Biomedical subjects

Domenico D'Antonio

Publications and source records attributed to Domenico D'Antonio.

12 recordsLinked to original sources

PubMed2006

Biofilm formation by the emerging fungal pathogen Trichosporon asahii: development, architecture, and antifungal resistance.

Trichosporon asahii is the most common cause of fatal disseminated trichosporonosis, frequently associated with indwelling medical devices. Despite the use of antifungal drugs to treat trichosporonosis, infection is often persistent and is associated with high mortality. This drove our interest in evaluating the capability of T. asahii to form a biofilm on biomaterial-representative polystyrene surfaces through the development and optimization of a reproducible T. asahii-associated biofilm model. Time course analyses of viable counts and a formazan salt reduction assay, as well as microscopy studies, revealed that biofilm formation by T. asahii occurred in an organized fashion through four distinct developmental phases: initial adherence of yeast cells (0 to 2 h), germination and microcolony formation (2 to 4 h), filamentation (4 to 6 h), and proliferation and maturation (24 to 72 h). Scanning electron microscopy and confocal scanning laser microscopy revealed that mature T. asahii biofilms (72-h) displayed a complex, heterogeneous three-dimensional structure, consisting of a dense network of metabolically active yeast cells and hyphal elements completely embedded within exopolymeric material. Antifungal susceptibility testing demonstrated a remarkable rise in the MICs of sessile T. asahii cells against clinically used amphotericin B, caspofungin, voriconazole, and fluconazole compared to their planktonic counterparts. In particular, T. asahii biofilms were up to 16,000 times more resistant to voriconazole, the most active agent against planktonic cells (MIC, 0.06 microg/ml). Our results suggest that the ability of T. asahii to form a biofilm may be a major factor in determining persistence of the infection in spite of in vitro susceptibility of clinical isolates.

Antifungal Agents↗

PubMed2005

Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia.

BACKGROUND: The prophylactic use of fluoroquinolones in patients with cancer and neutropenia is controversial and is not a recommended intervention. METHODS: We randomly assigned 760 consecutive adult patients with cancer in whom chemotherapy-induced neutropenia (<1000 neutrophils per cubic millimeter) was expected to occur for more than seven days to receive either oral levofloxacin (500 mg daily) or placebo from the start of chemotherapy until the resolution of neutropenia. Patients were stratified according to their underlying disease (acute leukemia vs. solid tumor or lymphoma). RESULTS: An intention-to-treat analysis showed that fever was present for the duration of neutropenia in 65 percent of patients who received levofloxacin prophylaxis, as compared with 85 percent of those receiving placebo (243 of 375 vs. 308 of 363; relative risk, 0.76; absolute difference in risk, -20 percent; 95 percent confidence interval, -26 to -14 percent; P=0.001). The levofloxacin group had a lower rate of microbiologically documented infections (absolute difference in risk, -17 percent; 95 percent confidence interval, -24 to -10 percent; P<0.001), bacteremias (difference in risk, -16 percent; 95 percent confidence interval, -22 to -9 percent; P<0.001), and single-agent gram-negative bacteremias (difference in risk, -7 percent; 95 percent confidence interval, -10 to -2 percent; P<0.01) than did the placebo group. Mortality and tolerability were similar in the two groups. The effects of prophylaxis were also similar between patients with acute leukemia and those with solid tumors or lymphoma. CONCLUSIONS: Prophylactic treatment with levofloxacin is an effective and well-tolerated way of preventing febrile episodes and other relevant infection-related outcomes in patients with cancer and profound and protracted neutropenia. The long-term effect of this intervention on microbial resistance in the community is not known.

Adolescent↗

PubMed2005

Invasive infections caused by Trichosporon species and Geotrichum capitatum in patients with hematological malignancies: a retrospective multicenter study from Italy and review of the literature.

Trichosporonosis is an uncommon but frequently fatal mycosis in immunocompromised patients. A multicenter retrospective study was conducted to characterize cases of proven or probable invasive trichosporonosis diagnosed over the past 20 years in Italian patients with hematological diseases. Of the 52 cases identified, 17 were classified as Trichosporon sp. infections and 35 were attributed to Geotrichum capitatum. Acute myeloid leukemia accounted for 65.4% of the cases. The incidence rates of Trichosporon sp. and G. capitatum infections in acute leukemia patients were 0.4 and 0.5%, respectively. Overall, 76.9% of cases had positive blood cultures. Pulmonary involvement was documented in 26.9% of cases. Death was reported for 57.1% of G. capitatum infections and for 64.7% of Trichosporon sp. infections. A literature review on trichosporonosis in patients with any underlying disease or condition reveals G. capitatum as a predominantly European pathogen, particularly in certain Mediterranean areas, while Trichosporon sp. infections are seen with similar frequencies on all continents. The majority of published Trichosporon sp. and G. capitatum infections occurred in patients with hematological diseases (62.8 and 91.7%, respectively). Well over half of these were suffering from acute leukemia (68 and 84% of patients with Trichosporon sp. and G. capitatum infections, respectively). Crude mortality rates were 77% for Trichosporon spp. and 55.7% for G. capitatum. The optimal therapy for trichosporonosis has yet to be identified; however, in vitro experiences are providing encouraging evidence of the potential role of the new triazoles, in particular, voriconazole.

