Invasive Fungal Infections Encountered in Saudi Arabia

Hail M. Al-Abdely, MD Section of Infectious Diseases Department of Medicine King Faisal Specialist Hospital & Research Center Riyadh, Saudi Arabia

Number of Allogeneic BMT Cases done at KFSH & RC 1984-2003

160 140 120 100 80 60 40 20 0 19841985198619871988198919901991199219931994199519961997199819992000200120022003

Total cases: 1407

“Common” Invasive Fungal Infections Encountered at KFSH&RC

Candidemia

Cases of Candidemia from 1990 to 2003

Adult compared to pediatric cases

Prevalence of C. albicans isolates compared to non-albicans Candida species

Distribution of non-albicans Candida species over the years

Distribution of cases of candidemia to medical units

Distribution of Candidemia Cases in adults by Clinical Service

Antifungal Prophylaxis and Candida species from blood

Aspergillosis

30 20 10 0

Aspergillosis at KFSH & RC 2001 - 2003

60 50 Total Cases Aspergillus sinusitis Invasive Aspergillosis 40 2001 2002 2003

%

90 80 70 60 50 40 30 20 10 0

Distribution of

Aspergillus species

in Sinus and Invasive Disease

A. fumigatus A. flavus A. terreus Sinus Invasive

Zygomycosis

Distribution of Mucormycosis Cases over the Years

Underlying Conditions in Patients with Mucormycosis

Site of Infection Related to Underlying Condition

Outcome of Patients with Mucormycosis

Outcome Related to Underlying Condition

Fusariosis

Fusarium Isolates at KFSH & RC 1992 - 2003 10 9 8 7 Total Invasive Non-invasive 6 5 4 3 2 1 0 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

Cryptococcosis

Cryptococcosis

 Rare infection in Saudi Arabia  Only 6 cases from 1985 to 2003  Two of the cases were courtesy of John Perfect visit 1995  4 HIVs, 1 brain tumor on steroids and 1 with idiopathic CD4 cytopenia

“Unique Cases”

“Survivor of the Middle-East Fungus”

History

 62 y/o male from AlAhasa with Type II DM on insulin  DM complications with retinopathy and nephropathy leading to ESRD  HD  February 12, 2000: NRLKTx in Iran.

 Uneventful perioperative course and normal graft function.

History

 22/4/2000:  Presented to ARAMCO hosp. With 2 days h/o left sided hemiparesis and hemisensory loss.

 No h/o fever, seizures or synchope.

 Meds  Cyclosporin, prednisone, Amlodipine.

Clinical

 Alert and oriented  Afebrile. BP 170/90  Left sided hemiparesis, power 4/5  Marked left hemisensory loss.

 Chest, CVS and abdomen: unremarkable

       WBC= 6.2

HgB= 118 Plt= 250 Creatinine=104 ALP= 168 ALT= 30 ALB= 31

Labs/imaging

• PPD= negative • CXR= unremarkable • USS abd.= normal • CT brain

Ramichloridium mackenziei

Hospital Course

 25/4/2000:  Started on Amphotericin B Lipid Complex (ABLC) 5 mg/kg/day and Itraconazole 200 mg BID.

 13/5/2000:  Neurologically the same.

 MRI brain

13 May 2000

Case 2- Hospital Course

 23/5/2000 (ARAMCO):  Slightly worse. More weak.

 On same meds.

 MRI brain

23 May 2000

Hospital Course

 31/5/2000: Transfer to KFSH.

 Clinically the same  Started on  AmBisome 5mg/kg/day,  Itraconazole 250mg IV Q12hrs  5-Flucytosine 20mg/kg IV Q8hrs.

KFSH Course

 13/6/2000:  Clinically the same  MRI brain

13 June 2000

 22/6/2000:

KFSH Course

Surgical evacuation

9 July 2000

 26/7/2000:

KFSH Course

 Current Antifungals were stopped.

 Started on Posaconazole (SCH56592) 200mg Q 6hrs for 2 wks then 400mg BID.

Outpatient visits

 8/8/2000 to 25/3/2002  Clinical improvement in motor and sensory functions.

