scholarly journals A Prospective Study on Neonatal Sepsis in a Tertiary Hospital, Nepal

2021 ◽  
Author(s):  
Ranjit Sah ◽  
Suraj Bhattarai ◽  
Srijana Basnet ◽  
Bharat Mani Pokhrel ◽  
Niranjan Prasad Shah ◽  
...  
Keyword(s):  
Neonatal Sepsis ◽  
Early Onset ◽  
Late Onset ◽  
Enterobacter Aerogenes ◽  
Gram Negative Bacteria ◽  
Acinetobacter Baumanii ◽  
Gram Negative ◽  
E Coli ◽  
Late Onset Sepsis ◽  
A Prospective Study

About 20 % of neonates develop sepsis and among them approximately 1% die due to sepsis-related causes. Bacterial pathogens are the commonest cause of neonatal sepsis which is either early-onset (<72 hours of age) or late-onset (>72 hours). Little is known about the epidemiology and antimicrobial susceptibility pattern of sepsis causing bacterial pathogens in Nepal. A prospective study was carried out among neonates suspected to have sepsis and admitted to Tribhuwan University Teaching Hospital from January to December 2016. Clinical suspicion of sepsis was made based on clinical findings and laboratory parameters, later confirmed by isolation of organisms in blood culture. Drug resistance pattern of Gram-positive and Gram-negative bacteria were studied by standard methods. Meropenem resistant Gram-negative bacteria were processed for the detection of β-lactamases and resistant genes were detected by X-pert Carba-R (Cepheid) Assays. Of 372 neonates with clinically suspected sepsis, 132 (35.4%) had blood culture positivity, with 47% early-onset and 53% late-onset sepsis. Coagulase-negative Staphylococcus aureus (CONS) was the most common (37.9%) etiological agent followed by Klebsiella pneumoniae (12.9%). Of all 132 isolates, 81 (61.3%) were Gram-positive of which 22 (27.2%) were multi-drug resistant (MDR), three (3.7%) were methicillin-resistant S. aureus (MRSA), and 14 (17.2%) were methicillin-resistant CoNS; and 50 (37.8%) were Gram-negative of which 26 (52%) were MDR and 29 (58%) were resistant to β-lactamases. The blaKPC gene was detected in four isolates of K. pneumoniae, two of E. coli, one ABC (Acinetobacter baumanii complex), and one Enterobacter aerogenes whereas blaNDM gene was detected in one isolate of K. pneumoniae, two of E. coli, two Pseudomonas aeruginosa, one Acinetobacter baumanii complex, and one Enterobacter aerogenes. Overall mortality due to sepsis-related causes was 7.6% (10 of 132). One-third of clinically suspected neonatal sepsis cases were culture positive. Late-onset sepsis was more common than early onset. CoNS was the predominant bacterial isolate followed by Klebsiella pneumoniae, with high rates of multi-drug resistance.

scholarly journals Bacterial Isolates of Early Onset Neonatal Sepsis and Their Antibiotic Susceptibility Pattern

2018 ◽  
Vol 17 (1) ◽  
pp. 3-8 ◽  
Author(s):  
Md Abdul Mannan ◽  
Shahed Iqbal ◽  
SM Rezaul Karim ◽  
Talim Uddin Ahmed ◽  
Md Hakimul Haque Khan ◽  
...  
Keyword(s):  
Neonatal Sepsis ◽  
Early Onset ◽  
Late Onset ◽  
Gram Positive ◽  
Gram Negative ◽  
E Coli ◽  
Late Onset Sepsis ◽  
Early Onset Sepsis ◽  
Sensitivity Pattern ◽  
Rule Out

