The current and future roles of neonatal infection surveillance programmes in combating antimicrobial resistance

doi:10.1016/j.earlhumdev.2015.08.012

Early Human Development

Volume 91, Issue 11, November 2015, Pages 613-618

https://doi.org/10.1016/j.earlhumdev.2015.08.012 Get rights and content

Abstract

Neonatal sepsis is an important cause of morbidity and mortality, particularly in premature or low birth weight babies. Hospital-acquired blood stream infections represent a significant and largely preventable cause of disease in this population. Neonatal units have been identified as a common site for the development and transmission of antimicrobial-resistant pathogens, a significant issue in modern medicine.

Neonatal surveillance programmes collect prospective data on infection rates and may be used to optimise therapy, benchmark practice and develop quality improvement programmes. Despite this, the number of networks is relatively few and these are largely concentrated in resource-rich nations. Furthermore, surveillance definitions may vary between programmes impairing our ability to draw comparisons between them. Better harmonisation is required between networks to ensure that they achieve their potential as a valuable tool for benchmarking of hospital-acquired infection rates between units.

Introduction

Infants are at a substantial risk of infection during the neonatal period, especially those who are born prematurely or with a very low birth weight (VLBW) [1]. Infection remains a significant cause of morbidity and mortality [2]. In addition, neonatal intensive care units (NICUs) are common sites for the acquisition of antimicrobial-resistant pathogens which may not be susceptible to first-line treatment regimens [1]. Failure to treat early with appropriate antimicrobials may therefore lead to poor outcomes. It is necessary to have a thorough understanding of the current epidemiology of neonatal infections in order to be able to select the best antimicrobial combinations for empiric treatment. This epidemiology is currently poorly defined both in terms of the common causative pathogens of neonatal infection and their antimicrobial resistance rates [3]. Neonatal infection surveillance programmes are an important means of collecting these data in order to optimise antimicrobial treatment protocols and prevent the development of resistance.

Section snippets

Classifications of neonatal sepsis

Neonatal sepsis has classically been divided into two distinct clinical groups which aim to categorise the infection episode by the likely source of the responsible pathogen. This classification system guides first-line empiric antibiotic therapy as clinical presentations are typically non-specific and it is necessary to initiate treatment before a positive culture result is available [1]. Early-onset sepsis (EOS) is variably defined as occurring before 48 or 72 h of life and is the result of

Early-onset sepsis

Neonatal intensive care specialists are hampered by a relative paucity in high quality epidemiological data on neonatal infections [4]. The incidence of EOS in the UK has been reported as 0.5–0.9 cases per 1000 live-births and 9 per 1000 neonatal admissions [3], [4]. Importantly, a disproportionate number of episodes of EOS occur in VLBW and premature infants < 32 weeks.

The epidemiology of EOS varies significantly between the UK and other countries. A prominent example of this can be seen when

Antimicrobial resistance

NICUs have been identified as a high-risk area with regards to the development and transmission of antimicrobial-resistant pathogens [20], [21]. This may in part be due to the overuse of antibiotics in NICUs with up to 95% of admitted infants receiving empirical antibiotics despite only 1–5% returning positive blood cultures [2].

There is a proven causal link between antimicrobial exposure and the development of resistance [15]. Injudicious use of antibiotics or preferential selection of

Neonatal infection surveillance programmes

Neonatal infection surveillance programmes collect prospective data on infection episodes from NICUs with the aim of monitoring the changes in the epidemiology of pathogens and their antimicrobial susceptibilities over time. This information may then be used to benchmark practice, inform policy and improve quality of care [3]. Infection surveillance may be single- or multi-centre in nature with both providing useful clinical information. Single-centre studies provide detailed information about

Conclusion

Neonatal sepsis is a significant cause of morbidity and mortality in the UK and worldwide, particularly in VLBW and preterm infants. The requirement of clinicians to treat in the absence of culture results means that a comprehensive understanding of the epidemiology of neonatal infections and associated levels of antimicrobial resistance is required. Neonatal infection surveillance programmes are a useful tool for improving our understanding of the epidemiology and for developing quality

Conflicts of interest

Nothing to declare.

