Early Human Development 90S1 (2014) S54–S56

Management of outbreaks in neonatal intensive care units Lidia Decembrino a, *, Antonella Maini a , Nunzia Decembrino b , Ivana Maggi a , Serafina Lacerenza a a b

Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

A R T I C L E Keywords: Outbreaks NICU Prevention

I N F O

A B S T R A C T Outbreaks in neonatal intensive care units (NICUs) have disastrous consequences for neonates and raise enormous concerns in staff, altering usual practice patterns of the NICU. Our objective was to perform a systematic analysis for gaining insights into the control and prevention of NICUs outbreaks. Epidemiology, risk factors and outcomes are reviewed. © 2014 Elsevier Ireland Ltd. All rights reserved.

1. Defining outbreaks in neonatal intensive care units (NICUs) An outbreak can be defined as two or more sterile site isolates of the same species, with the same antibiogram, from different babies (not twins) within the space of 2 weeks. Three or more babies colonized with the same Gram negative bacteria (GNB) in NICUs that routinely screen for GNB colonization, a single case of a rare or never seen GNB, a single systemic infection with an (extended spectrum lactamase producing (ESBL) carbapenem resistant GNB (because these multidrug-resistant organisms—MDR—confer a higher risk of treatment failure) or Pseudomonas aeruginosa (which is more likely than other GNB to indicate an environmental reservoir) can trigger alert [1]. NICUSs outbreaks represent 37.9% of all ICU outbreaks and 87.6% of the outbreaks reported in neonatology [2]. They are mainly due to Klebsiella spp. (20.3%), Staphylococcus spp. (15.9%), Serratia spp. (12%), Enterobacter spp. (9.4%), Pseudomonas spp., E.coli, Salmonella spp., Candida spp. (5.4%), Acinetobacter spp. (4.7%) [2]. Enterobacteriaceae as a group (Klebsiella spp., Serratia spp., Enterobacter spp., Escherichia spp., Salmonella spp., and Citrobacter spp.) account for 52.9% of NICUs outbreaks [2]. The 5 most frequent viral agents reported are rotavirus (23.44%), respiratory syncytial virus (17.19%), enterovirus (5.63%), hepatitis A virus (1.94%) and adenovirus (9.38%) [3]. In recent years, the extensive use of broadspectrum antibiotics has led to an increase of outbreaks caused by ESBL-Klebsiella pneumoniae (KP) [4,5], methicillin-resistant Staphylococcus aureus (MRSA) [6–8], vancomycin-resistant enterococci (VRE) [9], throughout the world. The most frequent type of infection are bloodstream infections (62.7%), probably related to extensive use of indwelling catheters and prolonged parenteral nutrition, followed by gastrointestinal infections (20.7%), Central nervous system in-

* Corresponding author: Lidia Decembrino, SC Neonatologia, Patologia Neonatale e Terapia Intensiva Neonatale, Fondazione IRCCS Policlinico “San Matteo”, Piazzale Golgi 11, 27100 Pavia (PV), Italy. Tel.: +39 0382-502704; fax: +39 0382-502477. E-mail address: [email protected] (L. Decembrino). 0378-3782/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved.