Background: Neonatal infections are the commonest cause of neonatal mortality along with perinatal asphyxia and consequence of Prematurity and Low Birth Weight (LBW) in Bangladesh. Early Onset Neonatal Sepsis (EONS) is neonatal sepsis occurring within the first 72 hours of birth and it is much more fulminant and has a higher mortality than Late Onset Sepsis (LOS). Sepsis in neonate remains a significant cause of mortality and morbidity in developing countries. Changing bacterial flora and emergence of resistant strains adds to the problem. Thus, neonatal sepsis requires accurate and timely clinical and laboratory diagnosis and proper management for better outcome. The organisms responsible for Early Onset Sepsis (EOS) are different than Late Onset Sepsis (LOS). In this study an attempt has been made to know the positivity rate of EOS and profile of bacteria responsible for EOS and determine the antimicrobial sensitivity pattern that were investigated for rule out sepsis. Methods: This was a prospective observation single centre study over a period of nine months (January to September, 2017) conducted on neonates born at Ad-din Medical College Hospital (AMCH), Dhaka and subsequently admitted in Neonatal Intensive Care Unit (NICU) within 72 hours of birth that were investigated for rule out sepsis. Dual blood sample for cultures from separate area along with essential investigations were sent by collecting samples under aseptic precautions. Empirical antimicrobial therapy was started according to antimicrobial guidelines in the NICU. The blood cultures test were carried out by BD BACTEC automated blood culture system and susceptibility testing was done for all blood culture isolates according to the criteria of the National Committee for Clinical Laboratory Standards by disk diffusion method. Results: A total of 700 neonates were investigated to rule out sepsis and 5.43% neonates were found with culture proven sepsis in the study. The gram positive bacteria accounted for 71% and gram negative 29% of the total isolates. Out of total 38 isolates, Coagulase-Negative Staphylococci (CONS) (68.4%) was the commonest followed by Acinetobacter (18.4%) and E. coli (7.9%) was common culture isolates. Among the gram positive, CONS (96.3%) was commonest isolate and in gram negative Acinetobacter (63.6%) was the most prevalent bacteria followed by E.coli (27.3%). Gram positive isolate, especially CONS (68.4%) was the major culprit for the early onset sepsis. Among the commonly used antibiotics, the susceptibilities were remarkably low to Amikacin (16%) in comparison to Ampicillin (42%) Cefotaxime (45%) and moderately high to Gentamicin (58%) for both gram positive & gram negative isolates. All (100%) gram positive isolates were resistant to Amikacin. Majority of the gram positive showed low susceptibilities to Meropenem (22%) Ciprofloxacin (41%) Ampicillin (48%) & Oxacillin (48%) in comparison to Cefotaxime (52%) Levofloxacin (55%) Gentamicin (70%), Linezolid (70%) and Vancomycin (74%). 50% of Coagulase Negative Staphylococcus (CONS) were resistant to Methicillin/Oxacillin. The sensitivity pattern of majority of gram negative isolates showed high level of resistance to Piperacillin+Tazobacterm (9%) and Ampicillin (27%) Gentamicin (27%) Cefotaxime (27%) less sensitive to Ciprofloxacin (45%); moderately high to Levofloxacin (54%) & Amikacin (54%) and highly sensitive to Imipenem/Meropenem (73%) & Colistin (91%). Gentamicin (58%) and Levofloxacin (55%) were showed marginal superiority compared to Ampicillin (42%) and Cefotaxime (45%) for effective coverage of both. Conclusion: Present study indicated that gram positive species especially CONS continue to be the predominant causative organism followed by Acinetobacter and E. coli in gram negative species. The antibiotic susceptibility profile suggested that for a given cohort empiric (initial) choice of Ampicillin and Gentamicin in EOS. Routine bacterial surveillance and their sensitivity patterns must be an essential component of neonatal care Chatt Maa Shi Hosp Med Coll J; Vol.17 (1); Jan 2018; Page 3-8

scholarly journals Patient characteristics, Bacteriological profile & outcome of Neonatal Sepsis: A Hospital Based Study

2013 ◽  
Vol 2 (1) ◽  
pp. 49-54
Author(s):  
Nasim Jahan ◽  
Zabrul SM Haque ◽  
Md Abdul Mannan ◽  
Morsheda Akhter ◽  
Sabina Yasmin ◽  
...  
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Neonatal Sepsis ◽  
Early Onset ◽  
Late Onset ◽  
Female Ratio ◽  
Gram Negative ◽  
Common Pathogen ◽  
Late Onset Sepsis ◽  
Early Onset Sepsis