References (23)

F. Schwab et al.
Reducing neonatal nosocomial bloodstream infections through participation in a national surveillance system
J Hosp Infect
(2007)
K.A. Fedler et al.
Assessment of pathogen frequency and resistance patterns among pediatric patient isolates: report from the 2004 SENTRY antimicrobial surveillance program on 3 continents
Diagn Microbiol Infect Dis
(2006)
B.A. Shah et al.
Neonatal sepsis: an old problem with new insights
Virulence
(2014)
C. Tzialla et al.
Neonatal infections due to multi-resistant strains: epidemiology, current treatment, emerging therapeutic approaches and prevention
Clin Chim Acta
(2015)
S. Vergnano et al.
Neonatal infections in England: the NeonIN surveillance network
Arch Dis Child Fetal Neonatal Ed
(2011)
N.D. Embleton
Northern region's perinatal mortality survey. Fetal and neonatal death from maternally acquired infection
Paediatr Perinat Epidemiol
(2001)
B. Muller-Pebody et al.
Empirical treatment of neonatal sepsis: are the current guidelines adequate?
Arch Dis Child Fetal Neonatal Ed
(2011)
L. Folgori et al.
A systematic review of strategies for reporting of neonatal hospital-acquired bloodstream infections
Arch Dis Child Fetal Neonatal Ed
(2013)
C.M. Healy et al.
Distinguishing true coagulase-negative Staphylococcus infections from contaminants in the neonatal intensive care unit
J Perinatol
(2013)
E.A. Biondi et al.
Blood culture time to positivity in febrile infants with bacteremia
JAMA Pediatr
(2014)

A.M. Fernando et al.

Antimicrobial policies in the neonatal units of the United Kingdom and Republic of Ireland

J Antimicrob Chemother

(2008)

Cited by (24)

