Case presentation 1
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A 69-year-old, 116-kg man with psoriatic arthritis presented with new swelling and pain in his right knee. His medical history also included hyperlipidemia, gastroesophageal reflux disease, and degenerative joint disease. Additionally, he had undergone right total knee arthroplasty due to complications from prosthetic joint infection (PJI) five years prior. Despite recurrent infections necessitating multiple arthroplasty revisions and treatment with various antimicrobials such as vancomycin, ceftriaxone, ampicillin, nafcillin, ciprofloxacin, and levofloxacin, his condition persisted. Methotrexate 10 mg, which he took on Wednesdays and Saturdays, was intermittently paused during treatment. However, he eventually achieved suppression of Escherichia coli infection with levofloxacin 500 mg orally daily.
Post-surgery, he was started on vancomycin 15 mg/kg intravenously (IV) Q12H and ertapenem 1 g IV Q24H. However, on postoperative day (POD) 1, he developed shaking chills and fever, prompting a change in his antibiotic regimen to piperacillin-tazobactam 3.375 g intravenously Q6H due to the possibility of aspiration pneumonia. By POD 4, he was afebrile and stable. He opted to hold his usual methotrexate dose that day and was switched to ceftriaxone 2 g every 24 hours for 6 weeks and metronidazole 500 mg orally TID for 7 days. Aside from this, no other changes were made to his medications at discharge.
On POD 8, outpatient laboratory tests showed normal results, allowing the patient to resume oral methotrexate. However, by POD 14, after receiving 12 doses of ceftriaxone and 3 doses of oral methotrexate, the patient's absolute neutrophil count (ANC) dropped significantly from 1,800 × 106/L to 300 × 106/L. Consequently, ceftriaxone and methotrexate were discontinued, and the patient was switched to daptomycin. Despite this change, the patient remained profoundly neutropenic with an ANC of 0, necessitating two doses of granulocyte colony-stimulating factor (G-CSF) for recovery. Throughout this period, the patient's serum creatinine concentration decreased from 1.2 mg/dL to 0.93 mg/dL by POD 19, while serum alanine transaminase concentration ranged from 13–30 IU/L. After 14 days of treatment with daptomycin and two doses of G-CSF, the patient's ANC recovered, allowing for the restart of methotrexate therapy at a dose of 10 mg orally twice weekly. Although an expected fluctuation in ANC occurred upon resumption of methotrexate, the patient did not experience neutropenia again.
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Case presentation 2
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A 54-year-old, 88-kg man with unspecified inflammatory arthritis for 10 years presented with shoulder pain. The patient had been on chronic immunosuppression with methotrexate 25 mg orally weekly, prednisone 2.5 mg orally daily, and hydroxychloroquine 200 mg orally twice daily, achieving good symptomatic control. His other home medications included diazepam as needed for anxiety, folic acid 1 mg BID, ibuprofen and hydrocodone-acetaminophen as needed for pain relief, omeprazole 20 mg daily, sulindac 200 mg BID, acetaminophen as needed for pain, and venlafaxine daily. Upon presentation, he was diagnosed with adhesive capsulitis and had undergone arthroscopic capsular release approximately 7 months prior. However, he subsequently developed a periarticular fluid collection, which tested positive for methicillin-sensitive Staphylococcus aureus, raising concerns for septic arthritis. Consequently, his methotrexate was discontinued, and he commenced outpatient vancomycin 1,750 mg IV Q12H and ceftriaxone 2 g IV Q24H as per instructions from his home care providers.
The patient was admitted to the institution for further treatment, with methotrexate being on hold for 3 weeks at that time. Suspecting subacute osteomyelitis of the humeral head, he underwent resection of the native joint with implantation of an antibiotic-impregnated spacer. Perioperative prophylaxis included cefazolin 2 g IV Q8H, transitioning to ceftriaxone 2 g IV Q24H for 6 weeks postoperatively due to prior growth of methicillin-sensitive Staphylococcus aureus and intraoperative cultures showing growth of Cutibacterium (Propionibacterium) acnes. There were no other major changes to his medications. On POD 1, his baseline serum creatinine concentration was 0.7 mg/dL, and it remained stable, not exceeding 0.73 mg/dL throughout the next month of weekly laboratory tests. His laboratory test results remained stable during the first 2 weeks of ceftriaxone therapy, prompting the decision to restart his home dosage of methotrexate. However, five days after initiating methotrexate, his ANC dropped from 1,510 × 106 /L to 430 × 106/L, and his white blood cell count (WBC) decreased from 4.17 × 109/L to 3.33 × 109/L. A methotrexate concentration test performed 8 days after the last dose showed detectable levels at 0.04 micromol/L. Consequently, methotrexate, prednisone, and ceftriaxone were stopped, and the patient was initiated on daptomycin 500 mg IV daily.
Two days later, his ANC increased to 1,380 × 106/L, and his WBC returned to 4.18 × 109/L. Following ANC recovery, he transitioned from daptomycin to ertapenem 1 g IV Q24H and completed 6 weeks of IV antibiotics. Methotrexate was restarted without adverse effects on ANC or WBC count. The patient continued on methotrexate, hydrochloroquine, and prednisone. After an observation period without antibiotics, he successfully underwent primary total shoulder arthroplasty.
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