Hematopoietic stem-cell transplantation in a zoo of multidrug-resistant organisms: Data from a cancer center in eastern India.

BACKGROUND: Infections by multidrug-resistant organisms (MDRO) are a major hurdle in hematopoietic stem-cell transplants (HSCTs). Conditioning regimens lead to mucosal barrier injury, which in-turn leads to transmigration of gut bacteria and sepsis. Pre-transplant stool and throat surveillance cultures can guide empirical antibiotic policy during the neutropenic period. In this paper, we document colonization with MDRO in pre-transplant surveillance cultures and the correlation with bloodstream infections in HSCT patients and analyze transplant outcomes with respect to these infections. METHODS: A single-center, retrospective study on HSCT was performed between January 2021 and December 2021. The incidence of bacterial infections, percentage of MDROs, correlation with pre-transplant stool/throat surveillance cultures, and their impact on overall 100-day and post-100-day to 6-month post-transplant survival were analyzed. RESULTS: Sixty-four patients were included in the study. Pre-transplant stool surveillance cultures were positive for MDRO in 85.9% of patients. Almost half (48.5%) of the isolates were positive for carbapenemase-producing genes (mainly New Delhi metallo-beta-lactamase-1 [NDM-1] and oxacillinase-48 [OXA-48]). Eighteen patients (18/64, 28%) had a positive blood culture for MDRO in the peri-engraftment neutropenic period. Correlation between surveillance and blood cultures was seen in 61% (11/18) of patients. All-cause mortality was 14.1% (9/64) and 25% (16/64) in patients at 100 days and 6 months post-HSCT, respectively. The 100-day and post-100-day all-cause mortality rates were higher in patients with Gram-negative MDRO bloodstream infections (p < .012 and <.008, respectively). CONCLUSION: MDRO infections can adversely affect HSCT outcomes. Pre-transplant stool and throat surveillance cultures may guide empirical antibiotic policy and lead to favorable transplant outcomes.

Multi-drug resistant (MDR) and extensively drug-resistant (XDR) bacteraemia rates among cancer patients in an oncology hospital in eastern India: an 11-year retrospective observational study.

Background: Trend analysis of bacteraemias caused by multi-drug resistant (MDR) and extensively drug resistant (XDR) bacteria helps to assess efficacy of infection prevention and control (IPC) practices. Data on the trends of MDR and XDR bacteraemias are lacking from cancer patients in India. Aims: To report antibiotic resistance rates over time in bacteraemias and to assess the effect of IPC practices where patient isolation facilities were limited on the rates and trends of MDR and XDR bacteraemias from a cancer centre in eastern India. Methods: A retrospective observational study was conducted in a specialist cancer hospital in India from 2011 to 2021. The study included both patients with haematological and solid organ malignancy. Data on blood cultures and surveillance culture samples were analysed. Blood cultures were processed using BACT/ALERT® (bioMérieux, Marcy-l'Étoile, France) and the identification and antibiotic susceptibilities of bacteria were performed using VITEK® 2 (bioMérieux, Marcy-l'Étoile, France). Surveillance cultures for MDR/XDR bacteria were performed on a subset of patients and processed based on a modified method described previously. Findings: 3rd-generation cephalosporin-resistant Gram negative bacilli were the commonest cause of MDR bacteraemia (57.6%) followed by carbapenem resistant organisms (CRO) (35.7%). Bacteraemias caused by vancomycin-resistant enterococci (VRE), meticillin-resistant Staphylococcus aureus (MRSA) and colistin-resistant Gram negative bacilli were responsible for 1.3%, 2.3% and 3.0% of laboratory confirmed bloodstream infections (BSI) respectively. The ranges of the rates of MDR/XDR BSI per 1000 in-patients during the study period were: MRSA (1-1.18), VRE (0-0.88), 3rd generation cephalosporin-resistant Gram negative bacilli (10.10-20.32), CRO (5.05-13.07) and colistin-resistant Gram negative bacilli (E. coli, Klebsiella, Pseudomonas aeruginosa, Acinetobacter spp (0-1.3). Surveillance cultures collected from a subset of patients showed ranges of MRSA detection in 0-2.11%, VRE in 1.67%-7.49%, 3rd generation cephalosporin-resistant Gram negative bacilli in 55%-89.91% and carbapenem resistant Gram negative bacilli in 18.33%-31.11% of patients. Conclusion: This is one of few studies providing trend data for MDR/XDR bacteraemia rates among cancer patients in India over a decade. In a high prevalence setting it was possible to keep the rates of MDR/XDR bacteraemia controlled with IPC strategies and without adequate isolation facilities. The results are of potential interest to policy makers, IPC specialists and clinicians.

