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Transmission Risk on a Neonatal Intensive Care Unit: Escherichia coli versus Klebsiella pneumoniae

Transmission Risk on a Neonatal Intensive Care Unit: Escherichia coli versus Klebsiella pneumoniae Hindawi Canadian Journal of Infectious Diseases and Medical Microbiology Volume 2018, Article ID 1525072, 5 pages https://doi.org/10.1155/2018/1525072 Research Article Transmission Risk on a Neonatal Intensive Care Unit: Escherichia coli versus Klebsiella pneumoniae 1 1 1 2 3 Tanja Artelt , Martin Kaase, Ivonne Bley, Helmut Eiffert, Alexander Mellmann, 4 4 1 Helmut Ku¨ster, Martina Lange, and Simone Scheithauer Infection Control and Infectious Diseases, University Medicine Goettingen, University Hospital Goettingen, Go¨ttingen, Germany Institute of Medical Microbiology, University Medicine Goettingen, University Hospital Goettingen, Go¨ttingen, Germany Institute of Hygiene, University Medicine Mu¨nster, University Hospital Mu¨nster, Mu¨nster, Germany Department of Pediatric Cardiology and Intensive Care Medicine, University Medicine Goettingen, University Hospital Goettingen, Go¨ttingen, Germany Correspondence should be addressed to Tanja Artelt; tanja.artelt@med.uni-goettingen.de Received 11 October 2017; Revised 17 March 2018; Accepted 4 April 2018; Published 29 April 2018 Academic Editor: Bruno Pozzetto Copyright © 2018 Tanja Artelt et al. +is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Isolation precautions required for neonatal intensive care units are part of a bundle with the aim to prevent transmission, colonization, and infection with multidrug-resistant gram-negative pathogens as neonates face an increased risk of mortality and morbidity in case of infection. +e following short report describes a transmission of 3MDRGN Klebsiella pneumoniae on a neonatal intensive care unit in a university hospital in Germany. +is transmission occurred even though intensified infection control measures were in place, which impressively shows the importance of surveillance, outbreak management, and awareness of contributing factors regarding outbreak situations. beta-lactamases- (ESBL-) producing Enterobacteriaceae in 1. Introduction the neonatal ICU. Recommendations of the European So- Detection of multidrug-resistant gram-negative pathogens ciety of Clinical Microbiology and Infectious Diseases (MDRGN) in prematurely and maturely born infants with (ESCMID) for the general patient population are stratified the need of intensive medical care causes major conse- according to species. +ey advise for single-room allocation quences. In case of infection, broad spectrum antibiotics are only for Klebsiella ssp. harbouring ESBL genes but not for needed for treatment. Infections due to MDRGN are as- Escherichia coli containing the genes. +is difference is based sociated with worse outcomes compared to infections due on the presumed different transmission potential on the to susceptible isolates. Isolation precautions required for species level. However, evidence is only limited and indirect. neonatal intensive care units (NICU) are part of a bundle In Germany, the following recommendations are given with the aim to prevent transmission, colonization, and for neonatal ICUs (Table 1). infection with MDRGN [1, 2]. Due to the high impact of 3MDRGN is defined as a gram-negative pathogen re- infections in the neonatal patient population, advice for sistant to three of the following four different classes of interventions aiming at reducing transmission risks are bactericidal antibiotics in vitro: broad spectrum penicillins, more extensive than in the general patient population in third or fourth generation cephalosporines, carbapenems some national recommendations [2–4]. According to in- (in neonates meropenem), and fluoroquinolones. 4MDRGN ternational standards, single-room isolation is strongly is a pathogen with in vitro resistance to all of the above- advised for carbapenemase-producing Enterobacteriaceae. mentioned antibiotics. As fluoroquinolones are not em- German standards go a step further and additionally rec- pirically used in neonates, the definition of 2MDRGN, ommend the isolation of patients with extended spectrum a gram-negative pathogen resistant to cephalosporines and 2 Canadian Journal of Infectious Diseases and Medical Microbiology Table 1: Isolation precautions required for NICU [1, 2]. screening included swabs from medical equipment and devices (ultrasound, X-ray, electrocardiography, and lami- Single Protective gowns and Pathogen Cohorting Mask nar air flow), swabs from surroundings in every