Negative Sepsis Research Articles

Diagnosing sepsis in the ICU: Comparison of a gene expression signature to pre-existing biomarkers

PurposeWe aimed to identify a gene signature that discriminates between sepsis and aseptic inflammation in patients administered antibiotics in the intensive care unit and compare it to commonly utilised sepsis biomarkers. Methods91 patients commenced on antibiotics were retrospectively diagnosed as having: (i) blood culture positive sepsis; (ii) blood culture negative sepsis; or (iii) aseptic inflammation. Bloods were collected after <24 h of antibiotic commencement for both gene expression sequencing analysis and measurement of previously identified biomarkers. Results53 differentially expressed genes were identified that accurately discriminated between blood culture positive sepsis and aseptic inflammation in a cohort of patients given antibiotics [aROC 0.97 (95% CI, 0.95–0.99)]. This gene signature was validated in a publicly available database. The gene signature outperformed previously identified sepsis biomarkers including C-reactive protein [aROC 0.72 (95% CI, 0.57–0.87)], NT-Pro B-type Natriuretic Peptide [aROC 0.84 (95% CI, 0.73–0.96)], and Septicyte™ LAB [aROC 0.8 (95% CI, 0.68–0.93)], but was comparable to Procalcitonin [aROC 0.96 (95% CI, 0.9–1)]. ConclusionsA gene expression signature was identified that accurately discriminates between sepsis and aseptic inflammation in patients given antibiotics in the intensive care unit.

439 - Comparison of characteristics and clinical outcomes in short (

439 - Comparison of characteristics and clinical outcomes in short (<72 hours) vs. prolonged (≥72 hours) antibiotic treatment in culture negative sepsis in very low birth weight neonates

The clinical differentiation of blood culture-positive and -negative sepsis in burn patients: a retrospective cohort study.

Sepsis is a potentially life-threatening condition that occurs when the body's response to infection leads to widespread inflammation and tissue damage. Negative cultures can make it difficult for clinicians to make a diagnosis and may raise questions about the validity of the definition of sepsis. In addition, the clinical distinctions between burn patients with blood culture-positive and -negative sepsis are also poorly understood. Therefore, this study aimed to examine the clinical differences between blood culture-positive and -negative sepsis in burn patients in order to improve the understanding of the pathophysiology and epidemiology of sepsis in this population. This study had a retrospective design, and the participants were adults aged ≥18 years. Patients diagnosed with sepsis were divided into two groups based on their blood culture results within 1 week of sepsis diagnosis. We enrolled 1643 patients admitted to our institution's burn intensive care unit between January 2010 and December 2021. pH, platelet count, bicarbonate and haematocrit were significant in both the positive and negative groups. However, lymphocyte, red cell distribution widthand blood urea nitrogen were significant only in the positive group, whereas lactate dehydrogenase was significant only in the negative group. Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumonia are common gram-negative bacterial species, and Staphylococcus aureus and Staphylococcus epidermidis are common gram-positive bacterial species seen in burn patients with positive blood cultures. Carbapenem resistance was found to be associated with an unfavourable prognosis in gram-negative bacteria, with the exception of P. aeruginosa. pH, platelet count, bicarbonate and haematocrit were routine biomarkers that demonstrated statistical significance in both groups. Lactate dehydrogenase was significant in the blood-negative group, while red cell distribution width, blood urea nitrogenand lymphocyte count were significant in the positive group. Furthermore, the most common causes of sepsis are gram-negative bacteria, including A. baumannii, K. pneumoniae and P. aeruginosa. Additionally, resistance to carbapenems is associated with unfavourable outcomes.

Gram-negative Late Onset Neonatal Sepsis in a Tertiary Care Center From Central India: A Retrospective Analysis.

Neonatal sepsis has been a major cause of neonatal mortality and morbidity globally. Late onset sepsis is on the rise mostly due to better health care services and improved survival of premature neonates. Gram-negative sepsis has emerged as a major public health problem constituting significant morbidity and mortality. There is limited data on gram-negative late onset sepsis from the central part of India, therefore this study was conducted at a tertiary care center from rural part of India. To determine the clinical profile and outcome among neonates with gram-negative late onset sepsis. It is a retrospective analysis conducted among neonates with gram-negative late onset sepsis at a tertiary care center from central India. All neonates below 28 days of age suspected to have late onset sepsis were enrolled in the study. The data for the period of January 2019 to December 2021 was collected and analyzed using software SPSS version 29. The outcome variables studied were discharge (good outcome) and death (poor outcome). In the present study, overall prevalence of gram-negative late onset sepsis was 4.8%. Respiratory distress (52.2%), seizure (18.9%), jaundice (15.6%), and lethargy (15.6%) were common clinical symptoms among neonates with sepsis. The most common organism isolated was Klebsiella spp. (36.7%) followed by Acinetobacter spp. (31.1%) and E. coli (17.8%). Low gestational age (n = 20 vs n = 7, P = .002) and low birth weight (n = 33 vs n = 4, P = .02) were associated with poor outcomes in neonates with gram negative LOS. The overall mortality rate was found to be 30% among neonates with gram negative sepsis. The prevalence of gram-negative sepsis was found to be 4.8%. Factors associated with poor outcome in gram-negative sepsis were low birth weight, and prematurity. Klebsiella spp. was found to be a common cause of gram-negative LOS, therefore, the empiric antibiotic policy must provide coverage against these micro-organisms.

