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. Author manuscript; available in PMC: 2021 Apr 5.
Published in final edited form as: Curr Opin Infect Dis. 2017 Aug;30(4):395–403. doi: 10.1097/QCO.0000000000000383

Outbreaks in the Neonatal Intensive Care Unit: A Review of the Literature

Julia Johnson 1, Caroline Quach 2,3
PMCID: PMC8020806  NIHMSID: NIHMS1684680  PMID: 28582313

Abstract

Purpose of review:

Neonates in the NICU are uniquely vulnerable to colonization and infection with pathogens such as multi-drug resistant Gram-negative bacteria, which in turn are associated with increased infection-related morbidities and higher case-fatality rates. We reviewed the English, French, and German language literature published between 2015 and 2017, for reports of NICU outbreaks.

Recent findings:

A total of 39 outbreaks in NICUs were reported with Gram-negative bacteria (n=21; 54%) causing most and ESBL-producing organisms being the most frequent resistance mechanism reported (n = 5). Five viral outbreaks were reported (RSV = 3). A significant proportion of outbreaks (33%) did not identify a source. Whole genome sequencing was used more (n = 6 reports). The most common described infection prevention and control interventions included staff and parent education on hand hygiene, patient isolation, additional contact precautions, including discontinuation of “kangaroo care” and cohorting. Reporting and publication bias are likely common.

Summary:

NICUs must be vigilant in identifying outbreaks, conduct comprehensive investigations, and implement targeted infection prevention and control strategies. Molecular epidemiology capacities are an essential element in outbreak investigation. More studies are needed to determine the added value of active colonization screening and their impact on outbreak development.

Keywords: Neonatal intensive care units, Outbreak, review

Introduction

Hospitalized neonates are uniquely vulnerable to nosocomial infections due to an immature immune system, administration of broad-spectrum antibiotics, contact with healthcare workers (HCWs), and exposure to invasive, life-sustaining procedures and surgical procedures. Healthcare-associated infections (HAI) in neonates admitted to the Neonatal Intensive Care Unit (NICU) are associated with increased healthcare costs and length of stay, as well as significant morbidity and mortality to the patients (1, 2). National point prevalence surveys conducted in NICUs in the United States in 1999 and in Europe in 2011 revealed that 11.2% and 10.7% of neonates were affected by HAI, respectively (3, 4). In outbreak settings, NICU patients are particularly vulnerable to colonization and infection with pathogens such as multi-drug resistant, Gram-negative bacteria, which in turn are associated with increased infection-related morbidities and higher case-fatality rates (5).

Outbreaks reported in the literature range from cases limited to colonization discovered through routine or active surveillance cultures to clinical infections with high case fatality rates. The detection and investigation of the occurrence of an outbreak caused by a particular pathogen will depend on a number of factors, including routine surveillance practices during non-outbreak periods, providers’ clinical expertise in recognizing infection in neonates, and laboratory capacity to perform cultures, antimicrobial susceptibility testing, and molecular strain typing. Most importantly, institutions must have sufficient capacity to conduct a timely, comprehensive outbreak investigation and implement appropriate infection prevention and control strategies that should include development of a case definition, generation of an epidemic curve, epidemiologic data acquisition, and implementation of appropriate preventative strategies (6). Attempt to identify the source of NICU outbreaks frequently involves extensive environmental sampling and screening of patients, family members, and HCWs. Yet, 48.6% of investigations fail to identify a source, as shown in a review of 276 NICU outbreaks (7). To standardize reporting of outbreak investigations, the use of the ORION (Outbreak Reports and Intervention Studies of Nosocomial Infection) statement has been emphasized, but not yet adopted routinely by those reporting NICU outbreaks (8).

Understanding the epidemiology of HAIs, especially in outbreak settings, will be paramount for clinicians and infection control practitioners seeking to prevent infection in vulnerable neonates. To this end, this review focuses on the epidemiology of outbreaks in the NICU reported in the literature from 2015 through 2017. Approaches to molecular epidemiology in outbreak investigations are addressed, and infection prevention and control strategies are reviewed.

Description of included studies

We reviewed the English, French, and German language literature published between January 1, 2015, and March 1, 2017, for reports of outbreaks of bacterial, viral, fungal, and parasitic infections in the NICU in Medline. In order to capture the highest proportion of reported outbreaks, we included studies for which English language abstracts were available, in the absence of full text available in one of these three languages. In total, 30 bacterial, 3 fungal, 5 viral, and 1 parasitic outbreak reports were published over the course of this period (947).

Epidemiology

Summary of causative pathogens

Reports of outbreaks caused by Gram-negative bacteria predominated, with 21 of 39 (54%) outbreaks (Table 1). Klebsiella pneumoniae was the single most commonly reported causative pathogen, responsible for seven outbreaks within NICUs; Serratia marcescens (n = 5) was also frequently implicated. Multidrug-resistant infections were common in outbreaks caused by Gram-negative pathogens; extended spectrum beta-lactamase (ESBL) production was the most common resistance mechanism described (n = 9). Among the nine Gram-positive bacterial outbreaks, seven were caused by S. aureus, and four of these were caused by methicillin-resistant Staphylococcus aureus (MRSA). Three fungal outbreaks were reported (Candida spp). Finally, respiratory syncytial virus (RSV) caused three of five viral outbreaks. The lone parasitic outbreak reported in the NICU was an infestation of Cimex hemipterus, the tropical bed bug. Characteristics of included outbreaks are summarized in Table 2.