Neonatal sepsis is a major cause of mortality and morbidity in newborn. The spectrum of bacteria which causes neonatal sepsis varies in different parts of the world. The organisms responsible for early onset and late onset sepsis are different. The objective of the study was undertaken to determine the pattern of bacterial isolates responsible for early and late onset neonatal sepsis. A prospective descriptive study over the period of one year was conducted at the Department of Neonatal Intensive care unit of Ad-din Women’s Medical College and Hospital, Dhaka, Bangladesh.Organisms were isolated from 8.7% of collected blood samples. The male female ratio of culture proven sepsis was 1.7:1. More than half (52.8%) of the evaluated neonates were preterm. & 56.3% had low birth weight. The gram positive and gram negative bacteria accounted for 24.1% and 75.9% of the isolates respectively. Around three fourth of the neonates (75.8%) presented with early onset sepsis, while 24.2% presented with late onset sepsis. Acinetobacter was the most common pathogen both in early onset (70%) and late onset (30%) sepsis. Pseudomonas (89.4%) was the second most common pathogen in early onset sepsis. Total mortality rate was 5.7%. Pre term, low birth weight and gram negative sepsis contributes majority of mortality.Gram negative organism especially Acinetobacter found to be commonest cause of sepsis. Pseudomonas was second most common but contributed highest in late onset sepsis and neonatal death due to sepsis. DOI: http://dx.doi.org/10.3329/cbmj.v2i1.14184 Community Based Medical Journal Vol.2(1) 2013 49-54

scholarly journals Neonate Bloodstream Infections (BSI) in China: Emerging Threat of Multidrug-resistant (MDR) pathogens

2020 ◽  
Author(s):  
hua zou ◽  
Ligang Zhou ◽  
Yan Shen ◽  
Chunli Li ◽  
Qiuhong Li
Keyword(s):  
Early Onset ◽  
Pathogenic Bacteria ◽  
Late Onset ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Multi Drug Resistance ◽  
Gram Negative Bacteria ◽  
Antibiotic Exposure ◽  
Gram Negative ◽  
E Coli

Abstract Background: Bloodstream Infections (BSIs) continue to be associated with significant morbidity and mortality worldwide, which multidrug-resistant (MDR) pathogens present an ever-growing burden in the hospital and community settings. Data on antimicrobial resistance and prevalence of BSIs pathogens among hospitalized neonates in China are few and not clearly defined. Methods: we retrospectively collected clinical and bacteria data about patients with BSI from 2013 to 2017 in Chongqing Health Center for Women and Children. The patients were divided into the early- and late-onset BSI groups according to if BSI occurred within or beyond 72 hours after admission.Results: 210 BSIs occurred from January 1st, 2014 to December 31th, 2019. Of all included 210 patients, there were 99(47.14%), 105 (50.00%), and 6 (2.86%) infected with gram-positive bacteria, gram-negative bacteria, and fungi, respectively. For early-onset BSI, the predominated pathogen was E. coli, accounting for 59.6% with 29.72% producing of extended-spectrum beta-lactamases (ESBLs). CNS (40.3%), K. pneumoniae (23.8%), and E. coli (20.9%) constitute the main causes of late-onset BSIs. Notably, 75.0% of K. pneumoniae produced ESBLs and 81.3% were MDR, which were higher than early-onset BSIs. Late onset BSIs and antibiotic exposure were significantly associated with MDR infection. Conclusion: Gram-negative bacteria gradually became the main pathogenic bacteria, among which E. coli and K. pneumoniae accounted for the largest proportion. The phenomenon of multi-drug resistance of bacteria is serious, and the first-line drug can't meet the practical needs. Late onset sepsis and antibiotic exposure were significantly associated with MDR infection.

scholarly journals Clinical, Bacteriological Profile & Outcome of Neonatal Sepsis in a Tertiary Care Hospital

2014 ◽  
Vol 26 (1) ◽  
pp. 18-21 ◽  
Author(s):  
Biplob Kumar Raha ◽  
Md Abdul Baki ◽  
Tahmina Begum ◽  
Nazmun Nahar ◽  
Nasim Jahan ◽  
...  
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Klebsiella Pneumoniae ◽  
Neonatal Sepsis ◽  
Early Onset ◽  
Late Onset ◽  
Gram Negative ◽  
Common Pathogen ◽  
Late Onset Sepsis ◽  
Early Onset Sepsis