Biofilm Formation and its Association with Gram Negative Sepsis Pathogenicity

Background and objectives: Biofilm formation is an important virulence factor that protects an organism from antimicrobial agents as well as host immune effectors, thus allowing organisms to invade, survive, and cause persistent-reoccurring infection in host cells. The aim of this study was to investigate the ability of sepsis-causing gram-negative bacteria to form biofilms, evaluate the association between antibiotic resistance pattern and biofilm formation, determine the role and influence of biofilm formation on pathogenicity and clinical outcome of sepsis. Methods: A prospective study conducted from October 2020 to August 2021, non-replicated gram-negative bacteria isolates were recovered from blood samples of patients with suspected bacteremia, sepsis, and sepsis shock and identified using biochemical procedures. Antimicrobial susceptibility patterns of GNB isolates were determined using the Kirby-Bauer disc diffusion method and interpreted using CLSI guidelines. The ability of GNB isolates to form biofilm was assessed using Congo red agar and the tissue culture plate method. Results: Of the 160 Gram-negative bacteria tested, biofilm formation was seen in 73 (45.63%) isolates. Isolates are Klebsiella pneumoniae (39.73%), Acinetobacter spp. (34.25%), Escherichia coli (23.29%), Pseudomonas aeruginosa (1.37%), and other non-fermenters (1.37%). Isolates were highly resistant to cephalosporins, fluoroquinolones, and the penicillin group of antibiotics. No statistical relationship was found between resistance pattern, clinical outcome, and biofilm formation. Conclusion: In the current study, we found that 45.63% of gram-negative bacteria causing sepsis were biofilm producers. Klebsiella pneumonia isolates exhibited the highest levels of biofilm formation and antimicrobial resistance. Based on the strength of biofilm formation, most isolates were weak biofilm producers, and there was no statistical correlation between the formation of biofilms and antimicrobial resistance, indicating that the formation of biofilms was not a determining factor for resistance.

324. Detection of Antibiotic Resistance Genes and Associated Genera Direct from Blood Samples by Multiplex PCR and Next Generation Sequencing

Abstract Background While blood culture and genotypic or phenotypic testing is standard procedure for identification of sepsis pathogens and resistance, blood culture negative sepsis occurs in 40-60% of patients. A culture independent diagnostic can identify pathogens that do not grow in culture and may provide a more sensitive indicator to blood stream infections. Here we discuss an assay that combines multiplex PCR with next generation sequencing (NGS) to detect resistance genes and pathogenic genera directly from whole blood. These genes include mecA, mecC, vanA, vanB, blaKPC, blaOXA-48 family, blaNDM, blaVIM, blaIMP, blaCMY-2, blaDHA, and blaCTX-M-14 and blaCTX-M-15 groups. Methods K2EDTA whole blood samples were spiked with low titers of antimicrobial resistant bacterial isolates. Sample processing involved chemical lysis of red blood cells, concentration and mechanical lysis of pathogen cells, and multiplex amplification of resistance genes and 16S rRNA gene. A synthetic DNA oligo was added at a fixed concentration as a read control. Samples were sequenced on Illumina platforms. NGS data was analyzed using a bioinformatics pipeline to process and match sequences to curated databases with BLAST. The number of reads per sequence was normalized by the number of reads for the read control, resulting in a read-control-normalized (RCN) value that could be used to establish positivity cutoffs. Results Resistance genes in bacterial pathogen spiked samples were identified at titers ≤ 10 CFU/mL. Owing to a unique dual indexing strategy, cross-reactivity was absent or low enough that cutoffs could be set using RCN values without reducing sensitivity. The expected genus was also detected at ≤ 10 CFU/mL for all samples; however, genera that may be representative of reagent or environmental contamination were observed at levels higher than a universal RCN cutoff in some samples. Conclusion We have shown that this NGS assay can detect 13 antimicrobial resistance genes with high sensitivity and specificity direct from blood. Bacterial genera associated with these genes were detected by this assay. As there is a risk of detection of contaminating species with a 16S target, further research into low DNA reagents or environmental controls may be required. Disclosures Daniel Gamero, BS, T2 Biosystems, inc: WO2018213641A8, EP3861013A1, WO2020055887A1, WO2020252084A1, WO2020257691A1|T2 Biosystems, inc: Stocks/Bonds Kelly Dabrowski, M.S., T2 Biosystems, Inc: Stocks/Bonds Analisa DeVito, B.S., T2 Biosystems, Inc: Stocks/Bonds Roger Smith, Ph.D., T2 Biosystems, Inc: US20180188195A1, EP3849938A1,WO2020257691A1, WO2020252084A1|T2 Biosystems, Inc: Stocks/Bonds Jessica L. Snyder, Ph.D., T2 Biosystems, Inc: CA3062882A1,US20180171388A1,WO2017180745A1 , EP3861013A1 , AU2020296183A1, WO2020055887A1, WO2020252084A1|T2 Biosystems, Inc: Stocks/Bonds.

