Hand hygiene versus additional non-sterile gloves and gowns use to prevent sepsis in preterm infants colonized with multi-resistant drug bacteria: the study protocol of the cluster-randomized, cross-over, non-inferiority BALTIC trial

Kirstin Faust^#^{1

2}, Clara Haug^#¹, Julia Pagel^{2

3}, Reinhard Jensen⁴, Anja Stein⁵, Ursula Felderhoff-Müser⁵, David Frommhold⁶, Kirsten Brebach⁶, Christian Wieg⁷, Georg Hillebrand⁸, Barbara Naust⁸, Esther Schmidt⁹, Lutz Koch¹⁰, Susanne Schmidtke¹¹, Arne Simon¹², Michael Zemlin¹³, Sascha Meyer^{13

14}, Christopher Scholzen¹³, Natascha Köstlin-Gille¹⁵, Christian Gille¹⁶, Ann-Carolin Longardt¹⁷, Manuela Kärlin¹, Mirjam Lusga¹, Wolfgang Göpel¹, Manuel Krone¹⁸, Stefanie Kampmeier¹⁸, Franziska Strecker¹, Dennis Nurjadi^{2

19}, Inke R König²⁰, Egbert Herting¹, Jan Rupp^{2

18}, Christoph Härtel^{21

22}

Affiliations

¹ Department of Pediatrics, University Hospital Schleswig-Holstein, Lübeck, Germany.
² German Center for Infection Research, Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany.
³ Department of Pediatrics, University Hospital Hamburg-Eppendorf, Hamburg-Eppendorf, Germany.
⁴ Children's Hospital Heide, Heide, Germany.
⁵ Department of Pediatrics I, Neonatology, University Hospital Essen, Essen, Germany.
⁶ Children's Hospital Memmingen, Memmingen, Germany.
⁷ Children's Hospital Aschaffenburg-Alzenau, Alzenau, Germany.
⁸ Children's Hospital Itzehoe, Itzehoe, Germany.
⁹ Helios Children's Hospital Schwerin, Schwerin, Germany.
¹⁰ Children's Hospital Wilhelmstift Hamburg and Marienhospital Hamburg, Hamburg, Germany.
¹¹ Neonatology, Asklepios Hospital Hamburg-Barmbek, Hamburg, Germany.
¹² Department of Pediatric Hematology and Immunology, Saarland University Medical Center, Homburg, Germany.
¹³ Department for General Pediatrics and Neonatology, Saarland University Medical Center, 66421, Homburg, Germany.
¹⁴ SKK Klinikum, Franz-Lust Klinik für Kinder und Jugendliche, Karlsruhe, Germany.
¹⁵ Department of Neonatology, University Hospital Tübingen, Tübingen, Germany.
¹⁶ Department of Neonatology, University Hospital Heidelberg, Heidelberg, Germany.
¹⁷ Department of Pediatrics, University Hospital Schleswig-Holstein, Kiel, Germany.
¹⁸ Infection Control and Antimicrobial Stewardship Unit, University Hospital Würzburg, Würzburg, Germany.
¹⁹ Department of Infectious Diseases and Microbiology, University Hospital Schleswig-Holstein, Lübeck, Germany.
²⁰ Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck, Germany.
²¹ German Center for Infection Research, Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany. haertel_c1@ukw.de.
²² Department of Pediatrics, University Hospital Würzburg, Josef-Schneider-Strasse 2, D-97080, Würzburg, Germany. haertel_c1@ukw.de.

^# Contributed equally.

PMID: 40189707
PMCID: PMC11973001
DOI: 10.1186/s40348-025-00192-2

Hand hygiene versus additional non-sterile gloves and gowns use to prevent sepsis in preterm infants colonized with multi-resistant drug bacteria: the study protocol of the cluster-randomized, cross-over, non-inferiority BALTIC trial

Kirstin Faust et al. Mol Cell Pediatr. 2025.

. 2025 Apr 7;12(1):4.

doi: 10.1186/s40348-025-00192-2.