fections (19.9%) [2]. Surgical site infections, lower respiratory and urinary tract infections are significantly less frequently. Several sources and environmental reservoirs have been described: patients (24.6%) environments (11.7%), personnel (10%), medical equipment devices (9.2%) drug (5%), food (3.3%), care equipment (1.6%), unknown (39.7%) [10]. Transmission are usually from patient to patient by way of the hands of health care workers or from contaminated multiuse equipment (e.g., ecographs, lights, laryngoscopes, breast pumps, stethoscope) [2]. 1.1. Outbreak risk factors Prematurity, low birth weight, invasive devices make neonates susceptible to infections. Poor hand hygiene, environmental colonization, inadequate cleaning of common-use equipment, injudicious use of antibiotics (broad spectrum and prolonged courses) are contributing factors to onset and spread of epidemic events [4,9]. Every day of delayed enteral feeding increases the risk of nosocomial infections. Inadequate spacing between cots, high cotoccupancy rates and low nurse/baby ratios promote errors and reduce the time for proper infection prevention practices. Nasal continuous positive airway pressure and caesarean section, are reported being risk factors for MRSA acquisition [8] as artificial fingernails [11]. 1.2. Outbreak outcomes An average of 1.5 neonates die during a NICU outbreak [2]. Survivors have more neurodevelopmental sequelae. 48.5-day longer length of stays (LOS) in infected infants and 12.8 day longer LOS in colonized infants, are reported [12]. Infants with MRSA infection have a median LOS of 51.83 vs 21.46 days [7]. The additional cost due to an ESBL-KP is approximately $350,000, $16,000 per each infected or colonized infant, related to overtime needed to care, to maintain the cohorting, to microbiology tests [12].

L. Decembrino et al. / Early Human Development 90S1 (2014) S54–S56

2. Action when an outbreak occurs The suspicion of an outbreak must be confirmed by comparing the presumed outbreak rate of infection with the unit surveillance data, published benchmark data or the microbiology laboratory reports. Once detected, a multidisciplinary outbreak control team should be formed, to limit outbreak strain spread, as soon as possible, through a review and change in the exiting infection control protocols. Clinical strategies such as less use of invasive procedures, and a restricted use of antibiotics relying on microbial surveillance to decrease resistance are encouraged [13]. In ESBL outbreaks, a second line antibiotics should include meropenem until outbreak is confirmed. Emphasis must be placed on the respect for hand hygiene and use of alcohol-based gels also for parents. Re-education, feedback and frequent audits, should lead to >95% compliance [2,10]. Patient screening cultures are used in the majority of outbreaks (65.7%) [2,10], for a defined period of 1–2 months or until the outbreak has resolved, to identify new cases among asymptomatic infants, because colonizations usually precede the infection. Some evidences underline the importance of at least weekly rectal swabs, and ETS for specific strains. In about half of the NICU outbreaks the classic method of preventing the spread of disease is to isolate the affected patients accomplished by the use of transmission based precautions: contact precautions for most of the MDR, droplet precautions for influenza or pertussis, and airborne precautions for varicella, measles, or tuberculosis organisms [14]. Cohorting is an additional measure to control the spread of infection so that those colonized/infected with the same organism are grouped together, and cared separately from the other neonates. Ideally, infected and colonized babies should not be moved between NICUs during an outbreak, but decisions should be made on a caseby-case. Try to deploy staff so that a separate group of nurses and doctors look after only the colonized or infected baby. An adequate supply of cover gowns, masks, and other barrier equipment are made easily available. Outbreak control is eventually achieved by reducing cots or closing to new admissions to improve spacing and nursing/baby ratios [15]. Usually this becomes necessary in 16.3% of NICUs outbreaks for about 14 days [2,15]. A total closure is one of the most expensive measures, responsible for one third of the total outbreak costs due to the lost revenue from blocked patient beds. Such an expensive measure is likely to be necessary in viral infections of the gastrointestinal or respiratory tract, due to the high transmissibility and low infectious dose of these pathogens [15]. During an outbreak it is important to pay attention to good communication with parents, particularly about their baby being colonized or infected, and when their baby is seriously unwell. As part of outbreak management, the efforts to locate the source of an outbreak may include equipment, and/or environmental screening. [1,2,10]. Water source, taps, sinks, air conditioning units, roof leaks, multiuse equipment and blood gas analyzers screening, in any room where the infected baby was, should be performed. This allowed to identify and remove the source of the outbreak in 51.4% of cases [2]. Consider deep-cleaning the environment [1] because prolonged survival time of the outbreak strain in the environment may contribute to the likelihood of transmission of pathogens. A personnel screening, performed in 43.8% of NICU outbreaks [2] lead to the identification of a high number of carriers among the staff. However, this does not prove that these persons had been the actual source of outbreaks, because of the possible temporary contamination from caring for infected or colonized babies.

