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Biomedical subjects

M Bassetti

Publications and source records attributed to M Bassetti.

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↗

Penetration of didanosine in semen of HIV-1-infected men.

OBJECTIVES: The disposition of antiretroviral agents into genital tissue and fluids is one of the factors implicated in the control of viral replication within the male genital tract and should be an objective of highly active antiretroviral therapy. We have investigated didanosine penetration in seminal plasma of 16 HIV-infected patients. PATIENTS AND METHODS: A total of 16 patients on didanosine (200 mg every 12 h or 400 mg once daily) participated in the pharmacokinetic study. After the didanosine morning dose, peripheral blood plasma and semen plasma were collected within the intervals 0-4, 4-8 and 8-12 h in the twice-daily regimen and 0-4, 4-12 and 12-24 h in the once-daily regimen. RESULTS: Within each sampling time interval didanosine concentrations in seminal plasma were higher than in blood. The interquartile range of concentrations in seminal plasma was 292-1217 ng/mL, compared with 50-150 ng/mL in blood plasma. Didanosine could be detected in 14 of the 16 semen samples analysed and in 8 of the 16 blood samples. CONCLUSIONS: We have demonstrated that didanosine penetrates into the seminal plasma in higher concentrations than in blood plasma.

Adult↗

Combination hepatitis C virus antigen and antibody immunoassay as a new tool for early diagnosis of infection.

Reduction of the window period of hepatitis C virus (HCV) infection represents an important goal in the transfusional and diagnostic setting. A prototype assay designed to simultaneously detect circulating HCV antigen and anti-HCV, has been developed. Aim of this study was to evaluate the performance of this new assay in terms of specificity and sensitivity and to compare its efficacy with commercial assays. To evaluate the specificity of the assay, 400 samples from the general population and 100 'difficult' sera, negative for anti-HCV, were tested. To assess sensitivity, the new test was used on 76 PCR-positive and anti-HCV negative sera, seven natural or commercial seroconversion panels that included 17 RNA-positive and anti-HCV negative sera and 31 anti-HCV positive sera, 20 weak anti-HCV positive sera, 80 viraemic and anti-HCV-positive sera from patients infected with different subtypes and 10 sera from patients with HBV-HCV or HIV-HCV co-infections. Of 500 anti-HCV negative samples, 499 (99.8%) were negative with a cut-off index <0.5, while one sample was within the grey zone. Of the 93 HCV-RNA positive and anti-HCV negative sera from patients and panels, 85 (91.4%) resulted positive, and one had the cut-off index in the grey zone. The reduction in the diagnostic window period observed with the new test and HCV-RNA assays were equal, on average, to 24 and 34.4 days respectively. All anti-HCV positive sera were positive. The new assay shows high sensitivity and specificity and could be a useful tool not only in the diagnostic setting, where procedures to reduce the window period, such as antigen or HCV-RNA detection, are not currently recommended, but also in the screening of blood donations, when nucleic acid technologies is not feasible because of costs, organization, emergency and/or logistic difficulties.

Enzyme-Linked Immunosorbent Assay↗

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↗

Bone quality in perinatally HIV-infected children: role of age, sex, growth, HIV infection, and antiretroviral therapy.

Appropriate supportive care and identification of long-term sequels of therapy are of paramount importance in HIV-infected pediatric patients. As low bone mineral quality (BMQ) in patients can be considered a marker of possible degeneration in osteopenia and osteoporosis in adulthood, we evaluated bone features in a pediatric population. Forty-four patients (23 females, 21 males; aged 3-17 years) were compared with a control population (1227 healthy children: 568 females, 641 males; aged 3-18 years). Seven patients were CDC stage C, 18 B, and 18 A. All patients were vertically infected; four were naive to any antiretroviral treatment, seven were taking two NRTIs, and 32 were on HAART. BMQ was assessed by a quantitative ultrasound (QUS) technique. It measures the amplitude-dependent speed of sound (AD-SoS, m/sec) and the bone transmission time (BTT, microsec). QUS values were significantly lower in cases than in controls, even after adjustment for age and body size (AD-SoS: 1924.7 +/- 64.9 and BTT: 0.97 +/- 0.3 in controls; AD-SoS: 1879.7 +/- 57.2 and BTT: 0.80 +/- 0.32 in cases; p < or = 0.001). The associations of AD-SoS and BTT with gender, type of therapy, and CDC stages were not significant. AD-SoS and BTT were significantly associated with age (r = 0.59, p < 0.0001), skeletal age SDS (r = 0.46, p = 0.002), height (r = 0.66, p < 0.0001), and therapy duration (r = 0.31, p = 0.04). Both AD-SoS and BTT values in patients fell below mean values of controls. Follow-up of bone mineral density is important in patients to prevent long-term problems of skeletal status.

