Posaconazole is a triazole with broad spectrum of activity against multiple fungi including members of the fungal order Mucorales. This activity has been shown both in clinical and in vitro studies, which are critically reviewed here. It has become very popular in prophylaxis in acute myelogenous leukemia (AML) induction and in the graft-versus-host disease (GVHD) settings after 2 recent prospective trials that showed advantage of posaconazole prophylaxis compared to fluconazole or itraconazole. In this report, 2 patients are presented, in whom, despite posaconazole prophylaxis, invasive and ultimately fatal Rhizopus pulmonary infections developed. These cases are similar to a previously reported case of Rhizopus infection in a stem cell transplant recipient who also received posaconazole, indicating a potential newly recognized pattern of breakthrough infections in patients receiving posaconazole prophylaxis.
Sepsis is associated with abnormalities of muscle tissue oxygenation and of microvascular function. We investigated whether the technique of near-infrared spectroscopy can evaluate such abnormalities in critically ill patients and compared near-infrared spectroscopy-derived indices of critically ill patients with those of healthy volunteers.
We studied 41 patients (mean age 58±22 years) and 15 healthy volunteers (mean age 49±13 years). Patients were classified into one of three groups: systemic inflammatory response syndrome (SIRS) (n=21), severe sepsis (n=8) and septic shock (n=12). Near-infrared spectroscopy was used to continuously measure thenar muscle oxygen saturation before, during and after a three-minute occlusion of the brachial artery via pneumatic cuff.
Oxygen saturation was significantly lower in patients with SIRS, severe sepsis or septic shock than in healthy volunteers. Oxygen consumption rate during stagnant ischaemia was significantly lower in patients with SIRS (23.9±7.7%/minute, P <0.001), severe sepsis (16.9±3.4%/minute, P <0.001) or septic shock (14.8±6%/minute, P <0.001) than in healthy volunteers (35.5±10.6%/minute). Furthermore, oxygen consumption rate was significantly lower in patients with septic shock than patients with SIRS. Reperfusion rate was significantly lower in patients with SIRS (336±141%/minute, P <0.001), severe sepsis (257±150%/minute, P <0.001) or septic shock (146±101%/minute, P <0.001) than in healthy volunteers (713±223%/minute) and significantly lower in the septic shock than in the SIRS group.
Near-infrared spectroscopy can detect tissue oxygenation deficits and impaired microvascular reactivity in critically ill patients, as well as discriminate among groups with different disease severity.
We sought to quantify patient morbidity throughout Pseudomonas aeruginosa bloodstream infection (PABSI) as a function of patient covariates. Individuals with PABSI were included in a retrospective, observational, cohort study. Morbidity was quantified by serial Sequential Organ Failure Assessment (SOFA) scores. Impact of active antimicrobial treatment was assessed as a function of changes in SOFA scores as the dependent variable. A total of 95 patients with PABSI were analyzed. Relative to baseline SOFA scores (day −2), scores following PABSI were increased by 37% on day 0 and 22% on day +2 but returned to baseline on day +7. Overall mortality was 37%, and mean length of hospital stay (post-culture) was 16 days. Most patients were appropriately treated, with n=83 (87%) receiving an active agent and n=61 (64%) receiving >1 agent. As a result, an effect of therapy on morbidity was not observed. Advanced age and elevated baseline SOFA scores predicted increased in-hospital mortality (p=0.01 and p<0.001, respectively) and morbidity at day +2 (p<0.05 and p<0.05, respectively) and day +7 (p<0.05 and p<0.001, respectively). Neutropenia was also associated with increased morbidity at day +2 (p<0.05). In treated PABSI, morbidity is highest the day of the diagnostic blood cultures and slowly returns to baseline over the subsequent seven days. Age and baseline severity of illness are the strongest predictors of morbidity and mortality. Since neither of these factors is modifiable, efforts to minimize the negative impact of PABSI should focus on appropriate prevention and infection control efforts.
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