Reactions Weekly | 2019
Multiple drugs
Abstract
with rare giant cells and histiocytes. After 9 days of combined antifungal therapy, her neutropenia and fever resolved. She S Multiple drugs was discharged home on voriconazole. A follow-up CT scan 1 month after discharged revealed reduction in number and Various toxicities: 4 case reports size of the lung micronodules and of the nodular localisations In a case series, 4 patients (3 men and 1 woman) aged to liver, spleen and kidneys. 34–66 years old were descried who developed neutropenia, Case 3: A 34-year-old man developed granulocyte count low granulocyte count, influenza virus-A infection (H1N1 decreased and sepsis with Saprochaete clavata and positive), carbapenem‐resistant Enterobacteriaceae, Enterococcus faecium infection during treatment with Saprochaete clavata infection, Escherichia coli infection, cyclophosphamide, etoposide, doxorubicin, vincristine and Pseudomonas aeruginosa infection or Enterococcus faecium unspecified steroids. The piperacillin/tazobactam, linezolid, bacteraemia during treatment with colistin, meropenem and colistin also contributed to Saprochaete cyclophosphamide, cytarabine, daptomycin, doxorubicin, clavata infection. The man, who was diagnosed with ALK etoposide, linezolid, meropenem, methylprednisolone, positive anaplastic large T-cell lymphoma (ALCL) with gastric piperacillin/tazobactam, quizartinib or vincristine [not all and lymph node localization, underwent complete dosages and duration of treatments to reaction onset stated; gastrectomy in the surgical ward. However, he developed routes not stated]. One of these patient died despite pneumonia and started receiving empirical treatment with voriconazole and amphotericin-B-liposomal. piperacillin/tazobactam and linezolid. He was febrile when Case 1: A 66-year-old man developed Saprochaete clavata transfer from the surgical ward to the haematology to receive infection during treatment with meropenem, linezolid and chemotherapy. Subsequently, he started receiving methylprednisolone. The man who was diagnosed with diffuse cyclophosphamide, etoposide, doxorubicin, vincristine and large B‐cell lymphoma (DLBCL), admitted with fever unspecified steroids for ALCL. His antibiotic regimen was and rapidly progressing respiratory distress. A chest CT scan switched to meropenem and colistin as piperacillin/ revealed bilateral regions of mild increased parenchymal tazobactam was unsuccessful. Five days after chemotherapy density with predominant basal and subpleural distribution initiation, he was re-admitted to the surgical unit due to consistent with small‐airway inflammation. He dehiscence of the surgical anastomosis. He was given started receiving empirical antimicrobial therapy with highanidulafungin as an antifungal prophylaxis. However, he dose, extended infusions of linezolid and meropenem. He was developed sepsis following low granulocyte count with also given methylprednisolone 1 mg/kg to control the DLBCL. positive blood cultures for Saprochaete clavata infection and After 5 days, his respiratory status continued to deteriorate. He Enterococcus faecium upon transfer back to the haematology was shifted to the ICU and non‐invasive ventilator unit. A rectal swab was also found to be positive for support (NIV) was initiated. A repeat CT scan revealed Saprochaete clavata . He was treated with voriconazole, progression of the bilateral pulmonary infiltrates to teicoplanin and granulocyte colony stimulating factors and parenchymal subpleural consolidations with an organising improved rapidly with resolution of fever within 48h. After 3 pneumonia pattern. A fibre optic bronchoalveolar lavage (BAL) days of treatment, a CT scan revealed no sites of disseminated was positive for influenza virus-A H1N1, galactomannan index infection and his granulocyte count normalised within an of 5.7 and Saprochaete clavata. He was treated with additional 72h. On clinical stabilisation, he underwent a repeat voriconazole and oseltamivir, but his respiratory status failed gastrectomy while continuing voriconazole. He was to improve over the following week. A repeat BAL revealed completely recovered without further infectious episodes. persistent H1N1 positivity and a low galactomannan index Case 4: A 64-year-old man developed Saprochaete clavata without the growth of Saprochaete clavata on culture. He infection during treatment with daptomycin. The man, who continued NIV along with antiviral/antifungal and antimicrobial had a history of AML, was scheduled for myeloablative treatment for an additional 15 days due to improved allogeneic haematopoietic stem cell transplantation for AML in respiratory function. He was subsequently readmitted back to remission. However, the transplantation was postponed one the same haematology unit to start the treatment for DLBCL. month prior following the detection of peripheral nodular Upon returning from the ICU, he was colonised by lesion. A BAL was positive for galactomannan, and he was carbapenem‐resistant Enterobacteriaceae detected by diagnosed with suspected invasive pulmonary aspergillosis. rectal swab and was housed in an isolation room. He started But a blood culture grew no organisms. He was treated for one receiving chemotherapy for DLBCL. He continued on month with isavuconazole resulting in reduction in the lesion voriconazole during the chemotherapy and discharged home diameter. Thereafter, he underwent a transplant. His without any sign of active fungal infection. A CT scan showed isavuconazole was switched to micafungin due to a concern of the resolution of the pulmonary infiltrates, with residual cerebral toxicity by triazoles. He was neutropenic due to fibrotic parenchymal changes. previous history of CNS thrombosis. On day 6 after the Case 2: A 48-year-old woman developed neutropenia, transplant, he developed fever and Enterococcus faecium extended spectrum beta-lactamases E. coli, Pseudomonas bacteraemia which was successfully treated with high-dose aeruginosa and Saprochaete clavata infection during treatment daptomycin. However, he developed fever, diarrhoea and with cytarabine and quizartinib for acute myeloid leukaemia respiratory distress while receiving daptomycin and (AML). She was treated with high-dose cytarabine and micafungin. He was shifted to the ICU. His daptomycin quizartinib in a clinical trial. She was hospitalised to a singletherapy was changed empirically and micafungin was patient room due to colonization by extended spectrum betaswitched back to isavuconazole with addition of granulocyte lactamases E. coli . During the neutropenia following colony stimulating factors. Blood cultures revealed yeast, and chemotherapy, she received anidulafungin as an antifungal his isavuconazole was changed to anidulafungin. prophylaxis for QT/QTc prolongation risk with quizartinib. Approximately 48h later, the yeast was identified as Eleven days after completing cytarabine, she developed high Saprochaete clavata. His anidulafungin was changed to fever and elevated levels of CRP and procalcitonin. She was voriconazole, but he worsened with evidence of disseminated started on empirical treatment with ceftolozane/tazobactam infection to the kidney, liver, spleen and CNS with for E. coli and to cover Pseudomonas aeruginosa . A blood multi‐organ failure. He died 1 week later despite culture grew Saprochaete clavata . She was immediately voriconazole and amphotericin-B-liposomal therapy. treated with voriconazole, amphotericin-B-liposomal and Author comment: Saprochaete clavata is a rare but granulocyte colony stimulating factors at standard doses. aggressive cause of breakthrough yeast infection in patients Thorax and abdominal CT scans revealed a dissemination of undergoing treatment for haematological malignancies . The the fungal infection to the liver, lungs, kidneys and spleen. She most common reported risk factors associated with developed multiple skin lesions with zones of central necrosis. disseminated [Saprochaete clavata] include active Biopsies of the skin lesions showed septate fungal hyphae haematological malignancy and/or prolonged neutropenia, around central regions of necrosis in the deep dermis, together 1