patient room disposable gloves room (e.g., disinfectant dispensers, soap dispensers, filter, 2MDRGN − + + −⁺ and accessories for nursing including medical preparations 3MDRGN + + + + like salves), and surroundings in parent rooms, kitchen, and 4MDRGN + + + + laboratory. Extensive contact precautions for all patients on ⁺Only at treatments with increased risk (e.g., ventilation procedures). the ward, consequent isolation and cohorting of the four colonized patients, and all direct contacts were determined. Common areas as for the nursing and parent rooms were broad-spectrum penicillins, is particularly important for shut down, and conversations with parents and relatives in neonatal ICUs. detail were accomplished. Furthermore, interdisciplinary In this context, current recommendations of the German rounds on the ward were arranged daily and documented in Commission on Hospital Hygiene and Infection Prevention detail. Members of the executive board also were involved. (KRINKO) at the Robert Koch Institute (RKI), Berlin, All procedures were maintained until the end of January focus on a weekly screening for MDRGN [2, 3]. +e global prevalence of colonization with MDRGN differs consider- ably. Considering the high influx of newly arrived refugees in 2015/16 mainly from high prevalence regions [5, 6], 2.2. Microbiological Methods. +e swabs of the environ- an advanced infection control strategy at the University mental screening were cultured in Caso-Bouillon (37 C/24 Medicine Goettingen (UMG) was established. In addition to hours) and subcultured on nutrient agar plates, followed by the implemented RKI recommendations, recently arrived differentiation and identification regarding morphological pediatric refugees were isolated in single rooms immediately and biochemical characteristics. at admission and directly screened for MDRGN. For in- +e patient screening samples of the weekly screening patient infants with a previous stay in abroad, screening for for MDRGN were examined regarding the minimum in- MRSA, 2MDRGN, 3MDRGN, 4MDRGN, and vancomycin- hibitory concentration (MIC) as part of determination of resistant enterococci (VRE) was established on the com- resistance via Vitek-MIC. bined NICU at admission with the aim to reduce or even Two of five 3MDRGN Klebsiella pneumoniae isolates prevent transmissions [7]. were recovered: patients number 2 and 3 (2015-12-15 in- guinal swab and 2015-12-17 rectal swab, Figure 1). Whole genome sequencing (WGS) of the detected Klebsiella 2. Materials and Methods pneumoniae strains was performed on an Illumina MiSeq platform after DNA isolation and library preparation as 2.1. Epidemiological Investigation. +e combined neonatal- previously described. Quality trimming, de novo assembly, pediatric 20-bed ICU has the resources to care for ten ex- and further analyses including core genome multilocus tremely premature infants and ten pediatric patients with sequence typing were performed using SeqSphere+ software cardiac diseases. (Ridom, Munster, ¨ Germany) [8]. An eight months old female refugee, who had recently arrived from Iran travelling via Turkey and Greece, was admitted to our combined neonatal-pediatric ICU in No- 3. Results and Discussion vember 2015. +e infant suffered from a severe cardiac malformation, but previous contact to the healthcare system Despite preemptive isolation and infection control measures had been denied several times. +e patient was isolated and and according to advanced infection control strategies, screened for resistant bacteria at admission in accordance a transmission of 3MDRGN Klebsiella pneumoniae occurred with the internal UMG guidelines. 3MDRGN Klebsiella after a period of four weeks. pneumoniae and 3MDRGN Escherichia coli were detected All environmental samples turned out to be negative for exclusively in a rectal swab without clinical symptoms. facultative pathogens except the swabs taken from the +erefore, the infant remained in single-room isolation nearest surrounding in the index patient room. On devices (2015-11-19 to 2016-01-09). Being in a difficult general like stethoscope, tape measure, several buttons, or xylo- condition, the colonization evolved to an infection, and the caine gel, only Staphylococcus epidermidis and aerobic infant needed specific antibiotic treatment. spores could be detected. Many samples even turned out After a period of four weeks without any findings, we to be sterile. Microbiological results concerning medical detected a colonization of K. pneumoniae in another infant devices and equipment in other rooms (patients, parents, with an identical