Results from a Phase 1/2 Study of Tandem, Bispecific Anti-CD20/Anti-CD19 (LV20.19) CAR T-Cells for Mantle Cell Lymphoma

Introduction: Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy with variable clinical course. The disease is characterized by presence of t(11;14) and bright CD20 expression. While frontline immunochemotherapy plus autologous hematopoietic cell transplant (HCT) has improved progression-free survival, invariably MCL patients (pts) relapse. Approved CD19 CAR T-cell therapy for relapsed/refractory (R/R) MCL provides durable disease control but is limited by high rates of Grade 3+ cytokine release syndrome (CRS) and neurological events with 15% and 31% of pts experiencing such toxicities. We hypothesized that bispecific, tandem, lentiviral CAR-T cell targeting both CD20 and CD19 B-cell antigens (LV20.19 CAR) with 4-1BB co-stimulatory signaling will improve clinical outcomes in R/R MCL and that expansion in IL7 and IL15 would produce less "exhausted” CAR product with more durable clinical activity. Methods: We conducted a Phase 1/2 single center, prospective trial (NCT04186520) evaluating LV20.19 CAR T-cells at a fixed dose of 2.5x10e6 cells/kg for pts with R/R B-cell non-Hodgkin Lymphoma. We report below outcomes from a Phase 1/2 cohort of MCL pts. LV20.19 CAR T-cells were manufactured onsite in the CliniMACS Prodigy device with IL7+15 for cell expansion with goal of fresh infusion at varying lengths of manufacturing (8 vs 12 days). After safety run-in, we opened a 14 patient single stage Phase II arm with flexible 8/12-day manufacturing with fresh infusion for MCL pts. Descriptive statistics were utilized for baseline characteristics and survival analyses were calculated utilizing the Kaplan-Meier method and differences between groups were evaluated via log-rank test. Results: To date, 10 MCL pts have received LV20.19 CAR T-cells at the specified dose of 2.5x10e6 cells/kg (Phase 1=3 pts and Phase 2=7 pts). 8 of 10 pts received 8-day manufactured CAR-T cells whereas two pts received a 12-day product in the Phase 1 cohort. Manufacturing was successful in 100% of pts and all received a fresh (non-cryopreserved) product. Median age was 62 years and median prior lines of therapy were 4 (range: 3-8). Three pts progressed after prior autologous HCT and 2 pts progressed after prior allogeneic HCT. Eight of 10 pts had progressed on a Bruton's Tyrosine Kinase inhibitor (BTKi) and 4 of these pts had additionally progressed on a non-covalent BTKi (pirtorbrutinib) administered on a clinical trial (Table 1). LV20.19 CAR T-cells produced in the CliniMACS Prodigy with IL-7/IL-15 had robust expansion with mean 5.4x10e8 CAR T-cells obtained on Day 7 of manufacturing. CAR T-cells from pts mostly consisted of central-memory and effector-memory phenotype T-cells with robust in-vivo expansion typically starting Day +4 after infusion. The Day 28 ORR was 100% (CR=60% and PR=40%). 7 of 9 pts with MRD assessed between Day 28-60 post CAR were negative. No patient has relapsed with a median follow-up of 18 months of among surviving pts. Regarding toxicity, all 10 pts (100%) had Grade 1-2 CRS (no grade 3+ events). Immune effector cell associated neurotoxicity syndrome (ICANS) occurred in 2 pts with one patient experiencing Grade 2 and the other Grade 3 toxicity. The patient with Grade 3 ICANS experienced a non-relapse mortality event due to gram negative sepsis after Day 28 evaluation. At 1-year the cumulative incidence of relapse and NRM were 0% and 10%, respectively while the 1-year PFS and OS were 90% each (Figure 1). Conclusions: Bispecific LV20.19 CAR T-cells expanded with IL7+15 are safe and efficacious for R/R MCL with ORR 100%, no relapses with a median follow-up of >1.5 years, and no Grade 3+ CRS and low rates of Grade 3+ ICANS (10%). All pts on the Phase II arm had CAR T-cells manufactured on-site utilizing an 8-day platform with fresh CAR T-cell infusion and lymphodepletion starting during manufacturing. Dual targeting of CD19 and CD20 with CAR-T cells may improve outcomes in pts with relapsed, refractory MCL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Low Dose Ruxolitinib in Indian Haplo-Identical Transplant Patients with Steroid Refractory Acute Graft Versus Host Disease