Authors

Affiliations

¹ Department of Pediatrics, University Hospital Schleswig-Holstein, Lübeck, Germany.
² German Center for Infection Research, Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany.
³ Department of Pediatrics, University Hospital Hamburg-Eppendorf, Hamburg-Eppendorf, Germany.
⁴ Children's Hospital Heide, Heide, Germany.
⁵ Department of Pediatrics I, Neonatology, University Hospital Essen, Essen, Germany.
⁶ Children's Hospital Memmingen, Memmingen, Germany.
⁷ Children's Hospital Aschaffenburg-Alzenau, Alzenau, Germany.
⁸ Children's Hospital Itzehoe, Itzehoe, Germany.
⁹ Helios Children's Hospital Schwerin, Schwerin, Germany.
¹⁰ Children's Hospital Wilhelmstift Hamburg and Marienhospital Hamburg, Hamburg, Germany.
¹¹ Neonatology, Asklepios Hospital Hamburg-Barmbek, Hamburg, Germany.
¹² Department of Pediatric Hematology and Immunology, Saarland University Medical Center, Homburg, Germany.
¹³ Department for General Pediatrics and Neonatology, Saarland University Medical Center, 66421, Homburg, Germany.
¹⁴ SKK Klinikum, Franz-Lust Klinik für Kinder und Jugendliche, Karlsruhe, Germany.
¹⁵ Department of Neonatology, University Hospital Tübingen, Tübingen, Germany.
¹⁶ Department of Neonatology, University Hospital Heidelberg, Heidelberg, Germany.
¹⁷ Department of Pediatrics, University Hospital Schleswig-Holstein, Kiel, Germany.
¹⁸ Infection Control and Antimicrobial Stewardship Unit, University Hospital Würzburg, Würzburg, Germany.
¹⁹ Department of Infectious Diseases and Microbiology, University Hospital Schleswig-Holstein, Lübeck, Germany.
²⁰ Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck, Germany.
²¹ German Center for Infection Research, Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany. haertel_c1@ukw.de.
²² Department of Pediatrics, University Hospital Würzburg, Josef-Schneider-Strasse 2, D-97080, Würzburg, Germany. haertel_c1@ukw.de.

^# Contributed equally.

PMID: 40189707
PMCID: PMC11973001
DOI: 10.1186/s40348-025-00192-2

Abstract

Background: Infections are highly relevant for neonatal mortality and long-term morbidities in survivors. Therefore, it is an urgent need to optimize and evaluate infection prevention and control (IPC) strategies. Several infection outbreaks in German neonatal intensive care units (NICUs) required rapid responses by hospitals and improved future preparedness. As a consequence, German authorities recommended weekly colonization screening on NICUs. This screening aims to detect multidrug-resistant organisms (MDRO) and bacteria with high transmissibility. According to these guidelines, infants colonized with multiresistant gram-negative (MRGN) bacteria with in-vitro resistance to piperacillin and cephalosporins (2MRGN) should be cared wearing non-sterile gloves and gowns in addition to standard hygiene precautions. Whether these extended IPC measures have an individual benefit for infants or contribute to the prevention of infection outbreaks has not yet been scientifically proven. This study aims to evaluate the effect of hand desinfection as compared to hand desinfection + gloves and gowns (barrier care) for the care of 2MRGN colonized infants in NICUs on infection and transmission rates through a multicenter, cluster randomized controlled trial (BALTIC study, Barrier protection to lower transmission and infection rates with Gram-negative 2-MRGN in preterm children).

Methods: 12 participating NICUs were randomly allocated to two trial arms: receiving the intervention "standard precautions with a special focus on hand desinfection" or control (standard precautions "plus" barrier care) for the care of 2MRGN positive infants. Cross over was performed after 12 months for another 12 months per site. Primary outcome was the rate of healthcare-associated (HA) Gram-negative bloodstream infections. Secondary outcomes included transmission rate with screening relevant bacteria, overall rate of clinical and culture-proven infections, number of antibiotic cycles and desinfectant use. Regular trainings and hygiene audits are standardized co-interventions.

Benchmarking results: According to our single center data, 9.3% of NICU-treated infants are colonized with 2MRGN during their hospital stay. BALTIC randomized the first center in October 2020 and finished data collection including close-out monitoring in January 2024. Data analysis will be completed in May 2025.

Conclusions: BALTIC should contribute to better evidence on the effectiveness of hand desinfection and extended barrier precautions in critically ill newborns. Further benefits include comprehensive multi-center data collection on MDRO colonization dynamics, an improved awareness on IPC strategies and establishment of network platforms including antimicrobial stewardship programs.

