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Biomedical subjects

F Menichetti

Publications and source records attributed to F Menichetti.

At least 37 records · Page 2Linked to original sources
PubMed1997

Teicoplanin in the treatment of enterococcal endocarditis: clinical and microbiological study.

Seven cases of enterococcal endocarditis treated with teicoplanin (7-10 mg/kg/day for 28-105 days) alone (one case) or in combination with aminoglycosides (six cases) were reviewed. All patients were cured. Serum bactericidal activity titres after intravenous gentamicin (5 mg/kg every 24 h) and teicoplanin (10 mg/kg every 24 h) were measured on day 7 of treatment in four patients against five enterococcal isolates: mean titres were 1:54 (range 1:16-64) and 1:22 (1:8-32) at 0.5 and 24 h post-infusion, respectively. Time-kill studies showed synergy between teicoplanin and gentamicin against three isolates. We conclude that single daily-dose teicoplanin/gentamicin combined therapy may represent a rational alternative to standard penicillin/gentamicin therapy and a useful regimen for home treatment of selected cases of enterococcal endocarditis.

Adolescent↗
PubMed1997

[Nosocomial infections: back to the future].

The increasing rate of nosocomial infections seems to be related to the wider use of invasive procedures. Evaluation of the patient risk factors for infection, use of SIRS classification and knowledge of the setting care should be utilized for the diagnostic approach. The empiric antibiotic therapy should take in account the site of the infection (bacteremia, pneumonia, urinary tract infection etc.) and the presumed pathogen; knowledge of the local epidemiology is a pre-requisite for the antibiotics choice. Among gram-positive microorganisms, methicillin-resistant staphylococci and vancomycin-resistant enterococci are responsible of difficult to treat infections; penicillin-resistant pneumococci, largely present in some european countries, might become an emerging pathogen also in Italy. The knowledge and ability of infectious diseases specialist encompasses clinical, microbiological and epidemiological fields to play a key role in the prevention and management of nosocomial infections.

English Abstract↗
PubMed1996

Fluconazole versus amphotericin B as empirical antifungal therapy of unexplained fever in granulocytopenic cancer patients: a pragmatic, multicentre, prospective and randomised clinical trial.

Amphotericin B, despite its intrinsic servere toxicity, is the most commonly used empirical antifungal therapy in cancer patients with unexplained fever not responding to empirical antibacterial therapy. The aim of this study was to show whether fluconazole was as effective as, and less toxic than, amphotericin, with no effort made to compare the antifungal activity of the two drugs. A group of 112 persistently febrile (> 38 degrees C) and granulocytopenic (< 1000 cells/mm3) cancer patients, not receiving any absorbable antifungal antibiotic for prophylaxis, with a mean age of 27 years (range 1-73 years), undergoing chemotherapy for a variety of malignancies and with a diagnosis of unexplained fever after at least 96 h of empirical antibacterial therapy, were randomised to receive either fluconazole (6 mg/kg/day up to 400 mg/day) or amphotericin B (0.8 mg/kg/day) as empirical antifungal treatment. Patients were required to have normal chest X-rays at randomisation, no previous history of aspergillosis and negative surveillance cultures for Aspergillus. The intention-to-treat analysis showed defervescence and survival without treatment modification in 42 of 56 patients (75%) in the fluconazole group and in 37 of 56 (66%) in the amphotericin B group (P = 0.4). Duration of therapy was 6 days (95% CI = 4-8 days) in both groups. Death occurred in 3 patients (5%) in the fluconazole and in 2 (4%) in the amphotericin B group. No fungal death was documented in either group. Adverse events developed in 18 of 56 patients (32%) in the fluconazole group and in 46 of 56 (82%) in the amphotericin B group (P < 0.001). In the amphotericin B group, 5 patients had treatment discontinued because of toxicity, versus none in the fluconazole group, a difference which approached statistical significance (P = 0.06). This study shows that fluconazole is by far less toxic than amphotericin B and suggests that it might be as effective as amphotericin B, in pragmatical terms and for this specific indication. However, numbers are too small to allow definitive conclusions about efficacy, and the use of fluconazole for this indication remains experimental. Future studies should try to identify patients more at risk of fungal infections, with the aim of individualising antifungal approaches.

Adolescent↗
PubMed1996

High-dose fluconazole therapy for cryptococcal meningitis in patients with AIDS.

