Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus.

BACKGROUND: The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear. METHODS: In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled. The patients were assigned to receive a 7-day course of intravenous doxycycline, azithromycin, or both (combination therapy). The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5. RESULTS: Among 794 patients (median age, 48 years) who were included in the modified intention-to-treat analysis, complications included those that were respiratory (in 62%), hepatic (in 54%), cardiovascular (in 42%), renal (in 30%), and neurologic (in 20%). The use of combination therapy resulted in a lower incidence of the composite primary outcome than the use of doxycycline (33% and 47%, respectively), for a risk difference of -13.3 percentage points (95% confidence interval [CI], -21.6 to -5.1; P = 0.002). The incidence with combination therapy was also lower than that with azithromycin (48%), for a risk difference of -14.8 percentage points (95% CI, -23.1 to -6.5; P<0.001). No significant difference was seen between the azithromycin and doxycycline groups (risk difference, 1.5 percentage points; 95% CI, -7.0 to 10.0; P = 0.73). The results in the per-protocol analysis were similar to those in the primary analysis. Adverse events and 28-day mortality were similar in the three groups. CONCLUSIONS: Combination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for the treatment of severe scrub typhus than monotherapy with either drug alone. (Funded by the India Alliance and Wellcome Trust; INTREST Clinical Trials Registry-India number, CTRI/2018/08/015159.).

Effectiveness of Adjunctive High-Dose Infliximab Therapy to Improve Disability-Free Survival Among Patients With Severe Central Nervous System Tuberculosis: A Matched Retrospective Cohort Study.

BACKGROUND: Few treatment options exist for patients with severe central nervous system (CNS) tuberculosis (TB) worsening due to inflammatory lesions, despite optimal antitubercular therapy (ATT) and steroids. Data regarding the efficacy and safety of infliximab in these patients are sparse. METHODS: We performed a matched retrospective cohort study based on Medical Research Council (MRC) grading system and modified Rankin Scale (mRS) scores comparing 2 groups of adults with CNS TB. Cohort A received at least 1 dose of infliximab after optimal ATT and steroids between March 2019 and July 2022. Cohort B received only ATT and steroids. Disability-free survival (mRS score ≤2) at 6 months was the primary outcome. RESULTS: Baseline MRC grades and mRS scores were similar between the cohorts. Median duration before initiation of infliximab therapy from start of ATT and steroids was 6 (IQR: 3.7-13) months and for neurological deficits was 4 (IQR: 2-6.2) months. Indications for infliximab were symptomatic tuberculomas (20/30; 66.7%), spinal cord involvement with paraparesis (8/30; 26.7%), and optochiasmatic arachnoiditis (3/30; 10%), worsening despite adequate ATT and steroids. Severe disability (5/30 [16.7%] and 21/60 [35%]) and all-cause mortality (2/30 [6.7%] and 13/60 [21.7%]) at 6 months were lower in cohort A versus cohort B, respectively. In the combined study population, only exposure to infliximab was positively associated (aRR: 6.2; 95% CI: 2.18-17.83; P = .001) with disability-free survival at 6 months. There were no clear infliximab-related side effects noted. CONCLUSIONS: Infliximab may be an effective and safe adjunctive strategy among severely disabled patients with CNS TB not improving despite optimal ATT and steroids. Adequately powered phase 3 clinical trials are required to confirm these early findings.

Facilitating Safe Discharge Through Predicting Disease Progression in Moderate Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study to Develop and Validate a Clinical Prediction Model in Resource-Limited Settings.