antibiotic susceptibility profile within the kitchen, and laboratory) also turned out to be sterile or weekly neonatal screening, but no E. coli. +e infant shared colonized with pathogens without relevance concerning an adjacent room with three more patients (Figure 1). infection control. +e frequent exploration of inanimate Consequently, a number of additional infection control surfaces detected Enterococcus faecalis on one thermom- measures according to the in-house standard operating eter. 3MDRGN Klebsiella pneumoniae or 3MDRGN procedure were implemented, as for cleaning twice daily not Escherichia coli was not found, neither in the bedroom only the affected rooms, but the entire unit. Environmental cohorting the four patients colonized nor in adjacent Canadian Journal of Infectious Diseases and Medical Microbiology 3 A 19.11./Room 3 1 ♀ 19.11. rectal: 3MDRGN K. pneumoniae + 3MDRGN E. coli + A 01.12./Room 4 T 23.12. 2 ♂ 15.12. inguinal: 3MDRGN K. pneumoniae + A 13.11./Room 4 T 28.12. 3 ♂ 17.12. rectal: 3MDRGN K. pneumoniae + A 22.11./Room 4 4 ♀ 30.12. rectal: 3MDRGN K. pneumoniae + A 09.11./Room 4 T 17.12. 5 ♂ 04.01. rectal: 3MDRGN K. pneumoniae + Infection Ward A A Admission Ward B T Transfer Colonization Figure 1: Transmission of 3MDRGN Klebsiella pneumoniae (linelist). Table 2: Antibiotic susceptibility, 3MDRGN Klebsiella pneumo- rooms. A point source could not be identied by in- niae, and rectal swabs. vestigating the samples. None of all patients devel- Patient 1 oped an infection with 3MDRGN Klebsiella pneumoniae Antibiotic Patient 2 Patient 3 Patient 4 Patient 5 (index) except the index patient. �e microbiological results of the weekly screening for Ampicillin R R R R R Ampicillin + MDRGN (rectal swabs) indicated the similarity of the R RR R R Sulbactam 3MDRGN Klebsiella pneumoniae isolates (Table 2). Piperacillin + All ve patient samples turned out to be positive for R RR R R Tazobactam ESBL (Vitec-MIC). Development of gentamicin-resistance Cefuroxim R R R R R often appears quickly due to the fact that ampicillin/ Cefotaxim R R R R R gentamicin is a rst-line antibiotic in pediatric therapy. Ceftriaxon R R R R R All 3MDRGN Klebsiella pneumoniae isolates available Ceftazidim R R R R R (Isolate 2 and 3, corresponding to patient 2 and 3, Figure 1) Imipenem S S S S S were typed by NGS, and they turned out to be identical Ertapenem S S S S n.d. (Figure 2). �e primary goal was to determine the clonal Meropenem S S S S S Gentamicin S S R R R relationship of the isolates for infection control purposes. In Cotrimoxazol R R R R R this context, therefore it was only checked for the presence of Moxišoxacin R R R R R extended-spectrum beta-lactamase genes. It was possible to R  resistant; S  sensible; n.d.  not done. extract the gene encoding CTX-M15 extended-spectrum beta-lactamase. �e retrospective analysis revealed an emergency situ- 3MDRGN colonization—the same nursing sta’ had been ation that had happened on the NICU a’ecting the two involved in both of the rooms. Our hypothesis was a singular patient rooms only a few days before detection of the transmission during this situation. 4 Canadian Journal of Infectious Diseases and Medical Microbiology Conflicts of Interest �e author declares that there are no conšicts of interest NC_009648 regarding the publication of this article. References [1] A. Simon, B. Gartner, ¨ L. A. Gortner et al., “Empfehlung der Arbeitsgruppe MRGN der Deutschen Gesellschaft fur ¨ Padiatrische ¨ Infektiologie und des Paed IC Projektes Infek- tionspraventives ¨ Vorgehen bei Nachweis von MRGN im Kindesalter,” Medecine Et Hygiene, vol. 39, no. 10, Isolate 2 pp. 392–399, 2014. Isolate 3 [2] Kommission f¨ur Krankenhaushygiene und Infektionspra¨ven- tion beim Robert Koch-Institut, “Erganzende Empfehlung zur Implementierung der Empfehlungen zur Pra¨vention nosoko- mialer Infektionen bei neonatologischen Intensivpšegepatienten Figure 2: Minimum spanning tree analysis according to core mit einem Geburtsgewicht unter 1.500 g aus dem Jahr 2007 und genome MLST via SeqSphere+ based on reference genome (NC) 2012,” Epidemiologisches Bulletin, vol. 42, pp. 421–432, 2013. and next generation sequencing (NGS). [3] Kommission f¨ur Krankenhaushygiene und Infektionspra¨vention beim Robert Koch-Institut, “Risikocharakterisierung intensiv- medizinisch behandelter Fr¨uh- und Neugeborener und Daten Further consequences of the outbreak management were zur Ist-Situation in deutschen neonatologischen Intensivp- šegestationen 2013,” Supplement zum Epidemiologisches Bulletin, the closure of beds and the postponement of elective ad- vol. 42, pp. 1–52, 