Fluconazole (800-1,000 mg i.v.) was administered to 14 consecutive patients with AIDS and cryptococcal meningitis. At 10 weeks the rate of clinical success was 54.5% (six of 11 patients responded to fluconazole); the Kaplan-Meier estimate of the response rate was 67.1%, and the overall mortality rate was 18.2% (two of 11 patients died). At the end of treatment, eight (72.7%) of 11 patients responded to fluconazole. The median time to the first negative cerebrospinal fluid (CSF) culture was 33.5 days (95% confidence interval, 18.3-67.3); the median time for patients with initial CSF cryptococcal antigen titers of > or = 1:1,024 was 66 days compared with 18 days for patients with initial CSF cryptococcal antigen titers of < 1:1,024 (P = .06). The median time to the first negative CSF culture for patients with an isolate for which the minimum inhibitory concentration (MIC) was 4 micrograms/mL was 56 days compared with 16 days for patients with an isolate for which the MIC was < 4 micrograms/mL (P = .11). The mean serum and CSF levels of fluconazole at steady state were 42.47 +/- 26.31 micrograms/mL and 36.63 +/- 21.08 micrograms/mL, respectively (ratio of CSF:serum, 0.86). No treatment was interrupted and no dose was tapered because of side effects. High-dose fluconazole might be an effective and well-tolerated therapeutic option for patients with AIDS and acute cryptococcal meningitis.

AIDS-Related Opportunistic Infections↗
PubMed1995

Empiric monotherapy in neutropenia: a realistic goal?

Infection remains the major cause of morbidity and mortality for cancer patients who become granulocytopenic as a result of chemotherapy. Treatment is instituted at the first sign of infection and before the identification of the causative pathogen (empiric treatment). For many years, standard empiric treatment has been combination therapy with beta-lactams and aminoglycosides. The advent of new broad spectrum antibiotics, such as ceftazidime, has introduced the possibility of empiric monotherapy. However, ceftazidime has only modest activity against infections due to Gram-positive organisms, which presently account for at least 50% of infections in neutropenic patients, and resistance to ceftazidime in Gram-negative organisms has been documented. Meropenem is a new carbapenem with a broad antibacterial spectrum with greater in vitro activity than ceftazidime against staphylococci, streptococci and many Gram-negative bacteria. A comparative study of intravenous meropenem (1 g 8-hourly) and ceftazidime (2 g 8-hourly) in the empiric treatment of febrile neutropenic patients with haematological malignancies has been conducted. In an open, randomised trial of the treatment of 338 febrile episodes, all patients survived to 72 hours on both treatments, and meropenem was found to be at least as clinically effective as ceftazidime in eradicating both Gram-positive and Gram-negative infections. Early modification of treatment (48-72 hours) was required for approximately 40% of patients but occurred less frequently in patients treated with meropenem than with ceftazidime. Tolerability of both treatments was good. Meropenem should be compared with standard combination therapy in a large randomised trial before adopting it as empiric monotherapy for febrile neutropenic patients.

Bacterial Infections↗
PubMed1994

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↗
PubMed1994

Effects of teicoplanin and those of vancomycin in initial empirical antibiotic regimen for febrile, neutropenic patients with hematologic malignancies. Gimema Infection Program.

The efficacy and toxicity of teicoplanin and vancomycin in the initial empirical antibiotic regimen in febrile, neutropenic patients with hematologic malignancies were compared in a prospective, randomized, unblinded, multicenter trial in the setting of 29 hematologic units in tertiary-care or university hospitals. A total of 635 consecutive febrile patients with hematologic malignancies and chemotherapy-induced neutropenia were randomly assigned to receive intravenously amikacin plus ceftazidime plus either teicoplanin at 6 mg/kg of body weight once daily or vancomycin at 1 g twice daily. An efficacy analysis was done for 527 evaluable patients: 275 treated with teicoplanin and 252 treated with vancomycin. Overall, successful outcomes were recorded for 78% of patients who received teicoplanin and 75% of those who were randomized to vancomycin (difference, 3%; 95% confidence interval [CI], -10 to 4%; P = 0.33). A total of 102 patients presented with primary, single-agent, gram-positive bacteremia. Coagulase-negative staphylococci accounted for 42%, Staphylococcus aureus accounted for 27%, and streptococci accounted for 21% of all gram-positive blood isolates. The overall responses to therapy of gram-positive bacteremias were 92 and 87% for teicoplanin and vancomycin, respectively (difference, 5%; CI, -17 to 6%; P = 0.22). Side effects, mainly represented by skin rash, occurred in 3.2 and 8% of teicoplanin- and vancomycin-treated patients, respectively (difference, -4.8%; CI, 0.7 to 8%; P = 0.03); the rate of nephrotoxicity was 1.4 and 0.8% for the teicoplanin and vancomycin groups, respectively (difference, 0.6%; CI, -2 to 1%; P = 0.68). Further infections were caused by gram-positive organisms in two patients (0.7%) treated with teicoplanin and one patient (0.4%) who received vancomycin (difference, 0.3%; CI, -0.9 to 1.0%; P = 0.53). Overall mortalities were 8.5 and 11% for teicoplanin- and vancomycin-treated patients, respectively (difference, -2.5%; CI, - 2 to 7%; P = 0.43); death was caused by primary gram-positive infections in three patients (1%) in each treatment group. When used for initial empirical antibiotic therapy in febrile, neutropenic patients, teicoplanin was at least as efficacious as vancomycin, but it was associated with fewer side effects.

