Predictors of 28-day mortality in melioidosis patients presenting to an emergency department: a retrospective cohort study from South India.

BACKGROUND: Septic melioidosis is associated with high mortality in resource-limited settings. The current study aims to find 28-d all-cause mortality predictors within 24 h of admission in melioidosis patients presenting to an emergency department. METHODS: This retrospective cohort study (2018-2022) included melioidosis patients divided into two groups based on their primary outcomes (28-d mortality). All the clinically relevant factors significant in univariate analysis were selected for binary logistic regression analysis. Those factors significant in logistic regression analysis were considered independent predictors of mortality. RESULTS: Of the 53 patients with melioidosis, the 28-d mortality of melioidosis patients admitted to the emergency department was 51% (n=27). Respiratory involvement, renal dysfunction, haemodynamic instability, elevated aspartate transaminase, elevated activated partial thromboplastin time, elevated CRP, elevated procalcitonin, decreased albumin, decreased absolute neutrophil count, decreased absolute lymphocyte count and use of piperacillin-tazobactam or azithromycin were significant predictors of mortality on univariate analysis. Vasopressor requirement (p=0.03) and low serum albumin level (0.041) at presentation were independent predictors of mortality. CONCLUSION: Vasopressor requirement and low albumin levels at presentation in the emergency department are independent predictors of mortality. There is a need to create awareness among primary care physicians to enable early diagnosis and prompt initiation of treatment.

Ceftazidime-avibactam and aztreonam combination for Carbapenem-resistant Enterobacterales bloodstream infections with presumed Metallo-ß-lactamase production: a systematic review and meta-analysis.

INTRODUCTION: Carbapenem-resistant Enterobacterales (CRE) due to Metallo-ß-lactamase (MBL) production are treated with either polymyxins or the novel combination of ceftazidime-avibactam and aztreonam (AA). This study aims to evaluate the 30-day mortality of AA in patients with BSI caused by MBL-CRE infections. METHODOLOGY: In this systematic review and meta-analysis, all articles up to June 2023 were screened using search terms like 'CRE', 'MBL', 'AA' and 'polymyxins'. The risk ratio for AA vs polymyxins was pooled using a random-effect model, and the results were represented by a point estimate with a 95% confidence interval. RESULTS: After removing the duplicates, the titles and abstracts of 455 articles were screened, followed by a full-text screening of 50 articles. A total of 24 articles were included for systematic review, and four comparative studies were included in the meta-analysis. All four studies had a moderate or serious risk of bias. The pooled risk ratio for 30-day mortality for AA vs. polymyxins was 0.51 (95%CI: 0.34-0.76), p < 0.001. There was no significant heterogeneity. CONCLUSION: The meta-analysis from studies with a high risk of bias shows that AA is associated with lesser 30-day mortality when compared to polymyxins in patients with MBL-producing CRE BSI. Registration with PROSPERO- CRD42023433608.

Ceftazidime-avibactam alone or in combination with Aztreonam versus Polymyxins in the management of carbapenem-Resistant Klebsiella pneumoniae nosocomial Infections (CAPRI study): a retrospective cohort study from South India.

INTRODUCTION: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections commonly cause hospital-acquired infections. The study aimed to compare the outcomes of CRKP infections between patients receiving ceftazidime avibactam +/- aztreonam and polymyxins in a hospital setting with a high prevalence of New Delhi Metallo Beta Lactamase production. METHODS: We conducted a retrospective cohort study from January 2020 to September 2022 in critically ill adult patients admitted to a non-COVID-19 medical intensive care unit with CRKP infection. The patients were followed up for a total of 30 days or death, whichever was later. RESULTS: Of a total of 106 patients included in the study, 65 patients received polymyxins and 41 patients received ceftazidime-avibactam +/- aztreonam. Higher 30-day mortality was noted in the polymyxin group (56.9% vs. 29.2%, P = 0.005). The mean time to event (mortality) in ceftazidime-avibactam +/- aztreonam was 23.9 + 1.5 days which was significantly higher compared to polymyxins (17.9 + 1.2 days, p = 0.006). On Cox regression analysis, after adjusting for the covariates, the hazard ratio for time to event with the use of polymyxin was 2.02 (95% CI: 1.03-3.9). CONCLUSION: Ceftazidime-avibactam + aztreonam is possibly associated with better clinical outcomes in patients infected with CRKP.

Successful Use of Cefepime-Zidebactam (WCK 5222) as a Salvage Therapy for the Treatment of Disseminated Extensively Drug-Resistant New Delhi Metallo-ß-Lactamase-Producing Pseudomonas aeruginosa Infection in an Adult Patient with Acute T-Cell Leukemia.

