George D'Souza

Ceftaroline fosamil versus ceftriaxone for the treatment of Asian patients with community-acquired pneumonia: a randomised, controlled, double-blind, phase 3, non-inferiority with nested superiority trial

BACKGROUND Ceftriaxone with or without a macrolide antibiotic is a recommended treatment for patients with community-acquired pneumonia requiring hospital admission and intravenous antibiotic treatment. We aimed to assess the efficacy and safety of ceftaroline fosamil compared with ceftriaxone in the treatment of Asian patients admitted to hospital with community-acquired pneumonia. METHODS In this international, randomised, controlled, double-blind, phase 3, non-inferiority with nested superiority trial, adult Asian patients with Pneumonia Outcomes Research Team (PORT) risk class III-IV acute community-acquired pneumonia were randomly assigned (1:1) to receive intravenous ceftaroline fosamil (600 mg every 12 h) or ceftriaxone (2 g every 24 h) for 5-7 days. Patients were randomly assigned via centralised telephone and web-based system; patients and treating clinicians were masked to treatment allocation. Investigators who did study assessments remained masked to treatment allocation until completion of the study. The primary endpoint was clinical cure at the test-of-cure visit (8-15 days after last dose of study drug) in the clinically evaluable population. Non-inferiority of ceftaroline fosamil was defined as a lower limit of the two-sided 95% CI for the difference in the proportion of patients clinically cured of -10% or higher; if non-inferiority was achieved, superiority was to be concluded if the lower limit of the 95% CI was greater than 0%. This trial is registered with ClinicalTrials.gov, number NCT01371838. FINDINGS Between Dec 13, 2011, and April 26, 2013, 847 patients were enrolled at 64 centres in China, India, South Korea, Taiwan, and Vietnam, of whom 771 were randomly assigned and 764 received study treatment. In the clinically evaluable population (n=498) 217 (84%) of 258 patients in the ceftaroline fosamil group and 178 (74%) of 240 patients in the ceftriaxone group were clinically cured at the test-of-cure visit (difference 9·9%, 95% CI 2·8-17·1). The superiority of ceftaroline fosamil was consistent across all preplanned patient subgroup analyses (split by age 65 years, age 75 years, sex, PORT risk class, and previous antibiotic use) apart from patients younger than 65 years. The frequency of adverse events was similar between treatment groups and the safety results for ceftaroline fosamil were consistent with the cephalosporin class and previous clinical trial data. INTERPRETATION Ceftaroline fosamil 600 mg given every 12 h was superior to ceftriaxone 2 g given every 24 h for the treatment of Asian patients with PORT III-IV community-acquired pneumonia. These data suggest that ceftaroline fosamil should be regarded as an alternative to ceftriaxone in empirical treatment regimens for this patient population. FUNDING AstraZeneca.

Pulmonary Hemorrhage in Henoch-Schönlein Purpura: Case Report and Systematic Review of the English Literature

BACKGROUND Diffuse alveolar hemorrhage (DAH) is a rare complication of Henoch-Schönlein purpura (HSP) and data on its prevalence, management, and outcomes are scant. OBJECTIVES To enable evidence-based management of DAH in HSP. METHODS A case report and a systematic review were conducted of all reported cases of DAH complicating HSP in the English literature. RESULTS DAH predominantly affects older male children and adults with HSP. The occurrence of DAH in HSP is rare and the reported prevalence ranged from 0.8% to 5%. DAH occurred variably after the diagnosis of HSP, ranging from 2 days to 18 years. Hemoptysis (75%), drop in hemoglobin (74%), and chest infiltrates (94%) were the most common clinical findings. Lung biopsy showed leukocytoclastic vasculitis with alveolar hemorrhage (69.2%) or only alveolar hemorrhage (31.8%) with variable IgA staining by immunofluorescence. DAH was frequently severe and 50% of the patients required mechanical ventilation. Cyclophosphamide and pulse methylprednisolone for DAH was associated with better outcomes, particularly in patients who were already receiving steroids at the time of DAH. Steroids and immunosuppressants were administered for a median duration of 9 and 4.5 months, respectively. Systemic recurrences (27.7%) and recurrences of DAH (8.3%) were frequent. DAH was associated with high mortality (27.6%) and morbidity (persistent urinary abnormalities, 12%; chronic renal failure, 9%; complications of therapy, 27%). CONCLUSIONS DAH is a life-threatening complication in HSP. Current protocols use pulse methylprednisolone and cyclophosphamide for 6 months.