5 Sept. 2000

25 March 2002

Course

 25 March 2002  Posaconazole trial closed  Switched to itraconazole 300 mg Q 12hrs  1/12/2002  Vertigo, facial weakness and dysarthria  MRI

4 Dec 2002

Course

 Admitted  Posaconazole was not available to us then  Voriconazole 200 mg iv Q12 for 3 weeks and discharged on po 200 mg Q8hrs  Clinical and radiological improvement

11 Aug 03

10 Dec 2003

Course

 23 Dec 2003  Posaconazole 800 mg Q12hrs  Patient is currently stable

Patients with R. mackenziei Infection

Country

Saudi Arabia Saudi Arabia Saudi Arabia

Age/ Sex

55 F 80 M 70 M Israel Qatar Oman UAE Saudi Arabia Saudi Arabia Saudi Arabia Kuwait Saudi Arabia Saudi Arabia Saudi Arabia Saudi Arabia Kuwait 60F 55M 32F NA 75M 60M 36M 58F 71M 42M 67F 65F 56M

Underlying Condition

None None Bowel surgery NA Kidney transplant Kidney transplant NA None None HD in remission Renal failure CML None Diabetes HD CLD

Number of abscesses

Multiple Solitary Multiple

Surgical drainage

Yes Yes Yes

Antifungal Therapy

AmB, 5FC, KTZ AmB, 5FC, KTZ AmB, 5FC Solitary Solitary Solitary Solitary Multiple Multiple Solitary multiple Solitary Solitary Solitary Solitary Solitary Aspirate Aspirate Aspirate Aspirate Aspirate Yes Yes Aspirate Yes Yes Aspirate Yes Yes NA NA NA NA NA AmB, 5FC, KTZ ITZ AmB, ITZ AmB, ITZ AmB, ITZ AmB AmB AmB

Outcome

Died after 6 months Died after 2 months NA NA Died NA Died Died Died after 8 weeks Died after 8 months Died after 4 wks Died after 10 days Died after 2 weeks Died after 10 days Died after 3 weeks Died after 18 days

“Cancer Analogy”

History

 2 Nov 1999    13 y/o Male previously healthy referred from Dahran Health Center with a 3months h/o generalized weakness & wt loss. RUQ pain.

CT abd revealed multiple hepatic lesions and mediastinal lymphadenopathy FNA from the liver showed fungal hyphae   Culture was negative Treated with ABLC and itraconazole for 4 weeks with no response

Course at KFSH

 Chronically ill. No fever  Hepatomegaly  WBC 8.25 with 35% eosinophils  Fundoscopy:  Multiple retinal lesions

 FNA from liver

Course

 Mediastinal lymph node bx

Cladophialophora bantiana

Course

 Therapy  AmBisome 7.5mg/kg/day (Stopped 7 May 2000)  Itraconazole 200mg Q12hrs  Improved clinically and radiologically

15 Jan 2000

1 July 2000 29 Dec 2001

Course

 30 June 2002  C/O nausea and vomiting and coordination impairment  Irregular on itraconazole for 2 months

2 July 2002

8 July 2002

8 July 2002

Course

 Treated with i.v itraconazole 250mg Q12 hrs  Discharged (30 July 2002) on liquid itraconazole 300 mg BID  Improved

Course

 27 Aug 02  Nausea , vomiting, bilateral weakness and discoordination  MRI worse  Therapy  i.v itraconazole  i.v 5-FC  i.v AmBisome

28 Sep 2002

Course

 Voriconazole 200mg i.v Q12 hrs for 3 weeks folloed by po.

 Remarkable improvement and discharged  Seen in clinic 11 Nov 2002  Excellent condition; walking independently and no coordination problems and gained several Kgs

11 Nov 02

Course

 19 Feb 2003  Acute confusion, weakness

19 Feb 2003

Ventriculoscopy

Course

 Therapy  i.v voriconazole  i.v Amisome  i.v Caspofungin  Intra-ventricular Ampho B  Intra-ventricular 5-FC

2 Apr 03

Course

 Nothing helped and the patients died on 13 April 2003 after 3 years of “palliative” therapy for disseminated Cladophialophora bantiana

“The Non-gravid Abdomen”

History

 A 19-year-old girl from Dammam.  completely healthy until May 2001  RIF pain and fever associated with constipation and weight loss  The pain was colicky and slowly progressive, moderate, non-radiating

History

 At the local hospital (DHC), she was found to have ileocecal mass (5/2001)  Colonoscopy showed ulcers of the Rt hemicolon and Bx was consistent with acute inflammation.

 Started empirically on ciprofloxacin + flagyl but without response

History

 Colonic biopsy ? Crohn’s.

 Started on oral steroids.

 Has temporary improvement and gained wt.

 Oct 2001, f/u showed an increase in the mass size clinically and confirmed by CT abdomen.