Table 1.

Pathogens responsible for neonatal intensive care unit outbreaks reported in the literature, 2015–2017.

Bacterial [cum. outbreaks] (n of individual outbreaks) Fungal (n of individual outbreaks)
Gram-positive [9] Candida albicans (1)
 Enterococcus faecium (1) Candida parapsilosis (2)
 Staphylococcus aureus (7)
 Staphylococcus epidermidis (1) Viral (n of individual outbreaks)
Human rhinovirus C (1)
Gram-negative [21] Parainfluenza-3 (1)
 Acinetobacter baumannii (1) Respiratory syncytial virus (3)
 Burkholderia cepacia (3)
 Escherichia coli (3) Parasite (n of individual outbreaks)
 Enterobacter ludwigii (1) Cimex hemipterus (1)
 Klebsiella pneumoniae (7)
 Pseudomonas aeruginosa (1)
 Serratia marcescens (5)

Table 2.

Outbreaks in the neonatal intensive care unit reported in the literature, 2015–2017.

Author (Year of Publication) Country (Year of Outbreak) Pathogen Types of Infection Source of Outbreak
Bacterial
Azarian et al (2015) USA (2010–2011) S. aureus (MRSA) Unspecified infections and Colonization Not available
Chong et al (2016) Canada (2011–2012) S. epidermidis Catheter-associated bloodstream infections Not available
Davis et al (2015) Australia (2013–2014) P. aeruginosa Conjunctivitis, pneumonia Sinks
Dawczynski et al (2016) Germany (2013–2014) S. marcescens Bacteremia, conjunctivitis None identified
Flores-Carrero et al (2016) Venezuela (2014) E. ludwigii (ESBL) Bacteremia None identified
Haller et al (2015) Germany (2009–2012) K. pneumoniae (ESBL) Bacteremia None identified
Hara et al (2016) Japan S. aureus (MRSA) Pneumonia, colonization Airborne transmission from neonate with Netherton syndrome
Hobzová et al (2016)* Czech Republic S. aureus (resistant to gentamicin) Not available Not available
Koroglu et al (2015) Turkey (2013) K. pneumoniae (ESBL) Bacteremia, meningitis, UTI Not described
Layer et al (2015) Germany (2012) S. aureus (MSSA) TSS, bacteremia HCW
Leroyer et al (2016) France (2010) S. aureus (MRSA) Bacteremia, colonization None identified
Lister et al (2015) Australia (2013–2014) E. faecium (VRE) Colonization only None identified
Löhr et al (2015) Norway (2008–2009) K. pneumoniae (ESBL) Bacteremia Contaminated breast milk
Montagnani et al (2015) Italy (2012) S. marcescens Bacteremia, GI, conjunctivitis Index case transferred from another facility
Morillo et al (2016)* Spain (2012–2013) S. marcescens Bacteremia, pneumonia, conjunctivitis Stored water, incubator surface after cleaning
Morris et al (2016) Ireland (2012) K. pneumoniae (ESBL) Bacteremia Not described
Nakamura et al (2016) Japan (2012) E. coli (ESBL) UTI Unpasteurized donor breast milk from single donor
Nannini et al (2015) Argentina (2013) B. cepacia Bacteremia Ultrasound gel
O’Connor et al (2017) Ireland (2013) E. coli (ESBL) UTI Mother-to-neonate vertical transmission
Paul et al (2016) India (2014) B. cepacia Bacteremia Contaminated open bottles of IV fluids, humidifier water
Roisin et al (2016)* Belgium (2012–2013) S. aureus (MSSA) Not available Not available
Schulz-Stübner et al (2015) Germany (2013) S. marcescens Bacteremia Commercial wash lotion
Shrivastava et al (2016) India (2015) B. cepacia Bacteremia Caffeine citrate
Silwedel et al (2016) Germany (2013) E. coli (ESBL) Bacteremia, UTI None identified
Soria et al (2016)* Ecuador (2013–2014) S. marcescens Bacteremia, conjunctivitis, SSI Index case transferred from another facility
Steensels et al (2016) Belgium (2011–2012) S. aureus (MRSA) Bacteremia, pneumonia HCW
Tsiatsiou et al (2015) Greece (2011) A. baumannii (CRAB) Bacteremia, respiratory, conjunctivitis None identified
Yu et al (2016) China (2015) K. pneumoniae (CRE, ESBL) Bacteremia, respiratory, UTI Index case transferred from another facility (outbreak 1); none identified (outbreak 2)
Zheng et al (2016) China (2014) K. pneumoniae (CRE) Bacteremia, respiratory, colonization Contaminated incubator water
Zhou et al (2015) China (2015) K. pneumoniae (CRE) Bacteremia Index case transferred from another facility
Fungal
Guducuoglu et al (2016) India C. albicans Fungemia TPN
Guo et al (2015) China (2014) C. parapsilosis Fungemia None identified
Megobo et al (2017)* South Africa (2009–2010) C. parapsilosis Fungemia Not available
Viral
Dunn et al (2017) England (2015) PIV-3 Respiratory None identified
Hammoud et al (2016) Kuwait (2012) RSV Respiratory Index case admitted from community
Marans et al (2016)* Israel RSV Respiratory Not available
Morena Parejo et al (2016)* Spain RSV Respiratory Not available
Reese et al (2016) USA Rhinovirus C Respiratory None identified
Parasite
Bandyopadhyay et al (2015) India (2013) C. hemipterus Rash Mother-to-neonate transmission

Abbreviations: CRAB = carbapenem-resistant Acinetobacter baumannii; CRE = carbapenem-resistant Enterobacteriaceae; ESBL = extended-spectrum β-lactamase; GI = gastrointestinal; HCW = healthcare worker; IV = intravenous; MRSA = methicillin-resistant Staphylococcus aureus; MSSA = methicillin-susceptible Staphylococcus aureus; PIV-3 = parainfluenza-3; RSV = respiratory syncytial virus; TPN = total parenteral nutrition; TSS = toxic shock syndrome; UTI = urinary tract infection; VRE = vancomycin-resistant Enterococci.

