outcomes in multidrug-resistant (mdr) gram-negative ...outcomes in multidrug-resistant (mdr)...
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Outcomes in Multidrug-Resistant (MDR) Gram-Negative bacilli (GNB) Sepsis
Sristy Agrawal, Anurag Fursule, Anup Thakur, Nikhil Tenetti, Manisha Mehta, Manoj Modi, Arun Soni, Pankaj Garg,
Satish Saluja, Neelam Kler
Department of neonatology, Sir Ganga Ram Hospital, New Delhi
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Introduction
• Gram negative bacillus (GNB) sepsis caused by multidrug-resistant
(MDR) organism in NICU has become a therapeutic challenge
• Major causes of emergence MDR Organism in neonatal sepsis
• empiric antibiotic prescriptions
• unregulated use of over-the-counter drugs
• high incidence of healthcare associated infections (HAI)
• lack of awareness about antibiotic stewardship program
• under staffing of neonatal intensive care units
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• Outbreaks of MDR sepsis can bring severe consequences in
terms of both morbidity and mortality
• There is very little information on the risk factors, types of
organisms, and outcomes in neonatal MDR GNB sepsis
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Objective
• To assess the risk factors and outcome of neonates with MDR
GNB sepsis
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Materials and Methods
• Study design
• Retrospective Observational study
• Setting
• Level III B NICU
• Study population
• All neonates diagnosed with GNB sepsis as per blood culture
report
• Study duration
• January 2017 to August 2019
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Materials and methods
• All cases of GNB sepsis were recorded from hospital
information system
• GNB sepsis was defined as at least 1 blood culture showing
gram negative bacilli growth out of 2 samples collected
from 2 different sites
• MDR was defined as isolate non-susceptible to at least 1
agent in 3 antimicrobial categories
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Materials and Methods
• Neonates with MDR and non MDR GNB sepsis were analyzed and compared for:
• Risk factors
• Clinical profile
• Outcome:
Primary outcome: Mortality
Secondary outcome: Duration of ventilation , inotropic requirement ,parenteral nutrition ,i /v antibiotics and hospital stay, need for blood products
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Statistical Analysis
• Data was collected in a predesigned proforma and entered
in the Microsoft Excel software
• Data analyzed using SPSS software
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Results
Total number of neonates with GNB sepsis -101Base line characteristics
MDR (n=67)(66.3%)
Non MDR(N=34)(33.7%)
P value
Mean gestation (weeks)*
35(3) 33(4) 0.892
Mean Birth Weight(g)*
2273(775) 1996(847) 0.06
Male gender n(%) 48( 71) 27(79) 0.712
VLBW n(%) 10( 14.9) 9 (26) 1.968
EOS n(%) 25( 37.4) 17( 50) 1.01
LSCS n(%) 53 (79.1) 30( 88.2) 1.2
*Mean (SD)
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Risk factors for GNB sepsis
* median( IQR)
Risk factors MDR GNB sepsis (N=67)
Non MDR GNB sepsis(N=34)
P value OR(CI)
PPROM n(%) 4(5.9) 10(29.4) <0.05 0.15(0.044,0.53)
Preterm labor n(%)
5(7.4) 4(11.7) 0.47 0.605( 0.15,2.41)
VLBW n(%) 10(14.9) 9(26.4) 0.16 0.487(0.17,1.36)
Extra –mural n(%) 54(80) 15(44.1) <0.05 5.2(2.1-12.9)
GI surgery n(%) 8(11.9) 2(5.8) 0.335 2.16 (0.43,10.8)
Age of onset of symptoms in days Median(IQR)
3(1,9) 3(1,5.5) 0.561
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Clinical Profile
Clinical Profile MDR sepsis(N=67)
Non MDR sepsis (N=34)
P value
Hypoglycemia n(%)
9(13.4) 4(11.7) 0.812
Respiratory failure n (%)
52(77.6) 25(73.5) 0.648
Hypothermia n(%)
4(5.9) 1(2.9)) 0.507
Shock n(%) 30(44.7) 10(29.4) 0.135
Feed Intolerance n(%)
28(41.7) 10(29.4) 0.992
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Results: Organism isolated
• MDR Klebsiella pneumoniae (56.7%)
Organism (N) MDR (N=67) Non MDR(N=34)
Klebsiella pneumoniae 38(56.7) 14(41.1)
Acinetobacter baumanii 13(19.4) 10(29.4)
Burkholderia cepacia 5(7.4) 2(5.8)
E.coli 3(4.4) 3(8.8)
Pseudomonas aeruginosa 3(4.4) 1(2.9)
Stenotophomonas maltophilla 2(2.9) 0
Enetrobacter 4(5.9) 2(5.8%)
Serratia marcesence 1(1.4) 0
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Primary Outcome
Outcome MDR sepsis ( N=67)
Non MDR sepsis ( N=34)
P value OR( CI)
Death n(%) 23 (34.3) 5(14.7) 0.006 3.02(1.03-8.88)
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Secondary outcomes
Duration, Median( IQR)
MDR sepsis Non MDR sepsis P value
IV antibiotics (days) 14(10,16) 14(14,16) 0.674
Parenteral nutrition(hrs)
96(48,200) 120(48,240) 0.088
Invasive ventilation(hrs)
96(48,135) 110(30,168) 0.098
Noninvasive ventilation (hrs)
54(24,120) 72(48,245) 0.779
Inotropic support (in hrs)
72(72,120) 60(27,94) 0.609
Total duration of Hospital stay (days)
14(13,21) 21(15,32) <0.05
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Secondary Outcome: Need for blood products
Bloodproduct
MDR sepsis ( N=67)
Non MDR sepsis ( N=34)
P value OR( CI)
Platelet n (%)
33(49.3) 10(29.4) <0.05 2.3( 0.97,5.61
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Discussion
• Previous studies assessing risk factors and outcome of MDR GNB sepsis
in newborns showed similar results
• Anucha et al found Klebsiella pneumonia as most common isolates
among MDR GNB organisms. There was a significant association of MDR
GNB sepsis with extra-mural neonates( p value 0.003).
• Mortality rate of 37% in MDR GNB sepsis vs 33.5% in non MDR GNB
sepsis.
• Duration of hospital stay, IV therapy was more in MDR group but our
study showed no statistical difference.
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Discussion
• A cohort study from Taiwan showed 18.6% of GNB sepsis
was caused by MDRO, most common organism was
Klebsiella pneumonia( 59.6%) and mortality of 28.6% in
MDR GNB sepsis group as compared to 10% in non MDR
GNB sepsis group.
• DeNIS study from India showed mortality of 15.7% in MDR
GNB sepsis vs 12% in non MDR GNB sepsis.
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Limitation
• Retrospective study design
• Data regarding other risk factors such as previous antibiotic
exposure, central catheter insertion was missing.
• Long term assessment of survivors with GNB sepsis was not
done
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Conclusion
• In this study, the major risk factor for MDR - GNB sepsis was
extramural delivery
• Severity of clinical profile on admission in MDR GNB sepsis
was more though statistically insignificant
• Most common organism causing MDR sepsis was Klebsiella
pneumonia
• Mortality was more with MDR GNB sepsis
• Need for blood products was more in MDR GNB sepsis
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Take home message
• MDR GNB sepsis is associated with higher morbidity and
mortality
• Clinicians should be aware of the condition and antibiotic
stewardship is the way forward.
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Thank You!!!