Oral antimicrobial agents in patients with short bowel syndrome: worth a try!—authors’ response

We read with interest the comments by Deleenheer et al.¹ on our study ‘Oral antimicrobial agents in patients with short bowel syndrome: worth a try!’ and thank the authors for the constructive reflection on our findings.² The authors suggest a more cautious interpretation of our findings and recommend therapeutic drug monitoring (TDM) for all drugs used in our study.

First, it is important to emphasize that our study was exploratory in nature—a first attempt to investigate the pharmacokinetics of oral antimicrobials in this population. This work is an initial step in building the knowledge necessary for the use of oral therapy in clinical practice in this group. We acknowledge that more research is needed before oral antimicrobial agents can be routinely used in all short bowel syndrome (SBS) patients. Deleenheer et al. raise fair points regarding the variable bioavailability and remaining small bowel length of our included patients, which are aspects we have certainly considered. Given the wide clinical heterogeneity of SBS patients, we acknowledge that the current use of oral antimicrobials in SBS patients requires TDM to warrant adequate drug exposure.

We respectfully differ in opinion on the potential interaction between flucloxacillin and fluconazole, as described by Deleenheer et al.¹ While indeed previous studies have documented interactions between flucloxacillin and voriconazole,^3,4 evidence to suggest a similar interaction with fluconazole is lacking. The pharmacokinetic profiles of different azole species vary, and the generalization of interactions across the entire azole class should be approached with caution. Fluconazole is primarily eliminated through renal excretion, with around 80% of the administered dose being excreted unchanged in the urine.⁵ Unlike many other azoles, fluconazole undergoes minimal hepatic metabolism, and only a small fraction (less than 11%) is metabolized in the liver.⁶ As fluconazole metabolism differs from other azoles, we do not expect a decreased fluconazole exposure when given after flucloxacillin.

Moving forward, it certainly is crucial to conduct more robust clinical multicentre research, including SBS patients with a more extensive variety of patient characteristics. These studies should also aim to clarify the absorption patterns for various oral antimicrobials and identify factors that impact bioavailability in this heterogenic patient population. In conclusion, while our initial findings provide a promising foundation, further research should confirm these observations to ensure the safe and effective use of oral antimicrobials in SBS patients.

Funding

None to declare.

Transparency declarations

None to declare.

References