Dr Sharanjit Dhoot. Chelsea and Westminster Hospital, London. 18 th Annual Conference of the British HIV Association (BHIVA)

Transcription

1 18 th Annual Conference of the British HIV Association (BHIVA) Dr Sharanjit Dhoot Chelsea and Westminster Hospital, London April 2012, The International Convention Centre, Birmingham

2 18 th Annual Conference of the British HIV Association (BHIVA) Dr Sharanjit Dhoot Chelsea and Westminster Hospital, London COMPETING INTEREST OF FINANCIAL VALUE > 1,000: Speaker Name Dr Sharanjit Dhoot: Statement None declared Date April April 2012, The International Convention Centre, Birmingham

3 The Virtual Clinic Multi-Drug Resistant Mycobacteria Dr Sharanjit Dhoot BSc MBBS Chelsea and Westminster NHS Foundation Trust

4 37 Nigerian Presented to QEH, Woolwich Diagnosed HIV + in Nigeria commenced HAART CD4= 13 VL 60,000 (RNA copies/ml) Treated for presumptive PCP and commenced Combivir and Nevirapine DNA d follow up and returned to Nigeria

5 Late 2007 presumed TB Re-presented having been diagnosed with presumed TB at Darent Valley Hospital. Initially treated in Nigeria for TB. Undetectable VL on Truvada and Efavirenz. CXR diffuse L lung opacification.

6 Feb 2008 Actually had M kansasii Sputum culture positive: Mycobacterium Kansasii. Culture POSITIVE Mycobacterium Kansasii isolated after 18 days (HR) Rifampicin (R) Amikacin, Capreomycin and Kanamycin (S) Clarithromycin, Ethambutol, Ethionamide, Prothionamide, Moxifloxacin and Ofloxacin

7 M. kansasii M kansasii infection is the second-most-common nontuberculous opportunistic mycobacterial infection associated with HIV and is the most common cause of NTM lung infection in patients without HIV infection M kansasii infection manifests late in the course of HIV. The lung is the organ most commonly involved. A retrospective study of South African gold miners treated for M kansasii infection reported mortality rates of 2% in those without HIV infection and 9% in patients with HIV infection

8 Feb 2008 Sputum culture positive: Mycobacterium Kansasii. Culture POSITIVE Mycobacterium Kansasii isolated after 18 days (HR) Rifampicin (R) Amikacin, Capreomycin and Kanamycin (S) Clarithromycin, Ethambutol, Ethionamide, Prothionamide, Moxifloxacin and Ofloxacin Commenced: Rifinah, Moxifloxacin, Ethambutol and Clarithromycin.

9 Does the panel agree with the treatment regime

10 1. