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Biomedical subjects

C Viscoli

Publications and source records attributed to C Viscoli.

At least 19 recordsLinked to original sources

Efficacy of the combination of levofloxacin plus ceftazidime in the treatment of hospital-acquired pneumonia in the intensive care unit.

To investigate the efficacy and tolerability of treatment with a combination of levofloxacin and ceftazidime in Gram-negative hospital-acquired pneumonia (HAP) in the Intensive Care Unit (ICU), we performed a prospective, open-label, non-comparative, 1-year study in an Italian ICU. Patients received levofloxacin 500 mg twice a day intravenously plus ceftazidime 2 g three times a day intravenously for 7-14 days. Primary efficacy variables were clinical and microbiological responses at test-of-cure visit. Twenty-one patients were enrolled. Pseudomonas aeruginosa and Klebsiella pneumoniae were the most frequently identified pathogens. Clinical success was achieved in 17/21 clinically evaluable patients (81%) and in 12/15 microbiologically evaluable patients (80%). Regarding only the group with ventilator-associated pneumonia, cure was achieved in 10/14 clinically evaluable patients (71%) and in 11/14 microbiologically evaluable patients (79%). Therapy was well tolerated. We conclude that this combination regimen is safe and clinically and microbiologically efficacious in the treatment of Gram-negative HAP.

Aged↗

Kinetics of galactomannan in surgical patients receiving perioperative piperacillin/tazobactam prophylaxis.

OBJECTIVES: The association between piperacillin/tazobactam and the positivity of the galactomannan (GM) detection ELISA test is well described. Little information is available about the kinetics of GM in patients treated with piperacillin/tazobactam. The present study aimed at clarifying the baseline interaction between piperacillin/tazobactam and GM in patients receiving this drug. PATIENTS AND METHODS: Seven patients undergoing abdominal surgery received perioperative prophylaxis with piperacillin/tazobactam. Each patient received three doses of 4.5 g of the drug, administered at 8 h intervals (one before and two after surgery). Three patients received antibiotic batches with 'medium' (GM-index = 1.782) and four patients received antibiotic batches with 'high' (GM-index = 6.665) GM content. Serum samples for GM evaluation were collected before drug infusion and at times +1, +3, +6 and +8 h after the first and third infusions. RESULTS: GM levels increased after infusion, in particular when batches with 'high' GM content were used. Moreover, a non-statistically significant increase between the first dose and the third dose was observed. All samples taken >6 h after administration were negative (GM-index < 0.2), both with the 'medium' and the 'high' GM content batches. CONCLUSIONS: The low content of GM 8 h after piperacillin/tazobactam infusion suggests that in non-neutropenic cancer patients with solid tumours receiving up to three doses of piperacillin/tazobactam, serum sampling for GM detection should be performed immediately before the next piperacillin/tazobactam administration.

Aged↗

Piperacillin-tazobactam monotherapy in high-risk febrile and neutropenic cancer patients.

Combination therapy with a beta-lactam plus an aminoglycoside has been the standard approach for treating febrile neutropenia for many years. More recently, beta-lactam monotherapy has also been shown to be a reliable and safe approach. In the present study, 763 eligible patients with fever and neutropenia received piperacillin-tazobactam monotherapy. On day 3, according to the study protocol, 165 patients with persistent fever who fulfilled the study entry criteria were randomised to receive vancomycin or a placebo. The success rate was 51% in the intention-to-treat analysis and 62% in the per-protocol analysis. The overall mortality rate was 8% (58/763), with only 18 (2.4%) deaths attributed to the initial or subsequent infection. Randomisation had no influence on the study endpoints. The adverse event rate was evaluated only in the patient population not included in the randomised part of the study. Among these patients, adverse events probably or definitely related to piperacillin-tazobactam therapy were uncommon, confirming the favourable safety profile of piperacillin-tazobactam. It was concluded that piperacillin-tazobactam could be considered as monotherapy for patients with high-risk febrile neutropenia.

Adolescent↗

Antimicrobial use and resistance among Gram-negative bacilli in an Italian intensive care unit (ICU).

Gram-negative bacilli antimicrobial resistance remains a significant problem for patients in the intensive care unit (ICU). We performed a retrospective analysis of microbiological data and antibiotic consumption over a 4-year period (2000-2003) in an Italian ICU. Pseudomonas aeruginosa and Klebsiella pneumoniae represented approximately 40% of all isolates. The most significant trend in antimicrobial use was an increase in use of 3(rd )generation cephalosporins, imipenem, and ciprofloxacin. A significant trend toward an increase in resistance rates to piperacillin, 3( rd )generation cephalosporins and ciprofloxacin was observed for K. pneumoniae and a positive correlation between resistance and drug-usage was evident for K. pneumoniae and piperacillin, cefotaxime, ceftazidime, cefepime, and ciprofloxacin, but not for piperacillin/tazobactam. No statistically significant correlations were evidenced for P. aeruginosa. Trends in resistances were studied also for Serratia spp and Proteus spp. Isolation rates of extended-spectrum beta-lactamase (ESBL)-producing strains in pathogens studied were high, especially for K. pneumoniae (72%, 160/222) and Proteus spp (41%, 18/43). In conclusion, the study showed high resistance among Gram-negative organisms isolated in the ICU and significant ESBL production. A significant correlation between antibiotic consumption and increasing resistance was evident for K. pneumoniae.

Anti-Bacterial Agents↗

Antifungal prophylaxis with azole derivatives.

In recent years, several reports have underlined the increasing role of fungal infections as a cause of morbidity and mortality in hospitalised patients. For this reason, and also in light of the high mortality rate associated with these infections, chemoprophylaxis has been advocated by several authors. The available evidence suggests that both fluconazole and itraconazole are able to decrease candida colonisation and infection, when compared with placebo or with nonabsorbable antifungals. Data seem also to suggest that a decrease in fungus-related mortality can be achieved with prophylaxis, although with little effect on overall mortality, probably because of the importance of severe underlying diseases. Itraconazole proved to be effective in the prevention of fungal infections, including invasive aspergillosis, although with increased incidence of side-effects, often leading to treatment discontinuation. The other side of the coin is that antifungal prophylaxis might have untoward effects, such as the selection of triazole-resistant Candida strains or the induction of resistance. In addition, some authors have suggested that the use of triazoles might modulate the pattern of infecting organisms in cancer patients, increasing the risk of both aspergillosis and bacteremia. In conclusion, antifungal prophylaxis with triazole antifungals should be used with caution, only in patients at high risk for invasive fungal infections. These include allogeneic bone marrow transplant patients (especially those with mismatched or unrelated donors), acute myeloid leukaemia patients treated with high-dose cytarabine (C-ara), very-low-birth-weight infants, patients with chronic granulomatous disease, and high-risk surgical and intensive-care unit patients.

Antifungal Agents↗

Vancomycin versus placebo for treating persistent fever in patients with neutropenic cancer receiving piperacillin-tazobactam monotherapy.

This prospective, double-blind trial assessed whether the addition of a glycopeptide would be able to reduce the time to defervescence in neutropenic patients with cancer who had persistent fever 48-60 h after the initiation of empirical piperacillin-tazobactam monotherapy. Of 763 eligible patients, 165 with persistent fever were randomized to receive piperacillin-tazobactam therapy plus either vancomycin therapy or placebo. Defervescence was observed in 82 (95%) of 86 patients in the vancomycin group and in 73 (92%) of 79 patients in the placebo group (P=.52). The distributions of the time to defervescence were not statistically significant between the 2 groups (estimated hazard ratio, 1.03; 95% confidence interval, 0.75-1.43; P=.75). The number of additional episodes of gram-positive bacteremia and the percentage of patients for whom amphotericin B was empirically added to their therapy regimen were also similar in both groups. This study failed to demonstrate that the empirical addition of vancomycin therapy to the treatment regimen is of benefit to persistently febrile neutropenic patients with cancer.

Adolescent↗

Successful treatment of Acremonium fungemia with voriconazole.

We report two cases of Acremonium fungemia with proven involvement of the skin and probably of the lung in patients who were both undergoing chemotherapy, one for mantle cell lymphoma and the other for acute lymphoblastic leukemia. Both patients failed amphotericin B deoxycholate treatment and were successfully treated with voriconazole with very mild toxicity.

Acremonium↗

Management of infection in cancer patients. studies of the EORTC International Antimicrobial Therapy Group (IATG).

Infection remains an important cause of morbidity and mortality in cancer patients, especially those undergoing chemotherapy for haematological malignancies. The practice of instituting an empirical broad-spectrum antibiotic therapy as soon as possible after the onset of fever has substantially reduced the clinical impact of this complication. In the last 25 years, the International Antimicrobial Therapy Group of the European Organisation for Research and Treatment of Cancer (EORTC-IATG) have published nearly 30 articles and a number of abstracts on several facets of the epidemiology and management of infection in cancer patients. With a progressive methodological refinement, the EORTC-IATG trials have established the standard for the management of febrile neutropenia, both by setting methodologies and definitions and by testing several antibiotic regimens that are active and effective for this indication. With the aim of supporting a more rational use of antibiotics in cancer patients, the most recent trials have dealt with the management of low risk patients, showing the safety and feasibility of oral therapy.

Anti-Bacterial Agents↗

Voriconazole in the management of invasive aspergillosis in two patients with acute myeloid leukemia undergoing stem cell transplantation.

The management of invasive aspergillosis in patients with hematological malignancies remains controversial. A major problem is how to manage patients who had invasive aspergillosis during remission induction and consolidation therapy and then undergo SCT. Indeed in these patients the mortality rate related to invasive aspergillosis recurrence remains unacceptably high. We report two cases of patients who underwent remission induction for AML, developed invasive aspergillosis during antifungal prophylaxis with itraconazole, failed amphotericin B deoxycholate and liposomal amphotericin B treatment, were successfully treated with voriconazole and eventually underwent SCT with voriconazole prophylaxis without reactivation of invasive aspergillosis.

Adult↗

Need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses.

Studies of invasive fungal infections have been and remain difficult to implement. Randomized clinical trials of fungal infections are especially slow and expensive to perform because it is difficult to identify eligible patients in a timely fashion, to prove the presence of the fungal infection in an unequivocal fashion, and to evaluate outcome in a convincing fashion. Because of these challenges, licensing decisions for antifungal agents have to date depended heavily on historical control comparisons and secondary advantages of the new agent. Although the availability of newer and potentially more effective agents makes these approaches less desirable, the fundamental difficulties of trials of invasive fungal infections have not changed. Therefore, there is a need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses, and this article summarizes the possible strategies in this area.

Antifungal Agents↗

Association between antifungal prophylaxis and rate of documented bacteremia in febrile neutropenic cancer patients.

Published data have suggested a correlation between antifungal prophylaxis and bacteremia in febrile neutropenia. This correlation was investigated among 3002 febrile neutropenic patients enrolled in 4 trials during 1986-1994. Globally, 1322 patients (44%) did not receive antifungal prophylaxis; 835 (28%) received poorly absorbable antifungal agents and 845 (28%) received absorbable antifungal agents. The rates of bacteremia for these groups were 20%, 26%, and 27%, respectively (P=.0001). In a multivariate model without including antifungal prophylaxis, factors associated with bacteremia were: age, duration of hospitalization, duration of neutropenia before enrollment, underlying disease, presence of an intravenous catheter, shock, antibacterial prophylaxis, temperature, and granulocyte count at onset of fever. When antifungal prophylaxis was included, the adjustment quality of the model improved slightly (P=.05), with an odds ratio of 1.19 (95% confidence interval [CI], 0.92-1.55) for patients receiving nonabsorbable and 1.42 (95% CI, 1.07-1.88) for those who were receiving absorbable antifungal agents. Antifungal prophylaxis with absorbable agents might have an impact on the rate of documented bacteremia in febrile neutropenia. This effect should be confirmed prospectively.

Adolescent↗

Incidence of septicaemias and invasive mycoses in children undergoing treatment for solid tumours: a 12-year experience at a single Italian institution.

We carried out a retrospective study on the infection rate--in episodes per 100 person months at risk (p/m/r)--of septicaemia and invasive mycoses in children with solid tumours treated at a single institution between 1985 and 1996. Among 982 patients, accounting for 8108 p/m/r, 257 infectious episodes were documented, for an infection rate of 3.2. The infection rate for "intensive" treatment was greater than that for "less intensive" treatments, 3.7 compared with 0.5, respectively; P<0.001. 58% of infectious episodes were associated with neutropenia, 22% were megatherapy-related, and 39% were related to central venous catheter (CVC), while in 13% of the episodes no risk factor was identified. Of the episodes, single organism Gram-positive bacteraemias accounted for 62%, single organism Gram-negative for 23%, multiple organism bacteraemias for 7%, invasive mycoses for 4%, and isolated fungaemias for 4%. The infection rate for Gram-positive organisms decreased significantly over time (-5.9% per year; P<0.01), but increased for the Gram-negative organisms (+3.4% per year; P=0.4). This study demonstrates that the risk of bacteraemia increases in parallel with the treatment intensity, and that a considerable number of children with solid tumours develop bacteraemia in the absence of an identifiable risk factor.

Adolescent↗

Intensified chemotherapy supported by DMSO-free peripheral blood progenitor cells in breast cancer patients.

BACKGROUND: The majority of high-dose chemotherapy (HDC)-related complications results from bone marrow aplasia, but the graft infusion per se may cause adverse reactions due to the injection of both dimethyl sulfoxide (DMSO) and cell lysis products. We evaluated the feasibility of a two-step chemotherapy regimen with peripheral blood progenitor cell (PBPC) support in association with a novel procedure to remove DMSO and products of cell lysis from the cryopreserved cells. PATIENTS AND METHODS: Stage III and IV breast cancer patients received induction chemotherapy with three cycles of CEF (cyclophosphamide 600 mg/m2, epirubicin 100 mg/m2, 5-fluorouracil 600 mg/m2) followed by three cycles of HDC consisting of escalating doses of cyclophosphamide (dose range 1200 3000 mg/m2) and carboplatin (dose range 600-1000 mg/m2), supported by DMSO-free PBPC reinfusion. DMSO was removed by a washing/enzymatic digestion procedure. RESULTS: Twenty patients received induction chemotherapy and eighteen completed the entire chemotherapy program; a total of fifty-four cycles of HDC were administered. Dose limiting toxicity of HDC was long-lasting grade 4 neutropenia associated with documented infection. The maximum tolerated dose (MTD) was cyclophosphamide 3000 mg/m2 and carboplatin 600 mg/m2. No side effects related to PBPC reinfusion were observed. CONCLUSIONS: The proposed two-step chemotherapy regimen, associated with a novel washing/enzymatic digestion procedure, is feasible in advanced breast cancer patients in the absence of complications related to the specific toxicity of PBPC reinfusion.

Adult↗

[Infectious complications in liver transplant in Italy: current status and prospectives].

The impact of infections in orthotopic liver transplantation (OLT) is remarkable. Studies have shown that about 60% of patient may develop at least 1 infectious episode during the first 3 months after transplant. Within the frame of a Finalized Research Project of the Italian Ministry of Health, during the year 2000 a group of investigators belonging to the major Italian Liver Transplant Centers (LTC)--18 out of 20 Centers--met three times in Genoa with the aim of constituting a Research Group aimed at improving our knowledge of infectious complications in liver transplant recipients (PITF = Program of Infections in Liver Transplantation). The group first collected information about anti-infective procedure in LTC. The study shows that no Center is supported by a Intensive Care Unit (ICU) exclusively dedicated to the LTC, although 37% of them have a partially dedicated Unit. Surveillance cultures are routinely performed and are frequently used to address the choice of the antibacterial and antifungal regimes. Selective Bowel Decontamination is also very common. The management of CMV infection is usually performed as indicated in international guidelines.

Anti-Bacterial Agents↗

Antigen detection in the diagnosis and management of a patient with probable cerebral aspergillosis treated with voriconazole.

This report describes the diagnosis and management of a 16-year-old boy who developed neurological signs and symptoms suggestive of cerebral aspergillosis following a haploidentical bone marrow transplant. A new sandwich enzyme-linked immunosorbent assay (ELISA) for the detection of Aspergillus galactomannan circulating antigens (Platelia Aspergillus, Sanofi Diagnostic Pasteur, France) was used on serum and cerebrospinal fluid to obtain a presumptive diagnosis and to monitor the course of the disease. Having failed conventional therapy with amphotericin B, the patient received compassionate treatment with voriconazole for a period of 37 days. High levels of voriconazole were observed in both serum and cerebrospinal fluid (CSF), with a trend toward accumulation. After 7 days a marked improvement in the patient's neurological symptoms was noted, and ELISA data indicated a corresponding decrease in Aspergillus galactomannan levels in both serum and CSF. Voriconazole was well tolerated, with only transient increases in ALT/AST recorded during therapy. Although the patient survived the acute Aspergillus infection, he subsequently died of an unrelated infection.

Adolescent↗

Clinical and laboratory features predicting a favorable outcome and allowing early discharge in cancer patients with low-risk febrile neutropenia: a literature review.

To value feasibility of early discharge in febrile granulocytopenic patients, 27 original paper published in the last 11 years were analyzed concerning these clinical and therapeutic approaches. A Medline search of English language literature published in the last 11 years (1988-1999) used the key words neutropenia, fever, cancer, home-antibiotic therapy, short course of antibiotic therapy, and early discharge. Twenty-seven original papers fulfilling the study criteria were identified. In these studies, 5208 episodes were evaluated: there were 538 failures with 87 deaths. Features of low-risk patients who developed life-threatening infectious disease were related to general clinical condition, cancer control, bone marrow function, presence of clinical signs of infection, and social features. Careful risk assessment can allow safe recognition of low-risk patients with febrile neutropenia who can be discharged early and can be used to follow outpatient treatment programs to improve patients' quality of life as well as the use of economic resources.

Adult↗

Bloodstream infections in children with cancer: a multicentre surveillance study of the Italian Association of Paediatric Haematology and Oncology. Supportive Therapy Group-Infectious Diseases Section.

A one-year prospective, multicentre surveillance study on aetiology, main clinical features and outcome of bloodstream infections in children with cancer was conducted in 18 paediatric haematology centres belonging to the Italian Association for Paediatric Haematology and Oncology. A total of 191 bloodstream infections were reported during the study period. Of them, 123 (64%) occurred in neutropenic and 68 (36%) in non-neutropenic patients. Gram-positive cocci caused 45% (85/191) of the episodes, gram-negative rods 41% (78/191), and fungi 9% (18/191). The remaining 5% (10/191) of the episodes were poly-microbial infections. A total of 204 pathogens were isolated (46% gram-positive cocci; 44% gram-negative rods; and 10% fungi). The aetiologic distribution was similar among neutropenic and non-neutropenic patients. A correlation between the infection and the presence of an indwelling central venous catheter was found in 20% (23/114) of the episodes among neutropenic patients and in 55% (23/62) among non-neutropenic patients. Gram-negative micro-organisms were isolated in an unusually high proportion of catheter-related infections (48%). The overall mortality rate from any cause within 30 days from the first positive blood culture was 11%, and was higher among patients who were neutropenic at the onset of the infection than among those who were not neutropenic (15 versus 4%, P = 0.03). In addition, the mortality was significantly higher in recipients of bone marrow transplantation than in patients with acute leukaemia or solid tumour (21, 11 and 6%, respectively) and was also higher in fungaemias and poly-microbial infections (22 and 30%) than in single gram-positive and gram-negative bacteraemias (11 and 6%).

Bacteremia↗