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Background An increasing number of antimycotics have become available for the treatment of dermatophytoses; however, there are reports suggesting recalcitrance to therapy or resistance of a dermatophyte against conventional treatment. Lipopeptides represent novel therapeutic drugs with a new mode of action. Objectives The aim of this study was to investigate the in vitro effects of the lipopeptide Pal-Lys-Lys-NH2 (PAL) alone and in combination with standard antifungal agents, such as fluconazole (FLU), itraconazole (ITRA) and terbinafine (TER) against 24 clinical isolates of dermatophytes belonging to four species. Methods A broth microdilution method following the Clinical and Laboratory Standards Institute recommendations (M38-A) was used for testing drugs alone and in combination. Results PAL minimum inhibitory concentrations (MICs) ranged from ≤ 0·25 to > 16 μg mL−1 and they were similar to those of FLU and higher than those of either ITRA or TER. Synergy, defined as a fractional inhibitory concentration (FIC) index of ≤ 0·50, was observed in 67%, 52% and 15% of PAL/ITRA, PAL/TER and PAL/FLU interactions, respectively. None of these combinations yielded antagonistic interactions (FIC index > 4). When synergy was not achieved, there was still a decrease in the MIC of one or both drugs used in the combination. Conclusions Our study demonstrates that PAL has potential activity against dermatophytes. In addition, the in vitro activity of PAL can be enhanced upon combination with standard drugs. This lipopeptide applied in the form of lacquer, spray or ointment, could represent an interesting new therapy, particularly when combined with conventional treatment in recalcitrant or resistant dermatophyte infections. [ABSTRACT FROM AUTHOR]

BACKGROUND: Medical devices used in clinical practice are often associated with biofilm-associated staphylococcal infections. METHODS: An in vitro antibiotic susceptibility assay of Staphylococcus aureus biofilms using 96-well polystyrene tissue-culture plates was performed to test the effects of RNAIII-inhibiting peptide (RIP), ciprofloxacin, imipenem, and vancomycin. Efficacy studies were performed using a rat model of central venous catheter (CVC)-associated infection. Twenty-four hours after implantation, the catheters were filled with RIP (1 mg/mL). Thirty minutes later, rats were challenged, via the CVC, with 1.0 x 10(6) cfu of S. aureus strain Smith diffuse. The antibiotic-lock technique was begun 24 h later. RESULTS: Minimum inhibitory concentrations of antibiotics in biofilms were at least 4-fold higher than those against the freely growing planktonic cells. When they were first treated with RIP, the cells in biofilms became as susceptible to antibiotics as did planktonic cells. These data were confirmed by the in vivo studies. In particular, when CVCs were treated with both RIP and antibiotics, the biofilm bacterial load was further reduced to 1 x 10(1) cfu/mL, and bacteremia was not detected, suggesting that there was 100% elimination of bacteremia and a 6 log10 reduction in biofilm bacterial load. CONCLUSION: RIP significantly reduces bacterial load and enhances the effect of antibiotics in the treatment of CVC-associated S. aureus infections. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 electrophoretickaryotyping (EK) and tested for their susceptibility to fluconazole (FLC),itraconazole (ITC), flucytosine (5-FC), and amphotericin B (AMB). Ourdata confirmed that EK is a useful technique for DNA typing of isolates of Candida parapsilosis and showed that the source of isolation is notassociated with a given DNA type. Although strains belonging to this speciesof Candida are susceptible to the most common antifungals, including the triazoles, the degree of ITC susceptibility was dose dependent (MIC rangingfrom 0.25–0.5 μg/ml) for 98% of the isolates. [ABSTRACT FROM AUTHOR]

To evaluate the Toxocara spp. eggs environmental contamination of the soil of the urban or suburban area Ancona (Italy), 22 public playgrounds were selected and several cores of soil were taken from any selected areas. To study the Toxocara seroprevalence in the inhabitants of Ancona, blood samples were collected from selected groups of individuals. One hundred and sixty-three blood samples were tested using an enzyme linked immunosorbent assay (ELISA) technique (Lofarma Lab, Milan, Italy) for the detection of IgG-specific antibodies to T.␣canis excretory–secretory antigens. Toxocara spp. eggs were found in the soil samples from 14 (63.6%) playgrounds. Toxocara seroprevalence was detected in blood specimens from six (8.1%) out of 74 symptomatic individuals and from one (1.1%) out of 89 asymptomatic controls. Among symptomatic individuals, the association between Toxocara seroprevalence and eosinophilia resulted statistically significant ( p = 0.029). The high environmental contamination frequency found make necessary to prompt preventive public health measures, such as control of stray animals, treatment of infected pets and hygiene education of the population. [ABSTRACT FROM AUTHOR]

