Drug monitoring during ciprofloxacin prophylaxis of allogeneic stem cell transplant patients: associations with bacterial infections through a monocentric observational prospective study

H E J Kaba; J Hasenkamp; H Tas; M Schulz; F Streit; H Eiffert; G Wulf; L Truemper; L Binder; M Kaase; S Scheithauer

doi:10.1016/j.jhin.2023.10.016

Drug monitoring during ciprofloxacin prophylaxis of allogeneic stem cell transplant patients: associations with bacterial infections through a monocentric observational prospective study

J Hosp Infect. 2024 Jan:143:160-167. doi: 10.1016/j.jhin.2023.10.016. Epub 2023 Nov 7.

Authors

H E J Kaba¹, J Hasenkamp², H Tas³, M Schulz¹, F Streit⁴, H Eiffert⁵, G Wulf², L Truemper², L Binder⁴, M Kaase¹, S Scheithauer⁶

Affiliations

¹ Department of Infection Control and Infectious Diseases, University Medical Centre Göttingen, Georg-August University of Göttingen, Göttingen, Germany.
² Department of Haematology and Medical Oncology, Göttingen Comprehensive Cancer Centre, University Medical Centre Göttingen, Georg-August University of Göttingen, Göttingen, Germany.
³ Department of Infection Control and Infectious Diseases, University Medical Centre Göttingen, Georg-August University of Göttingen, Göttingen, Germany; Department of Haematology and Medical Oncology, Göttingen Comprehensive Cancer Centre, University Medical Centre Göttingen, Georg-August University of Göttingen, Göttingen, Germany.
⁴ Institute for Clinical Chemistry, University Medical Centre Göttingen, Georg-August University of Göttingen, Göttingen, Germany.
⁵ Institute of Medical Microbiology and Virology, University Medical Centre Göttingen, Georg-August University of Göttingen, Göttingen, Germany; mbeds Holding GmbH, Göttingen, Germany.
⁶ Department of Infection Control and Infectious Diseases, University Medical Centre Göttingen, Georg-August University of Göttingen, Göttingen, Germany. Electronic address: krankenhaushygiene.leitung@med.uni-goettingen.de.

PMID: 37939885
DOI: 10.1016/j.jhin.2023.10.016

Abstract

Background: Bacterial infection ranks amongst the most common causes of morbidity and mortality in patients undergoing allogeneic haematopoietic stem cell transplantation (alloHSCT). Although ciprofloxacin (CIP) prophylaxis is recommended, information on serum levels and clinical course is lacking.

Aim: To investigate relationships between CIP level and failure of prophylaxis, particularly in terms of whether different pharmacokinetic (PK) indices [area under the concentration-time curve (AUC_0-24h) vs single time samples] correlate differently with the outcome.

Methods: This prospective observational monocentric study was conducted at a 1500-bed teaching hospital (March 2018-March 2019), including 63 adult patients with alloHSCT receiving CIP prophylaxis. Blood samples were drawn at three sampling times (1, 6 and 12 h post-administration), twice per week, and measured via high performance liquid chromatography. The onset of febrile episodes (FEBs) indicated suspected failure of CIP prophylaxis. Positive blood cultures [bloodstream infection (BSI)] indicated confirmed failure of prophylaxis.

Findings: Seven of 63 patients died without significant differences in their average CIP levels compared with survivors, with patients experiencing FEBs (54/63) displaying a 13% [95% confidence interval (CI) 4-22%] lower probability of survival. In total, 225 sets of three values (triplets) were obtained from 58 primary CIP episodes. Triplets preceding BSI with Gram-negative bacteria (GNB-BSI) showed lower AUC_0-24h on average, but similar single time sample indices. An AUC_0-24h of ≤21.61 mgh/L resulted in four-fold higher odds of GNB-BSI (adjusted odds ratio 3.96, 95% CI 1.21-13.00). These results were independent of the administration route, patient demographics or sampling protocol deviations, indicating reduced CIP exposure upon GNB-BSI events.

Conclusion: Monitoring CIP levels, using multiple sampling times, may be useful to reduce alloHSCT-associated bacterial infections. Further analysis is needed to investigate causality.

Keywords: Ciprofloxacin; Immunosuppressed; Prophylaxis; Resistant pathogens.

Publication types

Observational Study

MeSH terms

Adult
Bacteremia* / microbiology
Bacterial Infections* / drug therapy
Ciprofloxacin / therapeutic use
Drug Monitoring
Gram-Negative Bacterial Infections* / microbiology
Hematopoietic Stem Cell Transplantation* / adverse effects
Humans
Prospective Studies
Retrospective Studies
Sepsis* / microbiology
Stem Cell Transplantation

Substances

Ciprofloxacin