Background: The number of allogeneic bone marrow transplants done in India is increasing by year. Unlike west, this region had got its own unique complications in the post-transplant period especially multi drug resistant gram negative bacterial sepsis reflecting in a higher transplant related mortality. With increasing number of Haplo-identical transplants, the problem of steroid refractory Graft versus host disease (GVHD) is a major reason for post-transplant morbidity and mortality. As most available immunosuppressive agents worsen cytopenia and in turn sepsis, we need a relatively safer method of managing steroid refractory GVHD in our setting. In this observational study, we used a lower dose of 5mg per day Ruxolitinib for a period of minimum 60 days post-transplant to look into clinical benefit. This dose was chosen considering the recovering platelet count and financial considerations in our resource limited setting. Method: This observational study was conducted from July 2019 to January 2022. A total of 11 steroid refractory GVHD Haploidentical transplant patients were chosen for data analysis that completed the scheduled dosage regimen of Ruxolitinib. Nine out of 11 patients were Acute Myeloid leukemia and two were Acute Lymphoblastic leukemia. The standard conditioning regimen in all was Fludarabine / Busulfan & Cyclophosphamide based conditioning. Additional GVHD medications used were PTCy, Tacrolimus, MMF and steroids with oral budesonide. Tab Ruxolitinib was started around Day +5 post steroids in people who were fitting into steroid refractory acyte GVHD at a fixed dose of 5mg OD for a minimum period of ten weeks. Two cases had one week dose interruption due to cytopenia. Results : At start of Ruxolitinib seven patients had Grade III gut and liver GVHD and rest four had grade II GVHD. Skin was grade II in all patients. When evaluated at Day +58 of Ruxolitinib, all patients were alive and nine of them were on tapering doses of steroids. All continued Tacrolimus at therapeutic doses. No excess bleeding or cytopenia requiring transfusion support happened during this period. As mentioned earlier two cases Ruxolitinib was stopped in view of platelet counts going below 20,000. On evaluation at day +100 post transplant, two patients continued to have grade II Liver, gut and skin GVH and one patient expired on day +48 to sepsis. Rest of eight patients had a Grade I skin, liver and gut GVHD and were able to continue Ruxolitinib further. We started Ruxolitinib taper in cases where steroids were stopped. As case numbers were very low and it's a pilot observation study, we didn't do detailed statistical analysis which may be misleading and give false promises. Conclusion: In our setup, we were finding it a difficulty to use the prescribed 10mg BD Ruxolitinib dose in adults due to fear of worsening cytopenia /sepsis and financial toxicity. We tried to observe the benefit of a lower dose in steroid refractory GVHD post Haplo-identical bone marrow transplant. No pharmaco-genetic assays were done and it's a very small sample size. This observational study revealed a better efficacy and tolerability of this dosing regimen in Indian Haplo-identical patients with a considerable response without compromising blood counts. The results are looking more promising to conduct this study in a bigger scale to benefit our patients from resource limited settings. Reference Zhao Y, Shi J, Luo Y, Gao F, Tan Y, Lai X, Yu J, Wei G, Huang H. Calcineurin Inhibitors Replacement by Ruxolitinib as Graft-versus-Host Disease Prophylaxis for Patients after Allogeneic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2020 May;26(5):e128-e133. doi: 10.1016/j.bbmt.2020.01.012. Epub 2020 Jan 23. PMID: 31982545.

Implementation of a 24-hour empiric antibiotic duration for negative early-onset sepsis evaluations to reduce early antibiotic exposure in premature infants.