Antimicrobial use for treatment of healthcare-associated infections and bacterial resistance in a reference neonatal unit
2021, Jornal de Pediatria
Citation Excerpt :
As an empirical guide to treat these types of infections, they are grouped into two categories, early and late onset-infections.1,3,7–12 For the treatment of early sepsis, the bacteria in the maternal genital-urinary tract are considered; for late sepsis, the microbiological profile of the neonatal unit must be taken into account.1,3,7–12 Usually, the symptoms of HAI are nonspecific and similar to other common conditions of neonates, such as respiratory, metabolic, hydro electrolytic, and thermoregulatory disorders.1,6–11
The use of broad-spectrum antimicrobials, such as third and fourth-generation, are responsible for emergence of multidrug-resistant microorganisms in neonatal units. Furthermore, antimicrobial daily doses are not standardized in neonatology. This study aimed to investigate the association between the use of antimicrobial broad spectrum to bacterial sensitivity profile in a referral unit of neonatal progressive care.
This is a cohort study conducted in a referral neonatal progressive care unit from January 2008 to December 2016. The data of all hospitalized neonates was collected daily. The infection criteria used were the standardized national criteria, based on definitions of Center for Diseases Control and Prevention. In this study, the use of antimicrobials was evaluated as antimicrobial-day (ATM-day) and the ratio of multidrug-resistant microorganisms per 1000 ATM-day of broad spectrum was also calculated. The study was approved by the Institutional Review Board of the Universidade Federal de Minas Gerais (ETIC 312/08 e CAAE 58973616.2.0000.5149).
From 2008 to 2016, 2751 neonates were hospitalized, corresponding to 60,656 patient-days. The ratio of multidrug-resistant microorganisms per 1000 ATM-day of broad spectrum was 1,3 in the first period and 4,3 in the second period (p = 0,005).
It was observed that use of broad-spectrum antimicrobials, especially those with coverage for Gram-negative bacteria, was associated with an increase of multidrug-resistant bacteria.
Effect of a surveillance system for decreasing neonatal nosocomial infections
2019, Early Human Development
Nosocomial infection in very low birthweight (VLBW) infants is a common complication with high morbimortality. New strategies to reduce its occurrence have recently led to the development of neonatal surveillance programs.
To determine whether the NeoKissEs surveillance system implementation in our neonatal unit has been associated with a decrease in nosocomial infection in VLBW infants, as well as a reduction in the use of antibiotics and central venous catheters (CVC).
Retrospective and descriptive study of infants <1500 g admitted between January 2011 and December 2017. Rates of use of antibiotics and CVC were calculated, as well as late-onset sepsis incidence. Data were compared before and after the surveillance system implementation.
299 patients were recruited. We excluded seven patients, who died <72 h. Of the remainder (n = 292), 149 were in the pre-intervention period and 143 in the post-intervention period. We found a significant decrease in the incidence density of sepsis comparing these two periods (5.98 vs. 4.08) (p = 0.03). Although no differences in antibiotic and CVC rates of use between both groups were found, a significant decrease in antibiotic use was observed comparing the first and last year of the intervention (38% vs. 24%) (p = 0.03). A higher percentage of breastfed infants was observed (39% vs. 59%) (p = 0.001) in the post-intervention group.
Surveillance systems are useful to reduce nosocomial infection in VLBW infants. Reduction in antibiotic and CVC use requires longer intervention time. Promotion of breastfeeding seems to be a very effective associated strategy.
Barriers to implementing the NICE guidelines for early-onset neonatal infection: cross-sectional survey of neonatal blood culture reporting by laboratories in the UK
2018, Journal of Hospital Infection
The National Institute for Health and Care Excellence published guidelines for managing early-onset neonatal infections in 2012. It recommended provision for reporting blood cultures (BCs) with growth detected or not detected at 36 h. To determine if this was followed, a telephone survey was conducted amongst lead biomedical scientists based at microbiology laboratories (N = 209) in the UK. Overall, 202/209 responded and 139/202 had on-site facilities for BCs. BC results with growth detected or not detected at 36 h were available out-of-hours in 36/139 (26.6%) and 66/139 (47.5%) neonatal units, respectively. Early discontinuation of antibiotics should lead to improved antibiotic stewardship.
Characterisation and antimicrobial resistance of sepsis pathogens in neonates born in tertiary care centres in Delhi, India: a cohort study
2016, The Lancet Global Health
Citation Excerpt :
The currently available multisite studies on sepsis are from well-established surveillance networks in high-income countries such as the USA,4 the UK,5 and Germany.6 Such infection surveillance networks are a rarity in low-income and middle-income countries;3 the few available ones have used passive surveillance (eg, the National Neonatal Perinatal Database [NNPD]7 and the Asia-Pacific Neonatal Infections Study [APNIS]8). Most of the other studies from low-income and middle-income countries are typically from a single site, retrospective, or have relied on routine laboratory reports.9–12
Sepsis is one of the most common causes of neonatal deaths globally. Most sepsis-related deaths occur in low-income and middle-income countries, where the epidemiology of neonatal sepsis remains poorly understood. Most of these countries lack proper surveillance networks, hampering accurate assessment of the burden of sepsis, implementation of preventive measures, and investment in research. We report results of neonates born in hospital from a multicentre collaboration on neonatal sepsis.
In this cohort study, dedicated research teams prospectively followed up neonates born in one of three tertiary care centres in Delhi, India (Vardhaman Mahavir Medical College, Maulana Azad Medical College, and All India Institute of Medical Sciences [coordinating centre]) and subsequently admitted to the intensive care unit. Neonates were followed up daily until discharge or death. On clinical suspicion, neonates underwent sepsis work-up including blood cultures. The isolated organisms were identified and tested for antimicrobial susceptibility. We defined Gram-negative isolates resistant to any three of five antibiotic classes (extended-spectrum cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and piperacillin-tazobactam) as multidrug resistant.
13 530 neonates of 88 636 livebirths were enrolled between July 18, 2011, and Feb 28, 2014. The incidence of total sepsis was 14·3% (95% CI 13·8–14·9) and of culture-positive sepsis was 6·2% (5·8–6·6). Nearly two-thirds of total episodes occurred at or before 72 h of life (defined as early onset; 1351 [83%] of 1980). Two-thirds (645 [64%]) of 1005 isolates were Gram-negative including, Acinetobacter spp (22%), Klebsiella spp (17%), and Escherichia coli (14%). The pathogen mix in early-onset sepsis did not differ from that of late-onset sepsis (ie, after 72 h). High rates of multidrug resistance were observed in Acinetobacter spp (181/222, 82%), Klebsiella spp (91/169, 54%), and Escherichia coli (52/137, 38%) isolates. Meticillin resistance prevailed in 61% (85/140) of coagulase-negative staphylococci and 38% (43/114) of Staphylococcus aureus isolates. Nearly a quarter of the deaths were attributable to sepsis. The population-attributable risks of mortality were 8·6% in culture-negative sepsis, 15·7% in culture-positive sepsis by multidrug-resistant organisms, and 12·0% in culture-positive sepsis by non-multidrug-resistant organisms.
The high incidence of sepsis and alarming degree of antimicrobial resistance among pathogens in neonates born in tertiary hospitals underscore the need to understand the pathogenesis of early-onset sepsis and to devise measures to prevent it in low-income and middle-income countries.
Indian Council of Medical Research.
Inadequate use of antibiotics and increase in neonatal sepsis caused by resistant bacteria related to health care assistance: a systematic review
2018, Brazilian Journal of Infectious Diseases
Citation Excerpt :
Currently, it is a worldwide concern due to the associated high morbidity and mortality and increased hospitals costs.1,3,8,12 The inability of the pharmaceutical industry to create new drugs at the same rate as the development of resistance is also an important issue to consider.3,9–11 The excessive use of ATM, especially broad-spectrum agents, is already recognized as a key factor for the development of resistance.1,6,7,9,11–16
Technologies and life support management have enhanced the survival of preterm infants. The immune system of newborns is immature, which contributes to the occurrence of healthcare-associated infections. The overlap of several conditions with neonatal sepsis and the difficulty of diagnosis and laboratory confirmation during this period result in a tendency to over-treat neonatal sepsis. The use of antimicrobial agents is a risk factor for multidrug-resistant bacterial infections. This work aimed to perform a systematic review of the relationship between inadequate use of antimicrobial agents and increase in neonatal sepsis related to healthcare assistance, due to bacterial resistance.
Our population, exposition, comparison, outcome and study type was as follows: P: hospitalized neonates with sepsis diagnosis, E: inappropriate use of antimicrobial agents, C: adequate use of antimicrobial agents or no indication of infection, O: resistant bacterial infection, and S: original studies. We performed searches in the PubMed, Scopus, Virtual Health Library (Scielo, LILACS, and MEDLINE), and Embase without limits on time, language, and the references of the articles found. Fourteen studies were included and assessed using the Grading of Recommendations, Assessment, Development, and Evaluation, Newcastle, and the Strengthening the Reporting of Observacional Studies in Epidemiology methodologies.
All studies found were observational and started with a low-quality evidence level in the Grading of Recommendations, Assessment, Development, and Evaluation.
Despite their low-quality evidence, the studies demonstrated the association between inadequate use of antimicrobial agents and increase of neonatal resistant bacterial healthcare-associated infections in neonatal units. However, there is significant difficulty in conducting high-quality studies in this population due to ethical issues tied to randomized trials. Therefore, new studies should be encouraged to recommend adequate treatment of newborns without increasing the risk of healthcare-associated infections by multidrug-resistant bacteria.
A First Look into the Acute Effects of a Neonatal Inflammation Episode on the Nociceptive System
2023, Douleur et Analgesie