2013. missions on the combined neonatal-pediatric ICU as well as [4] A. Simon and T. Tenenbaum, “Surveillance of multidrug- on the adjacent neonatal standard care unit. resistant Gram-negative pathogens in high-risk neonates– Advanced infection control strategies were kept until the does it make a di’erence?,” Pediatric Infectious Disease end of January 2016. Altogether 199 bed days at the Journal, vol. 32, no. 4, pp. 407–409, 2013. neonatal-pediatric ICU and 122 bed days at the neonatal [5] C. Reinheimer, V. Kempf, S. Gottig et al., “Multidrug-resistant standard care unit were lost. organisms detected in refugee patients admitted to a Uni- versity Hospital, Germany June–December 2015,” Euro- surveillance, vol. 21, no. 2, 2016. 4. Conclusions [6] T. Artelt, M. Kaase, and S. Scheithauer, “Infektiologische Herausforderungen nach Migration,” Gynakologe ¨ , vol. 50, Despite the implementation of intensied comprehensive no. 2, pp. 134–138, 2017. infection control measures, beyond o£cial requirements, [7] T. Artelt, I. Bley, M. Lange et al., “Prevalence of multidrug- transmissions of MDRGN cannot be completely avoided in resistant bacteria in refugees: a 12-month surveillance study in clinical settings. In this case, it is remarkable that a trans- a university pediatric hospital in Germany,” in Proceedings of mission of 3MDRGN K. pneumoniae but not of 3MDRGN the 68th Annual Meeting of the German Society of Hygiene and E. coli occurred. �is is in accordance with recent ndings Microbiology (DGHM), Ulm, Germany, September 2016. [8] A. Mellmann, S. Bletz, T. Boking ¨ et al., “Real-time genome that K. pneumoniae is more transmissible than E. coli sequencing of resistant bacteria provides precision infection [9–11]. control in an institutional setting,” Journal of Clinical Mi- It becomes clear that proactive hygiene interventions crobiology, vol. 54, pp. 2874–2881, 2016. inšuence the daily routine care on the NICU permanently. [9] P. Tamma, P. Savard, T. Pa´l, A. Sonnevend, T. Perl, and A. Milstone, �ese interventions include strict isolation regimes for pa- “An outbreak of extended-spectrum β-lactamase–producing Kleb- tients with colonization or infection as well as patients with siella pneumoniae in a neonatal intensive care unit,” Infection contact to the index patients. Nevertheless, it is essential to Control and Hospital Epidemiology, vol. 33, no. 6, pp. 631–634, 2012. remember basic infection control measures and to observe [10] P. J. Stapleton, M. Murphy, N. McCallion, M. Brennan, compliance of hand hygiene, contact precautions, and take R. Cunney, and R. J. Drew, “Outbreaks of extended spectrum care of sta’ training and instruction [12]. beta-lactamase-producing Enterobacteriaceae in neonatal intensive care units: a systematic review,” Archives of Disease Pediatric refugee patients have a considerably higher in Childhood-Fetal and Neonatal Edition, vol. 101, no. 1, prevalence of colonization with MRSA as well as cefotaxime pp. 72–78, 2016. and/or ceftazidime-resistant E. coli and K. pneumoniae than [11] T. Gurieva, M. J. D. Dautzenberg, M. Gniadkowski, nonrefugee pediatric patients, as seen in the described case L. P. G. Derde, M. J. M. Bonten, and M. C. J. Bootsma, “�e and in the data analyzed at our university hospital [7]. transmissibility of antibiotic-resistant Enterobacteriaceae in Screening for multidrug-resistant bacteria is considered to intensive care units,” Clinical Infectious Diseases, vol. 66, no. 4, be of importance for infection control purposes and may pp. 489–493, 2018. o’er an additional benet for the empiric antibiotic treat- [12] S. Scheithauer, A. Oberrohrmann, ¨ H. Haefner et al., “Com- ment of infections in this population. �erefore, screening of pliance with hand hygiene in patients with MRSA and ESBL- pediatric refugee patients will be continued at our institution producing enterobacteria,” Journal of Hospital Infection, [5, 7, 13, 14]. vol. 76, no. 4, pp. 320–323, 2010. Canadian Journal of Infectious Diseases and Medical Microbiology 5 [13] European Centre for Disease Prevention and Control (ECDC), Communicable Disease Risks Associated with the Movement of Refugees in Europe during the Winter Season, ECDC, Stockholm, Sweden, 2015. [14] S. Karanika, T. Karantanos, M. Arvanitis, C. Grigoras, and E. Mylonakis, “Fecal colonization with extended-spectrum betalactamase–producing Enterobacteriaceae and risk fac- tors among healthy individuals: a systematic review and metaanalysis,” Clinical Infectious Diseases, vol. 63, no. 3, pp. 310–318, 2016. 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Transmission Risk on a Neonatal Intensive Care Unit: Escherichia coli versus Klebsiella pneumoniae

