Comparison of Three Eradication Treatment Protocols for Pseudomonas
                    Aeruginosa in Children and Adolescents with Cystic Fibrosis

Katharina Schütz; Simon Grewendorf; Julia Kontsendorn; Jan Fuge; Christine Happle; Isa Rudolf; Christian Dopfer; Ludwig Sedlacek; Gesine Hansen; Sibylle Junge; Anna-Maria Dittrich

doi:10.1055/a-1996-0074

Klin Padiatr 2023; 235(02): 75-83
DOI: 10.1055/a-1996-0074

Original Article

Comparison of Three Eradication Treatment Protocols for Pseudomonas Aeruginosa in Children and Adolescents with Cystic Fibrosis

Vergleich von drei Behandlungsprotokollen zur Eradikation von Pseudomonas aeruginosa bei Kindern und Jugendlichen mit Zystischer Fibrose

Katharina Schütz^*

¹Dep. of Paediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany

²Excellence Cluster RESIST – Resolving Infection Susceptibility, Hannover Medical School, Hannover, Germany

,

Simon Grewendorf^*

¹Dep. of Paediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany

,

Julia Kontsendorn

¹Dep. of Paediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany

³German Center for Lung Research, BREATH location, Hannover Medical School, Hannover, Germany

,

Jan Fuge

³German Center for Lung Research, BREATH location, Hannover Medical School, Hannover, Germany

,

Christine Happle

¹Dep. of Paediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany

²Excellence Cluster RESIST – Resolving Infection Susceptibility, Hannover Medical School, Hannover, Germany

³German Center for Lung Research, BREATH location, Hannover Medical School, Hannover, Germany

,

Isa Rudolf

¹Dep. of Paediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany

³German Center for Lung Research, BREATH location, Hannover Medical School, Hannover, Germany

,

Christian Dopfer

¹Dep. of Paediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany

,

Ludwig Sedlacek

⁴Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany

,

Gesine Hansen

¹Dep. of Paediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany

²Excellence Cluster RESIST – Resolving Infection Susceptibility, Hannover Medical School, Hannover, Germany

³German Center for Lung Research, BREATH location, Hannover Medical School, Hannover, Germany

,

Sibylle Junge

¹Dep. of Paediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany

,

Anna-Maria Dittrich

¹Dep. of Paediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany

³German Center for Lung Research, BREATH location, Hannover Medical School, Hannover, Germany

› Author Affiliations

Abstract

Background Pseudomonas aeruginosa (Pa) continues to affect disease progression in cystic fibrosis (CF). However, the best eradication regimen remains unclear. This work compares three different antibiotic eradication regimens in pediatric CF: an administration according to a standard-operating procedure (SOP) order vs. administration outside of this order (ooSOP).

Methods This observational study includes all CF patients<18 years who received one of three Pa eradication treatments in the past eight years at our center: 1) inhaled high-dose tobramycin (Hi-TOBI), 2) inhaled colistin+oral ciprofloxacin (COL/Cip), 3) inhaled low-dose tobramycin+4 intravenous 14-day Pa active antibiotic treatments (lo-Tobra/IV). We compared eradication rates of the three treatment regimens performed according to the SOP-based order vs. ooSOP. Logistic regression analysis was performed to identify risk factors for eradication failure.

Results Performed according to SOP order, Hi-TOBI showed the greatest efficacy, followed by lo-Tobra/IV and finally COL/Cip, while ooSOP lo-Tobra/IV was most successful, followed by COL/Cip and Hi-TOBI. Previous Pa-infections and Pa-therapies along with age at CF diagnosis were risk factors for eradication failure.

Conclusion Antibiotic treatment in SOP-based pre-defined order leads to significantly better eradication rates than individual modifications of the order of administration. A short course of inhalational high-dose Tobramycin is most successful at the first attempt. Prolonged antibiotic therapy seems to improve eradication after failed initial attempts.

Zusammenfassung

Hintergrund Pseudomonas aeruginosa (Pa) beeinträchtigt den Krankheitsverlauf bei zystischer Fibrose (CF). Das beste Eradikationsschema ist unklar. Wir vergleichen drei Antibiotika-Eradikationsschemata bei Kindern und Jugendlichen mit CF: Die Gabe nach einer Standard-Operating-Prozedur (SOP)-Reihenfolge gegenüber der nicht standardisierten Reihenfolge (ooSOP).

Methoden Diese Beobachtungsstudie umfasst alle CF-Patienten<18 Jahre, die in den letzten acht Jahren eine der drei Pa-Eradikationsbehandlungen in unserem Zentrum erhielten: 1) inhaliertes hochdosiertes Tobramycin (Hi-TOBI), 2) inhaliertes Colistin+orales Ciprofloxacin (COL/Cip), 3) inhaliertes niedrigdosiertes Tobramycin+4 intravenöse 14-tägige aktive Pa-Antibiotikabehandlungen (lo-Tobra/IV). Eradikationsraten gemäß der SOP-basierten Anordnung vs. ooSOP wurden verglichen sowie logistische Regressionsanalysen durchgeführt, um Risikofaktoren für ein Eradikationsversagen zu ermitteln.

Ergebnisse Bei Durchführung nach SOP-Reihenfolge zeigte Hi-TOBI die größte Wirksamkeit, gefolgt von lo-Tobra/IV und schließlich COL/Cip, während ooSOP lo-Tobra/IV am erfolgreichsten war, gefolgt von COL/Cip und Hi-TOBI. Frühere Pa-Infektionen und Therapien sowie Alter bei der CF-Diagnose sind Risikofaktoren für ein Scheitern der Eradikation.

Schlussfolgerung Eine Antibiotikabehandlung in einer SOP-basierten, vordefinierten Reihenfolge führt zu signifikant besseren Eradikationsraten als individuelle Modifikationen der Verabreichungsreihenfolge. Eine kurze inhalative Behandlung mit hochdosiertem Tobramycin ist beim ersten Pa-Eradikationsversuch am erfolgreichsten. Eine längere Antibiotikatherapie scheint die Eradikation nach fehlgeschlagenen ersten Versuchen zu verbessern.

Key words

Pseudomonas aeruginosa - eradication treatment protocol - Cystic fibrosis - pediatrics

Schlüsselwörter

Pseudomonas aeruginosa - Eradikationsschema - Zystische Fibrose - Pädiatriepublished online 2023

Full Text

References

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