S55

Visitation by infants’ families has not been shown to increase bacterial colonization or infection of neonates. Visits by family members can be safely permitted after each visitor screening by the nurse for potentially contagious diseases [13]. A literature search and review should be conducted about the organism implicated. The Outbreak Database (http://www. outbreak-database.com) is the largest collection of nosocomial outbreaks, continuously updated, providing relevant information or addressing scientific-oriented questions [10]. Only 26.1% of the NICU outbreaks are investigated applying a case control or cohort study design [2] including persons, places, time components, signs/symptoms and/or microbiology laboratory results. When the outbreak has ceased, the epidemiology team usually has the responsibility of writing up a final report of the outbreak. 2.1. Preventing an outbreak Outbreaks prevention requires an organization-wide approach. All NICUs should meet the recommendation for adequate cot spacing providing for two parents, monitors, ventilator and other equipment, as well as space for staff to undertake sterile procedures. An optimal staffing ratio for neonatal nurses is needed. A patient– nurse ratio 1 : 1 by nurses qualified for intensive care babies, 2:1 for high dependency and 4:1 for low dependency should be guaranteed [1]. Every NICU should have a Water Action Plan to reduce infections caused by waterborne pathogens, including Pseudomonas, Chrysebacterium and Stenotrophomonas. Equipment should be single use or dedicated to a baby. There should be robust cleaning routines for equipment and environment with a named responsible person. NICUs should adopt a policy for judicious use of the antibiotics for optimizing the prophylactic, empiric, and therapeutic antimicrobial use. A periodic data monitoring of cultures, susceptibility pattern and antibiotics rotation may delay a rapid spread of potentially MDR epidemic strains. Where possible introduce maternal breast milk on the first day of life in all preterm babies, avoiding to defrost frozen breast milk by placing the container in warm tap water. Active surveillance cultures should allow the infection prevention undertaking routine stool/rectal swabbing for specific strain to detect [4] the earliest possible an outbreak. In Israel four-year active continuous surveillance combined with contact precautions has been associated with a significant reduction of acquisition of ESBL-KP [16]. Moreover, in Germany weekly screening for MDR pathogens has been recently recommended to obtain a picture of local epidemiology, to control nosocomial transmission and to adjust the choice of the empirical treatment [17]. However, the effectiveness of colonization screening in NICUs remains in dispute. 3. Conclusions NICUs outbreaks, being frequent, raise increasing interest. Strict hospital infection control measures remain the only key to control outbreaks. However as several questions remain unanswered, many research fields may be implemented to prevent the occurrence like assess the feasibility and validity of weekly checks to identify colonizations, the use of molecular typing, improve infection diagnosis (molecular diagnostics, use of combination biomarkers) explore the impact of oral lactoferrin and probiotics [18,19]. Conflict of interest The authors declare that they do not have conflict of interest.

