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Dipyrone/linezolid/meropenem Agranulocytosis, fungal periprosthetic knee joint infection and lack of efficacy: case report

A 55-year-old woman developed agranulocytosis and fungal periprosthetic knee joint infection during analgesic treatment with dipyrone. Additionally, she experienced lack of efficacy during antibiotic treatment with linezolid and meropenem [dosages and routes not stated]. The woman, who had degenerative joint disease, underwent a complex primary total knee arthroplasty (TKA) in 2017 at an outside hospital using a constrained TKA for varus osteoarthritis. Her comorbidities included asthma and atopic dermatitis. After TKA, she was prescribed dipyrone [metamizole] as a pain medication and was discharged home. Five weeks after TKA, she was admitted to an external hospital. She presented in acute septic state with pancytopenia, phlegmonous soft-tissue inflammation in both the arms and atrial fibrillation. Bone marrow puncture showed a most likely dipyrone-induced agranulocytosis. Following blood cultures, Staphylococcus epidermidis was detected, whereas wound swabs from both the hands showed positive results for Serratia marcescens. Antibiotic treatment with meropenem and linezolid were given; however, she had a progressive sepsis. Consequently, she was shifted to the ICU. She had warm and erythematous soft-tissue swellings in both arms and a massively swollen and warm knee, which had undergone TKA as mentioned. She exhibited elevated levels of CRP and ferritin. Her WBC count was 0.38 × 103/µL. Blood differential count revealed a polymorphonuclear leukocyte percentage (PMN%) of 2.6. Orthopaedic consultation was made because an acute periprosthetic knee joint infection with systemic sepsis was suspected. Joint aspiration from the swollen knee was performed. The synovial WBC count was 0.085×103/µL with PMN% of 14%. Radiograph imaging showed no signs of prosthetic loosening. However, owing to the massively swollen, heated and red knee, explantation of the implant and insertion of a polymethylmethacrylate cement spacer, loaded with gentamicin, clindamycin and vancomycin, was performed on the same day. Synovial fluid and tissue samples obtained intraoperatively did not show bacterial or fungal growth; however, she had positive blood cultures for Escherichia coli. Owing to the suspected fasciitis with both arms being at risk of developing an acute compartment syndrome, she underwent an exploration of the upper extremities and fasciotomy with subsequent application of a vacuum-assisted closure device. The postoperative antibiotic treatment included meropenem, daptomycin and clindamycin. Within the following days, blood culture samples were negative. Repeated bone marrow puncture confirmed a most likely sepsis-triggered pancytopenia, developing from dipyrone-induced agranulocytosis. MRI of the left forearm showed contrast medium enhancement in both deep and superficial fasciae, falling in line with the phlegmonous clinical appearance. Other infectious foci such as endocarditis and respiratory or urinar