mucormycosis , an infection caused by fungi of the order mucorales , typically presents as an aggressive angio - invasive disease in immunosuppressed hosts . patients with hematological malignancies and recipients of hematopoietic stem cell transplants are at highest risk for pulmonary mucormycosis with reported mortality rates of up to 76% . early diagnosis and aggressive management with surgical debridement and antifungal treatment are critical for optimal outcomes . previously , the only two systemic antifungals available with reliable activity against mucorales were amphotericin b and posaconazole . isavuconazole , a new extended - spectrum triazole with activity against yeasts , molds and dimorphic fungi , has recently been approved for treatment of invasive aspergillosis and mucormycosis . we report a case of successful salvage treatment of pulmonary / splenic mucormycosis with isavuconazole , in a hematology patient intolerant of primary therapy with liposomal amphotericin b and posaconazole . a 59 year old male gardener was transferred from another hospital with left lower lobe pneumonia unresponsive to nine days of intravenous broad - spectrum antibiotics . this was on a background of a recent diagnosis of hypoplastic myelodysplastic syndrome ( mds ) . his hypoplastic mds had been treated , 38 days earlier , with antithymocyte globulin ( atg ) and five days of pulsed intravenous methylprednisolone ( 1  mg / kg / day ) . at presentation , he was taking cyclosporine 200  mg orally twice daily and a tapering dose of prednisolone , 5  mg daily . his neutrophil count was 1.1  cells / mm at presentation , however in the six weeks prior , had been < 1.0  cells / mm . antifungal prophylaxis with posaconazole oral solution , 200  mg three times daily ( tds ) , had been commenced at the onset of atg and methylprednisolone treatment . this was increased to 200  mg four times daily ( qid ) , following a sub - therapeutic serum concentration of 0.3  g / ml , seven days after commencement . his past medical history was significant for chronic kidney disease due to primary focal and segmental hyalinosis and sclerosis , presenting as nephrotic syndrome in 2012 , resulting in chronic proteinuria and a baseline creatinine clearance 91  ml / min . 1a ) revealed a cavitating left lower lobe lesion with contiguous splenic involvement , suspicious for invasive fungal disease ( ifd ) . empirical treatment was commenced with liposomal amphotericin b ( l - amb ) 5  mg / kg and piperacillin - tazobactam 4.5  mg qid . histopathology on a ct guided biopsy , obtained on day 2 of admission , demonstrated broad ribbon - like hyphae within necrotic tissue ( fig . 2 ) , consistent with mucormycosis . on day 4 of admission he underwent a left lower lobectomy , with latissimus dorsi muscle flap transposition . culture and pan - fungal pcr were negative , on both ct - guided biopsy and resected lung tissue . the patient deteriorated clinically 15 days post lobectomy ( day 19 of l - amb therapy ) with hypoxia , delirium , renal failure and raised inflammatory markers . repeat chest ct demonstrated bilateral pleural effusions with significant peri - bronchial consolidation in the remaining left lung and evidence of a new subcapsular splenic lesion concerning for disease progression ( fig . posaconazole oral solution , 300  mg tds , was added to l - amb 5  mg / kg and increased to 300  mg qid following a sub - therapeutic level of 0.38  g / ml , six days after commencement . the patient achieved clinical stability on day 21 , but was intolerant of high - dose posaconazole with severe nausea unresponsive to multiple anti - emetics , requiring a dose reduction to 200  mg tds . worsening renal function , with a reduction in creatinine clearance to 30  ml / min , after 46 days of l - amb and despite ceasing cyclosporine and isavuconazole was obtained on compassionate access and commenced on day 48 post lobectomy ( day 52 of l - amb ) according to the manufacturer 's instructions , with a loading dose of 200  mg intravenously tds for 2 days . the patient received a further four days of intravenous therapy 200  mg daily , before changing to oral therapy , also at a dose of 200  mg daily . serum concentrations of isavuconazole were monitored at regular intervals according to the manufacturer 's protocol ( fig . 3 ) and were considered to be within therapeutic range . the patient was discharged day 50 following lobectomy and six days after commencing isavuconazole . while on isavuconazole 200 mg orally daily , he continued to experience grade 1 nausea , requiring three anti - emetic agents , which was marginally improved relative to posaconazole therapy . his renal function improved to his baseline creatinine clearance of > 90  ml / min . to the best of our knowledge , this is the first report of the use of isavuconazole in australia . isavuconazole is a broad - spectrum triazole pro - drug , which is licensed for primary and salvage treatment of mucormycosis . a sub - group of 37 patients with proven / probable mucormycosis in a phase 3 , open - label , non - comparator trial ( vital )   achieved response rates of 31.6% for primary therapy and 36.4% for salvage therapy , . the mainstay of management of mucormycosis has , until recently , been polyene antifungal therapy and surgical debridement . amphotericin b has reported response rates of 3139%   and l - amb is recommended as first line therapy . in our case , empirical l - amb was delayed by nine days with delays in treatment of mucormycosis beyond three days associated with an increased mortality , . despite this , our patient recovered with aggressive surgical debridement and multiple antifungal agents including salvage isavuconazole therapy . posaconazole and l - amb had to be prematurely ceased due to gastrointestinal side - effects and nephrotoxicity , respectively . until recently , posaconazole and amphotericin b based formulations have been the only antifungal agents with reliable activity against the mucorales species . posaconazole has shown response rates of up to 60% as salvage therapy for mucormycosis , however erratic bioavailability of the oral solution has limited its use . posaconazole serum levels in our patient remained sub - therapeutic despite dose escalation up to 1200  mg daily , resulting in severe nausea . the favorable physico - chemical and toxicity profile of isavuconazole contributed to our patient 's successful outcome . isavuconazole has excellent oral bioavailability , a predictable pharmacokinetic profile and the absence of a solubilizing agent such as cyclodextrin , obviates concerns of nephrotoxicity in patients with underlying kidney disease . it has few reported significant adverse effects   and , other than nausea , was relatively well tolerated by our patient over prolonged treatment course lasting 102 days . similar tolerability was evident among the 5 patients from vital study who had complete response with treatment courses lasting 179 , 180 and 509 days , respectively for primary treatment and 86 and 735 days , respectively for disease refractory to other systemic antifungal therapy , . case reports have documented complete response of disseminated and sino - orbital mucormycosis with prolonged salvage therapy with isavuconazole lasting 29 weeks and 16 months days , respectively , . our case demonstrates a role for isavuconazole for treatment of mucormycosis when therapeutic options are limited due either to renal impairment or dose - limiting toxicities of other antifungal agents . com has been on the advisory board for , received investigator - initiated grants from and given lectures for gilead sciences , merck sharp and dohme and pfizer .