BACKGROUND: In locations where few people have received coronavirus disease 2019 (COVID-19) vaccines, health systems remain vulnerable to surges in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Tools to identify patients suitable for community-based management are urgently needed. METHODS: We prospectively recruited adults presenting to 2 hospitals in India with moderate symptoms of laboratory-confirmed COVID-19 to develop and validate a clinical prediction model to rule out progression to supplemental oxygen requirement. The primary outcome was defined as any of the following: SpO2 < 94%; respiratory rate > 30 BPM; SpO2/FiO2 < 400; or death. We specified a priori that each model would contain three clinical parameters (age, sex, and SpO2) and 1 of 7 shortlisted biochemical biomarkers measurable using commercially available rapid tests (C-reactive protein [CRP], D-dimer, interleukin 6 [IL-6], neutrophil-to-lymphocyte ratio [NLR], procalcitonin [PCT], soluble triggering receptor expressed on myeloid cell-1 [sTREM-1], or soluble urokinase plasminogen activator receptor [suPAR]), to ensure the models would be suitable for resource-limited settings. We evaluated discrimination, calibration, and clinical utility of the models in a held-out temporal external validation cohort. RESULTS: In total, 426 participants were recruited, of whom 89 (21.0%) met the primary outcome; 257 participants comprised the development cohort, and 166 comprised the validation cohort. The 3 models containing NLR, suPAR, or IL-6 demonstrated promising discrimination (c-statistics: 0.72-0.74) and calibration (calibration slopes: 1.01-1.05) in the validation cohort and provided greater utility than a model containing the clinical parameters alone. CONCLUSIONS: We present 3 clinical prediction models that could help clinicians identify patients with moderate COVID-19 suitable for community-based management. The models are readily implementable and of particular relevance for locations with limited resources.

The role and diagnostic accuracy of serology for COVID-19.

BACKGROUND: The role and performance of various serological tests for the diagnosis of COVID-19 are unclear. This study aimed to evaluate the performance of seven commercially available serological assays for SARS-CoV-2 antibodies by testing COVID-19 cases and controls. METHODS: Adult patients with fever for > 5 days, admitted to a tertiary-care teaching hospital in South India, were enrolled prospectively between June and December 2020. SARS-CoV-2 RT-PCR confirmed patients were classified as cases, and patients with febrile illness with laboratory-confirmed alternative diagnosis and healthy participants were controls. All participants were tested with SCoV-2 Detect™ IgM ELISA kit and SCoV-2 Detect™ IgG ELISA kit (InBios International, Seattle, USA) (Inbios), SARS-CoV-2 Total and SARS-CoV-2 IgG (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) (Siemens), Roche Elecsys® Anti-SARS-CoV-2 (Roche Diagnostics, Rotkreuz, Switzerland) (Roche), Abbott SARS-CoV-2 IgG (Abbott Diagnostics, IL, USA) (Abbott), and Liaison® SARS-CoV-2 S1/S2 IgG (DiaSorinS.p.A., Saluggia, Italy) (Liaison). The sensitivities, specificities, positive predictive values (PPV), negative predictive values (NPV), and accuracies were compared. RESULTS: There were 303 participants: 153 cases and 150 controls. ELISA detecting anti-S protein antibody was more sensitive (88.9% for IgG and 86.3% for IgM) than the CLIAs (82.4% for total antibodies and 76.5-85.6% for IgG). Among CLIAs, Roche IgG was most sensitive (85.6%) followed by Abbott (83%) and Liaison (83%). Abbot had the best PPV (88.8%) and was more specific (89.3%) than Liaison (82%) and Roche (82%). Siemens IgG was less sensitive (76.5%) than Siemens Total (82.4%). The specificity of all the serological assays was modest (75-90%). Antibody test positivity increased with the duration of illness reaching 90% after 10 days of illness. When cases were compared against pre-pandemic controls, the IgG gave excellent specificity (98-100%). For seroprevalence studies, InBios IgG had the best accuracy (90.8%) with 88.9% sensitivity and 97.6% specificity. CONCLUSION: The serological assays are important adjuncts for the diagnosis of COVID-19 in patients with persistent symptoms, especially in the second week of illness. The value of serological diagnostic tests is limited in the first week of illness and they provide additional value in seroprevalence studies. The diagnostic accuracy of the ELISA and CLIA platforms were comparable.

Direct Costs of Healthcare among Patients with Deliberate Self-harm: A Pilot Study from a Tertiary Care Hospital in South India.