The in vitro activity of buforin II, cecropin P1, indolicidin, magainin II and ranalexin, alone and in combination with eight clinically used antimicrobial agents was investigated against 12 multidrug-resistant strains of Acinetobacter baumannii isolated from immunocompromised patients. Antimicrobial activities were measured by MIC, MBC and viable count. The peptides had a varied range of inhibitory values: overall, the organisms were more susceptible to buforin II (MIC range 0.25–16 mg/L), cecropin P1 (0.50–32 mg/L) and magainin II (0.50–16 mg/L). Synergy occurred when magainin II was combined with β-lactam antibiotics. [ABSTRACT FROM PUBLISHER]

A rat model was used to investigate the efficacy of two polycationic peptides, ranalexin and buforin II, in the prevention of vascular prosthetic graft infection due to methicillin-resistant Staphylococcus epidermidis with intermediate resistance to glycopeptides. The in vitro activity of the peptides was compared with those of vancomycin and teicoplanin by MIC determination and time–kill study. Moreover, the efficacy of collagen-sealed peptide-soaked Dacron was evaluated in a rat model of graft infection. Graft infections were established in the dorsal subcutaneous tissue of 120 adult male Wistar rats. The in vivo study included a control group, one contaminated group that did not receive any antibiotic prophylaxis and four contaminated groups that received an antibiotic-soaked graft. Experiments demonstrated that the activities of buforin II and ranalexin were greater than those of vancomycin and teicoplanin. Particularly, rats with buforin II-coated Dacron grafts showed no evidence of staphylococcal infection while, for the rats with ranalexin-, vancomycin- and teicoplanin-coated Dacron grafts, the quantitative graft cultures demonstrated bacterial growth (1.9 × 102 ± 0.6 × 102 cfu/mL, 6.2 × 103 ± 1.9 × 103 cfu/mL and 5.1 × 104 ± 4.8 × 103 cfu/mL, respectively). The study demonstrated that the use of peptide-soaked Dacron graft can result in significant bacterial growth inhibition and indicates that these compounds may be potentially useful in prosthetic surgery. [ABSTRACT FROM PUBLISHER]

The in vitro activity of lactoferrins alone and in combination with clarithromycin, minocycline and pyrimethamine was investigated against three clinical isolates of Pneumocystis carinii. Susceptibility was tested by inoculating 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. At 20 mg/L, bovine lactoferrin, the most active agent, suppressed the growth of cystic and trophic forms by >60%. Human lactoferrin, at the same concentration, suppressed the growth of cystic and trophic forms by >50%. Lactoferrins at 20 mg/L combined with clarithromycin 4 mg/L had high anti-P. carinii activity, with a >90% decrease in cystic and trophic form counts. Our study suggests that lactoferrins may inhibit P. carinii growth in vitro and act synergically with other clinically used compounds. These findings lend experimental support to the use of iron-chelating agents in the therapy of pneumocystis infections. [ABSTRACT FROM AUTHOR]

The aim of this study was to define the epidemiology and clinical manifestations of late recurrent candidemia. For this purpose, late recurrent candidemia was defined as an episode of candidemia occurring at least 1 month after the apparent complete resolution of an infectious episode caused by the same Candida sp. A total of five patients with recurrent candidemia were investigated. For all patients, isolates from the initial and recurrent episodes of candidemia were available for in vitro susceptibility testing and genetic characterization by DNA-based techniques. The results revealed the following salient features: prolonged duration between the initial and recurrent episodes (range, 1–8 months); recurrence of candidemia despite antifungal therapy; importance of retained intravascular catheters, neutropenia, and corticosteroids as factors predisposing to recurrence; high morbidity and mortality; no emergence of antifungal drug resistance between the initial and recurrent episodes; and relapse of infection due to the original infecting strain, rather than reinfection with a new strain. These findings raise several issues about the management and follow-up of patients with candidemia, which require assessment in future studies. [ABSTRACT FROM AUTHOR]

The anti-cryptosporidial activity of four cationic peptides alone and in combination with five ion transport system (ITS) inhibitors was investigated for six clinical isolates of Cryptosporidium parvum recovered from stools of AIDS patients. The susceptibility tests were performed by inoculating the protozoa on to cell monolayers and determining the parasite count after 48 h incubation at 37 degrees C. The culture medium was supplemented with serial dilutions of cecropin P1, magainin II, indolicidin and ranalexin alone or in combination with amiloride and its analogues. No agent was able to inhibit parasite growth completely. The peptides had some inhibitory effect on parasite growth: cecropin P1, magainin II, indolicidin and ranalexin at a concentration of 50 microM produced 30.6, 33.2, 38.5 and 42.1% reductions, respectively, in schizont count. Conversely, the ITS inhibitors were scarcely effective. Positive interaction was demonstrated when the peptides were tested in combination with ITS inhibitors. [ABSTRACT FROM AUTHOR]

