Cost of off-label antibiotic therapy for bone and joint infections: a 6-year prospective monocentric observational cohort study in a referral centre for management of complex osteo-articular infections

Abstract

Abstract. Introduction: Costs related to bone and joint infection (BJI) management are increasing worldwide, particularly due to the growing use of off-label antibiotics that are expensive treatments (ETs), in conjunction with increasing incidence of multi-drug-resistant pathogens. The aim of this study was to evaluate the whole costs related to these treatments during the patient route, including those attributed to the rehabilitation centre (RC) stay in one regional referral centre in France. The total annual cost of ETs for managing complex BJIs in France was then estimated. Material and methods: A prospective monocentric observational study was conducted from 2014 to 2019 in a referral centre for BJI management (CRIOAc – Centre de Référence des Infections OstéoArticulaires complexes). Costs related to expensive treatments (“old” ETs, i.e. ceftaroline, ertapenem, daptomycin, colistin, tigecycline, and linezolid and “new” ETs, defined as those used since 2017, including ceftobiprole, ceftazidime-avibactam, ceftolozane-tazobactam, tedizolid, and dalbavancin) were prospectively recorded. In all cases, the use of these ETs was validated during multidisciplinary meetings. Results: Of the 3219 patients treated, 1682 (52.3 %) received at least one ET, and 21.5 % of patients who received ET were managed in RCs. The overall cost of ETs remained high but stable (EUR 1 033 610 in 2014; EUR 1 129 862 in 2019), despite the increase of patients treated by ETs (from 182 in 2014 to 512 in 2019) and in the cumulative days of treatment (9739 to 16 191 d). Daptomycin was the most prescribed molecule (46.2 % of patients in 2014 and 56.8 % in 2019, with 53.8 % overall), but its cost has decreased since this molecule was genericized in 2018; the same trend was observed for linezolid. Thus, costs for old ETs decreased overall, from EUR 1 033 610 in 2014 to EUR 604 997 in 2019, but global costs remained stable due to new ET utilization accounting for 46.5 % of overall costs in 2019. Tedizolid, used as suppressive antimicrobial therapy, represented 77.5 % of total new ET costs. In our centre, dalbavancin was never used. The cost paid by RCs for ETs and the duration of ET remained stable overall between 2016 and 2019. Conclusions: A high consumption of off-label ET is required to treat patients with BJIs in a CRIOAc, and the consequence is a high cost of antimicrobial therapy for these patients, estimated to be almost EUR 10 million in France annually. Costs associated with ET utilization remained stable over the years. On the one hand, the introduction of the generic drugs of daptomycin and linezolid has significantly decreased the share of old ETs, but, on the other hand, the need for new ETs to treat infections associated with more resistant pathogens has not led to decrease in the overall costs. A drastic price reduction of generic drugs is essential to limit the costs associated with more complex BJIs.

Does selective digestive decontamination (SDD) increase antibiotic resistance? Long-term comparison of two intensive care units (with and without SDD) of the same tertiary hospital

“…The increase along the period of study of linezolid and daptomycin consumption, both antibiotics indicated for the treatment of Gram-positive microorganism infections, more frequent in this ICU, may be due to the introduction of the generic drug products in the therapeutic guide of the hospital, linezolid in 2015 and daptomycin in 2018. The increase of prescription of these antibiotics after generic approval is also reported in other studies [ 30 ]. In a recent study [ 6 ], overall total daily defined doses for each antibiotic class were not significantly different between SDD and standard of care.…”

Why Product Information Should not be Set in Stone: Lessons from a Decade of Linezolid Therapeutic Drug Monitoring: An Opinion Paper

“…5,6 Although linezolid first became commercially available in 2000, its use has increased exponentially because of extensive on- and off-label use, and the recent availability of several generic formulations that have substantially reduced the cost of the drug. 7–9…”

“…5,6 Although linezolid first became commercially available in 2000, its use has increased exponentially because of extensive on-and offlabel use, and the recent availability of several generic formulations that have substantially reduced the cost of the drug. [7][8][9] The PI for linezolid (Xyvox, Zyvoxid, Pfizer) states that a '1 size fits all' convenient dosing regimen of 600 mg twice daily is appropriate for all adult patients regardless of weight, body mass index, age, presence of sepsis, and renal or hepatic function. 10 The PI also stated that the total treatment duration should not exceed 28 days because of the increased risk of toxicity, particularly myelosuppression and neuropathy.…”