that of the quinolonic antibiotic. Fosfomycin trometamol, pipemidic acid and Bactrim were equally effective against P. mirabilis infection, but FT was less active than norfloxacin or Bactrim for treatment of K. pneumonia cystitis. In conclusion, single dose treatment with fosfomycin trometamol was effective for treatment of experimental cystitis in the rat and might, by extrapolation, be of use in clinical practice for single dose treatment of uncomplicated urinary tract infections.

Antibacterial activity in human urine of fosfomycin trometamol in an in vitro model of the urinary bladder.

The urinary concentrations of fosfomycin trometamol, norfloxacin, pipemidic acid and cotrimoxazole were studied at various times after oral administration of drugs in healthy volunteers. Using the same urine, the bactericidal activity of four antimicrobial agents against Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae in an in vitro model simulating the treatment of bacterial cystitis was also evaluated. The results obtained show that very high concentrations of the drugs were achieved in urine particularly after the oral administration of the fosfomycin trometamol. In the bladder model bactericidal activity of fosfomycin trometamol, norfloxacin and pipemidic acid were higher than that of cotrimoxazole; no resistant mutants to drugs were selected over a period of 24 h.

Mycoses in immunocompromised patients. An histopathologic study of 61 cases.

The histopathologic pattern of secondary mycoses in 61 immunocompromised patients is presented. The underlying diseases were: neoplasms, organ transplants, AIDS and a variety of other debilitating diseases. Three patients with AIDS had a double fungal infection. Candida spp. accounted for the majority of deep-seated mycoses, with 27 cases (44.2%); disseminated candidiasis was responsible of 18.5% of these patients death. Aspergillosis was seen in 23 subjects (37.7%), 18 of them (78.2%) died for systemic infection. These patients were severely debilitated by disease and/or iatrogenic procedures. The other fungal infections were: actinomycosis (10 cases), gerotrichosis (2 cases), histoplasmosis (1 case) and cerebral phaeohyphomycosis (1 case).

Pasteur yeasts system, a test-kit for yeasts identification. Its evaluation in comparison with three commercial methods and conventional procedures.

The Pasteur Yeasts System is a commercial prepared kit and scheme for the rapid (48 h) identification of 23 yeasts belonging to 7 genera. The method consists of two parts: a gallery of media to evaluate germ tube production, urease activity, tetrazolium reduction, cycloheximide sensibility and fermentation of three carbohydrates, and an auxanographic method to determine the assimilation pattern of 16 carbohydrates. This system was tested in comparison with API 20 C Auxanogram, Mycotube, Candida Check and conventional procedures to identify 40 yeast strains. Pasteur Yeasts System provided correct identifications for 97.5% of the organisms and proved to have a high reproducibility, accuracy and reliability. The method is useful and facilitates the identification of pathogenic yeasts from clinical specimens in the routine laboratory.

New benzofuran-imidazoles as antimycotic agents. I. Synthesis and characterization.

With the aim of obtaining new drugs having antimycotic activity together with antibacterial and fewer side effects, we synthesized ten new benzofuran-2-yl-imidazoles.

New benzofuran-imidazoles as antimycotic agents. II. In vitro studies.

Ten new imidazole derivatives, benzofuran-imidazoles, were studied in vitro to establish their antimycotic activity against 70 fungal strains, in comparison with three known imidazoles and, for the dermatophytes only, griseofulvin. A very high inhibitory activity against dermatophytes was shown by five of the new substances. The other filamentous fungi and yeasts showed a more marked variation in their susceptibility. However a good sensitivity of some isolates of Candida albicans and other yeasts was seen.