Adolescent↗

PubMed2004

Biofilm formation by Stenotrophomonas maltophilia: modulation by quinolones, trimethoprim-sulfamethoxazole, and ceftazidime.

We investigated the in vitro effects of seven fluoroquinolones (ciprofloxacin, grepafloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, and rufloxacin), compared to those of trimethoprim-sulfamethoxazole (SXT) and ceftazidime on total biomass and cell viability of Stenotrophomonas maltophilia biofilm. S. maltophilia attached rapidly to polystyrene, within 2 h of incubation, and then biofilm formation increased over time, reaching maximum growth at 24 h. In the presence of fluoroquinolones at one-half and one-fourth the MIC, biofilm biomass was significantly (P < 0.01) reduced to 55 to 70% and 66 to 76% of original mass, respectively. Ceftazidime and SXT did not exert any activity. Biofilm bacterial viability was significantly reduced by all antibiotics tested at one-half the MIC. At one-fourth the MIC all antibiotics, except levofloxacin, significantly reduced viability. Treatment of preformed biofilms with bactericidal concentrations (500, 100, and 50 micro g/ml) of all fluoroquinolones caused, except for norfloxacin, significant reduction of biofilm biomass to 29.5 to 78.8, 64.1 to 83.6, and 70.5 to 82.8% of original mass, respectively. SXT exerted significant activity at 500 micro g/ml only. Ceftazidime was completely inactive. Rufloxacin exhibited the highest activity on preformed biofilm viability, significantly decreasing viable counts by 0.6, 5.4, and 17.1% at 500, 100, and 50 micro g/ml, respectively. Our results show that (i) subinhibitory (one-half and one-fourth the MIC) concentrations of fluoroquinolones inhibit adherence of S. maltophilia to polystyrene and (ii) clinically achievable concentrations (50 and 100 micro g/ml) of rufloxacin are able to eradicate preformed S. maltophilia biofilm.

Anti-Infective Agents↗

PubMed2004

In vitro pharmacodynamic characteristics of amphotericin B, caspofungin, fluconazole, and voriconazole against bloodstream isolates of infrequent Candida species from patients with hematologic malignancies.

Time-kill and postantifungal effect (PAFE) of amphotericin B, caspofungin, fluconazole, and voriconazole were determined against clinical isolates of Candida guilliermondii, Candida kefyr, and Candida lusitaniae. Azoles displayed fungistatic activity and no measurable PAFE, regardless of the concentration tested. Amphotericin B and caspofungin demonstrated concentration-dependent fungicidal activity, although amphotericin B only produced a significant dose-dependent PAFE against all isolates tested.

Amphotericin B↗

PubMed2004

Mucormycosis in hematologic patients.

BACKGROUND AND OBJECTIVES: To evaluate the clinical characteristics of patients affected by hematologic malignancies who developed mucormycosis and to ascertain the factors which influenced the outcome following mycotic infection. DESIGN AND METHODS: This was a retrospective study conducted over a 15-year period (1987-2001). The study included 59 patients with hematologic malignancies with a proven or probable mucormycosis admitted in 18 Hematology Divisions in tertiary care or university hospitals. RESULTS: The most frequent sites of infection were lung (64%) and orbito-sinus-facial (24%); cerebral involvement observed in 19% of cases was always associated with other sites of infection. Antifungal treatment was empirically administered in 49 patients (83%); 7 patients underwent radical surgical debridement (12%). Therapy was successful for only 18 patients (37%). Forty-seven patients died within 3 months of the diagnosis of fungal infection: the cause of death was mucormycosis in 41 patients (87%) and progression of hematologic disease in 6 patients (13%). At univariate analysis, the factors that correlated with a positive outcome from infection were the following: male sex, amphotericin B treatment, neutrophil recovery from post-chemotherapy aplasia. At multivariate analysis, the only factor that significantly correlated with recovery from infection was the liposomal amphotericin B treatment. INTERPRETATION AND CONCLUSIONS: Mucormycosis is a rare filamentous fungal infection that occurs most frequently in neutropenic patients with acute leukemia. It does not seem to have increased in recent years. Although a reduction of mortality has been observed recently, the mortality rate still remains high. Extensive and aggressive diagnostic and therapeutic procedures are essential in order to improve the prognosis in these patients.