Background: Deliberate self-harm (DSH) in developing nations has a significant impact on health and economic conditions of patients and families. Materials and methods: This retrospective study aims to study the cost of hospitalization and the factors affecting the cost of medical care. Adult patients with a diagnosis of DSH were included. Results: A total of 107 patients were included with the most common type of poison consumed being pesticides (35.5%) followed by a tablet overdose (31.8%). There was a male preponderance with a mean (SD) age of 30.04 (9.03) years. The median cost of admission was ₹13,690 (USD 195.57); DSH with pesticide increased the cost of care by 67% as compared to non-pesticides. Other factors which increased the cost were need for intensive care, ventilation, use of vasopressors, and development of ventilator-associated pneumonia (VAP). Conclusions: Pesticide-based poisoning is the most frequent cause of DSH. Among different types of DSH, pesticide poisoning is associated with a higher direct cost of hospitalization. How to cite this article: Barnabas R, Yadav B, Jayakaran J, Gunasekaran K, Johnson J, Pichamuthu K, et al. Direct Costs of Healthcare among Patients with Deliberate Self-harm: A Pilot Study from a Tertiary Care Hospital in South India. Indian J Crit Care Med 2022;26(7):836-838.

Changing trends in the profile of rodenticide poisoning.

Background: Deliberate self-poisoning (DSP) is one of the leading causes of mortality and morbidity, with rodenticides being common compounds used by many victims. However, comprehensive data regarding the spectrum and outcome of rodenticide poisoning is scant. Method: This retrospective study was conducted in the Emergency Department (ED) of a large tertiary care hospital in South India between January 2017 and December 2018. All patients with deliberate consumption of rodenticides were included in the analysis. Results: During the study period, 1802 patients presented with DSP, among which 145 (8%) consumed rodenticide compounds. The mean (SD) age was 27.9 (10.7) years. Young adults (16-30 years) comprised 73% (106/145) of the study population. The majority (87%) were triaged as priority 2, while 10% were triaged as priority 1. Common rodenticide compounds consumed were yellow phosphorous (57%: 82/145), coumarins (12%: 17/145), zinc phosphide (19%: 27/145), and aluminum phosphide (1%: 1/145). A significant proportion of patients (18.6%) were under the influence of alcohol. Among the 73 males, 25 (34.2%) gave a history of co-consumption of alcohol. There was a history of previous DSP attempts in 6%. The majority (68%) of the patients were discharged alive from the hospital, and the in-hospital mortality rate was 9%. Age >30 years (adjusted OR: 2.2; 95% CI: 1.00-5.05; p value: 0.04) was an independent predictor of poor outcome. Conclusion: Rodenticide compound consumption for DSP is prevalent in young adults and is associated with significant mortality, especially with yellow phosphorous poisoning. The current trend in our country of the increasing use of highly fatal phosphorous compounds over the innocuous coumarin derivatives is a cause of grave concern.

Scrub Typhus and Other Rickettsial Infections.

Scrub typhus and other rickettsial infections contribute to 25 - 50% of acute undifferentiated febrile illnesses in endemic regions. Delayed recognition and therapy increase the morbidity and mortality. The constellation of fever with eschar or rash and multisystem involvement should facilitate the diagnosis and initiation of appropriate therapy. The pathological hallmark of rickettsial infections is endothelial infection and inflammation causing vasculitis. Endothelial inflammation results in microvascular dysfunction and increased vascular permeability. Immune and endothelial activation may worsen microvascular dysfunction, predisposing to multi-organ failure. Serology is the mainstay of diagnosis, although false negatives occur early in the disease. Point-of-care rapid diagnostic tests and molecular techniques, such as quantitative polymerase chain reaction (qPCR), can hasten diagnostic processes. Intravenous doxycycline with a loading dose is the most widely used antibiotic in critically ill patients, with azithromycin as a suitable alternative. Early appropriate treatment and organ support can decrease the duration of illness and be life-saving. How to cite this article: Gunasekaran K, Bal D, Varghese GM, et al. Scrub Typhus and Other Rickettsial Infections. Indian J Crit Care Med 2021;25(Suppl 2):S138-S143.

Deliberate Self-poisoning due to Plant Toxins: Verdant Footprints of the Past into the Present.

