Melioidosis: Missed opportunities and opportunistic pathogens.

A 31-year Indian homemaker, known to have Systemic Lupus Erythematosus (SLE) and lupus nephritis, was admitted previously in another medical care unit with fever, hemoptysis, arthralgia, and joint swelling. She had been treated with antibiotics and corticosteroids for probable diffuse alveolar hemorrhage (DAH) with clinical and radiological resolution. She was readmitted one month later for similar complaints. Her autoimmune workup revealed evidence of active lupus. Her chest imaging showed the presence of well-circumscribed macronodular lesions with halo sign, but Bronchoalveolar Lavage (BAL) cultures and serum galactomannan were negative. BAL tested positive for hemosiderin-laden macrophages. She was treated with corticosteroids, plasmapheresis, and empiric antibiotics with partial clinical response. One week later, her fever recurred, and she developed new-onset myositis. Bactec blood cultures grew Burkholderia pseudomallei. She received treatment for 3 months with good clinical and radiological resolution. In hindsight, a CT-guided biopsy of the lung lesion may have provided an earlier diagnosis of melioidosis.

Favipiravir: A new and emerging antiviral option in COVID-19.

With over 16 million cases reported from across the globe, the SARS-CoV-2, a mere 125 microns in diameter, has left an indelible impact on our world. With the paucity of new drugs to combat this disease, the medical community is in a race to identify repurposed drugs that may be effective against this novel coronavirus. One of the drugs which has recently garnered much attention, especially in India, is an anti-viral drug originally designed for influenza, called favipiravir. In this article, we have tried to provide a comprehensive, evidence-based review of this drug in the context of the present pandemic to elucidate its role in the management of COVID-19.

Successful Management of Elizabethkingia meningoseptica Meningitis with Intraventricular Vancomycin.

Elizabethkingia meningoseptica, formerly Chryseobacterium meningosepticum usually causes neonatal meningitis and is a rare cause of nosocomial meningitis in adults. E. meningoseptica is resistant to most antibiotics, and the use of inactive drugs as empirical therapy may contribute to poor outcome in many patients. Vancomycin, alone or in combination with rifampicin, has been successful in the treatment of meningitis in infants1. We present a case of E. meningoseptica meningitis in an adult who was treated initially with intravenous vancomycin and oral rifampicin, but did not respond to the treatment. Thereafter, intraventricular vancomycin was added which resulted in good treatment response.

A fatal misidentification: Burkholderia pseudomallei misidentified as Acinetobacter spp.

A middle-aged uncontrolled diabetic with chronic kidney disease presented with high-grade fever, skin abscesses and cough for two weeks. His blood cultures grew Burkholderia pseudomallei. A few weeks prior, blood cultures drawn for PUO workup elsewhere grew an organism identified as Acinetobacter sp with an unusual susceptibility pattern. His fever responded to a short course of meropenem. In retrospect, the earlier blood culture had likely misidentified B.pseudomallei as Acinetobacter sp given the background history, risk factors and the peculiar susceptibility report. Through this case, we discuss important aspects of melioid diagnostics which may be clinically relevant to establish this diagnosis.

Tuberculosis of the Spinal Cord.

Tuberculosis involving the spinal cord is associated with high mortality and disabling long-term sequelae. Although tuberculous radiculomyelitis is the most frequent complication, pleomorphic clinical manifestations exist. Diagnosis can be challenging among patients with isolated spinal cord tuberculosis due to diverse clinical and radiological presentations. The principles of management of tuberculosis of the spinal cord are primarily derived from, and dependent upon, trials on tuberculous meningitis (TBM). Although facilitating mycobacterial killing and controlling host inflammatory response within the nervous system remain the primary objectives, several unique features require attention. The paradoxical worsening is more frequent, often with devastating outcomes. The role of anti-inflammatory agents such as steroids in adhesive tuberculous radiculomyelitis remains unclear. Surgical interventions may benefit a small proportion of patients with spinal cord tuberculosis. Currently, the evidence base in the management of spinal cord tuberculosis is limited to uncontrolled small-scale data. Despite the gargantuan burden of tuberculosis, particularly in lower and middle-income countries, large-scale cohesive data are surprisingly sparse. In this review, we highlight the varied clinical and radiological presentations, performance of various diagnostic modalities, summarize data on the efficacy of treatment options, and propose a way forward to improve outcomes in these patients.

Post covid cerebral phaeohyphomycosis by Rhinocladiella mackenziei: An unusual association.

Cerebral phaeohyphomycosis (CP) is a rare but a highly morbid fungal infection of the central nervous system caused by the fungi belonging to the order Chaetothyriales, which includes Cladophialophora bantiana, Exophiala dermatitidis, Rhinocladiella mackenziei (RM) etc. This disease is associated with poor clinical outcomes, with reported mortality of over 80%. We present the case of a 65-year gentleman who developed CP secondary to RM infection following COVID-19 and the associated challenges in his medical and surgical management.

Ceftazidime-resistant Burkholderia pseudomallei masquerading as isolated atypical neuromelioidosis.

A middle-aged recently diagnosed uncontrolled diabetic from Mumbai, India presented with fever and headache for 8 weeks. Two weeks prior to his symptoms, he travelled to Lonavala during the monsoons and gave history of indoor swimming in a chlorinated pool. Investigations showed isolated neurological involvement with multiple brain abscesses. Abscess cultures grew a non-lactose fermenter. Automated systems failed to identify it. After assessment of his background history and detailed microbiological analysis of the organism, specific investigations were requested which confirmed the suspected diagnosis of melioidosis. We report an unusual presentation of ceftazidime-resistant Burkholderia pseumodmallei as isolated neuromelioidosis with brain abscesses.

