LATE-ONSET SEPSIS (LOS) AND COLONISATION BY GRAM-NEGATIVE BACTERIA IN HOSPITALISED NEONATES IN A NEONATAL NETWORK- THE NeoHIEC-STUDY (ON BEHALF OF THE NeoHIEC CONSORTIUM, SOUTH-LONDON,UK)

Abstract Primary Subject area Neonatal-Perinatal Medicine Background Late-onset sepsis (LOS) is associated with adverse neonatal outcome. There is limited data on the long-term neurodevelopmental (ND) outcomes of infants based on type of bacteria causing LOS. We hypothesize that the type of bacterial pathogen causing late-onset sepsis influences the developmental outcome in extremely preterm infants. Objectives To compare the neurodevelopmental (ND) outcomes at 18-24 months corrected age (CA) of infants born < 29 weeks who had late-onset sepsis (LOS) caused by: (1) gram-positive bacteria; (2) gram-negative bacteria; (3) mixed (both gram-positive and gram-negative bacteria); and (4) those with no sepsis (that is, no sepsis or culture-negative sepsis). Design/Methods In this retrospective multicentre cohort study, we studied infants born at <29 weeks’ gestational age (GA) between January 2010 and December 2017 and evaluated for neurodevelopmental assessment at 18–24 months’ CA at nine Canadian Neonatal Follow-up Network centers. Infants with early-onset sepsis, major congenital anomalies, those who received palliative care at birth, those who died before 2 days of age, those with non-bacterial infections, and those lost to follow up were excluded. Exposure is late-onset sepsis (LOS) which is defined as the presence of a pathogenic organism in the blood or cerebrospinal fluid culture obtained from a neonate suspected of having sepsis after 2 days of age. The primary outcome was a composite of death or ND impairment (NDI) defined as the presence of any one of the following: cerebral palsy, Bayley-III score of <85 on any one of the components (Cognitive, Language, Motor composite score), hearing loss, and visual impairment. Demographic factors and ND outcomes were compared among the four groups using univariate and multivariate analysis. Results Of the 3640 infants included, 823 (22.6%) had late-onset sepsis (LOS). Of the 823 infants with LOS, 569 (69.1%) infants had gram-positive sepsis, 172 (20.9%) had gram-negative sepsis, and 82 (10%) had mixed sepsis. Maternal and neonatal characteristics and outcome are reported in Table 1. Outcome data after adjustment for gestational age (GA), sex, antenatal steroids, SNAP-II score, small for gestational age (SGA), maternal age, and caesarian delivery are presented in Table 2. Conclusion Late-onset bacterial sepsis, especially gram-negative sepsis and mixed infections, were associated with increased risk of composite outcome of death or neurodevelopmental impairment (NDI), or NDI alone, at 18-24 months corrected age (CA) in infants <29 weeks’ gestational age (GA).

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

Journal of Pure and Applied Microbiology ◽

10.22207/jpam.15.4.66 ◽

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.

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Predicting late-onset sepsis by routine neonatal screening for colonisation by gram-negative bacteria in neonates at intensive care units: a protocol for a systematic review

BMJ Open ◽

10.1136/bmjopen-2016-014986 ◽

2017 ◽

Vol 7 (3) ◽

pp. e014986 ◽

Cited By ~ 4

Author(s):

Thomas Harder ◽

Juliane Seidel ◽

Tim Eckmanns ◽

Bettina Weiss ◽

Sebastian Haller

Keyword(s):

Systematic Review ◽

Intensive Care ◽

Intensive Care Units ◽

Neonatal Screening ◽

Late Onset ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Late Onset Sepsis

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Risk factors and clinical outcomes for carbapenem-resistant Gram-negative late-onset sepsis in a neonatal intensive care unit

Journal of Hospital Infection ◽

10.1016/j.jhin.2017.05.025 ◽

2017 ◽

Vol 97 (1) ◽

pp. 52-58 ◽

Cited By ~ 16

Author(s):

I. Nour ◽

H.E. Eldegla ◽

N. Nasef ◽

B. Shouman ◽

H. Abdel-Hady ◽

...

Keyword(s):

Risk Factors ◽

Intensive Care Unit ◽

Intensive Care ◽

Neonatal Intensive Care Unit ◽

Clinical Outcomes ◽

Neonatal Intensive Care ◽

Late Onset ◽

Gram Negative ◽

Carbapenem Resistant ◽

Late Onset Sepsis

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Conventional Versus Prolonged Infusion of Meropenem in Neonates With Gram-negative Late-onset Sepsis

The Pediatric Infectious Disease Journal ◽

10.1097/inf.0000000000001445 ◽

2017 ◽

Vol 36 (4) ◽

pp. 358-363 ◽

Cited By ~ 18

Author(s):

Abd Elazeez Shabaan ◽

Islam Nour ◽

Heba Elsayed Eldegla ◽

Nehad Nasef ◽

Basma Shouman ◽

...

Keyword(s):

Late Onset ◽

Prolonged Infusion ◽

Gram Negative ◽

Late Onset Sepsis

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

Community Based Medical Journal ◽

10.3329/cbmj.v2i1.14184 ◽

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 Womens 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

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Meropenem vs standard of care for treatment of neonatal late onset sepsis (NeoMero1): a randomised controlled trial

10.1101/456871 ◽

2018 ◽

Author(s):

Irja Lutsar ◽

Corine Chazallon ◽

Ursula Trafojer ◽

Vincent Meiffredy de Cabre ◽

Cinzia Auriti ◽

...

Keyword(s):

Adverse Events ◽

Broad Spectrum ◽

Late Onset ◽

Standard Of Care ◽

Phase Iii ◽

Successful Outcome ◽

Broad Spectrum Antibiotic ◽

Gram Negative ◽

Late Onset Sepsis ◽

Full Analysis

AbstractBackgroundThe early use of broad-spectrum antibiotics remains the cornerstone for the treatment of neonatal late onset sepsis (LOS). However, which antibiotics should be used is still debatable, as relevant studies were conducted more than 20 years ago, were single centre or country, insufficiently powered, evaluated antibiotics not in clinical use anymore and had variable inclusion/exclusion criteria and outcome measures. Moreover, antibiotic-resistant bacteria have become a major problem in many countries worldwide. We hypothesized that efficacy of meropenem as a broad spectrum antibiotic is superior to standard of care regimen (SOC) in empiric treatment of LOS and thus aimed to compare the efficacy and safety of meropenem to SOC in infants aged <90 days with LOS.Methods and findingsNeoMero-1 was a randomized, open-label, phase III superiority trial conducted in 18 neonatal units in 6 countries. Infants with post-menstrual age (PMA) of ≤44 weeks with positive blood culture and one, or those with negative culture and at least with two predefined clinical and laboratory signs suggestive of LOS, or those with PMA >44 weeks meeting the Goldstein criteria of sepsis, were randomized in a 1:1 ratio to receive meropenem or SOC (ampicillin+gentamicin or cefotaxime+gentamicin) for 8-14 days. The primary outcome was treatment success (survival, no modification of allocated therapy, resolution/improvement of clinical and laboratory markers, no need of additional antibiotics and presumed/confirmed eradication of pathogens) at test-of-cure visit (TOC) in full analysis set. Stool samples were tested at baseline and day 28 for meropenem-resistant Gram-negative organisms (CRGNO).The primary analysis was performed in all randomised patients (full analysis set) and in patients with culture confirmed LOS. Proportions of participants with successful outcome were compared by using a logistic regression model adjusted for the stratification factors.From September 3rd 2012 to November 30th 2014, in total 136 patients in each arm were randomized; 140 (52%) were culture positive. Success at TOC was achieved in 44/136 (32%) in the meropenem arm vs. 31/135 (23%) in the SOC arm (p=0.087); 17/63 (27%) vs. 10/77 (13%) in patients with positive cultures (p=0.022). The main reason of failure was modification of allocated therapy. Adverse events occurred in 72% and serious adverse events in 17% of patients, the mortality rate was 6% with no differences between study arms. Cumulative acquisition of CRGNO by day 28 occurred in 4% in the meropenem and 12% in the SOC arm (p=0.052).ConclusionsMeropenem was not superior to SOC in terms of success at TOC, short term hearing disturbances, safety or mortality and did not outselect colonization with CRGNOs. Meropenem as broad-spectrum antibiotic should be reserved for neonates who are more likely to have Gram-negative LOS, especially in NICUs where microorganisms producing ESBL and AmpC beta-lactamases are circulating.

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