Molecular epidemiology of SARS-CoV-2 in healthcare workers and identification of viral genomic correlates of transmissibility and vaccine break through infection: A retrospective observational study from a cancer hospital in eastern India.

PURPOSE: Despite COVID vaccination with ChAdOx1 ncov-19 (COVISHIELD®) (ChAdOx1 ncov-19) a large number of healthcare workers (HCWs) were getting infected in wave-2 of the pandemic in a cancer hospital of India. It was important therefore to determine the genotypes responsible for vaccine breakthrough infections. METHODS & OBJECTIVES: Retrospective observational study of HCWs. Whole genome sequencing of SARS CoV-2 using Illumina NovaSeq was done. Mutations from both waves were compared to identify genomic correlates of transmissibility and vaccine breakthrough infections. RESULTS: Vaccine breakthrough infections were seen in 127 HCWs out of 1806 fully vaccinated staff (7.03%). Median number of HCWs infected per day in wave-1 was 0.92 versus 3.25 in wave-2. Majority of wave-1 samples belonged to B.1 and B.1.1 lineage. Variant of concern- Delta variant (90%), and variant of interest- Kappa variant (10%), was seen in only wave-2 samples. Total mutation observed in wave-2 samples (median â€‹= â€‹44) was 1.8 times than wave-1 sample (median â€‹= â€‹24). Spike protein in wave-2 samples had 13 non-synonymous mutation as compared to 8 seen in wave-1 samples. E484Q-vaccine escape mutant was detected in five samples of wave-2; T478K - highly infectious mutation was seen in 31 samples of wave-2. We identified a novelcoding disruptive in-frame deletion (c.467_472delAGTTCA, p. Glu156_Arg158delinsGly) in the Spike protein. This mutation was seen only in wave-2 (78%, n â€‹= â€‹39) samples. CONCLUSION: The circulating virus strains in wave-2 infections demonstrated a greater degree of infectivity. There was a significant change in the genotypes observed in wave-1 and wave-2 infections along with almost twice the number of mutations. We noted that vaccine breakthrough infections (although mostly mild).

Pythiosis in a patient with Acute Myeloid Leukemia: Diagnosis and clinical course.

Pythiosis, caused by Pythium insidiosum (a fungal-like stramenipila, a group of eukaryotes away from the true fungi). Pythium insidiosum causes rare human and animal infections. Transmission from animals to human is yet to be reported. Wet soil and plants near watery environments are the source of infection. We report here a fatal case of human pythiosis in a 9-year old child with acute myeloid leukemia. Organism was identified by DNA sequencing.

An analysis of the standard curve parameters of cytomegalovirus, BK virus and hepatitis B virus quantitative polymerase chain reaction from a clinical virology laboratory in eastern India.

PURPOSE: Quantitative real-time polymerase chain reactions (qPCRs) are important for accurate detection of nucleic acid target including that for viral load determination. Assessment of the quality of a PCR run is essential for quality control, diagnostics and research. In order to reduce subjectivity qPCR standard curves are accompanied with parametric values for slope, Y- intercept, correlation coefficient (R2) and PCR efficiency. In this study the performance of three qPCR assays-cytomegalovirus, hepatitis B virus and BK virus-with respect to standard curve parameters-slope, Y intercept, R2 and efficiency were examined. METHODS: Using ideal values (Slope (minus 3.32); Y intercept â€‹= â€‹the number of PCR cycles; R2 â€‹= â€‹1 and efficiency â€‹= â€‹100%) we estimated the intra-assay variability (range) and deviation from ideal parameters (Δ). We also calculated the standard deviation (SD) and coefficient of variation (CV) for each of these parameters. We have evaluated the quality of each of the three viral load assays (CMV, HBV, BKV) using these statistical approach. RESULTS: We found lab developed tests (CMV) to have least deviation from ideal Y intercept (limit of detection); however, commercial kit based assays had better linearity (scatter plot correlation between amplification factor and PCR efficiency). Using a scatter plot for the three assays we found the correlation with calculated amplification factor and PCR efficiency was most linear in case of BKV (0.9974), closely followed by the HBV assay (R2 â€‹= â€‹0.9968). Although the CMV quantitative standards were least linear (0.868), the CV (coefficient of variation) was also the least in case of the CMV assay. CONCLUSION: The study highlights an objective way of assessing qPCR assay quality and demonstrates a method to compare assays, validate tests and perform quality control.