Naturally Occurring Polymorphisms and Primary Drug Resistance Profile Among Antiretroviral-Naive Individuals in Bangalore, India

Although India has a large burden of HIV infection, good access to first-line antiretroviral therapy is widely available. However, understanding HIV resistance-associated mutations and polymorphisms is critical for continued success. The RT region of the HIV-1 pol gene was studied among 21 ART-naive HIV-1-infected individuals from South India. In addition, 421 published Indian HIV-1 subtype C sequences were analyzed for time trends in polymorphism frequency. Among primary isolates, all HIV-1 isolates were subtype C, and drug-resistant mutations were identified among two (9.56%) subjects. Mutations included E138A (etravirine resistance associated) and L210LS (thymidine analog mutation). The overall frequency of specific polymorphisms was similar to frequencies reported from different regions of India. Novel mutations were observed at positions Q23P/H and A129AG among isolates from our clinical cohort. Over a span of 10 years, the median polymorphism frequency among ART-naive subjects has remained unchanged, suggesting the slow evolution of HIV-1 subtype C in India.

Co-receptor tropism prediction among 1045 Indian HIV-1 subtype C sequences: Therapeutic implications for India

BackgroundUnderstanding co-receptor tropism of HIV-1 strains circulating in India will provide key analytical leverage for assessing the potential usefulness of newer antiretroviral drugs such as chemokine co-receptor antagonists among Indian HIV-infected populations. The objective of this study was to determine using in silico methods, HIV-1 tropism among a large number of Indian isolates both from primary clinical isolates as well as from database-derived sequences.ResultsR5-tropism was seen in 96.8% of a total of 1045 HIV-1 subtype C Indian sequences. Co-receptor prediction of 15 primary clinical isolates detected two X4-tropic strains using the C-PSSM matrix. R5-tropic HIV-1 subtype C V3 sequences were conserved to a greater extent than X4-tropic strains. X4-tropic strains were obtained from subjects who had a significantly longer time since HIV diagnosis (96.5 months) compared to R5-tropic strains (20.5 months).ConclusionsHigh prevalence of R5 tropism and greater homogeneity of the V3 sequence among HIV-1 subtype C strains in India suggests the potential benefit of CCR5 antagonists as a therapeutic option in India.

Increased risk of respiratory illness associated with kerosene fuel use among women and children in urban Bangalore, India

Background Kerosene is a widely used cooking and lighting fuel in developing countries. The potential respiratory health effects of cooking with kerosene relative to cooking with cleaner fuels such as liquefied petroleum gas (LPG) have not been well characterised. Methods We sampled 600 households from six urban neighbourhoods in Bangalore, India. Each households primary cook, usually the woman of the house, was interviewed to collect information on current domestic fuel use and whether there was any presence of respiratory symptoms or illness in her or in the children in the household. Our analysis was limited to 547 adult females (ages 18–85) and 845 children (ages 0–17) in households exclusively cooking with either kerosene or LPG. We investigated the associations between kerosene use and the likelihood of having respiratory symptoms or illness using multivariate logistic regression models. Results Among adult women, cooking with kerosene was associated with cough (OR=1.88; 95% CI 1.19 to 2.99), bronchitis (OR=1.54; 95% CI 1.00 to 2.37), phlegm (OR=1.51; 95% CI 0.98 to 2.33) and chest illness (OR=1.61; 95% CI 1.02 to 2.53), relative to cooking with LPG in the multivariate models. Among children, living in a household cooking with kerosene was associated with bronchitis (OR=1.91; 95% CI 1.17 to 3.13), phlegm (OR=2.020; 95% CI 1.29 to 3.74) and chest illness (OR=1.70; 95% CI 0.99 to 2.90) after adjusting for other covariates. We also found associations between kerosene use and wheezing, difficulty breathing and asthma in adults and cough and wheezing in children, though these associations were not statistically significant. Conclusions Women and children in households cooking with kerosene were more likely to have respiratory symptoms and illnesses compared with those in households cooking with LPG. Transitioning from kerosene to LPG for cooking may improve respiratory health among adult women and children in this population.

Infected Cavitating Pulmonary Infarction

The differential diagnosis of pulmonary cavitation is broad. The most common causes include infection and malignancy. Pulmonary thromboembolism is a common problem worldwide, with an estimated 650,000 cases in the United States annually. Pulmonary embolism does not usually lead to cavitation, given

Clinico-epidemiological profile of tobacco users attending a tobacco cessation clinic in a teaching hospital in Bangalore city