With limited and often toxic treatment options, carbapenem-resistant Gram-negative infections are associated with significant mortality. Cefepime-zidebactam is a promising antibiotic option undergoing a phase 3 trial that has activity against diverse antibiotic-resistant mechanisms in Gram-negative pathogens due to its ß-lactam enhancer mechanism, mediating multiple PBP binding. We report a case of disseminated infection caused by a New Delhi metallo-ß-lactamase-producing, extensively drug-resistant Pseudomonas aeruginosa isolate in a patient with acute T-cell leukemia, successfully managed with cefepime-zidebactam as a salvage therapy.

Reversal of uniocular blindness with corticosteroids in a solid organ transplant recipient with cryptococcal meningitis and immune reconstitution syndrome (IRIS): A case report.

Cryptococcal meningitis is a life-threatening infection commonly seen in patients with advanced HIV infection and solid organ transplant recipients. We report a case of cryptococcal meningitis with immune reconstitution syndrome (IRIS) who presented to us with a headache and complete loss of vision in the left eye. He was managed with antifungals and a short course of steroids, and he regained vision completely. In the hospital, he developed complications including tacrolimus toxicity, fluconazole-induced QT prolongation, and flucytosine-induced thrombocytopenia. Our case demonstrates the importance of a multidisciplinary approach in the management of complex cases like cryptococcal meningitis in solid organ transplant recipients.

Mitochondrial toxicity induced by linezolid causing lactic acidosis.

Linezolid-induced lactic acidosis is a rare, but life-threatening complication of a commonly used drug. Patients present with persistent lactic acidosis, hypoglycaemia, high central venous oxygen saturation and shock. Linezolid causes mitochondrial toxicity due to impaired oxidative phosphorylation. This is evidenced by cytoplasmic vacuolations in the myeloid and erythroid precursors of bone marrow smear as illustrated in our case. Discontinuation of the drug, administration of thiamine and haemodialysis reduces lactic acid levels.

Disseminated Medicopsis romeroi infection in a kidney transplant recipient: A case report.

Medicopsis romeroi is a rare, dematiaceous fungus that is difficult to identify using conventional fungal tests. Although uncommon, immunocompromised patients are particularly susceptible to this opportunistic fungus. Here, we report the case of a renal transplant recipient who presented with painful disseminated subcutaneous and soft tissue lesions. Sequencing of the Internal transcribed spacer (ITS) region of the ribosomal DNA identified the fungus as Medicopsis romeroi. Additionally, tissue samples from a non-healing wound on the left forearm grew Rhizopus spp. on Sabouraud dextrose agar, indicating a Mucormycosis superinfection. The patient's condition improved with surgical intervention and antifungal therapy with Posaconazole and Terbinafine. This case demonstrates the need for a high index of suspicion in order to facilitate early diagnosis and treatment and thus reduce the risk of dissemination.

Progressive multifocal leukoencephalopathy in a patient with systemic lupus erythematosus and autoimmune hepatitis.

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating central nervous system illness encountered in the setting of immunosuppressive conditions like human immunodeficiency virus / acquired immunodeficiency syndrome, autoimmune diseases and hematologic malignancies. We had a 54-year-old woman with systemic lupus erythematosus and coexisting autoimmune hepatitis who presented with progressive cognitive decline, right hemiparesis and ataxia who was found to have PML. She had severe CD4 lymphopenia. She was managed with low-dose prednisolone and plasma exchange after which she showed significant clinical improvement. This case highlights the diagnostic and therapeutic challenges encountered in managing a case of PML in the setting of autoimmune conditions with profound lymphopenia.

Hydroxychloroquine pre-exposure prophylaxis for COVID-19 among healthcare workers: Initial experience from India.

Background: Hydroxychloroquine (HCQ) had generated considerable interest for coronavirus disease 2019 (COVID-19) prophylaxis. We conducted a prospective observational study at a tertiary care hospital in India, with dedicated COVID-19 care facilities. Objectives: Primary objective was incidence of adverse effects, secondary objective being efficacy in preventing COVID-19. Methods: Healthcare workers were recruited and grouped based on voluntary HCQ prophylaxis as per national guidelines. Side effects in HCQ group were graded in accordance with national cancer institute-common terminology criteria for adverse events (NCI-CTCAE) version 5.0. At 3-7-week follow-up, groups were compared for COVID-19 exposure, symptoms development and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR results. Results: Among 358 participants recruited, 216 (60.3%) were males and mean age was 31.2 ± 6.6 years. Chemoprophylaxis was initiated by 258 (72%) participants. After loading dose, 7 (2.7%) reported grade 2 and 1 (0.4%) grade 3 adverse effects. Discontinuation of HCQ due to side effects was reported in 11 (4.3%) participants. Electrocardiogram was done by 50 (19.4%) participants on HCQ; no abnormalities were noted. A total of 106 (41%) among those taking and 63 (63%) among those not taking HCQ were tested for SARS-CoV-2 due to influenza-like illness or significant exposure. Among all participants, 25 (6.9%, 95% confidence interval [CI] 4.3-9.6) developed COVID-19 during the study period. In the group taking HCQ, 10 (3.9%) tested positive compared to 15 (15%) in the group not taking HCQ (P < 0.001). Odds ratio with HCQ intake was 0.34 (95% CI 0.13-0.83, P = 0.01) and the number needed to treat was 12. Conclusion: HCQ is safe at the recommended dose for pre-exposure prophylaxis of COVID-19.