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Hindawi Publishing Corporation
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Copyright © 2018 Tanja Artelt et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Hindawi Canadian Journal of Infectious Diseases and Medical Microbiology Volume 2018, Article ID 1525072, 5 pages https://doi.org/10.1155/2018/1525072 Research Article Transmission Risk on a Neonatal Intensive Care Unit: Escherichia coli versus Klebsiella pneumoniae 1 1 1 2 3 Tanja Artelt , Martin Kaase, Ivonne Bley, Helmut Eiffert, Alexander Mellmann, 4 4 1 Helmut Ku¨ster, Martina Lange, and Simone Scheithauer Infection Control and Infectious Diseases, University Medicine Goettingen, University Hospital Goettingen, Go¨ttingen, Germany Institute of Medical Microbiology, University Medicine Goettingen, University Hospital Goettingen, Go¨ttingen, Germany Institute of Hygiene, University Medicine Mu¨nster, University Hospital Mu¨nster, Mu¨nster, Germany Department of Pediatric Cardiology and Intensive Care Medicine, University Medicine Goettingen, University Hospital Goettingen, Go¨ttingen, Germany Correspondence should be addressed to Tanja Artelt; tanja.artelt@med.uni-goettingen.de Received 11 October 2017; Revised 17 March 2018; Accepted 4 April 2018; Published 29 April 2018 Academic Editor: Bruno Pozzetto Copyright © 2018 Tanja Artelt et al. +is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Isolation precautions required for neonatal intensive care units are part of a bundle with the aim to prevent transmission, colonization, and infection with multidrug-resistant gram-negative pathogens as neonates face an increased risk of mortality and morbidity in case of infection. +e following short report describes a transmission of 3MDRGN Klebsiella pneumoniae on a neonatal intensive care unit in a university hospital in Germany. +is transmission occurred even though intensified infection control measures were in place, which impressively shows the importance of surveillance, outbreak management, and awareness of contributing factors regarding outbreak situations. beta-lactamases- (ESBL-) producing Enterobacteriaceae in 1. Introduction the neonatal ICU. Recommendations of the European So- Detection of multidrug-resistant gram-negative pathogens ciety of Clinical Microbiology and Infectious Diseases (MDRGN) in prematurely and maturely born infants with (ESCMID) for the general patient population are stratified the need of intensive medical care causes major conse- according to species. +ey advise for single-room allocation quences. In case of infection, broad spectrum antibiotics are only for Klebsiella ssp. harbouring ESBL genes but not for needed for treatment. Infections due to MDRGN are as- Escherichia coli containing the genes. +is difference is based sociated with worse outcomes compared to infections due on the presumed different transmission potential on the to susceptible isolates. Isolation precautions required for species level. However, evidence is only limited and indirect. neonatal intensive care units (NICU) are part of a bundle In Germany, the following recommendations are given with the aim to prevent transmission, colonization, and for neonatal ICUs (Table 1). infection with MDRGN [1, 2]. Due to the high impact of 3MDRGN is defined as a gram-negative pathogen re- infections in the neonatal patient population, advice for sistant to three of the following four different classes of interventions aiming at reducing transmission risks are bactericidal antibiotics in vitro: broad spectrum penicillins, more extensive than in the general patient population in third or fourth generation cephalosporines, carbapenems some national recommendations [2–4]. According to in- (in neonates meropenem), and fluoroquinolones. 4MDRGN ternational standards, single-room isolation is strongly is a pathogen with in vitro resistance to all of the above- advised for carbapenemase-producing Enterobacteriaceae. mentioned antibiotics. As fluoroquinolones are not em- German standards go a step further and additionally rec- pirically used in neonates, the definition of 2MDRGN, ommend the isolation of patients with extended spectrum a gram-negative pathogen resistant to cephalosporines and 2 Canadian Journal of Infectious Diseases and Medical Microbiology Table 1: Isolation precautions required for NICU [1, 2]. screening included swabs from medical equipment and devices (ultrasound, X-ray, electrocardiography, and lami- Single Protective gowns and Pathogen Cohorting Mask nar air