Search PubMedSearch

Biomedical subjects

A Micozzi

Publications and source records attributed to A Micozzi.

At least 19 recordsLinked to original sources

Preventing fungal infection in neutropenic patients with acute leukemia: fluconazole compared with oral amphotericin B.

OBJECTIVE: To compare the efficacy and tolerability of fluconazole and oral amphotericin B in preventing fungal infection in neutropenic patients with acute leukemia. DESIGN: A randomized, controlled, multicenter trial. SETTING: 30 hematologic units in tertiary care or university hospitals. PATIENTS: 820 consecutive, afebrile, adult patients with acute leukemia and chemotherapy-induced neutropenia. INTERVENTION: Patients were randomly assigned to receive fluconazole, 150 mg, as a once-daily capsule, or amphotericin B suspension, 500 mg every 6 hours. MEASUREMENTS: An intention-to-treat analysis was done for 820 patients: 420 treated with fluconazole and 400 treated with oral amphotericin B. RESULTS: Definite systemic fungal infection occurred in 2.6% of fluconazole recipients and 2.5% of amphotericin B recipients; suspected systemic fungal infection requiring the empiric use of intravenous amphotericin B occurred in 16% of fluconazole recipients and 21% of oral amphotericin B recipients, a difference of 5 percentage points (95% CI for difference, -0.02% to 10%; P = 0.07). Superficial fungal infection was documented in 1.7% of fluconazole recipients compared with 2.7% of amphotericin B recipients, a difference of one percentage point (CI of difference, -0.9% to 3%; P > 0.2). The distribution of fungal isolates in systemic and superficial fungal infection was similar in both groups. The overall mortality rate accounted for 10% in both groups. An excellent compliance was documented for 90% of patients treated with fluconazole compared with 72% of those treated with amphotericin B suspension, a difference of 18 percentage points (CI for difference, 13% to 23%). Side effects were documented less frequently in fluconazole than in amphotericin B recipients (1.4% compared with 7%, a difference of 5.6 percentage points; CI for difference, 2% to 8%; P < 0.01). CONCLUSION: Fluconazole was at least as effective as oral amphotericin B in preventing systemic and superficial fungal infection and the empiric use of amphotericin B in neutropenic patients with acute leukemia but was better tolerated.

Acute Disease

Prospective study of Candida colonization, use of empiric amphotericin B and development of invasive mycosis in neutropenic patients.

The association between colonization with Candida spp., subsequent occurrence of invasive candidiasis and empiric use of amphotericin B was investigated prospectively in 139 neutropenic patients with hematologic malignancies. Treatment with amphotericin B was required in 67% of patients colonized in multiple non-contiguous body sites (multicolonized) versus 31% of patients colonized in single or contiguous sites (monocolonized) and in 21% of non-colonized patients (p = 0.0037 and p = 0.00026, respectively). Invasive candidiasis was documented in 22.2% of multicolonized versus 4.8% of monocolonized patients and in none of the non-colonized patients (p = 0.035 and p = 0.0036, respectively). Analysis of the spectrum of colonizing Candida spp. showed that multicolonized subjects were colonized with increased frequently by Candida albicans compared to monocolonized subjects, and that the association between multicolonization, invasive candidiasis and amphotericin B usage was statistically significant in patients colonized by Candida albicans but not in patients colonized by other Candida species. The association between Candida multicolonization and the occurrence of Candida infection seems to be confirmed by a double-blind placebo-controlled study performed in a small subgroup of the multicolonized patients treated with fluconazole.

Adolescent

Infections by ampicillin-resistant enterococci: a case-control study.

We identified 17 (20%) of 83 consecutive enterococcal isolates from hospitalized patients with documented infection as high-level ampicillin-resistant enterococci (ARE). Of these, 16 isolates were identified as Enterococcus faecium and 1 isolate as Enterococcus raffinosus. A case-control study found no significant differences with respect to underlying diseases, central venous catheterization, nosocomial acquisition of the infection and sites of infection. Patients with ARE infection were older and had a higher inhospital fatality rate than those with ampicillin-susceptible Enterococcus (ASE) infection. Hospitalization in a surgery service (usually for an abdominal procedure), prolonged hospital stay, prior treatment with antibiotics (in particular imipenem and metronidazole), were also more frequent among patients with ARE infection. ARE isolates were more frequently resistant to imipenem, ciprofloxacin and streptomycin than ASE isolates.

Adult

Fungemia in patients with leukemia.