BACKGROUND: Plant poisoning is one of the common methods of deliberate self-poisoning (DSP). Exposure to plants and its consequence account for a considerable number of deaths in rural India. MATERIALS AND METHODS: This retrospective observational study was conducted in the emergency department of a large tertiary care hospital in South India over a period of 2 years and recruited patients who presented with DSP from plant poisoning. RESULTS: During the study period, 150 cases of plant poisoning were included. The mean (standard deviation) age of presentation was 31.4 (12.2) years. The most common type of plant poison consumed was oleander (63%) followed by oduvanthalai (50%), Strychnos nux-vomica (3%), datura (3%), and others, which comprised about 5.3% included henna (1.3%), cactus (1.3%), and a case each of castor, Gloriosa superba, Adenanthera pavonina, and Abrus precatorius. Patients in age-group 16-30 years had the highest rate of ingestion. The seasonal pattern was found to peak in the month of April. Gastric lavage was done in 102/150:68%. Consumption of decoction [odds ratio (OR): 5, 95% confidence interval (CI): 2.27-14.00, p value: <0.001] and metabolic acidosis (pH <7.35) (OR: 11.48, 95% CI: 4.17-31.57, p value: <0.001) were more common in oduvanthalai poisoning as compared to oleander. The mortality among plant poisoning was 9.3% (14/150). CONCLUSION: Our study sheds light on the spectrum of local plants consumed for DSP. Oleander and oduvanthalai were most commonly used for DSP. Consuming a decoction of leaves leading to severe metabolic acidosis at presentation is seen associated with oduvanthalai poisoning. HOW TO CITE THIS ARTICLE: Abhilash KPP, Murugan S, Rabbi AS, Pradeeptha S, Pradeep R, Gunasekaran K. Deliberate Self-poisoning due to Plant Toxins: Verdant Footprints of the Past into the Present. Indian J Crit Care Med 2021;25(4):392-397.

Clinical Profile and Outcome of Critically Ill Patients with Tuberculosis.

AIM AND OBJECTIVE: Although studies have described the clinical profile of patients admitted to the intensive care unit (ICU) with tuberculosis, it is unclear if the type of tuberculosis (pulmonary, extrapulmonary, or disseminated) impacts outcome. MATRIALS AND METHODS: Demographic data, microbiology, treatment, and outcomes over 5 years (2012-16) were obtained from electronic records. Patients were categorized as pulmonary, extrapulmonary, or disseminated tuberculosis. Comparisons were done using t test and Fisher's exact test as appropriate. Predictors of outcome were explored using bivariate and multivariate logistic regression analysis and expressed as odds ratio (OR) with 95% confidence intervals (CI). RESULTS: Of the 428 ICU admissions with suspected tuberculosis, 212 (121 male) patients with mean (standard deviation) age of 41.9 (16.7) years and APACHE-II score of 20.8 (6.6) were diagnosed as pulmonary (n = 55) and extrapulmonary (n = 52) or disseminated tuberculosis (n = 105). In 50.5%, the diagnosis of tuberculosis was established during the current ICU admission when they presented with organ dysfunction. Overall, microbiological confirmation was possible in 75.5%; 14 (10.3%) isolates were Rifampicin resistant. ICU admission was required primarily for ventilation (n = 176; 83%) and hemodynamic instability (n = 67; 32%). Hospital mortality was 50%. Outcomes were similar in the three groups except for longer duration of stay (p value = 0.04) in disseminated tuberculosis. On multivariate logistic regression analysis, pulmonary tuberculosis (OR 2.83; 95% CI 1.15-6.95) and vasoactive treatment (OR 15.8; 95% CI 6.4-39.2) were independently associated with death; need for ventilation predicted mortality perfectly. CONCLUSION: In this cohort of patients admitted to ICU with tuberculosis, 50% were newly diagnosed during ICU admission. Pulmonary site of involvement and need for organ support are independent risk factors for death. HOW TO CITE THIS ARTICLE: Thomas L, Chacko B, Jupudi S, Mathuram A, George T, Gunasekaran K, et al. Clinical Profile and Outcome of Critically Ill Patients with Tuberculosis. Indian J Crit Care Med 2021;25(1):21-28.

Levonadifloxacin, a recently approved benzoquinolizine fluoroquinolone, exhibits potent in vitro activity against contemporary Staphylococcus aureus isolates and Bengal Bay clone isolates collected from a large Indian tertiary care hospital.