    27 Oct 2001,  laparatomy (at DHC) showed unresectable with intense inflammation involving the Rt. hemicolon mass Bx showed necrotizing granuloma with fungal hyphae. Culture was negative.

Treated with ABLC and continued low dose steroid On 11 Nov 2002  referred to KFSH&RC

 Pt was clinically unwell  P/E:  T 38.8ºC PR 110/min BP 120/70 RR 20 Wt 49 kg Ht 158 cm  Not in distress  No LN enlargement  Chest/heart exam  unremarkable

Abd Exam

 Soft, with large, irregular, ill-defined mass extending from the RUQ to RIF  No ascitis

WBC 14.0

Hb 92 Plt 305 ESR 15 Urea 4.9

Na 135 ALT 50 CXR  N

Labs

PMN 80% Cr 96 K+ 3.3

ALP 185 Alb 30 Bil 4

CT abdomen

12 November 2001

 Pt was spiking high grade Temp 40.0º C  Started on Ambisome + Pip/tazo  Pain control, NPO, TPN  Surgical opinion confirmed that the mass was non-operable

Course

 14 Nov 2001  FNA and True cut Bx

Basidiobolus ranarum

Methylprednisolone 1 mg/kg/d I.V. Itraconazole 250 mg BID

 She has rapid systemic improvement with no fever and no abd pain  Started on oral feed

20 Nov 2001

 11 Dec 2001  discharged on ketoconazole 600 mg p.o. OD, and steroids on tapering dose

8 Apr 2002

2 Sep 2002

7 July 2003

8 Dec 2003

Jarie A, AlMohsen I et al, PIDJ 2003

Jarie A, AlMohsen I et al, PIDJ 2003

More Basidiobolomycosis

Age

19F

Site

Colon 18F Huge pelvic mass 14M* Porta hepatis

Surgery

None Open Bx None

Antifungal Steroids

Itra, keto Yes Itra Yes itra Yes 14F 8M 10M Liver masses Cervical LN Open liver bx None lung, heart, liver, pancreas, abd LN None Itra Vori Itra Failed itra, caspo Yes No Yes

Outcome

well Well at 12m Lesion disappered Relapsed in 3m, Switched to vori Well at 2m Responded to vori. Well at 6 wks

“Another case for Keto”

History

 7 Feb 1999. Seen at derma clinic:  40 y/o female with 25 year history of R-foot swelling with discharging sinuses of black granules  Has resection 12 years earleir with temporary relilf for 2 years  Received a 6 year course of itraconazole with no response  Gave history of walking bare-footed during childhood and early adulthood.

7 Feb 1999

Course

 X-ray foot did not suggest osteomyelitis  Referred to orthopedics and recommended amputation  Referred to I.D

 Admitted for surgical debulking ,  Done on 22 Sep 1999

Course

 Culture was negative  Immunodiffusion test for Madurella mycetomatis was strongly postive  Started on ketoconazole 400 mg QD

22 March 2000

22 March 2000

22 March 2000

Course

 Got pregnant Jul 2000 and stopped keto Sep 2000  Delivered a healthy girl Feb 2001  6 more months of keto (DC Sep 2001)  Followed until May 2003- no relapse

“Too Fast, Too Devastating”

History

 A 35-year-old male  ESRD 9 years  S/P living non-related kidney transplant 8 years ago in India on CSA - Prednisone Azathioprine  DM & HTN

20.1.1999



24 days prior to transfer to KFSH:

 P

atient was admitted to another hospital with uraemic symptoms and diagnosed to have transplant rejection



Rx : Pulse steroid



6 days prior to transfer

 He had a generalized tonic clonic seizure for 5 min and dense Lt hemiplegia  Level of consciousness deteriorated rapidly.

 Spiked temperature

13.2.1999

   Transferred to KFSH-MSICU  BP = 173/103, P = 110/min regular, RR = 20 Ill, restless and irritable CNS :  Drowsy following simple commands Moving Rt side, with dense flacid hemiplegia Lt side

Scytalidium dimitiatum

Nattrassia mangiferae

Ambisome 10mg/kg/day



Patient deteriorated rapidly



Pronounced brain dead 2 days later.

Acknowledgment

 Asma Tulbah  Sahar Althawadi  Edna Aldomovar Pathology Microbiology Microbiology   Maher Hassonah Mahmood Aljurf Neurosurgery Hematology  Ibrahim Almohsen Pediatric Infectious Diseases  Sulaiman Al Jumaah Pediatric Infectious Diseases