Diego Viasus

Fatal cases of Chikungunya virus infection in Colombia: Diagnostic and treatment challenges

Although Chikungunya infection is emerging as an important public health problem in many countries, it is not regarded as a life-threatening disease. Information dealing with fatal cases is scarce. We herein describe three patients with Chickungunya infection who presented with multiple organ failure and died within 24h of admission. Two cases had positive anti-dengue IgM, but dengue coinfection was rejected based on the clinical features and results of real-time reverse transcription polymerase chain reaction. These cases illustrate the challenges of the diagnosis and management of severe Chikungunya infection.

The effect of simvastatin on inflammatory cytokines in community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial

Objectives It has been suggested that statins have an effect on the modulation of the cytokine cascade and on the outcome of patients with community-acquired pneumonia (CAP). The aim of this prospective, randomised, double-blind, placebo-controlled trial was to determine whether statin therapy given to hospitalised patients with CAP improves clinical outcomes and reduces the concentration of inflammatory cytokines. Setting A tertiary teaching hospital in Barcelona, Spain. Participants Thirty-four patients were randomly assigned and included in an intention-to-treat analysis (19 to the simvastatin group and 15 to the placebo group). Intervention Patients were randomly assigned to receive 20 mg of simvastatin or placebo administered in the first 24 h of hospital admission and once daily thereafter for 4 days. Outcome Primary end point was the time from hospital admission to clinical stability. The secondary end points were serum concentrations of inflammatory cytokines and partial pressure of arterial oxygen/fractional inspired oxygen (PaO2/FiO2) at 48 h after treatment administration. Results The trial was stopped because enrolment was much slower than originally anticipated. The baseline characteristics of the patients and cytokine concentrations at the time of enrolment were similar in the two groups. No significant differences in the time from hospital admission to clinical stability were found between study groups (median 3 days, IQR 2–5 vs 3 days, IQR 2–5; p=0.47). No significant differences in PaO2/FiO2 (p=0.37), C reactive protein (p=0.23), tumour necrosis factor-α (p=0.58), interleukin 6 (IL-6; p=0.64), and IL-10 (p=0.61) levels at 48 h of hospitalisation were found between simvastatin and placebo groups. Similarly, transaminase and total creatine kinase levels were similar between study groups at 48 h of hospitalisation (p=0.19, 0.08 and 0.53, respectively). Conclusions Our results suggest that the use of simvastatin, 20 mg once daily for 4 days, since hospital admission did not reduce the time to clinical stability and the levels of inflammatory cytokines in hospitalised patients with CAP. Trial registration number ISRCTN91327214.

Biomarkers for predicting short-term mortality in community-acquired pneumonia: A systematic review and meta-analysis

OBJECTIVES The pneumonia severity index and CURB-65 are risk assessment tools widely used in community-acquired pneumonia (CAP). However, limitations in these prognostic scores have led to increasing interest in finding biomarkers that might provide additional information. To date, the role of these biomarkers has not been fully elucidated. METHODS We systematically searched the Medline, Web of Knowledge, Science Direct, and LILACS databases. We included studies that assessed the accuracy of biomarkers for the prediction of in-hospital or ≤30-day mortality, in hospitalized adults with CAP. Two independent investigators extracted patient and study characteristics, which were thereafter pooled using a random effects model. Relationships between sensitivity and specificity of biomarkers and prognostic scores were plotter using the area under the receiver operator characteristic curve (AUC). RESULTS We included 24 articles and 2 databases from 1069 reviewed abstracts, which provided 10,319 patients for analysis. Reported mortality rates varied from 2.4% to 34.6%. The highest AUC values for predicting mortality were associated with pro-adrenomedullin (0.80) and prohormone forms of atrial natriuretic peptide (0.79), followed by cortisol (0.78), procalcitonin (0.75), copeptin (0.71), and C-reactive protein (0.62). There were no statistically significant differences between the AUCs of the studied biomarkers, other than for copeptin and C-reactive protein, which performed comparatively poorly. When compared with the CAP-specific scores, the AUCs were not significantly different from those of most biomarkers. CONCLUSIONS The identified biomarkers are able to predict mortality with moderate to good accuracy in CAP. However, biomarkers have no clear advantage over CAP-specific scores for predicting mortality.

Clinical and histopathological features of fatal cases with dengue and chikungunya virus co-infection in Colombia, 2014 to 2015.