*

Abstract only; full text article not available or not in English, French, or German.

Distribution of outbreaks

Strikingly, with the exception of four Indian outbreaks, all NICU outbreaks identified occurred in high income and upper middle income countries, using standard World Bank income classifications (Table 3) (48). Nearly half (17 of 39; 43%) of NICU outbreaks were reported by European institutions, with Germany having five publications since January 1, 2015. The German Commission for Hospital Hygiene and Infectious Diseases Prevention (KRINKO) updated its recommendations for the prevention of nosocomial infections in NICU patients in 2012, recommending the extension of active surveillance cultures from very low birth weight (VLBW, <1500 g), neonates to all infants admitted to the NICU, likely increasing detection of clusters of colonization in the NICU (13). Such active surveillance programs are rare in low resource settings, where detection of outbreaks largely hinges upon recognition of cases of infection. Reporting bias is likely a significant factor, especially in low resource settings; disincentives include negative publicity for affected medical institutions and the additional time and effort required to pursue publication.

Table 3.

Countries reporting outbreaks, 2015–2017, by World Bank income group (World Bank 2017)

High income (n = 26) Upper middle income (n = 9)
Australia (n = 2) Argentina (n = 1)
Belgium (n = 2) China (n = 4)
Canada (n = 1) Ecuador (n = 1)
Czech Republic (n = 1) South Africa (n = 1)
England (n = 1) Turkey (n = 1)
France (n = 1) Venezuela (n = 1)
Germany (n = 5)
Greece (n = 1) Lower middle income (n = 4)
Ireland (n = 2) India (n = 4)
Israel (n = 1)
Italy (n = 1) Low income
Japan (n = 2) None
Kuwait (n = 1)
Norway (n = 1)
Spain (n = 2)
United States (n = 2)

High-income enconomy = GNI per capita $12,476 or more; upper middle income between $4,036 and $12,475; lower middle income between $1,026 and $4,035; low income less than $1,025.

Outbreak detection and identification of source

Among the bacterial outbreaks reported, the majority were detected by recognition of clinical cases with culture-confirmed infection (n = 17) (9, 11, 15, 18, 2225, 29, 31, 3436, 40, 42, 44, 46) and routine surveillance cultures (n = 9) (12, 13, 20, 26, 33, 39, 41, 43, 47). The three Candida outbreaks were associated with fungemia (16, 17, 27). Viral outbreaks of parainfluenza, human rhinovirus and RSV were detected through identification of clinical cases, with confirmation by polymerase chain reaction (PCR) testing (14, 19, 30, 37). Testing of asymptomatic infants for RSV using a rapid RSV antigen detection test led to high rates of false positive results and should not be done (49).

The majority of outbreak investigations included the initiation of new surveillance programs or enhancement of existing surveillance practices, with specimens obtained from patients, healthcare workers, and family members. Through active surveillance, institutions sought to identify colonized individuals, to guide patient isolation and cohorting and to identify neonates at risk for infection with the outbreak pathogen. Additionally, surveillance cultures were used in attempts to identify the source of the outbreak; surveillance was frequently accompanied by environmental sampling, which rarely included healthcare worker screening.

The most common identified source was an index case transferred from another facility or admitted from the community (n = 5, 12.8%) (19, 29, 42, 45, 47). A significant proportion of investigations did not reveal a source (n = 13, 33%) (9, 11, 1315, 17, 18, 24, 25, 37, 41, 44, 45). Contamination of medications, intravenous (IV) fluids or total parenteral nutrition (TPN), ultrasound gel, or care products was implicated in five outbreaks (16, 34, 36, 39, 40). Transmission from a colonized healthcare worker was thought to be the source in two S. aureus outbreaks (23, 43). Sink or water contamination was discovered in three investigations (12, 31, 46), whereas two outbreaks were linked to transmission from colonized or infected mothers (10, 35). Two ESBL reports were associated with breast milk: contaminated maternal breast milk was implicated in one (26) and shared unpasteurized donor breast milk was responsible for another outbreak in a Japanese NICU (33). One outbreak of MRSA infection and colonization was attributed to airborne transmission from a neonate with Netherton syndrome, a condition associated with severely compromised skin integrity (20).

Molecular epidemiology

Identification and strain typing of pathogenic bacteria is instrumental in outbreak investigations and helps guide medical institutions in formulating an appropriate outbreak response. The gold standard for strain typing in outbreak investigations and surveillance is pulsed-field gel electrophoresis (PFGE); however, this laboratory technique is labor-intensive and requires analytical expertise (50). PFGE was one of the primary means of analyzing recent NICU outbreaks (n=15) (9, 11, 13, 16, 18, 22, 26, 32, 33, 35, 4244, 46, 47). An alternative to PFGE is matrix-assisted laser desorption/ionization mass spectrometry (MADI-TOF MS) for bacterial isolate identification and assessment of strain relatedness, with a reported 93% concordance with spa typing and PFGE in an investigation of a MRSA outbreak (43).

