A Systematic Literature Review of Economic Evaluations of Antibiotic Treatments for Clostridium difficile Infection

Abstract

Background and Objective Clostridium difficile infection (CDI) is associated with high management costs, particularly in recurrent cases. Fidaxomicin treatment results in lower recurrence rates than vancomycin and metronidazole, but has higher acquisition costs in Europe and the USA. This systematic literature review summarises economic evaluations (EEs) of fidaxomicin, vancomycin and metronidazole for treatment of CDI.MethodsElectronic databases (MEDLINE®, Embase, Cochrane Library) and conference proceedings (ISPOR, ECCMID, ICAAC and IDWeek) were searched for publications reporting EEs of fidaxomicin, vancomycin and/or metronidazole in the treatment of CDI. Reference bibliographies of identified manuscripts were also reviewed. Cost-effectiveness was evaluated according to the overall population of patients with CDI, as well as in subgroups with severe CDI or recurrent CDI, or those at higher risk of recurrence or mortality.ResultsOverall, 27 relevant EEs, conducted from the perspective of 12 different countries, were identified. Fidaxomicin was cost-effective versus vancomycin and/or metronidazole in 14 of 24 EEs (58.3%), vancomycin was cost-effective versus fidaxomicin and/or metronidazole in five of 27 EEs (18.5%) and metronidazole was cost-effective versus fidaxomicin and/or vancomycin in two of 13 EEs (15.4%). Fidaxomicin was cost-effective versus vancomycin in most of the EEs evaluating specific patient subgroups. Key cost-effectiveness drivers were cure rate, recurrence rate, time horizon, drug costs and length and cost of hospitalisation.ConclusionsIn most EEs, fidaxomicin was demonstrated to be cost-effective versus metronidazole and vancomycin in patients with CDI. These results have relevance to clinical practice, given the high budgetary impact of managing CDI and increasing restrictions on healthcare budgets.OtherThis analysis was initiated and funded by Astellas Pharma Inc.Electronic supplementary materialThe online version of this article (doi:10.1007/s40273-017-0540-2) contains supplementary material, which is available to authorized users.

Identification of significant protein markers by mass spectrometry after co‐treatment of cells with different drugs: An in vitro survey platform

“…The metabolism of ethosuximide is associated with drug‐induced liver injury; hence, we used this compound as the model drug to test the proposed platform after co‐treatment with phenytoin, cimetidine, ketotifen, metformin and metronidazole. Cimetidine, a histamine type 2 receptor antagonist, is used to treat patients with peptic ulcers; ketotifen is an oral antiallergic drug; metformin is used to treat diabetes; metronidazole is an antibiotic; and phenytoin is a non‐sedative barbiturate derivative used for anti‐seizure treatment . These drugs are routinely used and are likely to be prescribed to people who take ethosuximide.…”

“…metronidazole is an antibiotic 23 ; and phenytoin is a non-sedative barbiturate derivative used for anti-seizure treatment. 24 These drugs are routinely used and are likely to be prescribed to people who take ethosuximide.…”

“…Ethosuximide was used as the primary drug to test the proposed platform. Several drugs that are routinely used or are likely to be used in combination with ethosuximide, namely cimetidine (for peptic ulcers), ketotifen (for allergies), metformin (for diabetes), metronidazole (for bacterial infections) and phenytoin (for seizures), were used to co‐treat liver cells. Mitochondrial proteins were extracted and the protein markers associated with drug–drug interactions were identified by liquid chromatography combined with mass spectrometry and a pathway analysis tool.…”

Modern approach to the therapy of infections caused by Clostridium difficile

“…Therefore, despite the largest acquisition cost, in our opinion, fidaxomicin can be administered only as the first-choice therapy for different forms of CDI after its cost-effectiveness was unequivocally demonstrated in a particular indication at the national level in countries with a sufficiently large cost-effectiveness threshold. The latter is supported by the evidence from systematic review of economic evaluation of antimicrobial therapy for CDI by Burton HE et al, indicating that fidaxomicin could have a better cost-effectiveness ratio then other antibiotics for CDI treatment in patients with highrisk of complicated and recurrent CDI, when the majority of pharmacoeconomic outcomes were taken into account 18 . As an example, the study that was carried out in Serbia, a country passing throughout socioeconomic transition where the fidaxomicin has not been approved yet, suggests this drug could be more cost-effective option in patients refractory to metronidazole monotherapy in comparison to vancomycin, since it saves more lives, but does not avoid colectomies; this comparative advantage could be especially obvious in patients with the recurrent infection that must continue to use systemic antibiotics, particularly if free-market prices of health services in Serbia are allowed 19 .…”

Cost-Effectiveness Analysis of Bezlotoxumab Added to Standard of Care Versus Standard of Care Alone for the Prevention of Recurrent Clostridium difficile Infection in High-Risk Patients in Spain

“…Bezlotoxumab has been recently obtained the marketing authorization in Spain [ 20 ]. Although many studies have assessed the cost-effectiveness of antibiotic therapy for CDI [ 21 ], only one published cost-effectiveness analysis evaluating bezlotoxumab from a US payer perspective has been performed [ 22 ]. Due to the increasing burden of CDI and the efficacy of bezlotoxumab in reducing CDI recurrence, our aim was to assess the cost-effectiveness of bezlotoxumab in addition to SoC antibiotic therapy as compared to SoC alone for the prevention of recurrence in five subgroups of patients at high risk of CDI recurrence within the context of the Spanish NHS.…”