Antibiotic exposure increases the risk of morbidity and mortality in premature infants. Many centers use at least 48 hours of antibiotics in the evaluation of early-onset sepsis (EOS, <72 hours after birth), yet most important pathogens grow within 24 hours. We investigated the safety and efficacy of reducing empiric antibiotic duration to 24 hours. Quality improvement study. A tertiary-care neonatal intensive care unit. Inborn infants <35 weeks gestational age at birth (ie, preterm) admitted January 2019 through December 2020. In December 2019, we changed the recommended duration of empiric antibiotics for negative EOS evaluations from 48 hours to 24 hours. Patient characteristics before and after the intervention were similar. After the intervention, 71 preterm infants (57%) with negative EOS evaluations received ≤24 hours of antibiotics, an increase from 15 (10%) before the intervention. These 71 infants comprised 77% of infants with negative EOS blood cultures after excluding those treated as clinical sepsis (≥5 days of antibiotics). For all negative EOS blood cultures, the mean treatment duration decreased by 0.5 days from 3.9 days to 3.4 days. This finding equated to 2.4 fewer antibiotic days per 100 patient days for negative EOS blood cultures but similar antibiotic days per 30 patient days (7.2 days vs 7.5 days). This measure did not change over time. Subsequent sepsis evaluations <7 days after a negative EOS blood culture did not increase. Excluding contaminants, the median time to positivity was 13.2 hours (range, 8-23) in 8 positive blood cultures. Implementation of a 24-hour antibiotic course for negative EOS evaluations safely reduced antibiotic exposure in 77% of infants <35 weeks gestational age at birth in whom EOS was ruled out. All clinically significant pathogens grew within 24 hours.

S1896 A Rare Case of Strongyloides Cholangitis With Portal Vein Thrombus and Recurrent Intra-Abdominal Abscesses

Introduction: Strongyloides stercoralis infection outside of the gastrointestinal tract is extremely uncommon, particularly in an immunocompetent host. We present a rare case of S. stercoralis cholangitis complicated by portal vein thrombus and recurrent intra-abdominal abscesses in an immunocompetent patient. Case Description/Methods: A 65-year-old male who immigrated to the United States (US) over 40 years prior from Nigeria, presented with 4 days of epigastric pain, weakness, fevers and anorexia. His medical history was notable for COPD and an intra-abdominal abscess two years prior. His previous abscess was treated with percutaneous drainage and antibiotics. On arrival, he was afebrile and tachycardic to 110 bpm. He appeared jaundiced, and his abdomen was distended with right upper quadrant tenderness. Labs showed AST 121 IU/L, ALT 263 IU/L, ALP 267 IU/L, total bilirubin 8.3 mg/dL (direct 5.4 mg/dL), WBC 13.6 K/uL, eosinophils 0.28 K/uL. Non-contrast-enhanced abdominal computerized tomography (CT) scan showed an 8.4 cm subdiaphragmatic collection adjacent to the gastric fundus and intra- and extrahepatic ductal dilation. MRCP showed luminal irregularity of the common bile duct with multiple areas of stenosis of intra- and extrahepatic bile ducts and cavernous transformation of a chronic portal vein thrombus. Aspirates of the sub-diaphragmatic fluid collection and blood cultures grew Pseudomonas aeruginosa. Intravenous piperacillin-tazobactam was started. Upper endoscopy and endoscopic ultrasound of the stomach showed normal gastric and duodenal mucosa with multiple large periduodenal varices. Duodenal biopsies revealed Strongyloides species (Figure ). S. stercoralis serologies were positive and HIV antibodies were negative. He underwent surgical washout of the abdominal abscess and was treated with 2 weeks of oral ivermectin and ciprofloxacin. Discussion: S.stercoralis transmission occurs when human skin contacts the infective larvae. Carriers may remain asymptomatic for decades. Symptoms can include pruritus, diarrhea, weight loss and abdominal pain. Complications such as biliary tree invasion and portal vein thrombus are rare but have been reported. Deposition of eggs in the bowel wall can lead to bacterial gut translocation, gram negative sepsis and recurrent abscesses. Disseminated strongyloidiasis typically occurs in the setting of immunosuppression, HIV, or hematologic malignancies and rarely occurs in an immunocompetent host. Diagnosis can be challenging.Figure 1.: Strongyloides organism on duodenal biopsy.

A RARE CASE OF HAEMOPHILUS INFLUENZAE CELLULITIS LEADING TO BACTEREMIA IN A HEALTHY ADULT

A RARE CASE OF HAEMOPHILUS INFLUENZAE CELLULITIS LEADING TO BACTEREMIA IN A HEALTHY ADULT

Culture-negative sepsis after pediatric cardiac surgery: Incidence and outcomes.