Tale of compounding oddities.

We present a case of a 59-year-old man, who on being evaluated for abdominal pain and headache, was found to have a pancreatic head mass and inflammatory hypophysitis. Xpert MTB/Rif of the pancreatic mass biopsy showed the presence of tuberculosis (TB) with a very low load, and rifampicin resistance was detected with absence of probes A and B. Pyrosequencing (a novel genotypic test for TB) of the Xpert MTB/Rif isolate detected a single, rare, high-confidence mutation (S512T) in the rpoB region (rifampicin resistance determining region in the MTB genome). The TB mycobacteria growth indicator tube (TBMGIT) phenotypic drug susceptibility test (DST), however, showed rifampicin susceptibility. Incidentally, he was unable to tolerate rifampicin and responded well to a non-rifampicin-based regimen. We discuss a possible hypothesis of the Xpert-DST discordance in accordance with a recent literature review on phenotypic DST methods. We also discuss the utility of pyrosequencing in clinical practice for the diagnosis of TB and its resistance patterns.

Evaluation of CSF pyrosequencing to diagnose tuberculous meningitis: A retrospective diagnostic accuracy study.

BACKGROUND: We evaluated the performance of pyrosequencing, a genotypic test which detects TB and XDR-defining mutations within 6 h, directly on CSF samples for diagnosing TB meningitis(TBM). METHODS: This retrospective, diagnostic accuracy study was conducted in Hinduja hospital, Mumbai from May-2017 to May-2019. 107 consecutive patients with physician-suspected TBM for whom CSF pyrosequencing was requested were screened. Seven patients with incomplete data were excluded. Diagnostic accuracy of pyrosequencing was compared with Xpert MTB/Rif and TBMGIT (TB Mycobacterial Growth Indicator Tube) culture against the uniform case definition of definite or probable TBM. Susceptibility concordance rate of pyrosequencing with TBMGIT culture and Xpert MTB/Rif was determined. RESULTS: The study cohort comprised of 100 patients[Definite(n = 33), Probable(n = 20), Possible(n = 30), Alternative(n = 17)] with 50% males[median age(years):38(Range:2-87)]. Against the uniform case definition, pyrosequencing had 98·11%(95%CI 89·93-99·95; n = 52/53) sensitivity and 97·79%(86·31-99·67; n = 44/45) negative predictive value(NPV) compared with 43.39%(29·83-57·72; n = 23/53,p < 0.0001) sensitivity and 61.04%(55·31-66·48; n = 47/77) NPV for Xpert MTB/Rif and 45·28%(31·56-59·55; n = 24/53,p < 0.0001) sensitivity and 61·84%(55·92-67·43; n = 47/76) NPV for TBMGIT culture. Susceptibility concordance rate of pyrosequencing with phenotypic Drug Susceptibility Testing was 91.3%(n = 21/23) and with Xpert MTB/Rif was 95·45%(n = 21/22). CONCLUSION: CSF pyrosequencing is significantly more sensitive than Xpert MTB/Rif and TBMGIT culture for diagnosing TBM. Additionally, it facilitates early therapeutic decision-making by providing information on XDR-defining mutations.

Increased frequency of pneumothorax and pneumomediastinum in COVID-19 patients admitted in the ICU: A multicentre study from Mumbai, India.

BACKGROUND: There are limited data regarding the incidence of pneumothorax in COVID-19 patients as well as the impact of the same on patient outcomes. METHODS: A retrospective review of the medical records at three large tertiary care hospitals in Mumbai was performed to identify patients hospitalised with COVID-19 from March 2020 to October 2020. The presence of pneumothorax and/or pneumomediastinum was noted when chest radiographs or CT scans were performed. Demographic and clinical characteristics of patients who developed air leak were recorded. RESULTS: 4,906 patients with COVID-19 were admitted, with 1,324 (27%) having severe COVID-19 disease. The overall incidence of pneumothorax and/or pneumomediastinum in patients with severe disease was 3.2% (42/1,324). Eighteen patients had pneumothorax, 16 had pneumomediastinum and 8 patients had both. Fourteen patients (33.3%) developed this complication breathing spontaneously, 28 patients (66.6%) developed it during mechanical ventilation. Overall mortality in this cohort was 74%, compared with 17% in the COVID-19 patients without pneumothorax (p<0.001). CONCLUSIONS: Our study demonstrates that air leaks occur with a higher frequency in patients with COVID-19 than in other ICU patients. When present, such air leaks contributed to poor outcomes with almost 74% mortality rates in these patients.

Successful treatment of disseminated granulomatous aspergillosis in an apparently immunocompetent host.

A young Indian man presented elsewhere with a short history of haematuria and cough. Investigations revealed renal and pulmonary lesions. Histopathology of these lesions was reported as mucormycosis. He consulted us two months after onset of symptoms, asymptomatic and clinically well, having received no treatment. In view of clinico-histopathological discordance, a review of the biopsy slides was advised but the patient refused further work-up at that time. One week later, however, he was admitted with left hemiparesis. Brain imaging showed an abscess. He underwent surgical excision of the brain abscess and nephrectomy. Review of previous slides showed septate fungal filaments with granulomatous inflammation. Intraoperative cultures grew Aspergillus flavus. He received voriconazole for one year and is well at his two-year follow-up. His immunological work-up was negative for immunodeficiency. This case illustrates that granulomatous aspergillosis may be an indolent infection in apparently normal individuals and reiterates the importance of interpreting diagnostic reports in conjunction with clinical features.