Diagnosis of Neonatal Late-Onset Infection in Very Preterm Infant: Inter-Observer Agreement and International Classifications

Abstract

Background: The definition of late-onset bacterial sepsis (LOS) in very preterm infants is not unified. The objective was to assess the concordance of LOS diagnosis between experts in neonatal infection and international classifications and to evaluate the potential impact on heart rate variability and rate of “bronchopulmonary dysplasia or death”. Methods: A retrospective (2017–2020) multicenter study including hospitalized infants born before 31 weeks of gestation with intention to treat at least 5-days with antibiotics was performed. LOS was classified as “certain or probable” or “doubtful” independently by five experts and according to four international classifications with concordance assessed by Fleiss’s kappa test. Results: LOS was suspected at seven days (IQR: 5–11) of life in 48 infants. Following expert classification, 36 of them (75%) were considered as “certain or probable” (kappa = 0.41). Following international classification, this number varied from 13 to 46 (kappa = −0.08). Using the expert classification, “bronchopulmonary dysplasia or death” occurred less frequently in the doubtful group (25% vs. 78%, p < 0.001). Differences existed in HRV changes between the two groups. Conclusion: The definition of LOS is not consensual with a low international and moderate inter-observer agreement. This affects the evaluation of associated organ dysfunction and prognosis.

Epidemiology, risk factors, clinical presentation and complications of late-onset neonatal sepsis among preterm neonates in Cyprus: a prospective case-control study

“…However, the study is characterized by some limitations, with the most important one being the high percentage of LOS attributed to CoNS. Although CoNS is a frequently identifiable LOS pathogen [ 77 – 79 ], it is also a common blood culture contaminant. For this reason, a laboratory–confirmed bloodstream infection for CoNS requires 2 or more blood cultures drawn on separate occasions according to CDC/NHSN guidelines [ 31 ], although this was not the practice in our NICU.…”

“…For this reason, a laboratory–confirmed bloodstream infection for CoNS requires 2 or more blood cultures drawn on separate occasions according to CDC/NHSN guidelines [ 31 ], although this was not the practice in our NICU. Like in other settings, low blood volume and the need to start antibiotic therapy without delay, only rarely allow two blood cultures to be taken before treatment is initiated [ 79 ]. Although blood collection was carried out by competent staff using strict aseptic techniques, there is a possibility that some of the subjects were misclassified (i.e., included in the “Confirmed LOS” group, while these should have been classified as “Unconfirmed LOS”).…”

The Role of Coagulase-Negative Staphylococci Biofilms on Late-Onset Sepsis: Current Challenges and Emerging Diagnostics and Therapies

“…Despite the fair advances made in medicine over the years, LOS is still challenging to quickly and accurately diagnose, leading to delays in the application of an adequate treatment, which in turn may result in a higher risk of complications and, ultimately, a higher mortality rate [ 191 ]. This difficulty is attributed to several factors such as (i) variable or non-specific symptoms displayed by neonates [ 21 , 192 ], (ii) the maternal intrapartum antibiotic therapy that can mask the presence of bacteria [ 193 ] and (iii) the technical limitations of the diagnosis methods currently used [ 26 , 194 ]. Currently, the gold standard for the diagnosis of LOS is the identification of the causative agent through culture methods, namely from blood samples [ 195 , 196 ].…”