A number of sequence-based strain typing methods are available and provide more rapid, less labor-intensive means for assessing outbreaks. These methods include single-locus typing, such as spa typing for S. aureus, used by Layer and colleagues, multilocus sequence typing (MLST), and repetitive element polymerase chain reaction (rep-PCR) (23). MLST is not always appropriate for outbreak investigations, as it may have inadequate resolution to distinguish outbreak strains from background, endemic strains of the same pathogen (50).

The advent of whole genome sequencing (WGS) has transformed outbreak investigations for bacterial strain typing by offering a sophisticated method of epidemiologic analysis that is relatively low-cost and efficient, with rapid turnaround time (12, 50, 51). WGS can enhance outbreak investigations, as it can distinguish background strains from outbreak strains (50). WGS is a primary method of analysis utilized in six of the outbreak reports included in this review (9, 12, 18, 23, 25, 38). However, outbreaks frequently occur in settings where such testing is not available or is too costly.

Infection Prevention and Control Strategies

The majority of published studies describe a multi-faceted approach to infection prevention and control in response to a detected outbreak. The most common described interventions included staff and parent education on hand hygiene, patient isolation, additional contact precautions, including discontinuation of “kangaroo care” and cohorting (9, 12, 13, 15, 18, 20, 2325, 29, 30, 35, 4145, 47). Because understaffing has been reported as a risk factor for outbreak (52, 53), in particular in very low birth weight infants, an increase in the staff to patient ratio was reported (13). Other frequently used strategies included enhanced environmental cleaning with increase in concentration of disinfection and transition to single-use products when possible (9, 10, 12, 13, 15, 20, 25, 31, 35, 36, 44, 45, 47). For cases of outbreaks linked to a specific contaminated product, such as medication or ultrasound gel, the removal of the implicated substance was the chief intervention in halting the outbreak (34, 39, 40). The ESBL E. coli outbreak in a Japanese NICU due to contaminated unpasteurized donor breast milk ultimately resulted in the cessation of the shared milk program (33). RSV outbreak infection prevention and control strategies included the administration of prophylactic Palivizumab (19, 30). In rare cases of prolonged or severe outbreaks that did not abate with the implementation of other strategies, temporary or permanent ward closure was enacted (9, 10, 18, 35, 41, 44, 47).

Active screening for colonization

Colonization of infants in the NICU serves as reservoir for transmission. Reichert et al. showed that risk of bloodstream infection (BSI) in the NICU increased in the presence of another infant currently admitted or admitted in the past 30 days with a BSI caused by the same pathogen. The odds ratio (OR) of BSI clustered in two groups: Enterococcus spp., Enterobacter spp., Escherichia coli, Candida albicans, S. aureus, and Klebsiella spp. (OR between 3.06 and 9.21) and Serratia spp and Pseudomonas aeruginosa (OR of 53.08 and 33.75, respectively). Table 4 summarizes OR for each microorganism in the presence of a current or past BSI case. (54**) This increase in risk of BSI means that transmission between patients is likely and supports the recommendation for increased active surveillance for colonization for infants in the NICU, regardless of birth weight (13). The assumption is that earlier detection of transmission through detection of colonization with implementation of additional infection prevention and control measures should lead to decreased risk of outbreak of infections. The effectiveness and cost-effectiveness of active colonization screening has not been demonstrated, however. Moreover, regardless of colonization status and pathogen involved, compliance to horizontal infection prevention and control measures should curtail transmission of colonizing and potentially pathogenic organisms (55).

Table 4.

Risk of BSI in the presence or absence of an infant infected with the same pathogen [54]

Pathogen Presence of simultaneous same-pathogen BSI Presence of same-pathogen BSI in past 30 days
OR (95%CI) OR (95% CI)
S. aureus 6.9 (4.8 – 9.9) 3.6 (2.3 – 5.6)
Enterococcus spp 3.1 (2.1 – 4.4) 3.2 (2.1 – 4.9)
Enterobacter spp 4.9 (2.7 – 9.0) 4.0 (2.1 – 7.7)
E. coli 4.2 (2.0 – 8.9) 2.8 (1.2 – 6.4)
K. pneumoniae 9.2 (5.2 – 16.2) 5.5 (2.6 – 11.6)
Serratia spp 53.1 (18.9 – 149.0) 39.2 (14.0 – 109.2)
P. aeruginosa 33.8 (7.0 – 162.2) 24.7 (3.8 – 162.2)
C. albicans 4.4. (2.4 – 8.1) 2.1 (0.9 – 5.2)

BSI = Bloodstream infection

NICU environment

Brooks et al. showed that the NICU environment had an impact on neonates’ colonization: microorganisms were first found on NICU’s surfaces, then in infants’ gut, with the most probable reservoir being tubing (e.g., nasogastric feeding tube), infants’ incubators and sinks. Healthcare workers’ hands have shown variable amounts of potential fecal colonizers (56). Parents’ cell phones were shown to have bacterial contamination, with the same bacteria also found on hands (57). To minimize outbreaks in the NICU, “each neonate should be approached as though he or she harboured colonies of unique flora that should not be transmitted to any other neonate” (55).