OBJECTIVES: Levonadifloxacin (WCK 771; IV) and its prodrug alalevonadifloxacin (WCK 2349; oral) are benzoquinolizine fluoroquinolones, recently approved in India for the treatment of acute bacterial skin and skin structure infections with concurrent bacteraemia and diabetic foot infections. Ahead of its market launch, the present study aimed to assess the in vitro activity of levonadifloxacin against contemporary Staphylococcus aureus isolates collected from a large tertiary care hospital in India. Additionally, levonadifloxacin activity was tested against hVISA and Bengal Bay clone MRSA isolates. METHODS: Non-duplicate S. aureus (n = 793) isolates collected at Christian Medical College hospital, Vellore, India during 2013-19 were included in the study. MRSA isolates were identified using a cefoxitin disc diffusion assay. MICs of levonadifloxacin and comparator antibiotics were determined using the broth microdilution method. Mutations in QRDRs were identified for selected levofloxacin-non-susceptible isolates. MLST profiling was undertaken to detect the Bengal Bay clone. RESULTS: Among the 793 isolates, 441 (55.6%) were MRSA and 626 (78.9%) were non-susceptible to levofloxacin. Levonadifloxacin showed MIC50 and MIC90 values of 0.25 and 0.5 mg/L, respectively, for all S. aureus, which included hVISA and Bengal Bay clone MRSA. The potency of levonadifloxacin was 16 times superior compared with levofloxacin. CONCLUSIONS: The present study demonstrated potent activity of levonadifloxacin against contemporary S. aureus isolates, which included MRSA isolates, hVISA isolates, Bengal Bay clone isolates and a high proportion of quinolone-non-susceptible isolates. The potent activity of levonadifloxacin observed in this study supports its clinical use for the treatment of S. aureus infections.

MLST based serotype prediction for the accurate identification of non typhoidal Salmonella serovars.

Traditional serotyping based on the phenotypic variation of O- and H-antigen remains as the gold-standard for the identification and classification of Salmonella isolates for last 70 years. Although this classification is a globally recognized nomenclature, huge diversity of Salmonella serotypes have made the serovar identification to be very complex. Seven gene multilocus sequence typing (MLST) on the other hand can provide serovar prediction as well as the evolutionary origin between the serovars. In this study non typhoidal Salmonella (NTS) strains (n = 45) isolated from clinical samples (blood, faeces and pus) were identified by traditional phenotypic serotyping and biochemical testing. All the tested Salmonella isolates were designated as serovar Typhimurium based on phenotyping. However, by MLST 60% (27/45) of the isolates were S. Typhimurium, 35.5% (16/45) were S. Agona (ST13), 2.2% (1/45) were S. Kentucky (ST198) and 2.2% (1/45) were S. Saintpaul (ST27). MLST analysis assigned S. Typhimurium isolates as ST36 (18/127), ST19 (7/27) and ST313 (2/27). Mismatches in serovar designation between MLST database and phenotypic serotyping can be due to the misinterpretation of phenotypic serotyping as the antigenic structures of S. Typhimurium, S. Agona differs by a surface antigen. MLST based phylogeny of study isolates showed clustering according to sequence types. Concordance between MLST based sequence type and phenotypic serotype is important to provide insights into genetic population structure of Salmonella.

Scrub typhus meningitis: An under-recognized cause of aseptic meningitis in India.

