Antitubercular therapy causing drug reaction with eosinophilia and systemic symptoms manifesting multi-organ dysfunction syndrome and death in an elderly patient: A case report with review of literature.

We present the case of a drug reaction with eosinophilia and systemic symptoms (DRESS) manifesting multi-organ dysfunction syndrome (MODS) that led to death in an elderly patient during the intensive phase of antitubercular therapy (ATT). A 74-year-old male developed skin rash (morbilliform), patchy erythematous macules, pustular-purpuric nonblanching spots, fever, lymphadenopathy, liver dysfunction, leukocytosis, and eosinophilia during intensive phase of ATT (ATT: day 45). Laboratory tests revealed hypereosinophilia (eosinophils; 10500/µL), hyperacute fulminant hepatic failure (aspartate transaminase/alanine transaminase; 1444/1375 IU/L, total bilirubin; 11.3 mg/dL), hepatic encephalopathy (Child-Pugh score: 15), coagulopathy (international normalized ratio; 3.0 and activated partial thromboplastin time; 52 s), and acute renal failure (serum creatinine; 2.6 mg/dL). The patient was diagnosed with DRESS with a RegiSCAR score of 7 (definite). ATT was discontinued. Despite immediate treatment with pulse methylprednisolone, N-acetylcysteine and sustained low-efficiency dialysis, the patient's clinical condition evolved to shock due to MODS (sequential organ failure Assessment: 15 points), and on day 51, he succumbed. Concluding, an elderly patient with high-dose antitubercular drugs needs a clinical management review. Clinical symptoms pertaining to DRESS may paradoxically worsen after 3-4 days of discontinuation of the offending drug.

Compliance with status epilepticus management protocol and effect on clinical outcomes in children with status epilepticus.

BACKGROUND: Guidelines for the management of status epilepticus (SE) aid in rationalising the treatment for a better clinical outcome; however, published literature regarding the use of antiepileptics and compliance is limited, even after the availability of a consensus guideline. OBJECTIVES: To evaluate the use of antiepileptics in children with SE and to analyse the effect of compliance with the Status Epilepticus Management Protocol on clinical outcomes. METHODS: An open-label non-randomised prospective observational study was conducted in children with SE aged 1 month to 14 years for 8 months in a tertiary care teaching hospital. The recommended antiepileptics, sequence of drug administration and time frames of management offered to paediatric patients were assessed for compliance with the Status Epilepticus Management Protocol adopted in our hospital. Comparison of clinical outcomes (hospital stay, intubation, refractory and super-refractory SE, duration of SE cessation, functional motor deficits and cognitive decline) between compliant and non-compliant patients was assessed. RESULTS: A total of 40 patients were included in the study, of which 28 (70%) were boys. All the patients received midazolam nasal spray in the triage area. Only 18% of the patients received rescue benzodiazepine (BZD) antiepileptic drug (AED) therapy in pre-hospital settings. Median time (p25-p75) of administration of first-line AED (BZD) and second-line AED (non-BZD) was 11 (8-15) min and 30 (22-35) min, respectively. Administration of continuous infusion (IV midazolam) was delayed at 57 (45-69) min. Compliance with the Status Epilepticus Management Protocol was seen in 24 (60%) patients. Non-compliance with the treatment protocol in relation to the time frame significantly prolonged the length of hospital stay (9 vs 4 days, p=0.0008) and SE duration from first assessment (115 vs 50 min; p=0.005). At discharge, the proportion of patients returning to their functional baseline was significantly different in the compliant and non-compliant patient groups (79% vs 44%). There were no deaths. CONCLUSION: Rescue therapy in the pre-hospital setting needs attention. There was full compliance with the Status Epilepticus Management Protocol for choice of AED and sequence of AED therapy. Non-compliance in treatment management within time frames significantly affected the length of hospital stay, duration of SE and clinical outcome.

A Case of Cerebral Toxoplasmosis and Cryptococcosis Preferred Therapy Associated Adverse Drug Reactions in a Patient Newly Co-diagnosed with Acquired Immune Deficiency Syndrome.

PURPOSE: The simultaneous occurrence of cerebral toxoplasmosis and cryptococcosis is rare. The infections continue to be treated with sulfadiazine and amphotericin-B-based regimens (preferred therapy), respectively. Both these drugs are linked to some serious adverse drug reactions (ADRs). We report such a unique instance of both; the CNS co-infections and adverse drug reactions to the preferred therapy. CASE PRESENTATION: A 44-year-old Asian-Indian female was diagnosed with cerebral toxoplasmosis, impending cryptococcal meningoencephalitis, and acquired immune deficiency syndrome (AIDS). The preferred therapy of opportunistic CNS co-infections commenced. Within a week, she had an occurrence of fall in hemoglobin concentrations (11.3 g/dL to 5.6 g/dL; grade IV), reticulocytosis (1% to 3.2%), and indirect hyperbilirubinemia (0.5 mg/dL to 2.8 mg/dL; grade IV) after sulfadiazine administration. The drug was discontinued and the patient was treated with hematocrit transfusions. After amphotericin-B deoxycholate (AmBd) administration, the patient developed hypokalemia (serum potassium; 4.5 mmol/L to 2.7 mmol/L) and increased serum creatinine (1.0 to 2.2 mg/dL; stage-I) levels. Hence, AmBd was discontinued and potassium correction was given. The patient got diagnosed with sulfadiazine induced hemolytic anemia and AmBd induced acute renal failure. He was switched to alternative therapy regimens for the treatment of cerebral toxoplasmosis and cryptococcosis. Radiological investigations were followed up to confirm the clinical outcomes of alternative therapy. Complete recovery from the ADRs and opportunistic infections was observed. CONCLUSION: The preferred therapy regimens for toxoplasmosis and cryptococcosis are accompanied by potential adverse drug reactions, thus continuous monitoring is vital, especially in the initial phases of therapy. Discontinuation of the treatment should be the preliminary intervention in the management. Having said that, alternative therapy regimens had an optimal clinical response in the present case.

Time Elapsed from Onset of Pediatric Convulsive Status Epilepticus to Antiepileptic Administration-An Experience of Single Institute.

Data regarding time elapsed from the onset of pediatric convulsive status epilepticus (CSE) to antiepileptic (AED) administration remains scarce after the adoption of standard treatment-guidelines in Indian healthcare settings. A prospective observational analysis was performed on 52 children presenting to an urban, academic tertiary care teaching hospital diagnosed with CSE and evolving to refractory CSE (RCSE). Time frames of AED administration were compared to the adopted 'Status Epilepticus Management Protocol'. Fifty-two patients [36 (69.2%) male] were enrolled, with a median age of 4.1 y. After CSE onset, the median (p25-p75) time until the administration of the first-line, second-line, and third-line therapy phases of AED doses were 30 (25-37) min, 68 (48-79) min, and 105 (100-135) min, respectively. The second dose of non-BZD AED was administered at a median (p25-p75) of 90 (71-95) min. Twenty-six (50%) patients received at least one continuous infusion. The time elapsed from CSE onset to AED administration and escalation from one class to another was delayed.