Keywords: Gown; Hand hygiene; Multi-drug-resistant organisms; Non-sterile glove use; Preterm infants; Sepsis.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: The BALTIC study was approved by the institutional review board of the University of Lübeck (primary vote, 19–275) and by the review boards of all participating sites (secondary vote). No identifying data about the infants were collected. Consent for publication: Not applicable. Competing interests: JP received a grant from the German ministry of education and research (#01EO2106). MK has received honoraria for consulting, presentations, expert testimony, and advisory board participation from Abbott, GSK, Pfizer, and Sanofi outside the submitted work. He is member in the board of the AWMF-guidelines “sustainability in intensive care and emergency medicine” and “invasive ventilation and use of extracorporeal oxygenation in patients with respiratory failure” outside the submitted work and has received travel support from the Deutsche Gesellschaft für Hygiene und Mikrobiologie.The other authors have no conflicts of interest relevant to this article to disclose. Trial registration number: DRKS00019103.

Figures

**Fig. 1**
First detection of MRGN, MRSA, MRSA or Vancomycin resistant enterococci (VRE). MRDO = Multi-drug resistant organisms; KRINKO = German Commission on Hospital Hygiene and Infection Prevention, MRGN = Multidrug-resistant Gram negative bacteria, 2MRGN (resistant to Piperacillin and Cefotaxim or Ceftazidim), 3MRGN (resistant to Piperacillin and Cefotaxim or Ceftazidim and fluorchinolones), MRSA = methicillin-resistant *Staphylococcus aureus*, VRE = Vancomycin resistant *Enterococci*. Additional first detections after the 15th week of life: n = 4 2MRGN pathogens

**Fig. 2**
Study design of the BALTIC trial

See this image and copyright information in PMC

References

1. Humberg A, Härtel C, Rausch TK, Stichtenoth G, Jung P, Wieg C, Kribs A, von der Wense A, Weller U, Höhn T, Olbertz DM, Felderhoff-Müser U, Rossi R, Teig N, Heitmann F, Schmidtke S, Bohnhorst B, Vochem M, Segerer H, Möller J, Eichhorn JG, Wintgens J, Böttger R, Hubert M, Dördelmann M, Hillebrand G, Roll C, Jensen R, Zemlin M, Mögel M, Werner C, Schäfer S, Schaible T, Franz A, Heldmann M, Ehlers S, Kannt O, Orlikowsky T, Gerleve H, Schneider K, Haase R, Böckenholt K, Linnemann K, Herting E, Göpel W (2020) Active perinatal care of preterm infants in the German Neonatal Network. Archives of disease in childhood. Fetal and neonatal edition 105, 190–195 - PubMed
1. Flannery DD, Chiotos K, Gerber JS, Puopolo KM (2022) Neonatal multidrug-resistant gram-negative infection: epidemiology, mechanisms of resistance, and management. Pediatr Res 91:380–391 - PMC - PubMed
1. Härtel C, Faust K, Fortmann I, Humberg A, Pagel J, Haug C, Kühl R, Bohnhorst B, Pirr S, Viemann D, Simon A, Zemlin M, Poralla S, Müller A, Köstlin-Gille N, Gille C, Heckmann M, Rupp J, Herting E, Göpel W (2020) Sepsis related mortality of extremely low gestational age newborns after the introduction of colonization screening for multi-drug resistant organisms. Antimicrobial resistance and infection control 9, 144 - PMC - PubMed
1. Mukhopadhyay S, Puopolo KM, Hansen NI, Lorch SA, DeMauro SB, Greenberg RG, Cotten CM, Sanchez PJ, Bell EF, Eichenwald EC, Stoll BJ (2021) Neurodevelopmental outcomes following neonatal late-onset sepsis and blood culture-negative conditions. Archives of disease in childhood. Fetal and neonatal edition 106, 467–473 - PMC - PubMed
1. Schwartz DJ, Shalon N, Wardenburg K, DeVeaux A, Wallace MA, Hall-Moore C, Ndao IM, Sullivan JE, Radmacher P, Escobedo M, Burnham CD, Warner BB, Tarr PI, Dantas G (2023) Gut pathogen colonization precedes bloodstream infection in the neonatal intensive care unit. Sci Transl Med 15:eadg5562 - PMC - PubMed

LinkOut - more resources

Full Text Sources
- PubMed Central
- Springer
Research Materials
- NCI CPTC Antibody Characterization Program

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Hand hygiene versus additional non-sterile gloves and gowns use to prevent sepsis in preterm infants colonized with multi-resistant drug bacteria: the study protocol of the cluster-randomized, cross-over, non-inferiority BALTIC trial

Affiliations

Hand hygiene versus additional non-sterile gloves and gowns use to prevent sepsis in preterm infants colonized with multi-resistant drug bacteria: the study protocol of the cluster-randomized, cross-over, non-inferiority BALTIC trial

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources

Research Materials