Adolescent↗

Incidence, timing and site of infections among pancreas transplant recipients.

The incidence, timing and site of infections among the different categories of pancreas transplant recipients were investigated. Patients were divided into three groups: pancreas transplant alone (PTA), pancreas after kidney transplant (PAK), or simultaneous pancreas and kidney (SPK) transplants. Length of follow-up, time to death, pancreas graft survival, incidence, timing and site of bacterial infections were noted. Our study showed that at least 75% of pancreas transplant recipients experienced at least one infection (range from 77.8% in the PTA group to 86.7% in the PAK group). The SPK group presented the highest rate of infections with 35.1 infections per 1000/patient-days. Symptomatic urinary tract infections were the most common cause of infection in all patients. The incidence of infections was higher during the first month after transplantation, except for the SPK transplant group, where infections occurred over a longer time period.

Adult↗

Aspergillus vertebral osteomyelitis after simultaneous kidney-pancreas transplantation.

Aspergillus osteomyelitis is a rare complication of invasive aspergillosis after organ transplantation. This is the report of a 46-year-old man who underwent a simultaneous pancreas and kidney transplantation, complicated by an Aspergillus osteomyelitis and diskitis of the lumbar spine. Prompt diagnosis with needle biopsy, followed by antifungal therapy using caspofungin, a new antifungal agent recommended for the treatment of refractory aspergillosis, in combination with amphotericin B and an early surgical intervention led to clinical resolution of the infection. Reported cases of spinal aspergillosis after transplantation are reviewed in terms of clinical presentation, risk factors, therapeutic options, and outcome.

Aspergillosis↗

The relationship between ritonavir plasma trough concentration and virological and immunological response in HIV-infected children.

BACKGROUND: We studied a number of factors, including ritonavir plasma levels, and their capability of predicting response to therapy with ritonavir (RTV). METHODS: Eleven HIV-positive children, nucleoside reverse transcriptase inhibitor (NRTI)-experienced, protease inhibitor (PI) naive, receiving RTV in combination with two NRTIs were enrolled in the study. Demographic parameters were: median age (range) 10 (2-13) years, weight 26 (10-38) kg, body surface area (BSA) 0.93 (0.47-1.21) m(2). Baseline values of CD4, percent CD4 and viral load were 137 (2-1390) cells/microL, 9.5 (0.4-32.4)%, and 5.15 (4.30-6.18) log10 copies/mL, respectively. The dose of RTV was 318 (266-409) mg/m(2) twice daily. Peak (3.5 h after administration) and trough (predose) plasma concentrations of RTV were determined on one occasion at steady-state after a morning dose. Virological response to treatment was quantified as the difference between the baseline value of viral load and the value observed at 6 months of therapy (Delta(6)). RESULTS: The relationship between Delta(6) and demographic parameters (age, weight, BSA, and baseline CD4, percent CD4, and viral load) and plasma concentrations of RTV was studied by linear regression. Median (range) Delta(6) was 0.88 (0.77-2.62) log10 copies/mL. Peak and trough of RTV were 14.9 (3.2-31.4) and 5.0 (0.1-15.6) mg/L, respectively. Trough concentration of RTV was the best predictor of Delta(6), although the relationship between these two variables was not statistically significant (r = 0.56, P = 0.075). CONCLUSION: Our observation of a trend for a greater decrease in viral load in patients with higher trough concentration of RTV warrants further pharmacodynamic studies of PI in paediatric patients.

Area Under Curve↗

Gram-positive bacterial resistance. A challenge for the next millennium.

Penicillin G was first used in 1941. Since then, the trend in bacterial infections has changed. New antibiotics have been developed and bacterial resistance has spread as a consequence. The spread of Gram positive resistant bacteria is related to an inappropriate use of antibiotics. Antibacterial agents are abused or overused in various fields: medicine itself, veterinary science and zootechnics. Now, at the beginning of the third millennium we have been forced to limit our therapeutic options in order to combat these insidious enemies. Selective antibiotic pressure on the microbial population, notably on enterococci and staphylococci, made these two pathogens recalcitrant to traditional chemotherapy. It is a matter of concern that today, vancomycin-resistant Enterococcus spp. (VRE) and vancomycin-intermediate and resistant Staphylococcus aureus (VISA and VRSA) are now being observed worldwide among emerging pathogens. Most pharmaceutical companies are today developing antimicrobial drugs that are active against Gram-positive bacteria. Quinupristin/dalfopristin and linezolid are the most promising drugs and are available only for serious infections; future agents being developed for multi-resistant Gram-positive infections include daptomycin and the glycyclines, although these are still in the development phase. Nevertheless, our group has had the opportunity to treat some serious infections with these drugs and the good results achieved are reported in this review.