BACKGROUND: Central nervous system (CNS) involvement in scrub typhus is seen in up to a quarter of patients. However, the literature on cerebrospinal fluid (CSF) analysis and outcome in meningitis/meningo-encephalitis due to scrub typhus is scant. MATERIALS AND METHODS: This retrospective study included patients who were admitted to a medical college hospital with scrub typhus meningitis/meningo-encephalitis between 2005 and 2011. The clinical and laboratory profile, details of CSF analysis and outcome were documented. RESULTS: The study included 189 patients with meningitis/meningo-encephalitis due to scrub typhus. The mean age of the patients was 41 ± 4 years. The mean duration of fever before presentation was 9.4 ± 3 days. The common presenting complaints were headache (64.2%), nausea/vomiting (60%), altered sensorium (53.7%) and seizures (22.1%). The presence of an eschar was documented in 27.5% of the patients. The mean CSF white blood count was 80 cells/cu mm (range: 5-740). There was a clear lymphocyte predominance (mean 87.6%). The mean CSF protein level was 105 mg% (range: 13-640). The mean CSF sugar level was 63.9 mg% (range 25-350), and was less than 40 mg% in 11.1% of the cases. The case fatality rate was 5.8% (11/189). Univariate analysis showed the presence of an eschar (15.4% vs 2.2%; Odds Ratio [OR]: 8.1) and altered sensorium (9.8% vs 1.1%; OR: 9.2) to be significant predictors of mortality. CONCLUSIONS: In endemic regions, scrub typhus should be considered in the differential diagnosis of aseptic meningitis. Modest elevation of cells in the CSF with lymphocytic pleocytosis and multi-organ involvement may indicate scrub typhus meningitis/meningo-encephalitis.

Genotyping of Orientia tsutsugamushi circulating in and around Vellore (South India) using TSA 56 gene.

PURPOSE: The immunodominant TSA 56 gene of Orientia tsutsugamushi, (scrub typhus agent) has four variable regions (VD-I to VD-IV) making it useful for genotyping. This study was undertaken to determine Orientia tsutsugamushi genotypes circulating in and around Vellore using complete and partial TSA 56 gene. METHODS: Of the 162 patients positive by 47 â€‹kDa qPCR, on 21 samples PCR to amplify the complete TSA 56 gene (≈1605 bp: Long protocol) and the partial gene sequence using the Horinouchi (≈650bp) and the Furuya (≈480 bp) protocol was performed. Sanger and Nanopore sequencing was performed to obtain sequence data for assigning genotype. For 13 amplicons partial and complete gene data was obtained. RESULTS: Phylogenetic analysis of the complete gene (Long protocol) which includes VD-I to VD-IV region and partial gene (Horinouchi) which amplifies the VD-I to VD-III regions showed identical genotypes. Twelve belonged to TA763 genotype and one belongs to Karp genotype. The Furuya sequence (in silico) correctly identified the Karp genotype and 10 of the TA763 genotypes. Two TA763 genotypes (identified by complete and 650 bp partial gene analysis) were misidentified by Furuya sequence analysis as Karp genotype. CONCLUSIONS: Analysis of the 13 complete 56 â€‹kDa gene sequences suggests that TA763 is the commonest genotype in Vellore. Sanger sequencing of the 650 bp fragment gives similar results. However, these results need to be validated by larger prospective multi-centric studies.

Climate influences scrub typhus occurrence in Vellore, Tamil Nadu, India: analysis of a 15-year dataset.

Climate is one of the major factors determining the prevalence and seasonality of vector borne diseases like scrub typhus (ST). We analyzed, the association of the meteorological factors like temperature, rainfall and humidity with scrub typhus using the 15 years scrub typhus data from a tertiary care hospital in Vellore, South India. Demographic data of permanent residents of Vellore, who had IgM ELISA results for scrub typhus for the time period of May 2005 to April 2020 were included. Meteorological data was correlated with the monthly scrub typhus cases; negative binomial regression model was used to predict the relation between scrub typhus occurrence and climate factors. Maximum number of ST cases were reported between the months August and February with October recording the highest number of cases. Elderly people, farmers, agricultural workers and housewives were at higher risk for scrub typhus. For an increase of 1 °C in mean temperature, the monthly ST cases reduced by 18.8% (95% CI - 24.1, - 13.2%). On the contrary, for 1 percent increase in mean relative humidity (RH), there is an increase of 7.6% (95% CI 5.4, 9.9%) of monthly ST cases. Similarly, an increase of 1 mm of rainfall contributed to 0.5 to 0.7% of monthly ST cases (after 2 months) depending on the variables included in the analysis. This study provides information that meteorological factors influence ST occurrence in Vellore. The rise of scrub typhus cases is maximal 2 months post rainfall. Whereas a rise in relative humidity, causes a rise in scrub typhus cases in same month, while rise in temperature has a negative impact on scrub typhus during the same month. These findings based on a retrospective analysis need validation by prospective studies.