Significant proportion of congenital heart surgery (CHS) children exhibit sepsis, but have negative blood culture and defined "culture negative sepsis (CNS)." Retrospective analysis of CNS patients undergoing CHS. 437 consecutive CHS children grouped as controls (antibiotic prophylaxis), CNS, and culture positive sepsis (CPS). Incidences of CNS and CPS were 16% and 7%. Median mechanical ventilation (MV) in hours among CPS, CNS, and control was 116 (45-271), 63 (23-112), and 18 (6-28) (P < 0.001), respectively. Multivariable linear regression identified CPS (median ratio: 3.1 [2.3-4.1], P < 0.001), CNS (median ratio: 5.6 [3.7-8.4], P < 0.001), and weight (kg) (median ratio: 0.98 [0.96-0.99], P = 0.009) as associations of MV. Intensive care unit (ICU) stay (hours) was 192 (120-288) in CNS, 288 (156-444) in CPS, and 72 (48-120) in controls (P < 0.0001). Multivariable linear regression showed CNS (median ratio: 2.4 [2.0-2.9], P< 0.001) CPS (median ratio: 3.3 [2.5-4.4], P < 0.001), and weight (median ratio: 0.98 [0.97-0.99], P ≤ 0.001) prolonging ICU stay. Mortality was 10.7%, 2.9% and 1.2% in CPS, CNS, and control (P = 0.03). Multivariable regression identified CPS an independent predictor of mortality with odds ratio 8.6 (1.7-44.9; P = 0.010). 11.26% patients in CNS and 79.3% in CPS received antibiotics for more than 10 days. Incidence of CNS was 16%; duration of MV and ICU stay and mortality was significantly less in CNS than CPS patients.

Clinical Approach to Nosocomial Bacterial Sepsis.

Bacterial sepsis and septic shock are associated with a high mortality, and when clinically suspected, clinicians must initiate broad-spectrum antimicrobials within the first hour of diagnosis. Thorough review of prior cultures involving multidrug-resistant (MDR) pathogens along with other likely pathogens should be performed to provide an appropriate broad-spectrum empiric antibiotic coverage. The appropriate antibiotic loading dose followed by individualized modification of maintenance dose should be implemented based on the presence of hepatic or renal dysfunction. Use of procalcitonin is no longer recommended to determine need for initial antibacterial therapy and for de-escalation. Daily reevaluation of appropriateness of treatment is necessary based on the culture results and clinical response. All positive cultures should be carefully screened for possible contamination or colonization, which may not represent the true organism causing the sepsis. Culture negative sepsis accounts for one-half of all cases, and de-escalation of initial antibiotic regimen should be done gradually in these patients with close monitoring.

Do You Still Believe in the Existence of Culture Negative Sepsis in Neonates?

Do You Still Believe in the Existence of Culture Negative Sepsis in Neonates?

Efficacy and safety of outpatient based therapy in childhood acute lymphoblastic leukemia.

e22001 Background: Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood. With the improvements in effective antileukemic drugs and the risk stratification treatment approach, the cure rate for pediatric ALL has increased to &gt;90%. The effect of outpatient treatment and developing supportive care have a very important role in this success. We evaluated the disease outcomes and severe complications (complication causes hospitalization in ICU, encephalitis) of children who had been treated with the Children’s Oncology Group (COG) protocols, and follow-up protocol during a 20-year study period. Methods: From 1999 to 2020, 134 patients who had been diagnosed with ALL in the Department of Pediatric Hematology-Oncology at the Istanbul University Oncology Institute were included in the present study. Nine patients excluded from all analysis that 5 of them admitted with relapse, 2 had been diagnosed with mature aggressive B-cell acute leukemia, and 2 had been diagnosed with mixed phenotype and 7 who had been lost to follow-up were also excluded from survival analyses. Results: Mean age was 7.7±4.89 years old in 125 patients (Table). The 5- and 10-year and 20-year Event Free Survival (EFS) rates were 90.2% (standard error [SE], 4.2%) in standart risk B-ALL (n=54) and Overall Survival (OS) rates were 100%, 96% and 96% ([SE], 3.9%), respectively. In high risk group B-ALL (n=53) 5-year EFS was 80.7% (standard error [SE], 5.8%) and 78.2% ([SE], 6.1%) for both 10 and 20 year period and OS rates were 76.9% ([SE], 5.9%) for all periods. Although the number of patients is low in T-ALL (n=11), 5- and 10-year and 20-year EFS and OS rates were 63.6% (standard error [SE], 14.5%) for all periods. Fifteen severe complication recorded in 12 patients (10 B-ALL, 2 T-ALL). One patient hospitalized in ICU due to gram negative sepsis for 3-times and epidural hemorrhage. Conclusions: The survival rate for pediatric ALL has increased in recent years according to improvements of treatment.In our cohort, 20-year OS rate is 96% for standart risk B-ALL and 76.9% for high risk B-ALL. Additionally, regularly and closely monitored patients, complications can be effectively prevented, treated, and eliminated. In our study, the short hospitalization period, rapid analysis of laboratory tests, continuous supportive care, efficient education given to the parents of children increased the success of the therapy and ensured low complication rates. [Table: see text]

Suspecting Neonatal Severe Primary Hyperparathyroidism in Late Onset Neonatal Sepsis

