**1. Introduction**

Healthcare-associated infections (HAIs) are among the most serious preventable complications in neonatal intensive care units (NICUs) [1]. Preterm infants are susceptible to HAIs because of their immature immune systems and prolonged need for indwelling catheters [2]; the risk of these diseases is inversely associated with birth weight and gestational age and increases with time spent in care [3]. The most common type of HAI in NICUs is bloodstream infection (BSI), which can occur in isolation or in association with urinary tract infections and meningitis [3]. The main microorganisms responsible for HAIs include *Staphylococcus aureus*, coagulase-negative *Staphylococci*, and *Enterococci*. In addition, recent years have recorded a considerable increase in HAIs sustained by Gramnegative bacteria and fungi, especially *Candida* spp., which are mainly responsible for ventilator-associated pneumonia (VAP) and urinary tract infections, but also for peritonitis and meningitis [3,4].

According to a study conducted in 2016/2017 [5] using the European Centre for Disease Prevention and Control protocol, the prevalence of HAIs in Italian NICUs was around 5%. However, the organizational challenges experienced during the COVID-19 pandemic may have limited the effectiveness of traditional HAI prevention and control efforts, resulting in an increase in their incidence, as already reported for the adult intensive

**Citation:** Ceparano, M.; Sciurti, A.; Isonne, C.; Baccolini, V.; Migliara, G.; Marzuillo, C.; Natale, F.; Terrin, G.; Villari, P.; The Collaborating Group. Incidence of Healthcare-Associated Infections in a Neonatal Intensive Care Unit before and during the COVID-19 Pandemic: A Four-Year Retrospective Cohort Study. *J. Clin. Med.* **2023**, *12*, 2621. https://doi.org/10.3390/ jcm12072621

Academic Editors: Olivier Mimoz, Luca Brazzi and Giorgia Montrucchio

Received: 2 March 2023 Revised: 24 March 2023 Accepted: 29 March 2023 Published: 30 March 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

care unit (ICU) of Umberto I teaching hospital of Rome [6] or in a recent systematic review that investigated *Pseudomonas aeruginosa* bacteremia [7]. Indeed, despite NICUs having one of the lowest COVID-related caseloads among all ICUs, they are still vulnerable to indirect adverse effects of the COVID-19 pandemic [8]. During the pandemic, NICUs faced challenges that were different in nature from those in pediatric and adult ICUs; there were particular concerns relating to clinical workflows and parent–child interactions [9,10], including uncertainty in how to address the risk of exposure for mothers and their babies, reorganization of processes and operations aimed at minimizing risks to staff and patients, and frequent changes in clinical scenarios [8].

While the impact of the pandemic on incidence rates of nosocomial infections in adult ICUs has been investigated [6,11–13], data from the NICU setting are scarce. A few indirect effects of the pandemic on NICUs have been described, such as psychological distress or obstacles in implementing family-centered care [14]. In addition, a reduction in hospitalwide availability of alcohol-based hand rubs was reported to be associated with an increase in the rate of central line-associated BSIs in a single-center study [8]. However, few studies have investigated the impact of pandemic-related measures on the incidence of HAIs in preterm infants admitted to NICUs [8,15]. Therefore, the aim of this study was to analyze the occurrence of HAIs in neonates admitted to the NICU of Umberto I teaching hospital of Rome before and during the COVID-19 pandemic and to identify key factors associated with HAI onset.

#### **2. Materials and Methods**

#### *2.1. Setting*

In this cohort study, we retrospectively analyzed patients hospitalized in the NICU of Umberto I teaching hospital of Rome from 1 March 2018 to 28 February 2022. Patients were followed until discharge or 23 March 2022. The NICU has a total of six beds in which healthcare providers take care of critically ill babies born in this hospital or coming from other hospitals in Rome and the Lazio region via the Neonatal Emergency Transport Service. We followed the STROBE guidelines to report our findings. Microorganisms' antimicrobial susceptibility profiles were defined according to the classification proposed by Magiorakos et al. [16] (if applicable), whereas coagulase-negative *Staphylococci* were considered as susceptible or resistant to oxacillin and/or glycopeptides [17]. The institutional ethics board of the Umberto I teaching hospital of Rome approved this study (protocol no. 888/2022).

#### *2.2. Data Collection*

Data about patients hospitalized in the NICU were retrieved from the prospective patient-based HAI surveillance system that has been conducted in the unit since March 2014 by the Department of Public Health and Infectious Diseases of Sapienza University of Rome. The surveillance personnel routinely review and collect data from patients' medical records, including clinical data and microbiological findings, on a weekly basis using a standardized form. All neonates hospitalized in the NICU for at least 48 h are included and followed until their discharge from the NICU. Data on date of birth, date of admission and discharge, sex, gestational age, birth weight (BW), type of delivery, admission diagnosis (preterm birth, twin pregnancy, or respiratory distress syndrome), exposure to invasive devices (days of central line catheterization, including umbilical catheter, central venous catheter and peripherally inserted catheter, and days of mechanical ventilation), use of antimicrobial agents (days), site of infection, date of infection onset, and microorganism isolated are routinely collected. An infection is considered to be healthcare-associated if it occurs 48 h after birth or admission. The surveillance system records central/umbilical lineassociated bloodstream infections (CLABSIs) and ventilator-associated pneumonia (VAP) and any other type of infection that occurs during hospitalization, the diagnosis of which is determined by an infectious disease specialist. All infections are defined according to the

standard diagnostic criteria published by the Center for Disease Control and Prevention (CDC), adapted to neonatal pathology [18].
