Oral Minocycline As Systemic Therapy for Uncomplicated Venous Access Device-Related Bloodstream Infection with Coagulase-Negative Staphylococci in Patients after Allogeneic Hematopoietic Cell Transplantation
Authors: Bayoudh Firas , Descy Julie , Fontaine Corentin , Baron Frederic , Willems Evelyne , Beguin Yves , Giot Jean-Baptiste , Servais Sophie 
Published: November 2021

Abstract
Venous access device-related bloodstream infections (VAD-BSIs) with coagulase-negative staphylococci (CoNS) are common complications after allogeneic hematopoietic cell transplantation (alloHCT). So far, the standard systemic antimicrobial therapy for uncomplicated VAD-BSIs with methicillin-resistant CoNS consisted of intravenous (IV) vancomycin (vanco). This approach requires hospitalization, necessitates new competent venous access, exposes patients to potential (mainly renal) toxicity and increases the risk of commensal flora dysbiosis with selection of vanco-resistant enterococci. Patients after alloHCT are particularly at risk of iatrogenic and nosocomial complications. In addition, repeated hospitalizations can impact autonomy and quality of life and are associated with significant costs.
Minocycline (mino) is an oral antimicrobial agent that has strong in vitro effects on most Gram positive bacteria and potential anti-biofilm activity, and can be used in the clinic for some CoNS infections. Our infectious disease specialists proposed that systemic therapy with oral mino could be used for the management of uncomplicated VAD-BSIs, primarily when the reference treatment with IV vanco was not possible (renal failure or allergy) or when hospitalization was refused by patients. We retrospectively analyzed the results of this mino-based approach.
From January 2012 to December 2020, we treated 24 uncomplicated VAD-BSIs with CoNS in 23 alloHCT patients aged 17-72y with oral mino. Uncomplicated VAD-BSIs were defined as 2 or more blood cultures positive for the same CoNS drawn consecutively peripherally and through the VAD, in patients without signs of sepsis, cellulitis or suppurative thrombophlebitis and without endovascular implant or orthopedic material. VAD were implantable ports (n=17), tunneled catheter (n=1) or PICC-lines (n=6). Pathogens were S. epidermidis (n= 21) or S. haemolyticus (n=3). CoNS were in vitro susceptible to mino according to EUCAST guidelines (with MIC &lt;= 0.5mg/L, predominantly). Mino was administered at a dose of 100 mg BID for 7-14 days. For 8 VAD-BSIs, patients were initially treated with IV vanco for the first 1-3 days followed by oral mino, while 16 VAD-SIBs were managed with oral mino alone. VAD management consisted of catheter removal (for tunneled and PICC-lines, n=7) or antibiotic locks with vanco (n=15) or gentamicin (n=2) administered at least every other day for 14 days (for ports).
Overall, clearance of bacteremia (as assessed by negativity of surveillance peripheral blood cultures with the same CoNS drawn between d+3 and +30 after initiation of systemic therapy) was achieved in all but 1 patient (with port, treated with mino alone) who had persistent bacteremia at day +9. No complication such as suppurative thrombophlebitis, endocarditis or metastatic foci of infection was observed in any patient during the 3-month period after initiation of treatment. Among the 17 patients for whom VAD salvage was attempted, VAD decontamination was successful in 10 cases while 4 patients experienced persistently positive VAD-derived blood cultures during the early (d+3 to +14) surveillance period and 3 patients experienced delayed relapse of VAD-BSIs with the same CoNS 1-3 months later (with 1 patient with cellulitis). All these events led to VAD removal. Treatment with mino was well tolerated with the exception of mild skin rash in one patient.
Our results in this retrospective cohort suggest that oral mino can be a promising alternative to standard IV vanco for systemic therapy in VAD-BSIs with CoNS and that a strategy combining oral mino and antibiotic locks may salvage VAD in approximately half of the cases. This remains to be confirmed in prospective studies.

Disclosures
No relevant conflicts of interest to declare.