Methylprednisolone/tocilizumab

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

A 68-year-old man developed disseminated strongyloidiasis while receiving off-label methylprednisolone for coronavirus disease 2019 (COVID-19) pneumonia. Additionally, the man received off label therapy with tocilizumab and hydroxychloroquine for COVID-19.

The man presented with a 8-day history of cough, nausea, myalgia, headache and worsening dyspnoea. His medical history was significant for hypertension, diabetes mellitus and peripheral neuropathy. Based on the findings of physical and laboratory exam, chest X-ray and nasopharyngeal swab analysis, the diagnosis of COVID-19 was made. Consequently, he was admitted and started receiving off-label oral hydroxychloroquine 400mg two times a day (loading dose) followed by 200mg two times a day for 5 days. After admission, he developed hypoxaemic respiratory failure requiring intubation. Hence, he started receiving off-label IV tocilizumab per day along with three courses of IV methylprednisolone 40mg every 8 hours on hospital days 4−6, 8−10 and 12−13 due to a new fever that manifested on day 9 and persistent hypoxaemia. Further, he developed hypotension on day 12 and received norepinephrine for BP management. Blood cultures grew Streptococcus constellatus and Citrobacter Freundii and sputum culture from day 12 grew Pseudomonas aeruginosa and methicillin-susceptible Staphylococcus aureus. Consequently, methylprednisolone was withdrawn and he was treated with ciprofloxacin, cefazolin and metronidazole resulting in resolution of fever and hypotension. Thereafter, on day 18, he developed fever. At that time, his absolute eosinophil count was 200 /mL ³. His antibiotic therapy was switched to vancomycin and ciprofloxacin when his oxygenation improved and he was extubated the following day. Sputum culture obtained on the same day grew Pseudomonas aeruginosa and methicillin-sensitive Staphylococcus aureus. The following day serpiginous tracks were noted on a chocolate agar plate. Gram and iodine stains revealed larvae (280−300µm) with a short buccal canal and prominent genital primordium suggestive of Strongyloides species. Based on the findings strongyloidiasis was presumed.

The man's antibiotic therapy was discontinued and he was initiated on ivermectin. His WBC count increased to 39 200 /mL ³ and an absolute eosinophil count of 100 /mL ³. Chest X-ray showed multifocal bilateral pulmonary opacities. Due to lack of significant response from ivermectin, albendazole was added to his treatment regimen. Additionally, piperacillin/tazobactam was also initiated for suspected nosocomial pneumonia(aetilogy unspecified). Over the following days, his leucocytosis decreased. Stool analysis for ova and parasites and antibody test for Strongyloides were all negative. On day 25, he developed a new fever, confusion and hypotension requiring norepinephrine. Shortly thereafter, he was reintubated again. At that time, his WBC count was 43 000 /mL ³. Subsequent sputum and blood culture grew Pseudomonas aeruginosa and coagulase-negative Staphylococcus, respectively. Subsequent, stool ova and parasite were negative. His antibiotic therapy was switched to vancomycin, ceftazidime and metronidazole for suspected bacterial meningitis associated with disseminated strongyloidiasis. His disseminated strongyloidiasis was attributed methylprednisolone. A lumbar puncture was performed due to haemodynamic instability. Over the following days, his WBC count normalised, mental status improved and his fever and hypotension resolved. His absolute eosinophil count reached to 1 900 /mL ³ on day 28 and fell to 900 /mL ³ on day 33. CT scan on day 30 showed peripheral ground-glass opacities and peribronchial consolidation in the right lower lobe. Repeat blood and sputum culture showed no growth. A third stool ova and parasite were negative. He also received unspecified antibiotic therapy for suspected gram negative meningitis. Repeat Strongyloides serology was positive on day 38.