Adolescent↗

PubMed2004

Cryptococcosis in patients with hematologic malignancies. A report from GIMEMA-infection.

BACKGROUND AND OBJECTIVES: Cryptococcosis is an important cause of morbidity and death in immunocompromised patients. The aim of this study was to evaluate clinical and laboratory characteristics, and outcome of patients with cryptococcosis complicating hematologic diseases. DESIGN AND METHODS: This was a retrospective study, conducted over a ten-year period (1993-2002) in 21 hematology divisions, in tertiary care or university hospitals. RESULTS: This study evaluated 17 patients with hematologic diseases who developed cryptococcosis. Possible risk factors recognized before the onset of the infection were: administration of steroids for the underlying malignancy (6 patients), diabetes mellitus (4 patients), cutaneous lesions (2 patients) and autoimmune disease, hepatic cirrhosis, chronic renal failure and exposure to pigeons (1 patient each). Five patients received prophylaxis, consisting of fluconazole in 2 cases. Fever, neurological and respiratory signs developed according to the primary sites of infection (5 blood, 5 central nervous system, 4 lung, and 1 each in gut, skin and mouth). Diagnosis was made by positive microbiological culture, antigen detection in serum or cerebrospinal fluid, or polymerase chain reaction. All patients started specific treatment (fluconazole, 7 patients; amphotericin-B deoxycolate or liposomal amphotericin-B, 10 patients). Two patients died from cryptococcosis within 30 days after diagnosis. INTERPRETATION AND CONCLUSIONS: Cryptococcosis in patients with hematologic malignancies is a rare complication. In neutropenic patients, it is less fatal than other fungal infections (i.e. aspergillosis or candidemia). Specific treatment, started promptly, positively influences the outcome.

Adolescent↗

PubMed2002

Comparison of Etest, agar dilution, broth microdilution and disk diffusion methods for testing in vitro activity of levofloxacin against Staphylococcus spp. isolated from neutropenic cancer patients.

The susceptibility to levofloxacin of 194 consecutive staphylococcal (45 Staphylococcus aureus and 149 coagulase-negative staphylococci) isolates from neutropenic patients was determined by Etest and the results compared with those obtained using NCCLS-methods (broth microdilution, agar dilution and disk diffusion). Overall agreement at +/- 1log(2) dilution for Etest compared with broth microdilution and agar dilution was 99.0 and 83.5%, respectively. The Etest category agreement with broth microdilution and disk diffusion was 95.9 and 89.7%, respectively. Comparison of categories with Etest and agar dilution method gave only 67.0% absolute categorical agreement, with 29.9% minor errors and 10.7% major errors. No very major errors occurred by the four methods tested. Our results show that Etest is a valid alternative to the reference NCCLS-methods for monitoring the clinical usefulness of levofloxacin against staphylococci isolates from neutropenic patients.

Agar↗

PubMed2002

Multicenter evaluation of an enzyme immunoassay (Platelia Aspergillus) for the detection of Aspergillus antigen in serum.

Invasive aspergillosis is a serious problem for immunocompromised patients, especially if neutropenic. The diagnosis of this infection is complicated, since clinical symptoms are often similar to those of other fungal diseases. The chance of detecting the presence of a specific antigen in the serum could confirm the suspected clinical diagnosis and. perhaps, be useful for the follow-up of the patient. The Medical Mycology Committee of the Associazione Microbiologi Clinici Italiani (AMCLI) decided to evaluate in a multicenter prospective study (from I November 1998 to 28 February 1999) the performance of the Platelia Aspergillus Kit (Bio-Rad) for the detection of Aspergillus galactomannan in human serum. The enrolled patients included various groups of immunosuppressed patients (mostly neutropenic). Blood samples were drawn at the time of enrollment. This decision was based upon a clinical diagnosis of probable aspergillosis (antibiotic non-responsive fever for at least 96 hours, cough, hemophthosis and positive chest X-ray). Additional blood samples were drawn on days 3, 6, 9, 12, 15 and 21. Culture and histopathologic examinations were performed according to the individual laboratory workflow. For each patient the laboratory filled a form with all the available clinical information, to create a database on which to evaluate the results of the test. During the study, 187 patients with various kinds of immunosuppression were enrolled. A total of 256 sera were tested: for 117 patients (62.6%) only the basal sample was tested, whereas for the 70 symptomatic patients (37.4%) multiple specimens (range: 1-6) were tested. The results allowed the laboratories to exclude (68.6%) or confirm (31.5%: confirmed and/or probable) the clinical diagnosis of invasive aspergillosis; 4 cases remained undetermined. Based on the results of this study, it seems that the use of this test should be limited to those patients with clinical symptoms of aspergillosis.

Antigens, Fungal↗

PubMed2002

Catheter-related candidemia caused by Candida lipolytica in a patient receiving allogeneic bone marrow transplantation.