flow), swabs from surroundings in every patient room disposable gloves room (e.g., disinfectant dispensers, soap dispensers, filter, 2MDRGN − + + −⁺ and accessories for nursing including medical preparations 3MDRGN + + + + like salves), and surroundings in parent rooms, kitchen, and 4MDRGN + + + + laboratory. Extensive contact precautions for all patients on ⁺Only at treatments with increased risk (e.g., ventilation procedures). the ward, consequent isolation and cohorting of the four colonized patients, and all direct contacts were determined. Common areas as for the nursing and parent rooms were broad-spectrum penicillins, is particularly important for shut down, and conversations with parents and relatives in neonatal ICUs. detail were accomplished. Furthermore, interdisciplinary In this context, current recommendations of the German rounds on the ward were arranged daily and documented in Commission on Hospital Hygiene and Infection Prevention detail. Members of the executive board also were involved. (KRINKO) at the Robert Koch Institute (RKI), Berlin, All procedures were maintained until the end of January focus on a weekly screening for MDRGN [2, 3]. +e global prevalence of colonization with MDRGN differs consider- ably. Considering the high influx of newly arrived refugees in 2015/16 mainly from high prevalence regions [5, 6], 2.2. Microbiological Methods. +e swabs of the environ- an advanced infection control strategy at the University mental screening were cultured in Caso-Bouillon (37 C/24 Medicine Goettingen (UMG) was established. In addition to hours) and subcultured on nutrient agar plates, followed by the implemented RKI recommendations, recently arrived differentiation and identification regarding morphological pediatric refugees were isolated in single rooms immediately and biochemical characteristics. at admission and directly screened for MDRGN. For in- +e patient screening samples of the weekly screening patient infants with a previous stay in abroad, screening for for MDRGN were examined regarding the minimum in- MRSA, 2MDRGN, 3MDRGN, 4MDRGN, and vancomycin- hibitory concentration (MIC) as part of determination of resistant enterococci (VRE) was established on the com- resistance via Vitek-MIC. bined NICU at admission with the aim to reduce or even Two of five 3MDRGN Klebsiella pneumoniae isolates prevent transmissions [7]. were recovered: patients number 2 and 3 (2015-12-15 in- guinal swab and 2015-12-17 rectal swab, Figure 1). Whole genome sequencing (WGS) of the detected Klebsiella 2. Materials and Methods pneumoniae strains was performed on an Illumina MiSeq platform after DNA isolation and library preparation as 2.1. Epidemiological Investigation. +e combined neonatal- previously described. Quality trimming, de novo assembly, pediatric 20-bed ICU has the resources to care for ten ex- and further analyses including core genome multilocus tremely premature infants and ten pediatric patients with sequence typing were performed using SeqSphere+ software cardiac diseases. (Ridom, Munster, ¨ Germany) [8]. An eight months old female refugee, who had recently arrived from Iran travelling via Turkey and Greece, was admitted to our combined neonatal-pediatric ICU in No- 3. Results and Discussion vember 2015. +e infant suffered from a severe cardiac malformation, but previous contact to the healthcare system Despite preemptive isolation and infection control measures had been denied several times. +e patient was isolated and and according to advanced infection control strategies, screened for resistant bacteria at admission in accordance a transmission of 3MDRGN Klebsiella pneumoniae occurred with the internal UMG guidelines. 3MDRGN Klebsiella after a period of four weeks. pneumoniae and 3MDRGN Escherichia coli were detected All environmental samples turned out to be negative for exclusively in a rectal swab without clinical symptoms. facultative pathogens except the swabs taken from the +erefore, the infant remained in single-room isolation nearest surrounding in the index patient room. On devices (2015-11-19 to 2016-01-09). Being in a difficult general like stethoscope, tape measure, several buttons, or xylo- condition, the colonization evolved to an infection, and the caine gel, only Staphylococcus epidermidis and aerobic infant needed specific antibiotic treatment. spores could be detected. Many samples even turned out After a period of four weeks without any findings, we to be sterile. Microbiological results concerning medical detected a colonization of K. pneumoniae in another infant devices and equipment in other rooms (patients, parents, with an identical antibiotic susceptibility profile within the kitchen, and laboratory) also turned out to be sterile or weekly neonatal screening, but no E. coli. +e infant shared colonized with pathogens without relevance concerning an adjacent room with three more patients (Figure 1). infection control. +e frequent exploration of inanimate Consequently, a number of additional infection control surfaces detected Enterococcus faecalis on one thermom- measures according to the in-house standard operating eter. 3MDRGN Klebsiella pneumoniae or 3MDRGN procedure were implemented, as for cleaning twice daily not Escherichia coli was not found, neither in the bedroom only the affected rooms, but the entire unit. Environmental cohorting the four patients colonized nor in adjacent Canadian Journal of Infectious Diseases and Medical Microbiology 3 A 19.11./Room 3 1 ♀ 19.11. rectal: 3MDRGN K. pneumoniae + 3MDRGN E. coli + A 01.12./Room 4 T 23.12. 2 ♂ 15.12. inguinal: 3MDRGN K. pneumoniae + A 13.11./Room 4 T 28.12. 3 ♂ 17.12. rectal: 3MDRGN K. pneumoniae + A 22.11./Room 4 4 ♀ 30.12. rectal: 3MDRGN K. pneumoniae + A 09.11./Room 4 T 17.12. 5 ♂ 04.01. rectal: 3MDRGN K. pneumoniae + Infection Ward A A Admission Ward B T Transfer Colonization Figure 1: Transmission of 3MDRGN Klebsiella pneumoniae (linelist). Table 2: Antibiotic susceptibility, 3MDRGN Klebsiella pneumo- rooms. A point source could not be identied by in- niae, and rectal swabs. vestigating the samples. None of all patients devel- Patient 1 oped an infection with 3MDRGN Klebsiella pneumoniae Antibiotic Patient 2 Patient 3 Patient 4 Patient 5 (index) except the index patient. �e microbiological results of the weekly screening for Ampicillin R R R R R Ampicillin + MDRGN (rectal swabs) indicated the similarity of the R RR R R Sulbactam 3MDRGN Klebsiella pneumoniae isolates (Table 2). Piperacillin + All ve patient samples turned out to be positive for R RR R R Tazobactam ESBL (Vitec-MIC). Development of gentamicin-resistance Cefuroxim R R R R R often appears quickly due to the fact that ampicillin/ Cefotaxim R R R R R gentamicin is a rst-line antibiotic in pediatric therapy. Ceftriaxon R R R R R All 3MDRGN Klebsiella pneumoniae isolates available Ceftazidim R R R R R (Isolate 2 and 3, corresponding to patient 2 and 3, Figure 1) Imipenem S S S S S were typed by NGS, and they turned out to be identical Ertapenem S S S S n.d. (Figure 2). �e primary goal was to determine the clonal Meropenem S S S S S Gentamicin S S R R R relationship of the isolates for infection control purposes. In Cotrimoxazol R R R R R this context, therefore it was only checked for the presence of Moxišoxacin R R R R R extended-spectrum beta-lactamase genes. It was possible to R  resistant; S  sensible; n.d.  not done. extract the gene encoding CTX-M15 extended-spectrum beta-lactamase. �e retrospective analysis revealed an emergency situ- 3MDRGN colonization—the same nursing sta’ had been ation that had happened on the NICU a’ecting the two involved in both of the rooms. Our hypothesis was a singular patient rooms only a few days before detection of the transmission during this situation. 4 Canadian Journal of Infectious Diseases and Medical Microbiology Conflicts of Interest �e author declares that there are no conšicts of interest NC_009648 regarding the publication of this article. References [1] A. Simon, B. Gartner, ¨ L. A. Gortner et al., “Empfehlung der Arbeitsgruppe MRGN der Deutschen Gesellschaft fur ¨ Padiatrische ¨ Infektiologie und des Paed IC Projektes Infek- tionspraventives ¨ Vorgehen bei Nachweis von MRGN im Kindesalter,” Medecine Et Hygiene, vol. 39, no. 10, Isolate 2 pp. 392–399, 2014. Isolate 3 [2] Kommission f¨ur Krankenhaushygiene und Infektionspra¨ven- tion beim Robert Koch-Institut, “Erganzende Empfehlung zur Implementierung der Empfehlungen zur Pra¨vention nosoko- mialer Infektionen bei neonatologischen Intensivpšegepatienten Figure 2: Minimum spanning tree analysis according to core mit einem Geburtsgewicht unter 1.500 g aus dem Jahr 2007 und genome MLST via SeqSphere+ based on reference genome (NC) 2012,” Epidemiologisches Bulletin, vol. 42, pp. 421–432, 2013. and next generation sequencing (NGS). [3] Kommission f¨ur Krankenhaushygiene und Infektionspra¨vention beim Robert Koch-Institut, “Risikocharakterisierung intensiv- medizinisch behandelter Fr¨uh- und Neugeborener und Daten Further consequences of the outbreak management were zur Ist-Situation in deutschen neonatologischen Intensivp- šegestationen 2013,” Supplement zum Epidemiologisches Bulletin, the closure of beds and the postponement of