Neonatal sepsis is a major cause of mortality and morbidity in newborn, particularly in developing countries. The spectrum of bacteria which causes neonatal sepsis varies in different parts of the world. The organisms responsible for early onset and late onset sepsis are different. The objective of the study was undertaken to determine the pattern of bacterial isolates responsible for early and late onset neonatal sepsis based on the presence of one or more clinical signs, and its outcome. A cross- sectional prospective study was carried out in the special care baby unit (SCABU) from November 2008 to September 2009 under department of Paediatrics and Neonatology, BIRDEM General Hospital, Dhaka, Bangladesh. Organisms were isolated from 8.9% of collected blood samples. The male female ratio of culture proven sepsis was 1.7:1. Most of the culture proven septic neonates(71.88%) were preterm & 65.63% had low birth weight. The most frequent clinical presentations of patients with culture-proven sepsis were poor moro reflex (92.2%), feeding intolerance (90.6%), jaundice (87.5%), abdominal distention (76.6%), and lathergy (73.4%). The Gram positive and Gram negative bacteria accounted for 6 (9.4% ) and 58 (90.6%) of the isolates respectively. Around two third of the culture-proven septic neonates (70.3%) presented with early onset sepsis, while 29.7% presented with late onset sepsis. Klebsiella pneumoniae was the most common pathogen both in early onset (31.25%) and late onset (6.25%) sepsis. Serratia (18.75%) was the second most common pathogen in early onset sepsis. Total mortality rate was 9.38%. Preterm, low birth weight and Gram negative sepsis contributes majority of mortality. Gram negative organism especially Klebsiella pneumoniae contributed highest in early onset sepsis and neonatal death (6.25%) due to sepsis. DOI: http://dx.doi.org/10.3329/medtoday.v26i1.21306 Medicine Today 2014 Vol.26(1): 18-21

scholarly journals Emerging Threat of Multidrug Resistant Pathogens From Neonatal Sepsis

2021 ◽  
Vol 11 ◽  
Author(s):  
Hua Zou ◽  
Xiaojiong Jia ◽  
Xiao He ◽  
Yan Su ◽  
Ligang Zhou ◽  
...  
Keyword(s):  
Neonatal Sepsis ◽  
Southwest China ◽  
Late Onset ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
E Coli ◽  
Gram Positive Bacteria ◽  
Carbapenem Resistant ◽  
Late Onset Sepsis ◽  
Early Onset Sepsis

Multidrug-resistant (MDR) pathogens are responsible for a substantial burden of morbidity and mortality from neonatal sepsis; however, data on these sepsis-related pathogens among hospitalized neonates in China are not well characterized. In this study, a total of 240 strains were isolated from four Women and Children’s hospitals in Southwest China between 2014 and 2019. Of these included pathogens, 104 (43.33%) were gram-positive bacteria, 129 (53.75%) were gram-negative bacteria, and 7 (2.92%) were fungi. Escherichia coli (E. coli, 34.01%) and Klebsiella pneumoniae (K. pneumoniae, 15.35%) were the main pathogen of neonate bacteremia. ST167 were the most prevalent STs in E. coli and ST11 in K. pneumoniae. Our study found that E. coli (62.71%) was the predominate pathogen of early-onset sepsis, among which 64.86% were MDR. Late-onset sepsis was mainly caused by K. pneumoniae (28.31%) and E. coli (24.78%), with showing that 78.33% of these pathogens were MDR. Notably, the prevalence of EO/LO pathogens were quite different from Indian and south of China. Moreover, we found that blaCTX-M (42.06%) was most dominant resistant genes with about a third isolates (31.09%) were positive for blaCTX-M-15. All the carbapenem-resistant K. pneumoniae were positive for NDM-1. Moreover, late-onset sepsis and antibiotic exposure were significantly associated with MDR infection. Emerging multi-resistant pathogens of sepsis posts a serious threat to neonatal outcomes and emphasizes an urgent need to control their further spread.

CLINICAL PREVALENCE AND CAUSATIVE MICROBES RESPONSIBLE FOR NEONATAL SEPSIS IN NEONATES ADMITTED IN NMCH

2018 ◽  
Author(s):  
Dr. Ramjee Prasad Gupta ◽  
Dr. Mohan Kejriwal ◽  
Dr. Alka Singh
Keyword(s):  
Neonatal Sepsis ◽  
Early Onset ◽  
Late Onset ◽  
Gram Negative ◽  
Medical College ◽  
Late Onset Sepsis ◽  
Adequate Care ◽  
Early Onset Sepsis ◽  
Low Birth Weight Babies ◽  
Third Generation Cephalosporins