Discussion

In a recent systematic review of outbreaks of ESBL Enterobacteriaceae in NICUs, Stapleton and colleagues described the epidemiology of 75 outbreaks and reviewed intervention strategies implemented in response to such outbreaks (58*). Quantitative analysis was limited to 26 studies, and random effects meta-analysis revealed 42% of colonized neonates went on to develop infection (95% CI 29.117–54.787), though there was significant heterogeneity in screening practices and capacity to measure attack rates among studies. Meta-analysis of pooled data also revealed 31% of infected neonates died in these outbreaks (95% CI 20.261–42.751). Notably, 57% of the 75 included studies failed to identify a source of the outbreak, while 15% identified an index case with subsequent horizontal transmission of infection within the NICU. Our review of published NICU outbreak reports since 2015 revealed similar findings: a significant proportion of investigations failed to reveal an outbreak source, despite often extensive surveillance and environmental sampling. Environmental sampling is resource-intensive and rarely yields a likely outbreak source; it should be considered on a case-by-case basis, especially for pathogens commonly associated with environmental reservoirs, such as P. aeruginosa. However, in the case of outbreaks with pathogens frequently isolated in the environment in non-outbreak settings, environmental culture results are difficult to interpret, especially in settings where sophisticated molecular techniques are not available. Infection prevention and control strategies such as hand hygiene education, patient isolation and cohorting, and enhanced environmental cleaning should be prioritized to curb outbreaks and to enhance existing practices to prevent future outbreaks. Practices in the NICU that predispose to spread of pathogens, such as poor separation of clean and dirty equipment, insufficient cleaning of high touch surfaces, improper segregation of waste, and inadequate bed spacing should be assessed systematically to prevent outbreaks in the future.

Reporting and Publication Bias

As comprehensive outbreak investigations require laboratory infrastructure and significant human and financial resources, it is perhaps not surprising that the bulk of published outbreak reports originated from institutions within higher income countries. Over recent years, the number of NICUs in low income and low middle-income countries has increased. NICUs in these lower resource settings are likely at greatest risk of outbreaks, due to potential for overcrowding and insufficient infection prevention and control strategies. Unfortunately, many of these NICUs are also unlikely to have sufficient resources to perform thorough epidemiologic investigations and to seek subsequent publication. Moreover, publication often requires novelty. It is therefore unlikely that all outbreaks are reported and published. Pathogens that are highly resistant or that have been associated with high morbidity or mortality are more likely to be published.

Limitations

A limitation of this qualitative review is its exclusion of outbreak reports not published in English, French, and German. We did not review the gray literature, and some outbreak reports may be limited to conference abstracts not subsequently submitted for publication. Outbreak reports from high-income countries predominate, and the published literature offers an inadequate representation of the epidemiology of NICU outbreaks in low resource settings. Finally, quantitative analysis of attack rates and case fatality rates was not feasible, as a significant number of outbreak reports did not include differentiation between colonization and infection or report mortality data.

Summary

Neonates admitted to the NICU are at significant risk of acquiring HAI during the course of their admission, with outbreaks being associated with increased morbidity and mortality. NICUs must be vigilant in identifying outbreaks, conduct thoughtful, comprehensive investigations, and implement targeted infection prevention and control strategies swiftly to limit the impact on patients, family, and staff. Specific approaches to outbreak investigations may differ for specific causative pathogens and due to site-specific context, clinical and infection prevention and control resources, and laboratory capacity. Compliance with horizontal infection prevention and control measures, such as hand hygiene, proper environmental cleaning, respiratory etiquette, and refraining from working when sick should prevent most outbreaks in the NICU. Use of the ORION statement may help standardize outbreak reporting in the literature.

Key points:

  • Published outbreaks occurring in the NICU are most often caused by Gram-negative bacteria

  • Most recent published outbreaks that occurred in the NICU were due to multi-resistant organisms, mainly ESBL and MRSA

  • The source of the outbreak if seldom identified

  • Enhanced laboratory detection and capacities that include molecular epidemiology, in particular MALDI-TOF and whole genome sequencing, are key to differentiate outbreak strains from endemic strains

Acknowledgement:

Dr. Johnson is supported through an NIH T32 HL 125239-1 grant. Dr. Quach is supported through an external salary award (FRQ-S senior, grant # 26873)

Funding source:

This study was not funded.

Financial Disclosure:

Julia Johnson has received funding from Sage Products LLC (for a research grant unrelated to the current manuscript). Caroline Quach has received funding from Sage Products LLC and AbbVie (for research grants unrelated to the current manuscript).