A nine-year retrospective study on fungemia in patients with leukemia was conducted. A total of 79 episodes of fungemia in 77 patients with leukemia were documented. Candida parapsilosis fungemia was associated more frequently with the presence of a central venous line and to the use of parenteral nutrition than the other fungal species (p = 0.00026 and p = 0.01, respectively). The same fungus was isolated from both blood and surveillance cultures in 95% of Candida albicans and in 89% of Candida tropicalis fungemia (p < 0.01 and p = 0.02, respectively). The neutropenia and fungus colonization that resulted was associated significantly with the presence of invasive disease (p = 0.0024 and p = 0.0028, respectively). Conversely, central venous catheterization and parenteral nutrition appeared to be associated with episodes without deep tissue invasion (p = 0.000037 and p = 0.001, respectively). Invasive mycosis due to the fungus isolated from blood was documented in 51 patients with a mortality rate of 69%, whereas in 20 patients without invasive mycosis, mortality rate was 21% (p = 0.000059). In patients with fungemia, related or unrelated to the presence of a central venous catheter, mortality was 24% and 64%, respectively (p = 0.00042). Mortality was highest with C. tropicalis (p = 0.0017) and lowest with C. parapsilosis (p = 0.057). Severe neutropenia (polymorphonuclears < 100/mmc) appeared associated with a higher mortality rate (p = 0.012), whereas the recovery of neutropenia was related adversely to a fatal outcome (p < 0.01). With antifungal therapy, there was no statistically significant difference whether antifungal therapy was given or not.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Fluconazole treatment of catheter-related right-sided endocarditis caused by Candida albicans and associated with endophthalmitis and folliculitis.

An unusual case of catheter-related right-sided endocarditis, endophthalmitis, and extensive folliculitis, apparently caused by a single DNA biotype of Candida albicans, was successfully treated with a 6-month course of fluconazole plus two intravitreous doses of amphotericin B. The patient was a 21-year-old man who underwent colectomy for diffuse polyposis and developed the clinical syndrome just described following total parenteral nutrition for the treatment of purulent anal fistulas. Fluconazole was initially administered at a daily dose of 200 mg, with 600 mg daily given after 4 weeks. Clinical improvement resulted, with no relapse during 14 months of follow-up. Sequential measurements by an enzyme-linked immunosorbent inhibition assay demonstrated that levels of circulating mannoprotein antigen of C. albicans fell from 75 ng/mL to less than 1 ng/mL after the institution of fluconazole therapy. These observations seem to confirm previous reports on the efficacy of fluconazole as sole therapy for candidal endocarditis and suggest a role for serological studies in clinical monitoring of severe candidal infections.

Adult

Piperacillin plus amikacin vs. piperacillin plus amikacin plus teicoplanin for empirical treatment of febrile episodes in neutropenic patients receiving quinolone prophylaxis.

A prospective, randomized trial was initiated to evaluate the efficacy of two antibiotic regimens, differing in the agent included with activity against gram-positive bacteria, for the empirical treatment of febrile episodes in neutropenic patients with hematologic malignancies (group 1, piperacillin plus amikacin; group 2, piperacillin plus amikacin plus teicoplanin). After 72 hours of therapy, patients in group 1 who were still febrile were administered teicoplanin and those in group 2 were administered amphotericin B. A total of 158 evaluable episodes were observed within 8 months. The success rate was 50.6% in group 1 and 60% in group 2. The response rate among patients who did not respond to the original regimen increased to 86.7% with the addition of teicoplanin (group 1) and to 90% with the addition of amphotericin B (group 2). There were 86 unexplained febrile episodes and 56 documented episodes of bacteremia (34 caused by gram-positive organisms). Our results indicate that teicoplanin is safe, well tolerated, and effective for the treatment of documented episodes of gram-positive bacteremia and as an empirical agent. The inclusion of teicoplanin in the initial empirical regimen appears unnecessary if a combination of antibiotics active against gram-positive organisms is used, unless infections are due to oxacillin-resistant staphylococci.

4-Quinolones

4-week treatment of streptococcal native valve endocarditis with high-dose teicoplanin.

