To evaluate the efficacy and safety of voriconazole in acute invasive aspergillosis (IA), an open, noncomparative multicenter study was conducted. Immunocompromised patients with IA were treated with intravenously administered voriconazole 6 mg/kg twice a day (b.i.d.) twice and then 3 mg/kg b.i.d. for 6-27 days, followed by 200 mg b.i.d. administered orally for up to 24 weeks. Response was assessed by clinical and radiographic change. A total of 116 patients were assessable. IA was proven in 48 (41%) and probable in 68 patients. Voriconazole was given as primary therapy in 60 (52%). Good responses were seen in 56 (48%); 16 (14%) showed complete response and 40 (34%) partial response. A stable response was seen in 24 patients (21%), and 36 (31%) of the infections failed to respond to therapy. Good responses were seen in 60% of those with pulmonary or tracheobronchial IA (n=84), 16% with cerebral IA (n=19), 58% with hematologic disorders (n=67), and 26% of allogeneic stem cell transplant recipients (n=23). Voriconazole is efficacious in treating acute IA.

The aim of this study was to determine the current incidence of side-effects severe enough to cause intolerance of standard antituberculosis therapy with isoniazid, rifampin and pyrazinamide in patients hospitalized as a result of pulmonary tuberculosis. Five hundred and nineteen patients with proven pulmonary tuberculosis, who initially received standard antituberculosis therapy, were retrospectively studied in the department of infectious diseases in a teaching chest hospital. The incidence of severe side-effects related to the therapy, which led to the definitive termination of one of the three standard drugs, was measured and the risk factors for intolerance were analysed. Final termination of either isoniazid, rifampin or pyrazinamide because of severe side-effects was necessary in 121 of the 519 patients (23%). The most severe side-effects leading to final termination of one drug were hepatotoxicity (11%), exanthema (6%), and arthralgia (2%). Pyrazinamide showed more severe side-effects (15%) than isoniazid (7%) and rifampin (1.5%). Significant risk factors for intolerance of the standard therapy following a multivariate analysis were a history of hepatitis (odds ratio (OR) 3.4; 95% confidence interval (95% CI) 1.6-7.6; p = 0.0026) and an age > or = 60 yrs (OR 1.9; 95% CI 1.2-3.2; p = 0.017). Both of these risk factors were also significantly associated with the intolerance of pyrazinamide (history of hepatitis: OR 2.5; 95% CI 1.4-4.3; p = 0.0045; age > or = 60 yrs: OR 2.1, 95% CI 1.3-3.5; p = 0.0029) but not of isoniazid and rifampin. The side-effects of standard antituberculosis therapy are frequent in hospitalized patients aged > or = 60 yrs or with a history of previous hepatitis, and are probably due to pyrazinamide rather than to isoniazid or rifampin.

Post-influenza bacterial pneumonia is a major cause of morbidity and mortality associated with both seasonal and pandemic influenza virus illness. However, despite much interest in influenza and its complications in recent years, good clinical trial data to inform clinicians in their assessment of treatment options are scant. This paucity of evidence needs to be addressed urgently in order to improve guidance on the management of post-influenza bacterial pneumonia. The objectives of the current article are to evaluate the emergence of the 2009 H1N1 influenza pandemic and use this information as background for an in-depth review of the epidemiology of bacterial pneumonia complicating influenza, to review the bacterial pathogens most likely to be associated with post-influenza bacterial pneumonia, and to discuss treatment considerations in these patients. When determining optimal management approaches, both antiviral and antibacterial agents should be considered, and their selection should be based upon a clear understanding of how their mechanisms of action intervene in the pathogenesis of post-influenza acute bacterial pneumonia.

In adults, an initial dose of 7vPnC is likely to elicit higher and potentially more effective levels of antipneumococcal antibodies than is PPV. In contrast with PPV, for which the induction of hyporesponsiveness was observed when used as a priming dose, 7vPnC elicits an immunological state that permits subsequent administration of 7vPnC or PPV to maintain functional antipolysaccharide antibody levels.

Severe tuberculosis (TB) requiring intensive care unit (ICU) care is rare but commonly known to be of markedly bad prognosis. The present study aimed to describe this condition and to determine the mortality rate and risk factors associated with mortality.Patients with confirmed TB admitted to ICU between 1990 and 2001 were retrospectively identified and enrolled. Clinical, radiological and bacteriological data at admission and during hospital stay were recorded. A multivariate analysis was performed to identify the predictive factors for mortality.A total of 58 TB patients (12 females, mean age 48 yrs) admitted to ICU were included. Mean Acute Physiology and Chronic Health Evaluation (APACHE) II score at admission was 13.1¡5.6 and 22 of 58 (37.9%) patients required mechanical ventilation. The in-hospital mortality was 15 of 58 (25.9%); 13 (22.4%) patients died in the ICU. The mean survival of patients who died was 53.6 days (range 1-229), with 50% of the patients dying within the first 32 days. The factors independently associated with mortality were: acute renal failure, need for mechanical ventilation, chronic pancreatitis, sepsis, acute respiratory distress syndrome, and nosocomial pneumonia.These data indicate a high mortality of patients with tuberculosis requiring intensive care unit care and identifies new independently associated risk factors.