Archive | 2021
Pathogens Distribution and Antimicrobial Resistance in Bloodstream Infections in Twenty-Five Neonatal Intensive Care Units in China, 2017-2019
Abstract
Background: Overcrowding, abuse of antibiotics and increasing antimicrobial resistance negatively affect neonatal survival rates in developing countries. We aimed to define pathogens and their antimicrobial resistance (AMR) of early-onset sepsis (EOS), hospital-acquired late-onset sepsis (HALOS) and community-acquired late-onset sepsis (CALOS) in 25 neonatal intensive care units (NICUs) in China. Study design: This retrospective descriptive study included pathogens and their AMR from all neonates with bloodstream infections (BSIs) admitted to 25 tertiary hospitals in China from January 1, 2017, and December 31, 2019. We defined EOS as the occurrence of BSI at or before 72 h of life and late-onset sepsis (LOS) if BSI occurred after 72 h of life. LOS were classified as CALOS if occurrence of BSI was ≤ 48 h after admission, and HALOS, if occurrence was > 48 h after admission. Results: We identified 1092 pathogens of BSIs in 1088 infants from 25 NICUs. Thirty-two percent of all pathogens were responsible for EOS, 64.3% HALOS, and 3.7% CALOS. Gram-negative (GN) bacteria accounted for a majority of pathogens in EOS (56.7%) and HALOS (62.2%). The most frequent pathogens causing EOS were Escherichia coli (27.2%) and group B streptococcus (GBS; 14.6%) whereas in CALOS they were GBS (46.3%) and Staphylococcus aureus (41.5%). Klebsiella pneumoniae (27.9%), Escherichia coli (15.7%) and Fungi (12.8%) were the top three isolates in HALOS. Third-generation cephalosporin resistance rates in GN bacteria ranged from 9.7 to 55.6% in EOS and 26% to 63.3% in HALOS. Carbapenem resistance rates in GN bacteria ranged from 2.7 to 31.3% in HALOS and only six isolates in EOS were carbapenem resistant. High rates of multidrug resistance were observed in Klebsiella pneumoniae (60.7%) in HALOS and in Escherichia coli (44.4%) in EOS. All gram-positive bacteria were susceptible to vancomycin except for three Enterococcus faecalis in HALOS. All-cause mortality was higher among neonates with EOS than HALOS (7.4% VS 4.4%, [OR] 0.577, 95% CI 0.337–0.989; P = 0.045). © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Open Access *Correspondence: [email protected] 1 Department of Neonatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China Full list of author information is available at the end of the article Page 2 of 11 Liu et al. Antimicrob Resist Infect Control (2021) 10:121 Background Neonatal bloodstream infection (BSI) is the third most common cause of neonatal morbidity and mortality globally, and is an ongoing major global public health challenge [1, 2]. Asia and Africa have the highest burden of BSIs in the world [2]. Scarcity in resources, insufficient surveillance and infection control, abuse of antibiotics and increase of antimicrobial resistance in low-income and middle-income countries (LMICs) may contribute to this situation [3, 4]. The risk of emergence and spread of antibiotic resistance in South East Asia is thought to be among the highest among all the WHO regions [5, 6]. Monitoring resistance in disease causing pathogens is of particular importance for neonatal BSIs in LMICs, where most treatments are empirically prescribed but should be based on reliable contemporaneous resistance data. Neonatal sepsis was classified into early onset sepsis (EOS) and late onset sepsis (LOS) routinely [7, 8]. EOS generally reflects vertical transmission from mothers while LOS cases were likely due to pathogens acquired after delivery and often from nosocomial infections [9]. A previous meta-analysis reported that Staphylococcus species, especially Coagulase negative Staphylococcus (CoNS) continue to be the principal organisms of neonatal sepsis in China [10]. Nevertheless, more recent data described Klebsiella pneumoniae as the most frequent pathogen, with widespread antimicrobial resistance (AMR) [11]. Klebsiella pneumoniae was primarily associated with LOS, greater morbidity, mortality and limited treatment options in neonates [11, 12]. In China, multicenter reports on pathogens of neonatal BSI were scarce and were limited to specific gestational age groups or not involving resistance analysis of antibiotics [12, 13]. Currently, data on antimicrobial resistance (AMR) distinguishing between community-acquired LOS (CALOS) and hospitalacquired LOS (HALOS) in neonates are also scarce [3, 14]. Detecting emerging resistance in neonatal BSI is vital in order to optimise empiric antibiotic therapy in HALOS, in accordance with antimicrobial stewardship principle and to reduce mortality. The present study assessed the benchmark in neonatal sepsis, distinguishing between EOS, HALOS, and CALOS, and covering the neonatal population of entire gestational age groups. Methods Settings and infection control methods Twenty-five tertiary hospitals participated in the current study. Among the hospitals, twenty-three tertiary hospitals were located in Shandong province which involving 13 major cities, one tertiary hospital in Hebei province and the other one in the Inner Mongolia Autonomous Region. Nineteen hospitals were general hospitals and 6 were maternal and child health care hospitals. Because all 25 hospitals have their own maternity/ obstetric ward, most neonates were born on site and only a few were transferred. The number of beds ranged from 20 to 60. The ratio of nurses to bed ranged from 0.4 to 1.2 and physician to nurse ranged from 0.3 to 0.5. The bed occupancy rate was maintained above 90%. All 25 hospitals have an infection control committee. Trained infection control nurses were available at all units at all times. All NICUs had a hand hygiene policy, but no audits of staff compliance were undertaken. Alcohol-based hand rub solutions and disinfectant dispensers filled with betadine 7.5% were provided at hand-wash sinks, and clean disposable tissue papers for hand-drying were sufficiently available. None of 25 NICUs had laminar flow devices. Surveillance cultures were only used when an outbreak was suspected but were not routinely undertaken. Identification and susceptibility testing Blood cultures were performed for any infant presenting with clinical signs or symptoms of sepsis according to the local guidelines of each hospital. Blood samples were collected by trained nurses or physicians. Venipuncture sites were prepared with 75% isopropyl alcohol, followed by iodine tincture, and then wiped with alcohol. Skin site was allowed to dry for 1 min prior to venipuncture. A general policy of using one culture bottle exclusively for newborns with at least 1 ml of blood sample was adopted by all hospitals. The sample was delivered to the microbiology laboratory within 2 h of collection by staff members. Training of blood culture collection procedures were undertaken regularly in local hospitals. Each microbiology laboratory performed routine microbiology tests, including organism identification and antimicrobial susceptibility testing (AST). Blood cultures were performed at recruited hospital laboratories and incubated using Bactec FX system (Becton Dickinson, USA) in 15 hospitals and BacT/ALERT 3D system (bioMérieux, Conclusions: Escherichia coli, Klebsiella pneumoniae and GBS were the leading pathogens in EOS, HALOS and CALOS, respectively. The high proportion of pathogens and high degree of antimicrobial resistance in HALOS underscore understanding of the pathogenesis and emphasise the need to devise effective interventions in developing countries.