Neonatal sepsis is of two types; early onset sepsis and late onset sepsis. Early onset sepsis (EOS) present within first 72 hours of life. In severe cases, the neonates may be symptomatic at birth. Infants with EOS usually present with respiratory distress and pneumonia. Hence based on above findings the present study was planned to evaluate the immediate clinical outcomes of culture proven neonatal sepsis in the NICU. The study was planned by enrolling the 320 neonates admitted in Neonatal unit of Department of Paediatrics in Nalanda Medical College and Hospital, Patna, from Dec 2017 to Jun 2018. The 40 neonates were diagnosed positive for septicemia was enrolled in the present study.  The approval of the institutional committee was taken prior conduct of study. All the patients were informed consents. The data from the present study revealed that adequate care of the low birth weight babies is of utmost importance to prevent infection by Klebsiella pneumoniae. Amikacin should be used along with third-generation cephalosporins for empirical treatment of gram-negative neonatal sepsis. This empirical regimen should be modified later based on the antibiogram of the isolates. Keywords: neonatal sepsis, epidemiology, microbiology, etc.

NEONATAL SEPSIS AND IDENTIFICATION OF RISK FACTORS: STUDY IN AVBRH HOSPITAL SAWANGI

2019 ◽  
Vol 3 (6) ◽  
Author(s):  
Pramod P. Singhavi
Keyword(s):  
Risk Factors ◽  
Neonatal Sepsis ◽  
Early Onset ◽  
Late Onset ◽  
Signs And Symptoms ◽  
Premature Rupture ◽  
Maternal Risk ◽  
Late Onset Sepsis ◽  
Early Onset Sepsis ◽  
Meconium Stained Amniotic Fluid

Introduction: India has the highest incidence of clinical sepsis i.e.17,000/ 1,00,000 live births. In Neonatal sepsis septicaemia, pneumonia, meningitis, osteomyelitis, arthritis and urinary tract infections can be included. Mortality in the neonatal period each year account for 41% (3.6 million) of all deaths in children under 5 years and most of these deaths occur in low income countries and about one million of these deaths are due to infectious causes including neonatal sepsis, meningitis, and pneumonia. In early onset neonatal sepsis (EOS) Clinical features are non-specific and are inefficient for identifying neonates with early-onset sepsis. Culture results take up to 48 hours and may give false-positive or low-yield results because of the antenatal antibiotic exposure. Reviews of risk factors has been used globally to guide the development of management guidelines for neonatal sepsis, and it is similarly recommended that such evidence be used to inform guideline development for management of neonatal sepsis. Material and Methods: This study was carried out using institution based cross section study . The total number neonates admitted in the hospital in given study period was 644, of which 234 were diagnosed for neonatal sepsis by the treating pediatrician based on the signs and symptoms during admission. The data was collected: Sociodemographic characteristics; maternal information; and neonatal information for neonatal sepsis like neonatal age on admission, sex, gestational age, birth weight, crying immediately at birth, and resuscitation at birth. Results: Out of 644 neonates admitted 234 (36.34%) were diagnosed for neonatal sepsis by the paediatrician based on the signs and symptoms during admission. Of the 234 neonates, 189 (80.77%) infants were in the age range of 0 to 7 days (Early onset sepsis) while 45 (19.23%) were aged between 8 and 28 days (Late onset sepsis). Male to female ratio in our study was 53.8% and 46% respectively. Out of total 126 male neonates 91(72.2%) were having early onset sepsis while 35 (27.8%) were late onset type. Out of total 108 female neonates 89(82.4%) were having early onset sepsis while 19 (17.6%) were late onset type. Maternal risk factors were identified in 103(57.2%) of early onset sepsis cases while in late onset sepsis cases were 11(20.4%). Foul smelling liquor in early onset sepsis and in late onset sepsis was 10(5.56%) and 2 (3.70%) respectively. In early onset sepsis cases maternal UTI, Meconium stained amniotic fluid, Multipara and Premature rupture of membrane was seen in 21(11.67%), 19 (10.56%), 20(11.11%) and 33 (18.33%) cases respectively. In late onset sepsis cases maternal UTI, Meconium stained amniotic fluid, Multipara and Premature rupture of membrane was seen in 2 (3.70%), 1(1.85%), 3 (5.56%) and 3 (5.56%) cases respectively. Conclusion: Maternal risk identification may help in the early identification and empirical antibiotic treatment in neonatal sepsis and thus mortality and morbidity can be reduced.

scholarly journals Clinicobacteriological profile, antibiotic sensitivity patterns and mortality of neonatal sepsis in a tertiary care hospital in Kashmir, Jammu and Kashmir, India