The efficacy and safety of a 4-week course of intravenous teicoplanin (500 mg every 12 h for the first 2 days and 10 mg/kg of body weight every 24 h thereafter) in the treatment of streptococcal native valve endocarditis in 20 patients were evaluated. All blood isolates were inhibited by a concentration of 0.12 micrograms of teicoplanin per ml. Serum bactericidal activity levels were measured 1/2 and 24 h after antibiotic infusion on days 5 to 7 of therapy in 19 patients, and titers of greater than or equal to 1:32 and greater than or equal to 1:8, respectively, were obtained with 17 patients (89%). On the other hand, for two patients who were infected with teicoplanin-tolerant Streptococcus bovis, serum bactericidal activity levels of less than 1:2 were found. Of 20 patients, 4 were excluded from further analysis because of protocol violation or prosthetic valve infection. Of the remaining 16 patients, 6 did not complete teicoplanin therapy because of early death (1 patient) or drug fever (5 patients). Among patients who developed drug fever, three who discontinued teicoplanin by day 15 were switched to penicillin therapy, whereas the remaining two, who discontinued teicoplanin on day 22 and 25, respectively, did not receive any further therapy and have shown no relapse during the follow-up. Of 10 patients who completed trial therapy, 9 were cured and 1 relapsed. It is concluded that a 4-week course of high-dose teicoplanin may be a useful regimen for home treatment of selected cases of streptococcal native valve endocarditis. However, drug fever and infection with teicoplanin-tolerant S. bovis may be factors of concern with this therapeutic approach.

Endocarditis, Bacterial

Single daily dose ceftriaxone plus amikacin treatment of febrile episodes in neutropenic patients attending day hospital for hematologic malignancies.

Once-a-day ceftriaxone and amikacin was administered in case of fever to 46 neutropenic patients attending day hospital for hematologic malignancies. All patients were admitted to a short-term ward for infective complications, but were discharged in the event of prompt disappearance of fever and of clinical signs of infection continuing their therapy either by daily reporting to the hospital, or at home. Response to the initial empiric therapy was obtained in 37 cases (76%). Twenty-four patients who promptly responded to therapy completed their treatment on an outpatient basis, their mean number of days of hospitalization being reduced to 4.6 versus a mean of 9.6 days in the overall patient population being considered. Since the outpatient treatment accounted for 21% of the antibiotic therapy administered, the above treatment may result in cost containment and better quality of life for patients, provided that these data are confirmed by prospective randomized studies.

Adolescent

Species identification and detection of oxacillin resistance in coagulase-negative Staphylococcus blood isolates from neutropenic patients.

One hundred coagulase-negative staphylococcal isolates from septicemic neutropenic patients with hematologic malignancies were identified to a species level by means of the French API STAPH strip system and by the Automicrobic VITEK system. According to these two methods, which concurred in 95% of cases, S. epidermidis (80-82% of the isolates) was the most frequently identified species, followed by S. haemolyticus (6-7% of the isolates). The susceptibility to oxacillin was also evaluated by macrodilution MIC, Automicrobic VITEK system and agar screen, and 76, 78 and 79 of the 100 isolates, respectively, were found resistant to this antibiotic. All oxacillin-resistant isolates according to Automicrobic VITEK were confirmed resistant by agar screen. A 48h incubation was required to determine oxacillin resistance in 11 of 79 isolates with agar screen and in 10 of 76 isolates with macrodilution MIC. Automicrobic VITEK system may represent a useful method for rapid identification to a species level and early recognition of oxacillin resistance in coagulase-negative staphylococci.

Bacteremia

Fluconazole treatment of Blastoschizomyces capitatus meningitis in an allogeneic bone marrow recipient.

The first known case of Blastoschizomyces capitatus meningitis occurring in an allogeneic bone marrow recipient on steroid and cyclosporine therapy for chronic graft-versus-host disease is reported. An 11-month course of treatment with oral fluconazole resulted in resolution of the meningeal syndrome and eradication of Blastoschizomyces capitatus from the cerebrospinal fluid. Three months after discontinuation of fluconazole the patient died due to idiopathic interstitial pneumonia and bilateral pneumothorax, without clinical signs of meningitis. Post mortem examination showed meningeal fungus invasion consistent with Blastoschizomyces capitatus infection. Oral fluconazole treatment thus did not eradicate the fungal infection, but achieved significant control of the meningitis on an outpatient basis.

Adolescent

Teicoplanin in the treatment of gram-positive bacteraemia in neutropenic patients.