Importance and results of sterility testing of various products in a microbiology laboratory of eastern India.

Components of blood products from Blood bank, stem cells products from Haemotapoietic Stem Cell Transplant unit, CSSD (Central Sterile Supply Department) items, and pharrrmaceutical products, were sterility tested by liquid culture. 2.91% of the total 3122 samples sent for sterility testing from various departments were positive (i.e. showing contamination). CSSD products showed no contamination (0/37); products from blood bank and bone marrow transplant unit showed a contamination rate of 2.03% (47/2307) and 4.64% (31/667) respectively. The average cost of sterility test was Rs. 302 (INR). Sterility test requires stringent aseptic precautions which is resource intensive.

Impact of COVID-19 on peripheral stem cell collection and preservation at a hematopoietic cell transplant center in India: Experience 2020.

The prevailing corona virus disease 19 (COVID-19) pandemic has adversely affected the healthcare services globally. Hematopoietic cell transplantation (HCT) is considered as the preferred treatment option for several hematological malignancies, and HPC collection facilities have to function continuously along with implementing safety measures. Based on the national and international guidelines, we implemented additional measures and modifications to our standard operating procedure (SOP) to ensure secure HPC collection from patients as well as donors. Here, we report our experience with HPC collection and processing from 1st January, 2020 until 31st December, 2020. We collected 59 HPC products through apheresis and 41 cryopreservation procedures. Compared to 2019, there was a 33% decrease in the number of HPC transplants and 31% reduction in HPC collection procedures. However, we report an 86% (13 procedures) increase in the cryopreservation of HPC products from related donors, as several organizations recommend cryopreservation of HPC products. We report our institutional experience to better understand the impact of COVID-19 on HCT services in a tertiary care center in the developing world. It may also help in being prepared for any future waves of COVID-19 cases.

Arterial blood gas as a prognostic indicator in patients with sepsis.

Abnormal arterial blood gas (ABG) among patients with sepsis is an important prognostic indicator. All-cause mortality was the highest among patients with respiratory acidosis (4/9 = 44.4%), followed by those having metabolic acidosis (3/8 = 37.5%). Median length of hospital and intensive care unit stay was 15.75 days and 6.25 days for those with abnormal ABG and 11 and 3.5 days among those with normal ABG. Median health-care expenditure at the time of discharge or death of the patient was the highest in patients with respiratory acidosis ($14,473) and least in patients with normal ABG ($3,384) (average expenditure among patients with abnormal ABG was [$10,059]).

The importance of intra- and inter-institutional networks for capacity building in severe acute respiratory syndrome coronavirus 2 reverse transcription polymerase chain reaction services: experience from an oncology centre in eastern India.

High-throughput, accurate, cost-effective and rapid testing for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is the need of the hour in face of the global coronavirus disease pandemic. This target is achievable, within a relatively short time through capacity building of reverse transcription polymerase chain reaction (RT-PCR) tests by utilising the strengths of intra and inter institutional networks. These networks act as force multiplier for vital resources which are required for capacity building, namely, leadership, expertise, equipment, space, infection control inputs and human resources. In this article, we report the experience of capacity building for delivery of RT-PCR tests for SARS CoV-2 from a cancer hospital in Eastern India. The relevance, mode of operation and value addition of this essential public health service are discussed in the context of inter departmental collaboration and interaction with other institutes through the existing diagnostic, surveillance and infection control networks. This networking model for service development and delivery could be used by other centres.