2019 ◽  
Vol 6 (3) ◽  
pp. 917
Author(s):  
Gh Rasool Wani ◽  
Nazir Ahmed ◽  
Mohd Irshad ◽  
Mohd Ashraf ◽  
Bashir Ahmed Teli
Keyword(s):  
Blood Culture ◽  
Neonatal Mortality ◽  
Neonatal Sepsis ◽  
Early Onset ◽  
Late Onset ◽  
Antibiotic Sensitivity ◽  
Government Medical College ◽  
Gram Negative ◽  
Medical College ◽  
Early Onset Sepsis

Background: Neonatal sepsis refers to generalized bacterial blood stream infection in first 28 days of life documented by positive blood cultures. It is one of leading causes of neonatal mortality. Objectives was to study clinicobacteriological, antibiotic sensitivity patterns and mortality of neonatal sepsis.Methods: This prospective study was conducted in the Department of Pediatrics of Government Medical College Srinagar in collaboration with Department of Microbiology of same medical college after ethical clearance from ethical committee of Government Medical College Srinagar. One hundred (100) neonates out of 731 neonates admitted between octomber2007 and September 2008 with signs and symptoms of neonatal sepsis were included in our study by random sampling method. After history, examination and laboratory investigation blood culture results were analyzed by standard statistical methods.Results: The blood culture was positive in 40% of neonates. Fifty one (51) neonates were males while as 49 were females. Sixty three (63) neonates had late onset of sepsis while as 37 had early onset sepsis. The positive  blood culture was more common in males, late onset sepsis, babies born in rural areas, home born, vaginal births, preterm and other  low birth weight neonates .The gram negative isolates were most common followed by positive ones .The best sensitivity of gram negative isolates was to ciprofloxacin followed by amikacin and cephalosporins while as gram positive isolates were sensitive to imipenum followed by vancomycin. Pseudomonas was most responsive to pipercillin +tazobactum combination. The neonatal mortality was 35% being higher in early onset sepsis and low birth weights.Conclusions: This study depicts a high rate of neonatal sepsis, mainly caused by gram negative organisms followed by gram positive organisms with rising drug resistance that could bear far reaching implications to the times to come, mandating the implementation of sepsis preventive measures and administration of specific antibiotics.

A Shift in the Intestinal Microflora towards Pro-Inflammatory Bacteria and Signaling Via Toll-Like-Receptor 2 Triggers Early Onset of Graft-Versus-Host Disease.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2171-2171
Author(s):  
Axel Nogai ◽  
Markus M. Heimesaat ◽  
Stefan Bereswill ◽  
Eckhard Thiel ◽  
Ulf B. Goebel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Early Onset ◽  
Innate Immune ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Host Disease ◽  
E Coli ◽  
Graft Versus Host

Abstract Pattern recognition receptors such as Toll-like-receptors (TLR) and NOD proteins bind specifically to microbial components and activate innate immune responses. Reducing the bacterial load by antibiotic treatment has been shown to ameliorate the severity of graft-versus-host-disease (GvHD) after allogenic stem cell transplantation. The impact of bacteria and TLRs on the induction of T-cell-alloreactivity and GvHD was investigated in a murine transplantation model. C57B/10 wild-type (wt) mice served as recipients of MHC-mismatched Balb/c grafts after conditioning with treosulfan and cyclophosphamide. Analyses of the gut microbiota in fecal samples showed a pronounced increase of luminal load of both gram-positive and gram-negative bacteria within 11 days after stem cell transplantation. The increase in the Escherichia coli load was significantly correlated with the severity of graft-versus-host-disease and with decreased survival rates. Analysis of the kinetics of fecal E. coli load and the histologial and clinical GvHD scores revealed that the increase of the fecal E. coli load is detected simultanously to the onset of clinical overt GvHD. Because TLR 2 and 4 represent the major receptors for gram-positive and gram-negative bacteria, respectively, the incidence and severity of GvHD was investigated in TLR2, TLR4 and TLR2/4 deficient mice on a C57B/10 background. The onset of GvHD was delayed in recipient mice lacking TLR2 and both TLR2 and 4 (p&lt;0.05) whereas a single TLR4 deficiency had no influence. Interestingly, there was no correlation of E. coli load and GvHD in TLR2-deficient mice.Taken together, these results support potential roles of TLR2-dependent signaling and gut bacterial components in the induction and early onset of intestinal GvHD. In expansion of these findings, our data elucidate the role of the innate immune system and its receptors for the induction of alloreactive T-cell responses, providing evidence that modulation of the intestinal gut flora might prevent or reduce GvHD in humans.

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