Background: Neonatal severe primary hyperparathyroidism (NSPHPT) is disorder characterized by severe hypercalcemia and severe hyperparathyroidism resulting from a loss of function of the calcium-sensing receptor (CaSR), encoded by a gene located on the long arm of chromosome 3 (3q-13.3-21). It can be fatal if timely management is not initiated. Clinical Description: A 10-day-old exclusively breastfed girl presented with poor feeding, constipation, and lethargy for 2–3 days before admission. She was born of third-degree consanguinity to a primiparous woman with normal gestation. Born at term, with a birth weight of 3.1 kg, she was discharged uneventfully on day 3 of life. At admission, she was hemodynamically stable and normothermic but exhibited tachypnea, dehydrated with 15% weight loss as compared to birth weight, lethargy, and hypotonia. Salient investigations showed euglycemia, no dyselectrolytemia, and negative sepsis screen, but severe hypercalcemia and hyperparathyroidism. A final diagnosis of NSPHPT was made. Clinical exome sequencing showed homozygous CaSR gene frameshift mutation on chromosome 3. Management: Hypercalcemia was managed initially by standard protocol, including furosemide, hyperhydration, bisphosphonates, and cinacalcet. Subsequently, parathyroidectomy was performed at 2 months of age. Postoperatively, the infant is 5 months old and thriving well. Conclusion: NSPHPT should be considered in the presence of features of clinical sepsis, failure to timely regain birth weight, and a profile suggesting atypical calcium homeostasis.

MICROBIOLOGY AND DRUG RESISTANCE PATTERN IN CLINICALLY SIGNIFICANT ISOLATES OF URINE FROM MEDICAL WARDS OF A TERTIARY CARE HOSPITAL IN NORTH INDIA.

Urinary tract infections (UTIs) are one of the most common bacterial infections encountered in clinical practice both in community and hospital settings in all age groups. It is the second most frequently occurring infection in general population after upper respiratory tract infection .Urinary tract infections (UTIs) are the leading cause of Gram negative sepsis in hospitalized patients and are the origin for about half of all hospital acquired infections caused by urinary catheters and are associated with considerable cost in terms of morbidity and economic and research expenditure. Material And Methods: This prospective cross sectional study was carried out in the Department of Microbiology of Government Medical College, Srinagar. A total of 800 patients were taken up for the study. The sample falling under the set inclusion criteria were selected from the urine specimen received in the laboratory for urine culture and sensitivity from Hospitalized patients (IPD). Culture and sensitivity reports and patient data obtained from hospital records was analyzed for this study. Out of 800 samples taken up for the study 208 (26%) were culture positiv Results: e and 592 (74%) were negative. 208 positive samples 125(60.10%) were females and 83(39.90%) were males. female predominance was observed with 71% whereas 29% males were affected by UTI. UTI was predominantly in females of age group (21-40 yrs). most common organism isolated on culture was Escherichia coli(43.26%) both in short stay patients (&lt;48hrs hospital stay) /OPD 22.59% as well as in IPD (&gt;48hrs hospital stay) 20.67%.E.coli was isolated from patients of both uncomplicated and complicated UTI. The second most common organism isolated in our study was Enterococcus faecalis(22.59%), the rate of isolation was much higher 18.75% in inpatients (&gt;48hrs hospital stay) and only 3.84% in OPD/short stay patients (&lt;48hrs hospital stay). In our study Enterococcus spp ranked second amongst uropathogens, in IPD patients isolation rate was almost 5 times higher. Pseudomonas spp was 1 isolate in OPD (0.48%) and 6 (2.88%) in IPD, Acinetobacter 3 (1.44%), Proteus 1 (0.48%) found only in hospitalized patients (stay &gt;48hrs). E.coli showed following sensitivity pattern 96.7% to nitrofurantoin, 93.3% to imipenem, 90.0% to amikacin, 75.6% to gentamycin, 73.3% to cefoperazone-salbactam and meropenem both, 68.9% to pipercillin tazobactam.The sensitivity to TMP-SMX was 45.6%, and to ceftriaxone and cefipime was only 22.2% and 21.1% respectively. The organism also showed resistance to drugs like levofloxacin 82.2% and ciprofloxacin 76.7%.Enterococcus faecalis isolated in our study was sensitive to Vancomycin 95.74% followed by Linezolid (93.6%), Nitrofurantoin (78.7%), HL-Amikacin (74.5%),HLGentamycin (70.2%). Enterococcus faecalis showed resistance to drugs commonly used to treat UTI i.e. 91.5% resistant to Ciprofloxacin and 89.4% resistant to Levofloxacin. Gram negative bacteria were most predominant Conclusion: microorganisms resulting in more than 50% infections causing urinary tract infection. In our study we have seen that Gram positive cocci especially Enterococcus result in UTI in a significant proportion of patients. In our study Enterococcus spp ranked second amongst uropathogens, in IPD patients isolation rate was almost 5 times higher. The implementation of antibiotic stewardship programs is crucial to minimize resistance. Appropriate antibiotics need to be prescribed based on the antibiotic susceptibility testing which will be narrow spectrum, effective and less expensive with least side effects.

