Adjunctive Systemic Corticosteroids for Hospitalized Community-Acquired Pneumonia: Systematic Review and Meta-Analysis 2015 Update

Previous randomized controlled trials (RCTs) and meta-analyses evaluated the efficacy and safety of adjunctive corticosteroids for community-acquired pneumonia (CAP). However, the results from them had large discrepancies. The eligibility criteria for the current meta-analysis were original RCTs written in English as a full article that evaluated adjunctive systemic corticosteroids adding on antibiotic therapy targeting typical and/or atypical pathogen for treating hospitalized human CAP cases. Four investigators independently searched for eligible articles through PubMed, Embase, and Cochrane databases. Random model was used. The heterogeneity among original studies and subgroups was evaluated with the I2 statistics. Of 54 articles that met the preliminary criteria, we found 10 eligible RCTs comprising 1780 cases. Our analyses revealed following pooled values by corticosteroids. OR for all-cause death: 0.80 (95% confidence interval (95% CI) 0.53-1.21) from all studies; 0.41 (95% CI 0.19-0.90) from severe-case subgroup; 0.21 (95% CI 0.0-0.74) from intensive care unit (ICU) subgroup. Length of ICU stay: -1.30 days (95% CI (-3.04)-0.44). Length of hospital stay: -0.98 days (95% CI (-1.26)-(-0.71)). Length to clinical stability: -1.16 days (95% CI (-1.73)-(-0.58)). Serious complications do not seem to largely increase by steroids. In conclusion, adjunctive systemic corticosteroids for hospitalized patients with CAP seems preferred strategies

Posaconazole Serum Drug Levels Associated With Pseudohyperaldosteronism

Posaconazole tablets are well tolerated and efficacious in the prophylaxis and treatment of aspergillosis, mucormycosis, and other invasive fungal infections. There have been case reports of posaconazole-induced pseudohyperaldosteronism (PIPH); however, its occurrence and association with serum posaconazole drug levels have not previously been investigated.; In this single-center, retrospective, observational study, we examined the occurrence of PIPH in outpatients newly starting posaconazole and evaluated differences in serum posaconazole concentrations and clinical characteristics between those with and without this syndrome.; Sixty-nine patients receiving posaconazole were included, of whom 16 (23.2%) met the definition of PIPH. Patients with PIPH were significantly older (61.1 vs 44.7 years, P = .007) and more frequently had hypertension prior to starting posaconazole (68.8% vs 32.1%, P = .009). Patients with PIPH had a significantly higher median serum posaconazole level than those without PIPH (3.0 vs 1.2 µg/mL, P ≤ .0001). There was a positive correlation between serum posaconazole levels and changes in systolic blood pressure (r = .37, P = .01), a negative correlation between serum posaconazole levels and changes in serum potassium (r = -.39, P = .006), and a positive correlation between serum posaconazole levels and serum 11-deoxycortisol (r = .69, P < .0001).; Posaconazole is associated with secondary hypertension and hypokalemia, consistent with pseudohyperaldosteronism, and development is associated with higher serum posaconazole concentrations, older age, and baseline hypertension

Posaconazole Serum Drug Levels Associated with Pseudohyperaldosteronism

BackgroundPosaconazole tablets are well tolerated and efficacious in the prophylaxis and treatment of aspergillosis, mucormycosis, and other invasive fungal infections. There have been case reports of posaconazole-induced pseudohyperaldosteronism (PIPH); however, its occurrence and association with serum posaconazole drug levels have not previously been investigated.MethodsIn this single-center, retrospective, observational study, we examined the occurrence of PIPH in outpatients newly starting posaconazole and evaluated differences in serum posaconazole concentrations and clinical characteristics between those with and without this syndrome.ResultsSixty-nine patients receiving posaconazole were included, of whom 16 (23.2%) met the definition of PIPH. Patients with PIPH were significantly older (61.1 vs 44.7 years, P = .007) and more frequently had hypertension prior to starting posaconazole (68.8% vs 32.1%, P = .009). Patients with PIPH had a significantly higher median serum posaconazole level than those without PIPH (3.0 vs 1.2 µg/mL, P ≤ .0001). There was a positive correlation between serum posaconazole levels and changes in systolic blood pressure (r = .37, P = .01), a negative correlation between serum posaconazole levels and changes in serum potassium (r = -.39, P = .006), and a positive correlation between serum posaconazole levels and serum 11-deoxycortisol (r = .69, P &lt; .0001).ConclusionsPosaconazole is associated with secondary hypertension and hypokalemia, consistent with pseudohyperaldosteronism, and development is associated with higher serum posaconazole concentrations, older age, and baseline hypertension

No evidence for the effectiveness of systemic corticosteroids in acute pharyngitis, community-acquired pneumonia and acute otitis media

Corticosteroids have been used to treat infectious diseases for more than 50\ua0years but, although it has been shown that they are highly effective in improving the clinical course of some diseases, their effects have not been clearly defined in others. Nevertheless, they are still used by a considerable number of physicians. This review analyses the role of systemic corticosteroids in the treatment of acute pharyngitis (AP), community-acquired pneumonia (CAP) and acute otitis media (AOM). A number of trials involving patients with AP have been carried out, but most are marred by methodological flaws that do not allow any firm conclusions to be drawn. The number of trials involving CAP patients is even higher, and the data suggest that corticosteroids may reduce the risk of death only in patients with severe disease. There are very few data concerning AOM, and there is currently no reason for prescribing corticosteroids to treat it. Overall, the data showed that there is, currently, no indication for the universal use of systemic corticosteroids in any of the reviewed diseases and, further, high-quality studies of all of these respiratory tract infections are needed in order to identify the patients for whom the prescription of corticosteroids is rationally acceptabl

Is prolonged low-dose glucocorticoid treatment beneficial in community-acquired pneumonia?

Community-acquired pneumonia (CAP) has a significant impact on public health in terms of short-term and long-term morbidity and mortality. Irrespective of microbiological etiology, the host's inability to fully downregulate systemic inflammation is the dominant pathogenetic process contributing to acute and long-term morbidity and mortality in CAP. Glucocorticoids are the natural regulators of inflammation, and their production increases during infection. There is consistent evidence that downregulation of systemic inflammation with prolonged low-dose glucocorticoid treatment in patients with severe sepsis and acute respiratory distress syndrome improves cardiovascular and pulmonary organ physiology. A recent meta-analysis of pooled controlled small trials (n = 970) of patients admitted with CAP found improved short-term mortality in the subgroup with severe CAP and/or receiving >5 days of glucocorticoid treatment. We have expanded on this meta-analysis by including patients with CAP recruited in trials investigating prolonged low-dose glucocorticoid treatment in septic shock and/or early acute respiratory distress syndrome (n = 1,206). Our findings confirm a survival advantage for severe CAP (RR 0.66, 95% confidence interval 0.51-0.84; p = .001). A large randomized trial is in progress to confirm the aggregate findings of these small trials and to evaluate the long-term effect of this low-cost treatment