View all citing articles on Scopus

¹: Address: St. Georges, University of London, Jenner Wing, Level 2, London SW17 0RE, UK. Tel.: + 44 20 8725 2788; fax: + 44 20 8725 0716.

²: Address: St. Georges, University of London, Jenner Wing, Level 2, London SW17 0RE, UK. Tel.: + 44 20 8725 5382; fax: + 44 20 8725 0716.

³: Address: St. Georges, University of London, Jenner Wing, Level 2, London, SW17 0RE, UK. Tel.: + 44 20 8725 5980; fax: + 44 20 8725 0716.

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ReviewThe current and future roles of neonatal infection surveillance programmes in combating antimicrobial resistance

Abstract

Introduction

Section snippets

Classifications of neonatal sepsis

Early-onset sepsis

Antimicrobial resistance

Neonatal infection surveillance programmes

Conclusion

Conflicts of interest

J Hosp Infect

Diagn Microbiol Infect Dis

Neonatal sepsis: an old problem with new insights

Virulence

Neonatal infections due to multi-resistant strains: epidemiology, current treatment, emerging therapeutic approaches and prevention

Clin Chim Acta

Neonatal infections in England: the NeonIN surveillance network

Arch Dis Child Fetal Neonatal Ed

Northern region's perinatal mortality survey. Fetal and neonatal death from maternally acquired infection

Paediatr Perinat Epidemiol

Empirical treatment of neonatal sepsis: are the current guidelines adequate?

Arch Dis Child Fetal Neonatal Ed

A systematic review of strategies for reporting of neonatal hospital-acquired bloodstream infections

Arch Dis Child Fetal Neonatal Ed

Distinguishing true coagulase-negative Staphylococcus infections from contaminants in the neonatal intensive care unit

J Perinatol

Blood culture time to positivity in febrile infants with bacteremia

JAMA Pediatr

Antimicrobial policies in the neonatal units of the United Kingdom and Republic of Ireland

J Antimicrob Chemother

Review
The current and future roles of neonatal infection surveillance programmes in combating antimicrobial resistance