Granulocyte infusion in Gram negative sepsis- Timely intervention saves Life: Experience from tertiary cancer care centre

Granulocyte infusion in Gram negative sepsis- Timely intervention saves Life: Experience from tertiary cancer care centre

Bacteriological Profile of Sepsis among Low Birth Weight Neonates: A Hospital-based Cross-sectional Study from Northern India

Introduction: Septicaemia in neonates is characterised by the generalised bacteriological infection which is characterised with a blood culture positivity after 28 days of birth along with clinical presentation of systemic infection. It is one of the common causes of death among Low Birth Weight (LBW) neonates. Incidence of sepsis varies based on different variables, such as hospitals, obstetric and nursing procedures, gender, period of gestation, weight of the baby at birth, place of delivery status, mother’s health and nutrition and perinatal care. Aim: To know the bacteriological profile and antibiotic susceptibility patterns of organisms causing sepsis in LBW neonates. Materials and Methods: This cross-sectional hospitalbased observational was conducted in tertiary care hospital, Moradabad, Western Uttar Pradesh, India. LBW newborns (Birth weight &lt;2.5 kg) hospitalised in the Neonatal Intensive Care Unit (NICU) over a period of one year from June 2019 to May 2020 with a diagnosis of clinical sepsis were enrolled. Relevant investigations and treatment were started as per our NICU protocol. Data was entered sequentially in Microsoft Excel spreadsheet and analysed in Statistical Package for the Social Sciences (SPSS) (version 20.0) using Chi-square test. Results: During the study period, total 145 LBW neonates were admitted in NICU. Out of whom, 83 neonates were admitted with clinical sepsis. A 87.9% of LBW neonates were preterm. Blood culture reports were positive in 30 (36.2%) LBW neonates. In culture proven sepsis, 20 (67%) neonates had early onset neonatal sepsis and 10 (33%) had late onset neonatal sepsis. In culture proven early onset neonatal sepsis, 13 (65%) LBW neonates had gram negative sepsis and 7 (35%) had gram positive sepsis. The most frequently isolated organisms were Acinetobacter baumannii (23.3%) and Klebsiella pneumoniae- (16.7%). These organism were resistance to cefotaxime, ampicillin, amikacin and ciprofloxacin. Conclusion: Acinetobacter sepsis in LBW neonates is surging rapidly and is associated with high degree of Antimicrobial Resistance (AMR). Therefore, knowledge and awareness of multidrug resistant organism causing sepsis in LBW neonates and their latest antimicrobial sensitivity pattern is essential to choose most appropriate antibiotics.

Neutrophil-lymphocyte Count Ratio as Section an Indicator of Culture Positive versus Culture Negative Sepsis: A Singlecentre Cross-sectional Study

Introduction: In sepsis patients, the Neutrophil-lymphocyte Count Ratio (NLCR) is a laboratory statistic that can indicate bacterial infection. Aim: To measure NLCR in patients with sepsis and compare the NLCR in patient with culture positive and culture negative sepsis. Materials and Methods: This single-centre, cross-sectional study was conducted in the Department of General Medicine at R.L. Jalappa Hospital (Sri Devaraj URS Medical College), Kolar, Karnataka, India, from October 2021 to December 2021. A total of 120 patients above 18 years of age with sepsis, diagnosed as per the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), were included in the study. Participants were evaluated for sepsis and septic shock (society of critical care medicine conference definitions) the principles of initial resuscitation (fluid therapy, vasopressors, inotropic support), and infection issues (source identification and control, appropriate antibiotic therapy) were followed regularly and the outcome studied. Neutrophil count, lymphocyte count, and calculation of NLCR were done at the time of admission. The correlation studies of NLCR in culture-positive and culturenegative was done and compared. Data was analysed by using coGuide software (version 1.03). Results: The mean age of patients was 58.98±17.78 years, ranged from 20 to 96 years, 47 (39.17%) were male and 73 (60.83%) were female, majority 93 (77.50%) out of 120 patients had fever. Majority 78 (65%) had type 2 diabetes mellitus. Neutrophilto-Lymphocyte ratio (NLR) was 10±1.67, ranging from 7.40 to 14.50. The area under the ROC curve was 0.522. There was no statistically significant relationship between the NLCR and culture report (p-value=0.216). The NLCR had poor predictive validity in predicting culture positive, as indicated by the area under the curve {0.522 (95% CI: 0.417 to 0.626, p-value= 0.988)}. Conclusion: NLCR can be considered as predictor for the initiation of treatment of patients with sepsis.