Evolutionary Transition of Hypervirulent Klebsiella pneumoniae to multidrug-resistant Hypervirulent Klebsiella pneumoniae: Indian experience.

An emerging pathotype of Klebsiella pneumoniae, initially identified in Southeast Asian countries, has now spread to multiple countries, including India. These convergent strains, carrying both resistance and virulence determinants, are classified as multidrug-resistant Hypervirulent Klebsiella pneumoniae (MDR-HvKp). Since the initial reports, there has been a concerning surge in infections caused by this pathotype globally. In this context, we aim to shed light on the evolutionary changes that have taken place in this relatively novel pathotype. Understanding these changes is crucial for devising diagnosis and targeted intervention strategies to mitigate the spread of MDR-HvKp infections.

Association of antibiotic duration and all-cause mortality in a prospective study of patients with ventilator-associated pneumonia in a tertiary-level critical care unit in Southern India.

OBJECTIVES: To estimate all-cause mortality in ventilator-associated pneumonia (VAP) and determine whether antibiotic duration beyond 8 days is associated with reduction in all-cause mortality in patients admitted with VAP in the intensive care unit. DESIGN: A prospective cohort study of patients diagnosed with VAP based on the National Healthcare Safety Network definition and clinical criteria. SETTING: Single tertiary care hospital in Southern India. PARTICIPANTS: 100 consecutive adult patients diagnosed with VAP were followed up for 28 days postdiagnosis or until discharge. OUTCOME MEASURES: The incidence of mortality at 28 days postdiagnosis was measured. Tests for association and predictors of mortality were determined using χ2 test and multivariate Cox regression analysis. Secondary outcomes included baseline clinical parameters such as age, underlying comorbidities as well as measuring total length of stay, number of ventilator-free days and antibiotic-free days. RESULTS: The overall case fatality rate due to VAP was 46%. There was no statistically significant difference in mortality rates between those receiving shorter antibiotic duration (5-8 days) and those on longer therapy. Among those who survived until day 9, the observed risk difference was 15.1% between both groups, with an HR of 1.057 (95% CI 0.26 to 4.28). In 70.4% of isolates, non-fermenting Gram-negative bacilli were identified, of which the most common pathogen isolated was Acinetobacter baumannii (62%). CONCLUSION: In this hospital-based cohort study, there is insufficient evidence to suggest that prolonging antibiotic duration beyond 8 days in patients with VAP improves survival.

Evaluation of Remdesivir to the outcomes of hospitalized patients with COVID-19 infection in a tertiary-care hospital in southern India.

INTRODUCTION: Remdesivir was the only antiviral used in the treatment of COVID-19 in the first wave of the COVID-19 pandemic, following the adaptive COVID-19 treatment trial-1 interim analysis report. However, its use in moderate to critical hospitalized COVID-19 patients continues to be controversial. METHODOLOGY: In a cohort of 1,531 moderate to critical COVID-19 patients, we retrospectively performed a nested case-control study where 515 patients on Remdesivir were compared to 411 patients with no Remdesivir. Cases and controls were matched for age, sex and severity. The primary outcome was in-hospital mortality and secondary outcomes were duration of hospital stay, need for intensive care unit (ICU), progression to oxygen therapy, progression to non-invasive ventilation, progression to mechanical ventilation, and duration of ventilation. RESULTS: Mean age of the cohort was 57.05 + 13.5 years. 75.92% were males. Overall, in-hospital mortality was 22.46% (n = 208). There was no statistically significant difference in all-cause mortality among cases and controls (20.78% vs. 24.57%, p = 0.17). Progression to non-invasive ventilation was lower in the Remdesivir group (13.6% vs 23.7%, p < 0.001), however progression to mechanical ventilation was higher in the Remdesivir group (11.3% vs 2.7%, p value < 0.001*). In a subgroup analysis of critically ill patients, the use of Remdesivir lowered mortality (OR 0.32 95% CI: 0.13 - 0.75). CONCLUSIONS: Remdesivir did not decrease the in-hospital mortality in moderate to severe COVID-19 but decreased progression to non-invasive ventilation. Its mortality benefit in critically ill patients needs further evaluation. Remdesivir may be useful if given early in the treatment of patients with moderate COVID-19.