Adolescent↗
PubMed1993

The new fluorinated quinolones for antimicrobial prophylaxis in neutropenic cancer patients.

Fluoroquinolones are the most attractive agents for prophylactic use in neutropenic cancer patients, due to their broad antimicrobial spectrum, high concentration in the faeces, systemic bactericidal activity, uncommon emergence of resistant strains and good tolerability. They have proved to be more effective than placebo, oral non-absorbable antibiotics or cotrimoxazole in the prevention of Gram-negative infections. In a prospective, randomised multicentre study performed by the GIMEMA infection program, ciprofloxacin was demonstrated to be more effective than norfloxacin for the reduction of febrile episodes, use of systemic antibiotics, and Gram-negative infections in neutropenic patients with haematological malignancies. The greater efficacy may be related to its better systemic or greater antibacterial activity. The potential problems related to the prophylactic use of fluoroquinolones are the increasing prevalence of Gram-positive infections caused by streptococci and coagulase-negative staphylococci; the reported emergence and nosocomial spread of resistant strains, especially among coagulase-negative staphylococci; the lack of their usefulness as empirical therapy in febrile neutropenic patients. Fluoroquinolones are today the better choice for preventing Gram-negative infections in neutropenic patients and ciprofloxacin should probably be preferred. More information on their efficacy and their relationship to the overall susceptibility of micro-organisms in patients with cancer would be valuable, and careful monitoring of patients treated with these drugs is therefore warranted.

Anti-Bacterial Agents↗
PubMed1991

The role of gram-positive therapy in the neutropenic patient.

The increasing prevalence of Gram-positive infections in neutropenic cancer patients seems to be related to the use of central venous catheters, chemotherapy-induced oral and gastrointestinal mucositis, and the prophylactic use of fluoroquinolones. The need for anti-Gram-positive therapy in the neutropenic patient is supported by the increasing prevalence and the changing resistance of Gram-positive pathogens, as well as by the poor response of Gram-positive bacteraemia to aminoglycoside plus beta-lactam regimens. Combined therapy with either vancomycin or teicoplanin and other empirical antibiotics, has proved efficacious in adults and children with neutropenia, fever and Gram-positive infection. Vancomycin exerts greater antibacterial activity against strains of coagulase-negative staphylococci than teicoplanin and there is more data on its routine clinical use. In its favour, teicoplanin is less toxic and easier to administer. The time when a glycopeptide antibiotic should be introduced is still a matter of debate; support for both initial therapy and subsequent rescue therapy is found in the current literature. Large clinical trials are warranted to clarify further the role of anti-Gram-positive therapy in the neutropenic patient.

Aminoglycosides↗
PubMed1990

Using teicoplanin for empiric therapy of febrile neutropenic patients with haematological malignancies.

The cumulative experience with teicoplanin in treating febrile neutropenic patients included in three different comparative clinical trials conducted at a single institution during a 3-year period, is presented. 152 febrile episodes in 129 neutropenic patients were treated with i.v. teicoplanin (6 mg/kg/d) combined with amikacin (15 mg/kg/d) plus ceftazidime (90 mg/kg/d). The study population comprised 75 patients with acute leukaemia and 77 marrow recipients: 53% (81/152) had a central venous catheter in place and 68% (103/152) had severe neutropenia (less than 100/mm3) at the beginning of the febrile episode. The overall response rate of the evaluable febrile episodes was excellent: 88% (107/122) improved. Bacteraemias due to Gram-positive cocci accounted for 75% of the total (42/56) and pathogens in the blood isolates were mostly staphylococci (coagulase-negative 14, coagulase-positive 13) and streptococci (13). The response rate of Gram-positive bacteraemias was good: 88% (37/42) improved and 75% (9/12) of Gram-positive bacteraemias having teicoplanin as the only antibiotic with in vitro activity against the infective strains were cured. Death due to infection accounted for 7% of total febrile episodes (11/152). Side effects were documented in 14% of the episodes. In a setting of high prevalence of Gram-positive infections caused by strains with a high rate of resistance to aminoglycoside and beta-lactam antibiotics, there may be an advantage in including teicoplanin in the initial empiric antibiotic regimen for febrile neutropenic cancer patients.

Acute Disease↗
PubMed1989

Ceftriaxone versus imipenem/cilastatin as empirical monotherapy for infections in cancer patients.

We conducted a prospective randomized clinical trial to compare the efficacy and tolerability of monotherapy with ceftriaxone (active ingredient of Rocephin) (CRO) versus imipenem/cilastatin (I/C) in febrile cancer patients with or without neutropenia. 120 febrile episodes were randomized and 89 (75%) were evaluable for efficacy analysis. The overall response rates to both regimens were good (86 and 79% improved in response to CRO and I/C, respectively). Overall mortality was low and similar in the two groups. Both regimens were well tolerated. Our preliminary data corroborate the efficacy of CRO or I/C as empirical monotherapy for febrile episodes in cancer patients. It will be up to future investigations to show whether one of these regimens is superior to the other.

Adult↗