We report clinical features and histopathological findings in fatal cases with dengue (DENV) and chikungunya (CHIKV) co-infection identified at the Colombian National Institute of Health between September 2014 and October 2015. Seven such cases were documented. Dengue serotype 2 virus was identified in six cases. All patients were adults and comorbidities were present in four. Fever, arthralgia or myalgia was present in all cases. The frequency of rash, haemorrhage, oedema, and gastrointestinal symptoms was variable. Laboratory findings such as thrombocytopenia, renal failure, and leukocyte count were also inconsistent between cases. Post-mortem tissue examination documented focal hepatocellular coagulative necrosis in three cases, incipient acute pericarditis in one and tubulointerstitial nephritis in one. This study provides evidence of mortality in patients with DENV and CHIKV co-infection. Fatal cases were characterised by variable clinical and laboratory features. Evaluation of histopathology of autopsy tissues provided evidence of the pathological consequences of the disease.

Impact of antibiotic de-escalation on clinical outcomes in community-acquired pneumococcal pneumonia

Background Although antibiotic de-escalation is regarded as a measure that reduces selection pressure, adverse drug effects and costs, evidence supporting this practice in community-acquired pneumococcal pneumonia (CAPP) is lacking. Methods We carried out a retrospective analysis of prospectively collected data of a cohort of hospitalized adults with CAPP. Pneumococcal aetiology was established in patients with one or more positive cultures for Streptococcus pneumoniae obtained from blood, sterile fluids or sputum, and/or a positive urinary antigen test. De-escalation therapy was considered when the initial antibiotic therapy was narrowed to penicillin, amoxicillin or amoxicillin/clavulanate within the first 72 h after admission. The primary outcomes were 30 day mortality and length of hospital stay (LOS). Adjustment for confounders was performed with multivariate and propensity score analyses. Results Of 1410 episodes of CAPP, antibiotic de-escalation within the first 72 h after admission was performed in 166 cases. After adjustment, antibiotic de-escalation was not associated with a higher risk of mortality (OR = 0.83, 95% CI = 0.24–2.81), but it was found to be a protective factor for prolonged LOS (above the median) (OR = 0.46, 95% CI = 0.30–0.70). Similar results were found in patients classified into high-risk pneumonia severity index classes (IV–V), those with clinical instability and those with bacteraemia. No significant differences were documented in adverse drug reactions or readmission (<30 days). Conclusions Antibiotic de-escalation seems to be safe and effective in reducing the duration of LOS, and did not adversely affect outcomes of patients with CAPP, even those with bacteraemia and severe disease, and those who were clinically unstable.

Solithromycin for the treatment of community-acquired bacterial pneumonia.

ABSTRACT Introduction: Community-acquired pneumonia is a major public health problem worldwide. In recent years, there has been an increase in the frequency of resistance to the antimicrobials such as β-lactams or macrolides which have habitually been used against the causative pathogens. Solithromycin, a next-generation macrolide, is the first fluoroketolide with activity against most of the frequently isolated bacteria in community-acquired pneumonia, including typical and atypical bacteria as well as macrolide-resistant Streptococcus pneumoniae. Areas covered: A detailed assessment of the literature relating to the antimicrobial activity, pharmacokinetic/pharmacodynamic properties, efficacy, tolerability and safety of solithromycin for the treatment of community-acquired bacterial pneumonia Expert commentary: Recent randomized controlled phase II/III trials have demonstrated the equivalent efficacy of oral and intravenous solithromycin compared with fluoroquinolones in patients with lower mild-to-moderate respiratory infections, and have shown that systemic adverse events are comparable between solithromycin and alternative treatments. However, studies of larger populations which are able to identify infrequent adverse events are now needed to confirm these findings. On balance, current data supports solithromycin as a promising therapy for empirical treatment in adults with community-acquired bacterial pneumonia.

Antibiotic stewardship in community-acquired pneumonia

ABSTRACT Introduction: Community-acquired pneumonia (CAP) continues to be associated with significant mortality and morbidity. As with other infectious diseases, in recent years there has been a marked increase in resistance to the antibiotics commonly used against the pathogens that cause CAP. Antimicrobial stewardship denotes coordinated interventions to improve and measure the appropriate use of antibiotics by encouraging the selection of optimal drug regimens. Areas covered: Several elements can be applied to antibiotic stewardship strategies for CAP in order to maintain or improve patient outcomes. In this regard, antibiotic de-escalation, duration of antibiotic treatment, adherence to CAP guidelines recommendations about empirical treatment, and switching from intravenous to oral antibiotic therapy may each be relevant in this context. Antimicrobial stewardship strategies, such as prospective audit with intervention and feedback, clinical pathways, and dedicated multidisciplinary teams, that have included some of these elements have demonstrated improvements in antimicrobial use for CAP without negatively affecting clinical outcomes. Expert commentary: Although there are a limited number of randomized clinical studies addressing antimicrobial stewardship strategies in CAP, there is evidence that antibiotic stewardship initiatives can be securely applied, providing benefits to both healthcare systems and patients.