Background: Tobacco-attributable mortality in India is estimated to be at least 10%. Tobacco cessation is more likely to avert millions of deaths before 2050 than prevention of tobacco use initiation. Objective: To describe the clinico-epidemiological profile of attendees of a tobacco cessation clinic in a teaching hospital in Bangalore city. Materials and Methods: A descriptive study of 189 attendees seen over 2 years in the Tobacco Cessation Clinic of a tertiary-care teaching hospital in Bangalore, with information on socio demographic characteristics, tobacco-use details, nicotine dependence, family/medical history, past quit attempts, baseline stage-of-change, and treatment initiated. Results: Only 5% were ‘walk-in’ patients; 98% of attendees were smokers; 97% were males. The mean (±SD) age of attendees was 48.0 (±14.0) years. Most participants were married (88%), and predominantly urban (69%). About 62% had completed at least 8 years of schooling. Two-thirds of smokers reported high levels of nicotine dependence (Fagerström score >5/10). About 43% of patients had attempted quitting earlier. Four-fifths (79%) of tobacco-users reported a family member using tobacco. Commonly documented comorbidities included: Chronic respiratory disease (44%), hypertension (23%), diabetes (12%), tuberculosis (9%), myocardial infarction (2%), stroke (1%), sexual dysfunction (1%) and cancer (0.5%). About 52% reported concomitant alcohol use. At baseline, patients’ motivational stage was: Precontemplation (14%), contemplation (48%), preparation/action (37%) and maintenance (1%). Treatment modalities started were: Counseling alone (41%), nicotine replacement therapy alone (NRT) (34%), medication alone (13%), and NRT+medication (12%). Conclusions: This is the first study of the baseline profile of patients attending a tobacco cessation clinic located within a chest medicine department in India. Important determinants of outcome have been captured for follow-up and prospective documentation of outcomes.

Chylothorax in gastric adenocarcinoma: A case report and systematic review of the English literature

Background: Chylothorax is a rare complication of gastric adenocarcinoma and data on its identification, prevalence and outcomes are scant. Objectives: To enable identification of gastric carcinoma as a cause of chylothorax. Methods: A case report and a systematic review were conducted of all reported cases of gastric adenocarcinoma with chylothorax as the presenting complaint in the English literature. Results: Chylothorax is a rare presenting complaint of gastric adenocarcinoma. There are only 18 case reports in the world literature, of which six are in English. Chylothorax occurred variably in gastric adenocarcinoma, either as a presenting feature or as a complication of therapy. Here, we analyze the index case and six patients in whom gastric carcinoma presented with chylothorax as the initial symptom. Respiratory features of cough and dyspnea preempted any abdominal complaint. Bilateral chylothorax (66%) with associated chylous ascites (50%) was common. Four of the six patients had skin lymphedema also as a prominent feature. The chylothoraces have been treated by therapeutic pleurocentesis, intercoastal tube drainage and restriction of oral intake. Gastric adenocarcinoma was associated with high mortality (50%) and morbidity. Conclusions: Chylothorax can be the presenting feature of gastric adenocarcinoma. A thorough search for this life-threatening disease should be done before labeling the chylothorax as idiopathic.

Use of pleural fluid ceruloplasmin in the differentiation of exudative and transudative pleural effusion.

Background: Differentiating into transudate or exudate is the first step in the evaluation of effusions. Light′s criteria is the standard but a significant number of transudates may not be differentiated based on these criteria. Acute phase proteins (APP) are present in plasma, which increase or decrease by about 25% during an acute inflammatory response. Ceruloplasmin (CP) is a positive APP. Hence, this study was done to know the diagnostic value of pleural fluid (pf) CP and pf to serum ceruloplasmin ratio (CPr) to differentiate the pleural effusion (PE) into exudate and transudate as compared to Light′s criteria. Materials and Methods: Setting: Medical wards of St John′s Medical College Hospital, Bangalore. Design: Cross-sectional descriptive study. Patients with PE were divided into exudate and transudate by definitive diagnosis. pfCP, CPr and Light′s criteria were compared with definitive diagnosis for the differentiation of pf into exudate and transudate. Results: The mean value of the pfCP and CPr was found to be significantly different between exudates and transudates. Sensitivity and specificity of pfCP at ≥ 13.34 mg/dl is 89.7% and 83.3%, CPr at ≥ 0.37 is 91.4% and 83.3%, Light′s criteria 94.82% and 83.3%, respectively. Light′s criteria, pfCP and CPr have similar PPV (98%) with Light′s criteria having higher NPV (62.5%) than pfCP (45%) and CPr (50%), respectively. CPr has higher NPV than pfCP. Conclusions: pfCP and CPr can differentiate pf into exudate and transudate with comparable PPV to Light′s criteria.

Recurrent spontaneous pneumomediastinum in a young female: Hamman's crunch revisited(†).

Presence of free air in the mediastinum without any identifiable cause is defined as spontaneous pneumomediastinum (SPM). SPM is more common in young males. The common inciting event leading to SPM are retching, vomiting, acute asthma attack, intense sport activity, inhalation of drugs and weight loss as seen in anorexia nervosa. Analgesics and rest is the mainstay of treatment. Recurrence of SPM is rare. We present a case of recurrent SPM occurring in a young female within few months interval. We also present a brief literature review.