elective ad- vol. 42, pp. 1–52, 2013. missions on the combined neonatal-pediatric ICU as well as [4] A. Simon and T. Tenenbaum, “Surveillance of multidrug- on the adjacent neonatal standard care unit. resistant Gram-negative pathogens in high-risk neonates– Advanced infection control strategies were kept until the does it make a di’erence?,” Pediatric Infectious Disease end of January 2016. Altogether 199 bed days at the Journal, vol. 32, no. 4, pp. 407–409, 2013. neonatal-pediatric ICU and 122 bed days at the neonatal [5] C. Reinheimer, V. Kempf, S. Gottig et al., “Multidrug-resistant standard care unit were lost. organisms detected in refugee patients admitted to a Uni- versity Hospital, Germany June–December 2015,” Euro- surveillance, vol. 21, no. 2, 2016. 4. Conclusions [6] T. Artelt, M. Kaase, and S. Scheithauer, “Infektiologische Herausforderungen nach Migration,” Gynakologe ¨ , vol. 50, Despite the implementation of intensied comprehensive no. 2, pp. 134–138, 2017. infection control measures, beyond o£cial requirements, [7] T. Artelt, I. Bley, M. Lange et al., “Prevalence of multidrug- transmissions of MDRGN cannot be completely avoided in resistant bacteria in refugees: a 12-month surveillance study in clinical settings. In this case, it is remarkable that a trans- a university pediatric hospital in Germany,” in Proceedings of mission of 3MDRGN K. pneumoniae but not of 3MDRGN the 68th Annual Meeting of the German Society of Hygiene and E. coli occurred. �is is in accordance with recent ndings Microbiology (DGHM), Ulm, Germany, September 2016. [8] A. Mellmann, S. Bletz, T. Boking ¨ et al., “Real-time genome that K. pneumoniae is more transmissible than E. coli sequencing of resistant bacteria provides precision infection [9–11]. control in an institutional setting,” Journal of Clinical Mi- It becomes clear that proactive hygiene interventions crobiology, vol. 54, pp. 2874–2881, 2016. inšuence the daily routine care on the NICU permanently. [9] P. Tamma, P. Savard, T. Pa´l, A. Sonnevend, T. Perl, and A. Milstone, �ese interventions include strict isolation regimes for pa- “An outbreak of extended-spectrum β-lactamase–producing Kleb- tients with colonization or infection as well as patients with siella pneumoniae in a neonatal intensive care unit,” Infection contact to the index patients. Nevertheless, it is essential to Control and Hospital Epidemiology, vol. 33, no. 6, pp. 631–634, 2012. remember basic infection control measures and to observe [10] P. J. Stapleton, M. Murphy, N. McCallion, M. Brennan, compliance of hand hygiene, contact precautions, and take R. Cunney, and R. J. Drew, “Outbreaks of extended spectrum care of sta’ training and instruction [12]. beta-lactamase-producing Enterobacteriaceae in neonatal intensive care units: a systematic review,” Archives of Disease Pediatric refugee patients have a considerably higher in Childhood-Fetal and Neonatal Edition, vol. 101, no. 1, prevalence of colonization with MRSA as well as cefotaxime pp. 72–78, 2016. and/or ceftazidime-resistant E. coli and K. pneumoniae than [11] T. Gurieva, M. J. D. Dautzenberg, M. Gniadkowski, nonrefugee pediatric patients, as seen in the described case L. P. G. Derde, M. J. M. Bonten, and M. C. J. Bootsma, “�e and in the data analyzed at our university hospital [7]. transmissibility of antibiotic-resistant Enterobacteriaceae in Screening for multidrug-resistant bacteria is considered to intensive care units,” Clinical Infectious Diseases, vol. 66, no. 4, be of importance for infection control purposes and may pp. 489–493, 2018. o’er an additional benet for the empiric antibiotic treat- [12] S. Scheithauer, A. Oberrohrmann, ¨ H. Haefner et al., “Com- ment of infections in this population. �erefore, screening of pliance with hand hygiene in patients with MRSA and ESBL- pediatric refugee patients will be continued at our institution producing enterobacteria,” Journal of Hospital Infection, [5, 7, 13, 14]. vol. 76, no. 4, pp. 320–323, 2010. Canadian Journal of Infectious Diseases and Medical Microbiology 5 [13] European Centre for Disease Prevention and Control (ECDC), Communicable Disease Risks Associated with the Movement of Refugees in Europe during the Winter Season, ECDC, Stockholm, Sweden, 2015. [14] S. Karanika, T. Karantanos, M. Arvanitis, C. Grigoras, and E. Mylonakis, “Fecal colonization with extended-spectrum betalactamase–producing Enterobacteriaceae and risk fac- tors among healthy individuals: a systematic review and metaanalysis,” Clinical Infectious Diseases, vol. 63, no. 3, pp. 310–318, 2016. 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