Acetamides↗

The effect of formulary restriction in the use of antibiotics in an Italian hospital.

OBJECTIVE: To compare the expenditure and usage of antibiotics at the San Martino Teaching Hospital, a 2500-bed hospital in Genoa, Italy, before and after the implementation of an antibiotic control program that streamlined the hospital formulary and the creation of a restricted group of antibiotics requiring approval before use. METHODS: Usage and expenditure data for all antibiotics were collected from 1996 to 1998. Antibiotic usage was standardised by defined daily doses (DDDs) per 100/patient-days. Cost data were expressed in Euros. Changes in antibiotic usage was determined by comparing the mean usage during 1996 and 1997, the period before the implementation of the antibiotic control program, to 1998 when the streamlined formulary and restricted group of antibiotics, controlled by the Infectious Disease Team (IDT). were initiated. The Wilcoxon rank sign test was used to determine statistical significance of the changes in overall antibiotic use; a P value of less than 0.05 was considered significant. RESULTS: After the implementation of the antibiotic control program, overall antibiotic usage decreased by 8.5%, 28.00 DDD/100 patient-days during 1996-1997 to 25.62 DDD/100 patient-days during 1998. The control program resulted in overall savings of 342,927 Euros after the first year of implementation. The usage and expenditure in the restricted group of antibiotics decreased by 78.5% and 53.5%, respectively, (P=0.03). Restricting the use of ceftazidime and imipenem accounted for the majority of the decreased usage and savings. In the non-restricted group of antibiotics, usage increased only by 32.6% resulting in a net reduction of 46.3% in all antibiotic use. CONCLUSION: Although antibiotic control programs have been successful in other countries, this represents the first attempt at successful antibiotic control in a large Italian teaching hospital. Streamlining the formulary to control antibiotic choices and the creation of a restriction program using the expertise of infectious disease physicians resulted in significant reductions in the use of and expenditure for antibiotics.

Anti-Bacterial Agents↗

Comparative antimicrobial activity of gatifloxacin with ciprofloxacin and beta-lactams against gram-positive bacteria.

Gatifloxacin is a new 8-methoxy fluoroquinolone. The in-vitro antibacterial activity of gatifloxacin was compared to that of ciprofloxacin, ceftriaxone, imipenem, piperacillin/tazobactam and amoxicillin/clavulanic acid against 165 streptococcal isolates, 369 staphylococcal isolates, and 50 enterococcal isolates recently recovered from clinical isolates. Gatifloxacin was the most active agent tested against streptococci including penicillin-nonsusceptible Streptococcus pneumoniae (MIC(90) 0.5 microg/mL). Imipenem and gatifloxacin (MIC(90) 0.5 microg/mL) were the most active agents tested against viridans group streptococci. All the agents demonstrated excellent activity against methicillin-susceptible S. aureus. Imipenem, piperacillin/tazobactam, amoxicillin/clavulanic acid, and gatifloxacin had good activity against methicillin-sensitive S. epidermidis. Among the methicillin-sensitive and methicillin-resistant coagulase-negative staphylococci tested, gatifloxacin was the most active agent. Amoxicillin/clavulanic acid and gatifloxacin were the most active agents against E. faecalis. Thus, gatifloxacin possesses equal or superior activity when compared to ciprofloxacin and beta-lactams making it a promising new fluoroquinolone for clinical use in treating Gram-positive infections.

Anti-Bacterial Agents↗

The organization of infection control in Italy.

This paper describes the organization of infection control in Italy with respect to regulatory requirements, the tasks and training of the infection control physician and nurse, and the function and responsibilities of the infection control committee. Moreover, the paper reports on incidence and prevalence of hospital-acquired infections (HAI), antibiotic usage and antimicrobial resistance in Italy.

Anti-Bacterial Agents↗

Linezolid treatment of prosthetic hip Infections due to methicillin-resistant Staphylococcus aureus (MRSA).

Prosthetic joint infection is an infrequent but serious complication of total joint arthroplasty. Complete removal of all foreign material is essential, however when prosthesis removal is not possible or contraindicated, suppressive antibiotic therapy with retention of the functioning hip arthroplasty may be considered. Linezolid, the first approved oxazolidinone, appears to be a promising new agent for the treatment of serious Gram-positive infections. We report two cases of Methicillin-resistant Staphylococcus aureus (MRSA) prosthetic hip infections successfully treated with a long course of linezolid. This observation suggest that linezolid is a promising drug for the treatment of prosthetic joint infections due to MRSA or other Gram-positive pathogens, particularly when other therapeutic approaches are not feasible or a long-term antibiotic therapy is required.

Acetamides↗