References

  • 1.Curtis C, Shetty N. Recent trends and prevention of infection in the neonatal intensive care unit. Curr Opin Infect Dis. 2008;21(4):350–6. [DOI] [PubMed] [Google Scholar]
  • 2.Hooven TA, Polin RA. Healthcare-associated infections in the hospitalized neonate: a review. Early Hum Dev. 2014;90 Suppl 1:S4–6. [DOI] [PubMed] [Google Scholar]
  • 3.Sohn AH, Garrett DO, Sinkowitz-Cochran RL, Grohskopf LA, Levine GL, Stover BH, et al. Prevalence of nosocomial infections in neonatal intensive care unit patients: Results from the first national point-prevalence survey. J Pediatr. 2001;139(6):821–7. [DOI] [PubMed] [Google Scholar]
  • 4.Zingg W, Hopkins S, Gayet-Ageron A, Holmes A, Sharland M, Suetens C, et al. Health-care-associated infections in neonates, children, and adolescents: an analysis of paediatric data from the European Centre for Disease Prevention and Control point-prevalence survey. Lancet Infect Dis. 2017. [DOI] [PubMed] [Google Scholar]
  • 5.Tsai MH, Chu SM, Hsu JF, Lien R, Huang HR, Chiang MC, et al. Risk factors and outcomes for multidrug-resistant Gram-negative bacteremia in the NICU. Pediatrics. 2014;133(2):e322–9. [DOI] [PubMed] [Google Scholar]
  • 6.Sood G, Perl TM. Outbreaks in Health Care Settings. Infect Dis Clin North Am. 2016;30(3):661–87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.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. [DOI] [PubMed] [Google Scholar]
  • 8.Stone SP, Cooper BS, Kibbler CC, Cookson BD, Roberts JA, Medley GF, et al. The ORION statement: guidelines for transparent reporting of outbreak reports and intervention studies of nosocomial infection. Lancet Infect Dis. 2007;7(4):282–8. [DOI] [PubMed] [Google Scholar]
  • 9.Azarian T, Cook RL, Johnson JA, Guzman N, McCarter YS, Gomez N, et al. Whole-genome sequencing for outbreak investigations of methicillin-resistant Staphylococcus aureus in the neonatal intensive care unit: time for routine practice? Infect Control Hosp Epidemiol. 2015;36(7):777–85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Bandyopadhyay T, Kumar A, Saili A. Bed bug outbreak in a neonatal unit. Epidemiol Infect. 2015;143(13):2865–70. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Chong J, Quach C, Blanchard AC, Poliquin PG, Golding GR, Laferriere C, et al. Molecular Epidemiology of a Vancomycin-Intermediate Heteroresistant Staphylococcus epidermidis Outbreak in a Neonatal Intensive Care Unit. Antimicrob Agents Chemother. 2016;60(10):5673–81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Davis RJ, Jensen SO, Van Hal S, Espedido B, Gordon A, Farhat R, et al. Whole Genome Sequencing in Real-Time Investigation and Management of a Pseudomonas aeruginosa Outbreak on a Neonatal Intensive Care Unit. Infect Control Hosp Epidemiol. 2015;36(9):1058–64. [DOI] [PubMed] [Google Scholar]
  • 13.Dawczynski K, Proquitte H, Roedel J, Edel B, Pfeifer Y, Hoyer H, et al. Intensified colonisation screening according to the recommendations of the German Commission for Hospital Hygiene and Infectious Diseases Prevention (KRINKO): identification and containment of a Serratia marcescens outbreak in the neonatal intensive care unit, Jena, Germany, 2013–2014. Infection. 2016;44(6):739–46. [DOI] [PubMed] [Google Scholar]
  • 14.Dunn GL, Tapson H, Davis J, Gobin M. Outbreak of Piv-3 in a Neonatal Intensive Care Unit in England. Pediatr Infect Dis J. 2017;36(3):344–5. [DOI] [PubMed] [Google Scholar]
  • 15.Flores-Carrero A, Labrador I, Paniz-Mondolfi A, Peaper DR, Towle D, Araque M. Nosocomial outbreak of extended-spectrum beta-lactamase-producing Enterobacter ludwigii co-harbouring CTX-M-8, SHV-12 and TEM-15 in a neonatal intensive care unit in Venezuela. J Glob Antimicrob Resist. 2016;7:114–8. [DOI] [PubMed] [Google Scholar]
  • 16.Guducuoglu H, Gultepe B, Otlu B, Bektas A, Yildirim O, Tuncer O, et al. Candida albicans outbreak associated with total parenteral nutrition in the neonatal unit. Indian J Med Microbiol. 2016;34(2):202–7. [DOI] [PubMed] [Google Scholar]
  • 17.Guo W, Gu HF, Zhang HG, Chen SB, Wang JQ, Geng SX, et al. An outbreak of Candida parapsilosis fungemia among preterm infants. Genet Mol Res. 2015;14(4):18259–67. [DOI] [PubMed] [Google Scholar]
  • 18.Haller S, Eller C, Hermes J, Kaase M, Steglich M, Radonic A, et al. What caused the outbreak of ESBL-producing Klebsiella pneumoniae in a neonatal intensive care unit, Germany 2009 to 2012? Reconstructing transmission with epidemiological analysis and whole-genome sequencing. BMJ Open. 2015;5(5):e007397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Hammoud MS, Al-Taiar A, Raina A, Elsori D, Al-Qabandi S, Al-Essa M. Use of palivizumab with other infection control measures to control respiratory syncytial virus outbreaks in neonatal care units. J Trop Pediatr. 2016;62(5):409–14. [DOI] [PubMed] [Google Scholar]
  • 20.Hara S, Yamamoto H, Kawabata A, Azuma T, Ishii S, Okumura N, et al. Airborne transmission from a neonate with Netherton syndrome during an outbreak of MRSA. Pediatr Int. 2016;58(6):518–20. [DOI] [PubMed] [Google Scholar]