A clinico-epidemiological profile, coinfections and outcome of patients with Influenza Like Illnesses (ILI) presenting to the emergency department during the COVID-19 pandemic.

Background: During the COVID-19 pandemic, many patients presented to the emergency department (ED) with features of Influenza-like illnesses (ILI) and with other atypical presentations. This study was done to determine the etiology, co-infections, and clinical profile of patients with ILI. Methods: This prospective observational study included all patients presenting to the ED with fever and/or cough, breathing difficulty, sore throat, myalgia, gastrointestinal complaints (abdominal pain/vomiting/diarrhea), loss of taste and altered sensorium or asymptomatic patients who resided in or travelled from containment zones, or those who had contact with COVID-19 positive patients during the first wave of the pandemic between April and August 2020. Respiratory virus screening was done on a subset of COVID-19 patients to determine co-infection. Results: During the study period, we recruited 1462 patients with ILI and 857 patients with the non-ILI presentation of confirmed COVID-19 infection. The mean age group of our patient population was 51.4 (SD: 14.9) years with a male predominance (n-1593; 68.7%). The average duration of symptoms was 4.1 (SD: 2.9) days. A sub-analysis to determine an alternate viral etiology was done in 293 (16.4%) ILI patients, where 54 (19.4%) patients had COVID 19 and co-infection with other viruses, of which Adenovirus (n-39; 14.0%) was the most common. The most common symptoms in the ILI-COVID-19 positive group (other than fever and/or cough and/or breathing difficulty) were loss of taste (n-385; 26.3%) and diarrhea (n- 123; 8.4%). Respiratory rate (27.5 (SD: 8.1)/minute: p-value < 0.001) and oxygen saturation (92.1% (SD: 11.2) on room air; p-value < 0.001) in the ILI group were statistically significant. Age more than 60 years (adjusted odds ratio (OR): 4.826 (3.348-6.956); p-value: <0.001), sequential organ function assessment score more than or equal to four (adjusted OR: 5.619 (3.526-8.957); p-value: <0.001), and WHO critical severity score (Adjusted OR: 13.812 (9.656-19.756); p-value: <0.001) were independent predictors of mortality. Conclusion: COVID-19 patients were more likely to present with ILI than atypical features. Co-infection with Adenovirus was most common. Age more than 60 years, SOFA score more than or equal to four and WHO critical severity score were independent predictors of mortality.

The economic impact of a COVID-19 illness from the perspective of families seeking care in a private hospital in India.

Background: The Covid-19 pandemic had a tremendous impact that caused significant morbidity, mortality, and financial stress for families. Our study aimed to determine the Out-of-pocket expenses and economic impact of a Covid-19 illness for households where patients were admitted to a private hospital in India. Methodology: This was a cost-of-illness study from a tertiary care academic institute where adult patients diagnosed with COVID-19 from May 2020 to June 2021 were included. Patients with an admission of less than one day or who had any form of insurance were excluded. The clinical and financial details were obtained from the hospital information system and a cross-sectional survey. This was stratified across three clinical severity levels and two epidemiological waves. Results: The final analysis included 4445 patients, with 73 % admitted in Wave 1 and 99 patients interviewed. For patients with severity levels 1, 2 and 3, the median admission days were 7, 8 and 13 days respectively. The total cost of illness (general category) was $934 (₹69,010), $1507 (₹111,403) and $3611 (₹266,930) and the direct medical cost constituted 66%, 77% and 91% of the total cost for each level respectively. Factors associated with higher admission costs were higher age groups, male gender, oxygen use, ICU care, private admission, increased duration of hospital stay and Wave 2. The median annual household income was $3247 (₹240,000) and 36% of families had to rely on more than one financial coping strategies, loans with interest being the commonest one. The lockdown period affected employment and reduced income for a considerable proportion of households. Conclusion: A Covid admission of higher severity was a significant financial burden on families. The study reaffirms the need for collaborative and sustainable health financing systems to protect populations from hardships.$-US Dollar; ₹- Indian Rupees.