Candida lipolytica was recovered from the blood and the central venous catheter in a patient receiving allogeneic bone marrow transplantation. Two C. lipolytica strains from different geographical areas and the ATCC 9773 strain of C. lipolytica were used as controls. C. lipolytica was identified by standard methods. MICs indicated antifungal susceptibilities to amphotericin B, fluconazole, and itraconazole for all strains. In vitro testing and scanning electron microscopy showed that C. lipolytica was capable of producing large amounts of viscid slime material in glucose-containing solution, likely responsible for the ability of the yeast to adhere to catheter surfaces. Restriction fragment length polymorphisms revealed an identical profile for all clinical isolates, unrelated to those observed for the control strains. This finding suggested the absence of microevolutionary changes in the population of the infecting strain, despite the length of the sepsis and the potential selective pressure of amphotericin B, which had been administered to the patient for about 20 days. The genomic differences that emerged between the isolates and the control strains were indicative of a certain degree of genetic diversity between C. lipolytica isolates from different geographical areas.

Adolescent↗

PubMed2002

Chronic disseminated candidiasis in patients with hematologic malignancies. Clinical features and outcome of 29 episodes.

BACKGROUND AND OBJECTIVES: To evaluate the characteristics of patients affected by hematologic malignancies who developed a chronic disseminated candidiasis (CDC), and to ascertain the factors that influenced the outcome, in a retrospective study conducted between January 1990 and December 2000, in 4 Hematology Divisions. DESIGN AND METHODS: CDC was diagnosed by clinical features combined with radiological and/or histologic and/or microbiological data. RESULTS: Twenty-eight patients (male/female 14/14; average age 42 years, range 12-67) developed a CDC. Twenty had acute myeloid leukemia, 5 had acute lymphocytic leukemia and 3 had non-Hodgkin's lymphoma. All patients received chemotherapy, including cytarabine for 21 of them (75%). Before the infection, 22 patients (79%) were neutropenic (absolute neutrophil count < 0.5 x 10(9)/L) for an average of 20 days (8-36), but at CDC diagnosis only 3 patients (11%) were neutropenic. Twenty-two patients (75%) received antifungal prophylaxis for an average of 15 days (10-60). Before diagnosis of CDC, 9 patients (32%) had a candidemia. The sites compromised by CDC were: liver in 27 patients (96%) and/or spleen in 11 patients (38%). Ten patients had other organs involved: lung in 6 patients (21%), kidney in 4 patients (14%), other sites 2 patients (7%). Abdominal ultrasonography was positive in 96% of patients (27/28), and abdominal computed tomography-scan was positive in 100% of cases in which it was performed (21/21). Liver biopsy was positive in 10/15 patients (67%). The main signs and symptoms were: fever 86%, abdominal pain 54%, diarrhea 32%, tenderness 25%, vomiting 25%, jaundice 29%, dysphagia 7%. Among chemical analyses, the most sensitive test was alkaline phosphatase, with a 3-5-fold increase in 24 patients (86%); an increase of liver transaminases and g-glutamyl transferase was observed in less than 50% of patients. By 30 days after diagnosis 4 patients had died, 1 from infection, and 3 progression of the hematologic malignancy without signs of active CDC. Within 3 months from diagnosis 14 out of the remaining 24 patients (58%) received further chemotherapy: in particular, 2 patients underwent transplantation procedures. INTERPRETATION AND CONCLUSIONS: In our experience CDC is not a fatal complication of patients with hematologic malignancy, on the contrary to that observed for other fungal infections (i.e. aspergillosis, candidemia), characterized by a higher mortality rate. The major problem of this fungal complication is correlated to the delay in the following treatment for the hematologic malignancy with a high risk of progression of malignancy.

Adolescent↗

PubMed2001

Single primer pair for PCR identification of Candida parapsilosis group I isolates.

A DNA fragment, isolated from a genomic DNA mini-library of Candida parapsilosis group I reference strain ATCC 22019, was sequenced and characterised. The fragment was first probed by Southern blotting against a pool of DNA from several yeasts. The hybridisation tests revealed that the probe was specific for strain ATCC 22019 and 49 (90.74%) of 54 C. parapsilosis clinical and soil isolates that were attributed to C. parapsilosis group I by the electrophoretic images of their restriction fragment length polymorphisms (RFLPs) and electrophoretic karyotype (EK). The remaining five negative isolates, according to the same criteria, were attributed to group II (one isolate) and III (four isolates). Two primers were selected from the probe DNA sequence and a PCR-based test was developed for specifically detecting C. parapsilosis group I isolates, which represent the majority of the common clinical isolates. The PCR assay confirmed the Southern hybridisation results. This PCR assay could be a simple and reproducible tool for the rapid, sensitive and species-specific identification of C. parapsilosis major group I isolates.

Base Sequence↗