  • 21.Hobzova L, Splino M, Chlibek R, Zemlickova H, Ryskova L. [Outbreak of SARG in a neonatal intensive care unit]. Klin Mikrobiol Infekc Lek. 2016;22(4):148–51. [PubMed] [Google Scholar]
  • 22.Koroglu M, Ozbek A, Demiray T, Hafizoglu T, Guclu E, Altindis M, et al. Investigation of clonal relationships of K. pneumoniae isolates from neonatal intensive care units by PFGE and rep-PCR. J Infect Dev Ctries. 2015;9(8):829–36. [DOI] [PubMed] [Google Scholar]
  • 23.Layer F, Sanchini A, Strommenger B, Cuny C, Breier AC, Proquitte H, et al. Molecular typing of toxic shock syndrome toxin-1- and Enterotoxin A-producing methicillin-sensitive Staphylococcus aureus isolates from an outbreak in a neonatal intensive care unit. Int J Med Microbiol. 2015;305(7):790–8. [DOI] [PubMed] [Google Scholar]
  • 24.Leroyer C, Lehours P, Tristan A, Boyer F, Marie V, Elleau C, et al. Outbreak in newborns of methicillin-resistant Staphylococcus aureus related to the sequence type 5 Geraldine clone. Am J Infect Control. 2016;44(2):e9–11. [DOI] [PubMed] [Google Scholar]
  • 25.Lister DM, Kotsanas D, Ballard SA, Howden BP, Carse E, Tan K, et al. Outbreak of vanB vancomycin-resistant Enterococcus faecium colonization in a neonatal service. Am J Infect Control. 2015;43(10):1061–5. [DOI] [PubMed] [Google Scholar]
  • 26.Lohr IH, Hulter N, Bernhoff E, Johnsen PJ, Sundsfjord A, Naseer U. Persistence of a pKPN3-like CTX-M-15-encoding IncFIIK plasmid in a Klebsiella pneumonia ST17 host during two years of intestinal colonization. PLoS One. 2015;10(3):e0116516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Magobo RE, Naicker SD, Wadula J, Nchabeleng M, Coovadia Y, Hoosen A, et al. Detection of neonatal unit clusters of Candida parapsilosis fungaemia by microsatellite genotyping: Results from laboratory-based sentinel surveillance, South Africa, 2009–2010. Mycoses. 2017. [DOI] [PubMed] [Google Scholar]
  • 28.Marans R, Eventov-Friedman S, Cohen E, Schwartz C, Averbukh D, Bar-Oz B. [Controlling an Outbreak of Respiratory Syncytial Virus (Rsv among Nicu Patients and the Medical Team]. Harefuah. 2016;155(1):20-3, 68. [PubMed] [Google Scholar]
  • 29.Montagnani C, Cocchi P, Lega L, Campana S, Biermann KP, Braggion C, et al. Serratia marcescens outbreak in a neonatal intensive care unit: crucial role of implementing hand hygiene among external consultants. BMC Infect Dis. 2015;15:11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Moreno Parejo C, Morillo Garcia A, Lozano Dominguez C, Carreno Ochoa C, Aznar Martin J, Conde Herrera M. [Respiratory syncytial virus outbreak in a tertiary hospital Neonatal Intensive Care Unit]. An Pediatr (Barc). 2016;85(3):119–27. [DOI] [PubMed] [Google Scholar]
  • 31.Morillo A, Gonzalez V, Aguayo J, Carreno C, Torres MJ, Jarana D, et al. A six-month Serratia marcescens outbreak in a Neonatal Intensive Care Unit. Enferm Infecc Microbiol Clin. 2016;34(10):645–51. [DOI] [PubMed] [Google Scholar]
  • 32.Morris D, O’Connor M, Izdebski R, Corcoran M, Ludden CE, McGrath E, et al. Dissemination of clonally related multidrug-resistant Klebsiella pneumoniae in Ireland. Epidemiol Infect. 2016;144(2):443–8. [DOI] [PubMed] [Google Scholar]
  • 33.Nakamura K, Kaneko M, Abe Y, Yamamoto N, Mori H, Yoshida A, et al. Outbreak of extended-spectrum beta-lactamase-producing Escherichia coli transmitted through breast milk sharing in a neonatal intensive care unit. J Hosp Infect. 2016;92(1):42–6. [DOI] [PubMed] [Google Scholar]
  • 34.Nannini EC, Ponessa A, Muratori R, Marchiaro P, Ballerini V, Flynn L, et al. Polyclonal outbreak of bacteremia caused by Burkholderia cepacia complex and the presumptive role of ultrasound gel. Braz J Infect Dis. 2015;19(5):543–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.O’Connor C, Philip RK, Kelleher J, Powell J, O’Gorman A, Slevin B, et al. The first occurrence of a CTX-M ESBL-producing Escherichia coli outbreak mediated by mother to neonate transmission in an Irish neonatal intensive care unit. BMC Infect Dis. 2017;17(1):16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Paul LM, Hegde A, Pai T, Shetty S, Baliga S, Shenoy S. An Outbreak of Burkholderia cepacia Bacteremia in a Neonatal Intensive Care Unit. Indian J Pediatr. 2016;83(4):285–8. [DOI] [PubMed] [Google Scholar]
  • 37.Reese SM, Thompson M, Price CS, Young HL. Evidence of nosocomial transmission of human rhinovirus in a neonatal intensive care unit. Am J Infect Control. 2016;44(3):355–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Roisin S, Gaudin C, De Mendonca R, Bellon J, Van Vaerenbergh K, De Bruyne K, et al. Pan-genome multilocus sequence typing and outbreak-specific reference-based single nucleotide polymorphism analysis to resolve two concurrent Staphylococcus aureus outbreaks in neonatal services. Clin Microbiol Infect. 2016;22(6):520–6. [DOI] [PubMed] [Google Scholar]
