A 79-year-old man was hospitalized for 6 weeks with L4-L5 spondylodiscitis in September 2019. His medical history consisted principally of membranoproliferative glomerulonephritis treated with rituximab several years ago (currently in remission), hypertension, alcoholic liver disease with chronic cholestasis without signs of portal hypertension, and elastometry fibrosis score estimated at F3. Hepatitis-C serology was negative. In August 2019, he developed sudden-onset low back pain with a marked inflammatory syndrome. Lumbar magnetic resonance imaging (Fig. S1 in the Supplement) showed what appeared to be infectious L4-L5 spondylodiscitis with a  mm infiltration in the adjacent right psoas, circumferential epiduritis and bilateral, but predominantly right, posterior L4-L5 articular arthritis. At this stage, renal function and a complete liver work-up were normal, with prothrombin time (PT) at 91 %. Factor V was not determined.
We performed two puncture disco-vertebral biopsies, but no pathogen could be isolated from them. Brucella, Bartonella and Coxiella serologies were negative. Assuming methicillin-sensitive Staphylococcus because of the radiographic appearance, or of non-hemolytic streptococci because of the poor oral hygiene of the patient, cefazolin was started at 2 g every 8 h, after the sampling of the different biopsies. However, histological examination of the two disco-vertebral biopsies found a granulomatous appearance with necrotic micro-foci, which led to the priority search for a mycobacterium, notably tuberculosis. His neurological deterioration led to emergency laminectomy on hospitalization day 5. Cultures of intra-operative samples remained sterile after prolonged incubation in enriched media and mycobacterial cultures. Histology of intra-operative samples showed necrotic micro-foci as well.
Because the diagnosis of infectious spondylodiscitis was certain, because of the negativity of standard and prolonged cultures, because of the presence of features compatible with both types of infections (classical bacteria and mycobacteria), and because of a high risk of complications, a multidisciplinary discussion (between internists and specialists in infectious diseases) led to cefazolin continuation for a total of 6 weeks combined with anti-tuberculous quadritherapy (isoniazid, rifampicin, ethambutol and pyrazinamide) for 2 months, followed by a dual therapy for a further 4 months.
On day 24 of cefazolin administration and day 7 of quadritherapy, the patient developed abundant hematemesis. Cefazolin was temporarily withdrawn. The laboratory work-up found PT at 5 %, normal factor V (76 %) and factors II, VII and X severely collapsed (respectively, 28 %, 2 % and 7 %). After intravenous (IV) vitamin-K (10 mg) supplementation and human pro-coagulation complex, endoscopy identified necrotic esophagitis of the lower two-thirds of the esophagus and a necrotic bulbar ulcer. Proton-pump inhibitors administered by electric syringe achieved rapid improvement; the control endoscopy 48 h later found the peptic esophagitis appearance markedly attenuated. No carcinomatous- or lymphomatous-like cellular infiltration was seen during histological examination of esophagus samples.
Determination of serum cefazolin concentrations did not indicate an overdose (continuous concentration of 33.4 mg/L for a targeted value of 20-40 mg/L). After vitamin-K supplementation, cefazolin was restarted for a total duration of 6 weeks, with close monitoring of hemostasis. The anti-tuberculous regimen reintroduced combined ethambutol, moxifloxacin, isoniazid and pyrazinamide.