The in vitro activity of nitazoxanide alone and in combination with azithromycin and rifabutin was investigated against four clinical isolates of Cryptosporidium parvum. The susceptibility tests were performed by inoculation of the isolates on toe cell monolayers and determination of the parasite count after 48 h incubation at 37°C. The culture medium was supplemented with Dulbecco's modified Eagle's medium containing serial dilutions of each agent. Antibiotic-free plates were used as controls. Experiments were performed in triplicate. Nitazoxanide showed moderate anticryptosporidial activity: it suppressed the growth of parasites by >50% at 8 mg/L. A parasite reduction of 79.8–83.9% was observed when nitazoxanide 8 mg/L was combined with azithromycin 8 mg/L and rifabutin 8 mg/L. The study suggests that nitazoxanide may be active in inhibiting C. parvum growth in vitro upon combination with azithromycin or rifabutin. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

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 × 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 × 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. [ABSTRACT FROM PUBLISHER]

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  50% and  90% at 5 and 50 μM, respectively, with the exception of indolicidin. Ranalexin, the most effective compound against C. parvum, suppressed its growth by  40% at 50 μM. [ABSTRACT FROM PUBLISHER]

We investigated the in-vitro activity of three selected dicationic aromatic compounds for nine clinical isolates of Cryptococcus neoformans and 93 clinical isolates of Candida spp., representing 12 different species, using a broth macrodilution method following NCCLS recommendations. All the clinical isolates were also tested for fluconazole susceptibility. The in-vitro data demonstrate that compounds 39 and 57 have excellent in-vitro activity for all tested strains (MIC 0.19-1.56 mg/L) except Candida pelliculosa. Moreover, compound 39 showed excellent in-vitro fungicidal activity against Candida krusei, Candida glabrata, Candida lusitaniae and Cryptococcus neoformans with MFCs in the range 0.39-6.25 mg/L. Both compounds 39 and 57 showed excellent in-vitro activity against fluconazole-resistant Candida albicans isolates, including a C. albicans strain that contains all known fluconazole-resistant mechanisms. Comparing MIC data from compounds 21, 39 and 57 with fluconazole, we found a statistically significant difference only with compound 39 (P = 0.043). However, comparing MFC data from compounds 21, 39 and 57 with fluconazole, we found statistically significant differences with all three compounds (P < 0.00001). These data indicate the potential antifungal breadth of two bis-benzimidazoles (compounds 39 and 57) as antifungal agents against yeasts. If it can be determined that compounds 39 and 57 are effective and non-toxic in vivo, the prospect of these compounds as clinically useful antifungal agents will be enhanced. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

A broth microdilution method and an agar dilution method were used for testing fluconazole, itraconazole, ketoconazole, flucytosine and amphotericin B against 98 clinical isolates belonging to seven species of Candida. The approximate rank order of fluconazole MICs was Candida lusitaniae approximately Candida kefyr < Candida famata approximately Candida guilliermondii < Candida pelliculosa approximately C. lipolytica approximately Candida inconspicua. Candida lypolitica and C. pelliculosa were the species least susceptible to itraconazole and ketoconazole. Flucytosine MICs revealed the highest prevalence of resistant strains among C. lipolytica and C. lusitaniae. All isolates were susceptible to amphotericin B. [ABSTRACT FROM AUTHOR]

A 24-year-old HIV-positive heterosexual woman with disseminated cryptosporidiosis was monitored from January 1998 to May 1999. During this period, consecutive stool, sputum, and bile examinations showed the constant presence of Cryptosporidium oocysts. Although the patient was repeatedly treated with oral paromomycin and azithromycin and, finally, nitazoxanide, her condition continued to deteriorate. In order to monitor the in vitro susceptibility of the parasite, specimens from various sites were collected periodically. When the first clinical isolate was tested, the antimicrobial agents used (azithromycin at a concentration of 8 mg/l, paromomycin at of 1 mg/ml, and nitazoxanide at 10 mg/l) produced a decrease in parasite counts of 26.5%, 63.4%, and 67.2%, respectively. Subsequent isolates of Cryptosporidium parvum showed similar susceptibilities. This case demonstrates that failure of clinical treatment corresponded to inadequate growth inhibition of the parasite in vitro. [ABSTRACT FROM AUTHOR]

