Mucoropfinallast

Michele Todman, MD Michele Todman, MD Yoash Enzer, MD Yoash Enzer, MD

November 3, 2009November 3, 2009

Grand Rounds

PresentationPresentation 19 y/o F with bilateral periorbital erythema/edema and left

facial/cheek erythema and swelling x 5 days prior to admission; seen by PCP 3 days prior to admission and prescribed Augmentin with no improvement– s/p renal transplant cadaveric x 2 (1996, 2006) for focal segmental

glomerulosclerosis with post transplant diabetes (Hgba1c=14.7)– Meds: glipizide, lisinopril, cellcept 750mg 2x daily, prednisone

5mg daily, sirolimus 2mg 1xdaily– No history of trauma– No new meds, ocular discharge, fevers or chills

Exam on hospital day #2: Va 20/25 OU; trace chemosis OU, remainder of eye exam WNL

– No dacryocystitis, clear demarcation line or visible skin lesions– No RAPD, ophthalmoplegia, proptosis, or ocular hypertension

Hospital Day #1

Hospital Day #5Hospital Day #5

On unasyn x 1 day changed to zosyn (GN and pseudomonas) x 4 days and vancomycin x 2 days with no improvement

Hospital Day #5

Hospital Day #5

Hospital Day #5

Exam on Hospital Day #5Exam on Hospital Day #5

Va: 20/20 OD, 20/30 OSPupils: no RAPD OUMotility: (-3 laterally, -4 inferiorly, -1 nasally OD); full OSConfrontation VF full OUNo proptosis or resistance to retropulsionExternal exam: Hard, indurated, edematous and

erythematous left side tracking down to upper lip with bilateral periorbital erythema and edema

SLE: Chemosis inferiorly OSDFE:WNL OU

Hospital Day #5

Sinus Surgery x 1 Sinus Surgery x 1 on Hospital Day #5on Hospital Day #5

Left ethmoid contents left maxillary sinus aspirate and left cheek aspirate, all sent for cultures.

Changed antibiotic coverage and added antifungal to include: meropenem 1g IV q 8 hours and posaconazole 200 mg qid

Hospital Day #5

Preliminary Culture Results Preliminary Culture Results Hospital Day #6Hospital Day #6

Found to have presumed mucormycosis (aseptate broad band hyphae) involving her left sinuses, her left cheek and her left ethmoid bone

ID added Amphotericin B 5mg/kg IV per 24 hours and continued vancomycin, meropenem and posaconazole. Stopped sirolimus, decreased Cellcept from 750mg 2x daily to 250mg 2x daily and continued prednisone 5mg daily.

Control of blood sugars followed by endocrine and glipizide and insulin drip on board. Hgba1c=14.7.

Acid/base status also tightly controlled.

MRI to r/o intracranial abscess MRI to r/o intracranial abscess and cavernous sinus thrombosisand cavernous sinus thrombosis

on Hospital Day #6on Hospital Day #6No evidence of cavernous sinus thrombosis,

intracranial abscess, or intraconal abscess.Thickening and enhancement of the medial

left orbital periosteum, compatible with post-septal, extraconal extension of the inflammatory process involving the preseptal and facial soft tissues along the periosteum. No definite evidence of intraconal extension. Motion Artifact.

Sinus surgery x 2 Sinus surgery x 2 combined with Oculoplastics combined with Oculoplastics

Hospital Day # 7Hospital Day # 7 Left orbitotomy with spinal catheter placement Debridement of sinuses and medial orbit with

drain placement in maxillary sinus External ethmoidectomy for necrotic ethmoid

bone 2ml of amphotericin B at 0.25mg/ml infused

through catheter in both orbit and maxillary sinus q 6 hours

Hospital Day #7

Hospital Day #9

Sinus Surgery x 3Sinus Surgery x 3Hospital Day #10Hospital Day #10

Incision and drainage of anterior cheek abscess

Left Maxillary sinus debridement, left inferior turbinectomy(necrotic), caldwell luc procedure (intraoral procedure for entering the maxillary antrum through the canine fossa above the maxillary premolar teeth)

Exam Hospital Day #11Exam Hospital Day #11

Va:20/20 OU

Pupils:4mm OU, PERRL OU, No RAPD OU

Ta: + Resistance to retropulsion OS

EOMS:(-1)medially and superiorly,

(-2)laterally and inferiorly

Hospital Day #11

Sinus Surgery x 4Sinus Surgery x 4Hospital Day #16Hospital Day #16

Replace the existing catheter with a Bardport MRI implanted port, 6.6-French, open-ended single lumen catheter so that MRI could easily be performed with this new catheter

Further debrided necrotic tissue in the sinuses or orbit

Hospital Day #16

Hospital Day #16

MRIMRIHospital Day #17Hospital Day #17

Stable left orbital cellulitis with extraconal phlegmon adjacent to the left lamina papyracea

There is no drainable fluid collection. Stable pansinusitis. Interval decrease in size of the 1.1 x 0.7 cm rim-enhancing fluid collection anterior to the left maxilla consistent with improving abscess

No intracranial extension of infection

Discharged hospital day #23Discharged hospital day #23

Va 20/20 OU; EOMS: Full OU; Pupils: No RAPD OU; Globe soft

Drains removed ( 2ml of amphotericin B at 0.25mg/ml infused through catheter in both orbit and maxillary sinus q 6 hours x 2 weeks)

Discharged home on:

IV amphotericin 385mg once daily, glipizide 20mg twice a day, CellCept 250mg every 12 hours, posaconazole 400mg po 2xdaily, and prednisone 5mg once a day. Sirolimus held.

Once MRI fully resolved and creatinine completely normalized will

stop all antifungals except posaconazole 400mg 1x daily (not

treatment dose) and restart immunosuppressive therapy at full strength.

Mortality Rate of Mucormycosis is 50%-80%, Mortality Rate of Mucormycosis is 50%-80%, once CNS involvement mortality rate is once CNS involvement mortality rate is ≥≥ 80% 80%

This is War!This is War!

Must have high index of suspicion early Aggressive management is a must and should include an all out

war: debridement, a polyene both IV and direct through catheter in orbit and sinus, combination IV therapy (LFAB-deferasirox) and if possible hyperbaric oxygen.

Must reverse underlying disease- Control DM tightly, normalize acid/base status, and decrease or stop immunosuppressive therapy so body can fight infection

MRI is key to check for CNS or orbital involvement Total duration of therapy is individualized but stop when:

resolution of clinical signs and symptoms of infection, resolution or stability on serial imaging, and resolution of underlying immunosuppression.

If no resolution of immunosuppression possible then prophylaxis such as posaconazole should be instituted for life.

QuestionsQuestions

What are the keys to successful management of these patients?

How long should antifungal therapy be given and how to balance that with restarting immunosuppressive therapy?

What about prophylactic antifungal therapy for life?