Pharmacotherapy for community-acquired pneumonia in the elderly

ABSTRACT Introduction: Community-acquired pneumonia (CAP) is an increasing problem in the elderly that is associated with elevated morbidity and mortality. Given the expected increased life expectancy, this problem is only likely to worsen, so it has been considered that treatment effects must be examined separately in elderly adults with CAP. Areas covered: In this narrative review, we give an update of the available data of antibiotics for elderly patients with CAP. Clinical features, drug pharmacokinetics and pharmacodynamics, adverse effects, and outcomes differ in CAP depending on patient age. Older age, for example, can affect the effect of specific antibiotic regimens on important CAP clinical outcomes. Current guidelines do not offer specific recommendations for the management of CAP in elderly patients. Expert opinion: Most of our knowledge about the treatment of CAP in elderly patients has been gained from studies in young populations. However, elderly patients with CAP deserve special attention because there are several factors in this population that could influence their response to antibiotic regimens in CAP.

Impact of an Educational Program to Reduce Healthcare Resources in Community-Acquired Pneumonia: The EDUCAP Randomized Controlled Trial

Background Additional healthcare visits and rehospitalizations after discharge are frequent among patients with community-acquired pneumonia (CAP) and have a major impact on healthcare costs. We aimed to determine whether the implementation of an individualized educational program for hospitalized patients with CAP would decrease subsequent healthcare visits and readmissions within 30 days of hospital discharge. Methods A multicenter, randomized trial was conducted from January 1, 2011 to October 31, 2014 at three hospitals in Spain. We randomly allocated immunocompetent adults patients hospitalized for CAP to receive either an individualized educational program or conventional information before discharge. The educational program included recommendations regarding fluid intake, adherence to drug therapy and preventive vaccines, knowledge and management of the disease, progressive adaptive physical activity, and counseling for alcohol and smoking cessation. The primary trial endpoint was a composite of the frequency of additional healthcare visits and rehospitalizations within 30 days of hospital discharge. Intention-to-treat analysis was performed. Results We assigned 102 patients to receive the individualized educational program and 105 to receive conventional information. The frequency of the composite primary end point was 23.5% following the individualized program and 42.9% following the conventional information (difference, -19.4%; 95% confidence interval, -6.5% to -31.2%; P = 0.003). Conclusions The implementation of an individualized educational program for hospitalized patients with CAP was effective in reducing subsequent healthcare visits and rehospitalizations within 30 days of discharge. Such a strategy may help optimize available healthcare resources and identify post-acute care needs in patients with CAP. Trial Registration Controlled-Trials.com ISRCTN39531840

A Lachnospiraceae-dominated bacterial signature in the fecal microbiota of HIV-infected individuals from Colombia, South America

HIV infection has a tremendous impact on the immune system’s proper functioning. The mucosa-associated lymphoid tissue (MALT) is significantly disarrayed during HIV infection. Compositional changes in the gut microbiota might contribute to the mucosal barrier disruption, and consequently to microbial translocation. We performed an observational, cross-sectional study aimed at evaluating changes in the fecal microbiota of HIV-infected individuals from Colombia. We analyzed the fecal microbiota of 37 individuals via 16S rRNA gene sequencing; 25 HIV-infected patients and 12 control (non-infected) individuals, which were similar in body mass index, age, gender balance and socioeconomic status. To the best of our knowledge, no such studies have been conducted in Latin American countries. Given its compositional nature, microbiota data were normalized and transformed using Aitchison’s Centered Log-Ratio. Overall, a change in the network structure in HIV-infected patients was revealed by using the SPIEC-EASI MB tool. Genera such as Blautia, Dorea, Yersinia, Escherichia-Shigella complex, Staphylococcus, and Bacteroides were highly relevant in HIV-infected individuals. Differential abundance analysis by both sparse Partial Least Square-Discriminant Analysis and Random Forest identified a greater abundance of Lachnospiraceae-OTU69, Blautia, Dorea, Roseburia, and Erysipelotrichaceae in HIV-infected individuals. We show here, for the first time, a predominantly Lachnospiraceae-based signature in HIV-infected individuals.