The prevalence of Blastocystis hominis in stool specimens of individuals with gastrointestinal symptoms was evaluated to study a possible link between the protozoan and the irritable bowel syndrome. According to the Rome diagnostic criteria, 388 patients were evaluated. Altogether, 81 patients were classified as affected by irritable bowel syndrome. Blastocystis hominis was recovered from the stools of 38 subjects, 15 of whom belonged to the group with irritable bowel syndrome ( P=0.006). In addition, patients with irritable bowel syndrome were significantly more likely to have five or more Blastocystis hominis organisms per field ( P=0.031). In conclusion, there was a set of patients with irritable bowel syndrome in whom the presence of Blastocystis hominis may not be incidental. [ABSTRACT FROM AUTHOR]

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≥8.0 μg/ml), while 43% of the isolates showed reduced susceptibility to itraconazole (MIC≥0.25 μg/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 inititation of antifungal therapy with either of these drugs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The activity of eight topoisomerase inhibitors was investigated against five clinical isolates of Pneumocystis carinii. Susceptibility tests were performed by inoculation of the organisms on to a cell monolayer and parasites were counted after 72 h incubation at 37 degrees C. Culture plates were added with Dulbecco's modified Eagle's medium containing serial dilutions of lomefloxacin, norfloxacin, ofloxacin, pefloxacin, rufloxacin, camptothecin, amsacrine and etoposide. Atovaquone, pentamide isethionate and co-trimoxazole were used as control drugs. Etoposide gave inhibition comparable to that observed with atovaquone. Poor activity was demonstrated by pefloxacin, while the other topoisomerase inhibitors had no significant effect. [ABSTRACT FROM AUTHOR]

The anti-Pneumocystis carinii activity of atovaquone, dapsone and sulphamethoxazole alone and combined with dihydrofolate reductase (DHFR) inhibitors and macrolides was investigated against five clinical isolates of P. carinii. The susceptibility tests were performed by inoculation of the organisms on to cell monolayer and parasite count after 72 h incubation at 37 degrees C. Culture plates were added to Dulbecco's modified Eagle's medium containing serial dilutions of atovaquone, dapsone and sulphamethoxazole alone or in combination with diaveridine, pyrimethamine, trimethoprim, azithromycin, clarithromycin and roxithromycin. Atovaquone, dapsone and sulphamethoxazole were found to be effective at levels well below the concentrations that could be achieved clinically, while DHFR inhibitors were shown to combine effectively with dapsone and sulphamethoxazole. No synergy could be demonstrated between atovaquone and DHFR inhibitors or macrolides. A mild synergic effect was noted when macrolides were combined with dapsone and sulphamethoxazole. Pyrimethamine (0.5 mg/L) combined with dapsone and trimethoprim (0.5 mg/L) combined with sulphamethoxazole exerted the strongest inhibitory effect. [ABSTRACT FROM AUTHOR]

The anticryptosporidial activity of four macrolides alone and in combination with other antimicrobial agents was investigated against ten clinical isolates of Cryptosporidium parvum recovered from stools of AIDS patients. The susceptibility tests were performed by inoculation of the protozoa 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 azithromycin, clarithromycin, roxithromycin, spiramycin, alone or in combination with artemisin, atovaquone, dapsone, minocycline or pyrimethamine. Most of the agents had an inhibitory effect on parasite growth, but only at high concentrations. No agent was able to inhibit parasite growth completely, even at the highest concentrations used. The more effective agents, azithromycin, clarithromycin, roxithromycin, minocycline and pyrimethamine, produced no more than a 13.1-27.8% reduction in oocyst count and no more than a 15.1-35.7% in schizont count. Positive interaction was clearly demonstrated when macrolides were tested in combination with minocycline or pyrimethamine. [ABSTRACT FROM AUTHOR]

The MICs and MBCs of paromomycin for 32 Mycobacterium avium complex (MAC) strains isolated from patients with the acquired immunodeficiency syndrome were determined by a radiometric broth dilution method. The MICs for the majority of strains were either 8 or 16 mg/L and the MBCs were four- to eight-fold higher. Paromomycin merits further evaluation as oral prophylaxis against disseminated MAC infection. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 ofCandida albicans. Forty-seven strains ofCandida 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 ofCandida 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. [ABSTRACT FROM AUTHOR]

The ability of imipenem and meropenem in subinhibitory concentrations to influence the results of disk diffusion susceptibility tests was assessed. Selection of stably derepressed mutants resistant to beta-lactam antibiotics other than carbapenems was also investigated. Beta-lactams were shown to be subject to carbapenem-mediated antagonism in the disk diffusion test. On the other hand in vitro selection of stably derepressed mutants resistant to other beta-lactams could not be demonstrated. [ABSTRACT FROM AUTHOR]