S56

L. Decembrino et al. / Early Human Development 90S1 (2014) S54–S56

References [1] Anthony M, Bedford-Russell A, Cooper T, Fry C, Heath PT, Kennea N, et al. Managing and preventing outbreaks of Gram-negative infections in UK neonatal units. Arch Dis Child Fetal Neonatal Ed 2013;98(6):F549–53. [2] Gastmeier P, Loui A, Stamm-Balderjahn S, Hansen S, Zuschneid I, Sohr D, et al. Outbreaks in neonatal intensive care units—They are not like others. Am J Infect Control 2007;35(3):172–6. [3] Civardi E, Tzialla C, Baldanti F, Strocchio L, Manzoni P, Stronati M. Viral outbreaks in neonatal intensive care units: what we do not known. Am J Infect Control 2013;41(10):854–6. [4] Shamshad Ali, Shahid Abbasi, Irfan Ali Mirza, Inam Ullah Khan, Muhammad Fayyaz Aamir Hussain, Luqman Satti. Outbreak of multidrug-resistant Klebsiella pneumoniae sepsis in Neonatal Intensive Care Unit. Gomal J Medical Sci 2012;10(1):154–7. [5] S Mitra, P Sivakumar, J Oughton, I Ossuetta. National surveillance study of extended spectrum B lactamase (ESBL) producing organism infection in neonatal units of England and Wales. Arch Dis Child 2011;96(Suppl 1):A47. [6] Iacobelli S, Colomb B, Bonsante F, Astruc K, Ferdynus C, Bouthet MF, et al. Successful control of a methicillin-resistant Staphylococcus aureus outbreak in a neonatal intensive care unit: a retrospective, before–after study. BMC Infect Dis 2013;13:440. [7] Khoury J, Jones M, Grim A, Dunne WM Jr, Fraser V. Eradication of methicillinresistant Staphilococcus aureus from a neonatal intensive care unit by active surveillance and aggressive infection control measures. Infect Control Hosp Epidemiol 2005;26(7):616–621. [8] Ramsing BGU, Arpi M, Andersen EA, Knabe N, Mogensen D, Buhl D, et al. First Outbreak with MRSA in a Danish Neonatal Intensive Care Unit: Risk Factors and Control Procedures. 2013;8(6):e66904. http://www.plosone.org. [9] Iosifidis E, Evdoridou I, Agakidou E, Chochliourou E, Protonotariou E, Karakoula K, et al. Vancomycin-resistant Enterococcus outbreak in a neonatal intensive care unit: epidemiology, molecular analysis and risk factors. Am J Infect Control 2013;41(10):857–61.

[10] Vonberg RP, Weitzel-Kage D, Behnke M, Gastmeier P. Worldwide Outbreak Database: the largest collection of nosocomial outbreaks. Infection 2011;39(1):29–34. [11] Jefferies JM, Cooper T, Yam T, Clarke SC. Pseudomonas aeruginosa outbreaks in the neonatal intensive care unit—a systematic review of risk factors and environmental sources. J Med Microbiol 2012;61(Pt 8):1052–61. [12] Stone PW, Gupta A, Loughrey M, Della-Latta P, Cimiotti J, Larson E, et al. Attributable costs and length of stay of an extended-spectrum beta-lactamase producing Klebsiella pneumoniae outbreak in a neonatal intensive care unit. Infect Control Hosp Epidemiol 2003;24(8):601–6. [13] Bagla J, Ghosh V, Ramji S, Gothi D. Antimicrobial susceptibility patterns following change in antibiotic policy in NICU. Pediatr Infect Dis 2013;5(2):59– 63. [14] Haas JP, Trezza LA. Outbreak Investigation in a Neonatal Intensive Care Unit. Semin Perinatol 2002;26(5):367–78. [15] Hansen S, Stamm-Balderjahn S, Zuschneid I, Behnke M, Rüden H, Vonberg RP, et al. Closure of medical departments during nosocomial outbreaks: data from a systematic analysis of the literature. J Hosp Infect 2007;65(4):348–53. [16] Benenson S, Levin PD, Block C, Adler A, Ergaz Z, Peleg O, et al. Continuous surveillance to reduce extended-spectrum β-lactamase Klebsiella pneumonia colonization in the neonatal intensive care unit. Neonatology 2013;103(2):155–60. [17] Simon A, Tenenbaum T. Surveillance of multidrug-resistant Gram negative pathogens in high risk neonates—does it make a difference? Pediatr Infect Dis J 2013;32(4):407–9. [18] Borghesi A, Stronati M. Strategies for the prevention of hospital-acquired infections in the neonatal intensive care unit. J Hosp Infect 2008;68(4):293– 300. [19] Manzoni P, De Luca D, Stronati M, Jacqz-Aigrain E, Ruffinazzi G, Luparia M, et al. Prevention of nosocomial infections in neonatal intensive care units. Am J Perinatol 2013; 30(2):81–8.