CNS cryptococcosis presenting with cerebellar stroke and spinal arachnoiditis.

A 67-year-old man presented with a low-grade fever for 2 months, weakness of all four limbs for five days and altered sensorium for two days. He was recently diagnosed with AIDS and was treatment-naive. Investigations revealed a CD4 count of 27cells/mm3 MRI brain and spine exhibited bilateral cerebellar lesions with diffusion restriction, and severe arachnoiditis at the level of the lumbar spine. High suspicion of central nervous system tuberculosis in an endemic country like ours, led us to start antitubercular therapy and steroids. Repeated lumbar punctures resulted in a dry tap leading to a delay in diagnosis. Serum cryptococcal antigen detection came positive, following which antifungal treatment was initiated. Later a small amount of cerebrospinal fluid sample was obtained which confirmed the diagnosis of cryptococcosis. However, the patient worsened and succumbed to the illness. This case highlighted the rare presentation of cryptococcal cerebellar stroke and spinal arachnoiditis.

The conundrum of Thiamine Responsive Acute Pulmonary Hypertension (TRAPH) syndrome in the Emergency Department.

BACKGROUND: Management of acute pulmonary hypertension in the Emergency Department(ED) can be challenging. The treatment is specialised, requires rapid identification and correction of the precipitating cause; failing which the patient enters a vortex of deterioration. We describe a lesser-known cause for the same, Thiamine responsive acute pulmonary hypertension (TRAPH) syndrome where timely appropriate treatment can result in dramatic improvement. METHODOLOGY: Medical records with ICD code E51.12 (Wet Beriberi) from Mar 2018 to Mar 2020 were screened. The data regarding presenting symptoms, initial vitals, lab and radiological investigations, and treatment received were retrieved from patient files and the Hospital Informatics System, entered into an MS Excel sheet and compared. RESULTS: The study includes eight cases, which we believe to be TRAPH syndrome. Majority were young adult males, ethanol users. All patients presented with acute shortness of breath with tachypnea and shock index more than 0.9. Gross right atrioventricular dilatation, tricuspid regurgitation and mild to moderate pulmonary arterial hypertension was identified in echocardiography. The initial blood gas revealed median pH 6.98 (IQR 6.81-7.09), Bicarbonate 3.4 meq/L (IQR 2.5-5) and lactate 172 mg/dL (IQR 132-200) which improved within 12-16 h of admission. Patients received median 400 mg IV Thiamine. The mean duration of ICU stay was 2.5 days and total hospital stay was 7 days. CONCLUSION: Thiamine Responsive Acute Pulmonary Hypertension (TRAPH) Syndrome is an under-recognised entity which should be included in differentials for acute right ventricular dysfunction in the ED. Early diagnosis and rapid protocolised management of the same can cause quick recovery of patients.

Role of Voriconazole in the Management of Invasive Central Nervous System Aspergillosis: A Case Series from a Tertiary Care Centre in India.

Invasive central nervous system (CNS) aspergillosis is acquired by either hematogenous dissemination or direct spread from a sinus infection. We describe a series of nine patients with CNS aspergillosis from a tertiary care teaching institute in North India who were treated with voriconazole alone or in combination with surgery. All patients who had clinical and radiological features consistent with fungal CNS infection, showed the presence of septate hyphae on histopathology/microscopy and were either culture positive for Aspergillus spp. or had serum galactomannan positivity were diagnosed as CNS aspergillosis. Clinical features, risk factors, diagnostic modalities, treatment details and outcome at last follow-up were recorded for all patients diagnosed with CNS aspergillosis. A total of nine patients were diagnosed with CNS aspergillosis. The median duration of presentation at our hospital was six months (IQR-2-9 months). Six patients had concomitant sinus involvement, while two patients had skull-base involvement as well. All patients were treated with voriconazole therapy, and three of these patients underwent surgery. All but one patient survived at the last follow-up (median duration was 14 months (IQR- 8-21.5). Two patients had complete resolution, and voriconazole was stopped at the last follow-up, and the rest of the patients were continued on voriconazole. Of the six patients who were continued on voriconazole, all but one had more than 50% radiological resolution on follow-up imaging. Invasive CNS aspergillosis is an important cause of CNS fungal infection that is often diagnosed late and requires long-term voriconazole-based therapy.