The increasing incidence of bacteraemia caused by Gram-positive bacteria in neutropenic patients prompted the authors to evaluate, in a prospective trial, the role of teicoplanin in the treatment of this infection. Over a 15-month period, 76 cases of bacteraemia (out of 265 evaluable episodes of fever) were observed at the Division of Haematology, University La Sapienza, Rome. Of the 76 cases studied, 46 (60%) were caused by Gram-positive bacteria and 28 (37%) were caused by Gram-negative bacilli. All febrile episodes were treated randomly and empirically with piperacillin plus amikacin with or without teicoplanin. Overall, 41 (54%) of the 76 cases of bacteraemia responded to the initial antibiotic regimen; with subsequent modifications the response rate rose to 96%. In the treatment of Gram-positive bacteraemia, first-line administration of teicoplanin was found to be associated with early defervescence and with a significantly higher rate of success without modification of treatment (P less than 0.01). Addition of teicoplanin as second-line therapy produced a favourable outcome in 12 (70%) out of 17 cases of bacteraemia unresponsive to the initial piperacillin + amikacin regimen. No cases of Gram-positive bacteraemia associated with septic shock or adult respiratory distress syndrome were observed in either treatment group. Only two late deaths were observed, and these occurred in patients with streptococcal septicaemia who were not receiving early teicoplanin. The above data do not endorse the use of glycopeptide antibiotics in the early treatment of fever in neutropenic patients: rather, these compounds should be reserved for proven or presumed Gram-positive infections which do not respond to initial beta-lactam/aminoglycoside treatment.

Adolescent

Candida colonization and systemic infection in neutropenic patients. A retrospective study.

The results of surveillance cultures in 424 neutropenic patients with hematologic malignancies were analyzed to evaluate the relationship between colonization and infection by Candida species. Eighteen (32%) of 56 patients with multiple noncontiguous colonized sites developed proven (13 cases) or probable (five cases) systemic candidiasis, versus two patients with proven candidiasis (1.2%) of 170 with one colonized site (P less than 0.00000001), and one patient with proven candidiasis (0.5%) of 198 without any evidence of Candida colonization (P less than 0.00000001). Twenty-two patients with multiple colonized sites who developed a febrile episode resistant to antibiotics were treated with empiric amphotericin B. Nine of 11 given empiric amphotericin B within day 6 survived versus three of 11 receiving antifungal therapy after day 6 (P = 0.014). The above data seem to justify further prospective studies on Candida colonization as indication to early antifungal therapy in febrile neutropenic patients.

Adolescent

Comparative in vitro activities of new fluorinated quinolones and other antibiotics against coagulase-negative Staphylococcus blood isolates from neutropenic patients, and relationship between susceptibility and slime production.

We evaluated the in vitro antibiotic susceptibilities of 31 coagulase-negative Staphylococcus isolates causing septicemia in neutropenic patients undergoing norfloxacin prophylaxis. All the strains but one were resistant to 1 microgram of norfloxacin per ml. At the same concentration, ciprofloxacin, ofloxacin, imipenem, and pefloxacin were inhibitory for 19 (61%), 19 (61%), 18 (58%), and 14 (45%) of the evaluated strains, respectively. Imipenem had an MBC/MIC ratio of greater than or equal to 32 against 19 (61%) of the evaluated isolates, and resistant subpopulations were detected at 5 micrograms/ml in 16 of 17 oxacillin-resistant strains and in 3 of 14 oxacillin-susceptible or -tolerant strains. Resistance to gentamicin was seen with increased frequency among slime-producing strains.

4-Quinolones

Teicoplanin in the treatment of gram-positive-bacterial endocarditis.

Intravenous teicoplanin has been used to treat 23 cases of gram-positive-bacterial endocarditis, usually with 3 to 7 mg/kg every 12 h on the first day, followed by 3 to 7 mg/kg every 24 h. For some cases (staphylococcal and enterococcal endocarditis), the dosage was 8 to 14.4 mg/kg per day and/or other antibiotics were given. The mean duration was 48.2 days (range, 23 to 130 days). Of 23 patients, 21 (91.3%) had negative cultures or were cured. A total of 18 patients were treated with teicoplanin alone; of these, 4 had surgery, and all (except 2 who relapsed) were cured. Teicoplanin was combined with one or more antibiotics in five cases; in all cases appropriate cultures were negative, but three patients died during therapy or follow-up. Mild renal impairment was seen in two patients; both were receiving teicoplanin in combination with an aminoglycoside. We conclude that intravenous teicoplanin administered once a day at doses of 7 to 14 mg/kg per day is well tolerated, easy to administer, and may represent an efficacious therapy for gram-positive-bacterial endocarditis.

Anti-Bacterial Agents