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

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

• 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

Objective

• To assess the risk factors and outcome of neonates with MDR

GNB sepsis

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

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

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

Statistical Analysis

• Data was collected in a predesigned proforma and entered

in the Microsoft Excel software

• Data analyzed using SPSS software

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)

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

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

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

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)

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

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

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.

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.

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

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

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.

Thank You!!!