The performance of the MB-Check system (Roche) in the recovery of mycobacteria from clinical specimens was compared with that of the Bactec radiometric system and conventional culture on Löwenstein-Jensen medium. A total of 1,582 clinical specimens were used for the study; 74 yielded mycobacteria. Organisms of the Mycobacterium tuberculosis and Mycobacterium avium complexes accounted for the majority of isolates. The rate of recovery of all mycobacteria with the Bactec system was 91.9%, with the MB-Check system 79.7% and on Löwenstein-Jensen medium only 54.1%. Combination of the Bactec and MB-Check systems allowed recovery of 100% of isolates. The Bactec system showed a faster detection time than the other two methods. [ABSTRACT FROM AUTHOR]

The laboratory findings in a case of Australia antigen (Au-Ag) positive chronic hepatitis in a 4-year-old boy are given. Studies by the electron microscope technique of thin sectioning revealed the presence of 200Å particles in the nuclei of hepatocytes. These particles are identical to those described previously in occasional specimens of Au-Ag-positive liver tissue. However, the pattern found here differs from previous descriptions inasmuch as no heavily infected nuclei could be found but almost all nuclei could be shown to contain extremely small numbers of these particles. The significance of this finding is discussed and the danger that it would be easy to obtain false negatives in similar tissue pointed out. [ABSTRACT FROM PUBLISHER]

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The in vitro anti-cryptosporidial activity of buforin II alone and in combination with azithromycin and minocycline was investigated. Buforin II showed moderate activity, which increased with increasing concentration to 55.7% suppression of growth at 20 microM. Moreover, its activity was enhanced when it was combined with either azithromycin or minocycline with >90% parasite reduction at the highest concentration tested. Buforin II may be active in inhibiting Cryptosporidium parvum growth in vitro upon combination with either azithromycin or minocycline. [ABSTRACT FROM AUTHOR]

The in vitro anticryptosporidial activities of ranalexin, lasalocid and azithromycin alone and in combination were investigated against four clinical isolates of Cryptosporidium parvum. Susceptibility was tested by inoculating the isolates on to cell monolayers and determining the parasite count after 48 h incubation at 37 degrees C. The culture medium was supplemented with Dulbecco's modified Eagle's medium containing serial dilutions of the above-mentioned compounds. Ranalexin showed moderate anticryptosporidial activity: at a concentration of 64 mg/L it reduced parasite counts by 33.8%. Azithromycin at a concentration of 8 mg/L gave inhibition comparable to that observed with the highest concentration of ranalexin. Lasalocid showed the highest activity, with a 70.3% reduction in parasite counts at 2 mg/L. The combination of ranalexin 64 mg/L and lasalocid 2 mg/L completely suppressed parasite growth without harming the monolayer. [ABSTRACT FROM AUTHOR]

The in vitro activity of ranalexin alone and in combination with other cationic peptides, macrolides, rifampin, and rifabutin was investigated against a clinical isolate of Cryptosporidium parvum. Susceptibility tests were performed by inoculation of the isolate onto cell monolayers and determining the parasite count after 48 h of incubation at 37 °C. Antibiotic-free cultures were used as controls in the study. Ranalexin showed low anticryptosporidial activity: it suppressed the growth of parasites by ≥40% at 50 μM. Ranalexin showed enhanced activity when it was combined with noninhibitory concentrations of other compounds: a 74.4–94.1% reduction in the number of parasites was observed when ranalexin 50 μM was combined with magainin II 50 μM, indolicidin 50 μM, clarithromycin 8 mg/l, azithromycin 8 mg/l, rifampin 8 mg/l, and rifabutin 8 mg/l. The results suggest that ranalexin may be effective in inhibiting Cryptosporidium parvum growth in vitro upon combination with other peptides and hydrophobic antibiotics. [ABSTRACT FROM AUTHOR]

A broth macrodilution method, performed as recommended by the National Committee for Clinical Laboratory Standards, was used for comparative testing of the new echinocandin antifungal agent MK-0991 and fluconazole against 50 yeast isolates belonging to 12 species of Candida. MK-0991 was shown to be highly effective against both fluconazole-susceptible and -resistant Candida spp., yielding minimum inhibitory concentrations ranging from ≤0.19 to 0.78 μg/ml. Fungicidal activity was exerted at ≤1.5 μg/ml for 73% of the isolates tested. This study suggests that MK-0991 has significant potential for clinical development. [ABSTRACT FROM AUTHOR]