  • 39.Schulz-Stubner S, Zimmer P, Leonards P, Knipp U, Michels H, Kunitz O, et al. [Colonization-outbreak of two clonally different strains of Serratia marcescens in a neonatal intensive care unit]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2015;58(2):190–6. [DOI] [PubMed] [Google Scholar]
  • 40.Shrivastava B, Sriram A, Shetty S, Doshi R, Varior R. An unusual source of Burkholderia cepacia outbreak in a neonatal intensive care unit. J Hosp Infect. 2016;94(4):358–60. [DOI] [PubMed] [Google Scholar]
  • 41.Silwedel C, Vogel U, Claus H, Glaser K, Speer CP, Wirbelauer J. Outbreak of multidrug-resistant Escherichia coli sequence type 131 in a neonatal intensive care unit: efficient active surveillance prevented fatal outcome. J Hosp Infect. 2016;93(2):181–6. [DOI] [PubMed] [Google Scholar]
  • 42.Soria C, Nieto N, Villacis JE, Lainez S, Cartelle M. [Serratia marcescens outbreak in Neonatal Intensive Care Unit: Guayaquil, Ecuador]. Rev Chilena Infectol. 2016;33(6):703–5. [DOI] [PubMed] [Google Scholar]
  • 43.Steensels D, Deplano A, Denis O, Simon A, Verroken A. MALDI-TOF MS typing of a nosocomial methicillin-resistant Staphylococcus aureus outbreak in a neonatal intensive care unit. Acta Clin Belg. 2016:1–7. [DOI] [PubMed] [Google Scholar]
  • 44.Tsiatsiou O, Iosifidis E, Katragkou A, Dimou V, Sarafidis K, Karampatakis T, et al. Successful management of an outbreak due to carbapenem-resistant Acinetobacter baumannii in a neonatal intensive care unit. Eur J Pediatr. 2015;174(1):65–74. [DOI] [PubMed] [Google Scholar]
  • 45.Yu J, Tan K, Rong Z, Wang Y, Chen Z, Zhu X, et al. Nosocomial outbreak of KPC-2- and NDM-1-producing Klebsiella pneumoniae in a neonatal ward: a retrospective study. BMC Infect Dis. 2016;16(1):563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Zheng R, Zhang Q, Guo Y, Feng Y, Liu L, Zhang A, et al. Outbreak of plasmid-mediated NDM-1-producing Klebsiella pneumoniae ST105 among neonatal patients in Yunnan, China. Ann Clin Microbiol Antimicrob. 2016;15:10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Zhou J, Li G, Ma X, Yang Q, Yi J. Outbreak of colonization by carbapenemase-producing Klebsiella pneumoniae in a neonatal intensive care unit: Investigation, control measures and assessment. Am J Infect Control. 2015;43(10):1122–4. [DOI] [PubMed] [Google Scholar]
  • 48.World Bank. World Bank Country and Lending Groups 2017. [Available from: https://datahelpdesk.worldbank.org/knowledgebase/articles/906519.
  • 49.Elbadawi LI, Haupt T, Reisdorf E, Danz T, Davis JP. Use and Interpretation of a Rapid Respiratory Syncytial Virus Antigen Detection Test Among Infants Hospitalized in a Neonatal Intensive Care Unit - Wisconsin, March 2015. MMWR Morb Mortal Wkly Rep. 2015;64(31):857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.MacCannell D Bacterial strain typing. Clin Lab Med. 2013;33(3):629–50. [DOI] [PubMed] [Google Scholar]
  • 51.Kwong JC, McCallum N, Sintchenko V, Howden BP. Whole genome sequencing in clinical and public health microbiology. Pathology. 2015;47(3):199–210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Leistner R, Thurnagel S, Schwab F, Piening B, Gastmeier P, Geffers C. The impact of staffing on central venous catheter-associated bloodstream infections in preterm neonates - results of nation-wide cohort study in Germany. Antimicrob Resist Infect Control. 2013;2(1):11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Rogowski JA, Staiger D, Patrick T, Horbar J, Kenny M, Lake ET. Nurse staffing and NICU infection rates. JAMA Pediatr. 2013;167(5):444–50. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • **54.Reichert F, Piening B, Geffers C, Gastmeier P, Buhrer C, Schwab F. Pathogen-Specific Clustering of Nosocomial Blood Stream Infections in Very Preterm Infants. Pediatrics. 2016;137(4). [DOI] [PubMed] [Google Scholar]
  • 55.American College of Obstetricians and Gynecologists. Infection Control. In: Hauth JC, Merenstein GB, editors. Gudelines for Perinatal Care. 4th ed. Elk Grove Village: American Academy of Pediatrics; 1997. p. 251–77. [Google Scholar]
  • 56.Brooks B, Firek BA, Miller CS, Sharon I, Thomas BC, Baker R, et al. Microbes in the neonatal intensive care unit resemble those found in the gut of premature infants. Microbiome. 2014;2(1):1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Beckstrom AC, Cleman PE, Cassis-Ghavami FL, Kamitsuka MD. Surveillance study of bacterial contamination of the parent’s cell phone in the NICU and the effectiveness of an anti-microbial gel in reducing transmission to the hands. J Perinatol. 2013;33(12):960–3. [DOI] [PubMed] [Google Scholar]
  • *58.Stapleton PJ, Murphy M, McCallion N, Brennan M, Cunney R, Drew RJ. Outbreaks of extended spectrum beta-lactamase-producing Enterobacteriaceae in neonatal intensive care units: a systematic review. Arch Dis Child Fetal Neonatal Ed. 2016;101(1):F72–8. [DOI] [PubMed] [Google Scholar]

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