Ethics of cancer care: beyond biology and medicine.

Treatable cancers are on the rise due to improved early diagnosis and more innovative treatments, and preventative strategies against cancer are becoming a global concern. With the rapidly increasing complexity of cancer treatment, a clear definition of what constitutes ethical cancer care has become a matter of great debate. This situation is more complex in a developing country where healthcare resources are limited. Doctors, nurses and public health professionals engaged in the prevention, screening, diagnosis, treatment and research of cancers are often posed with ethical dilemmas while making complex choices. With a special focus on low- and middle-income countries, this paper is intended to highlight these real-world ethical concerns facing those involved in the management of cancer patients. While taking a neutral view, this paper has adopted a theme-wise approach to discuss barriers in cancer care.

Epidemiology and clinical outcomes of invasive mould infections in Indian intensive care units (FISF study).

BACKGROUND AND AIM: Due to limited data on invasive mould infections (IMIs) in the intensive care units (ICUs) of developing countries, we ascertain epidemiology and management of IMIs at 11 ICUs across India. METHODS: Consecutive patients with proven or probable/putative IMIs were enrolled during the study period. Subjects were categorized into classical (neutropenia, malignancy, transplant recipients on immunosuppression) and non-classical (chronic obstructive pulmonary disease, diabetes, liver disease and glucocorticoids) risk groups. We analyzed the demographic, laboratory variables and outcomes of these patients. RESULTS: 398 patients with IMIs (96 proven, 302 probable) were identified, amounting to a prevalence of 9.5 cases/1000 ICU admissions. The mean ±â€¯SD age of the participants was 45.6 ±â€¯21.9 years. The mean ±â€¯SD APACHE II score was 14.3 ±â€¯11.4. The IMIs were diagnosed at a median of 4 days after ICU admission. There were 145 and 253 subjects with classical and non-classical risk groups, respectively. Although Aspergillus spp. were the commonest (82.1%) isolates, Mucorales were detected in 14.4% subjects. A high APACHE II score and IMI due to mucormycosis were significant predictors of mortality. CONCLUSIONS: The study highlights the distinct epidemiology of IMIs in India ICUs with high burden, new susceptible patient groups and considerable number of non-Aspergillus mould infections. [clinicaltrials.gov: NCT02683642].

Cytomegalovirus reactivation and disease amongst patients with allogeneic haematopoietic stem cell transplantation in Eastern India: Epidemiology, outcome and healthcare cost.

PURPOSE: Data from developing countries about incidence, prognosis and healthcare cost of cytomegalovirus (CMV) reactivation amongst patients with allogeneic hematopoietic stem cell transplantation (AHSCT) remain scarce. The purpose of the study was to describe the epidemiology, outcome and cost implications of CMV reactivation and CMV disease amongst patients with AHSCT in cancer hospital in Eastern India. MATERIALS AND METHODS: The study design was a retrospective audit of clinical records. RESULTS: Ninety-nine per cent of patients and 94% of the donors were found to be CMV seropositive. CMV reactivation rate was 43.8% amongst patients with AHSCT (n = 130 patients). CMV reactivation occurred 118 days after AHSCT (median; range: 28-943 days). Patients with any grade of graft-versus-host disease (GVHD) had higher CMV reactivation rate than patients without GVHD. Patients with CMV reactivation had more frequent GVHD than patients without CMV reactivation. Use of steroids was associated with CMV reactivation. We found no differences in overall survival of patients with or without CMV reactivation. The cost of in-house CMV-polymerase chain reaction at our centre was USD $57 (Rs. 3650), cost for intravenous ganciclovir was USD $26 (Rs. 1665) per infusion and oral valganciclovir USD $8 (Rs. 512)/900 mg tablet. The median duration of anti-CMV therapy was 14 days (interquartile range: 14-28 days) and the average cost per patient per month directed towards CMV management ranged between USD $800 and USD $1,300 (Rs. 51,238-Rs. 83,264). Three patients (2.3%) in this series had CMV disease, all of whom died. CONCLUSION: In an increasingly globalised world, where medical tourism is common, data from developing countries regarding cost and outcome of CMV infections in AHSCT patients are of relevance.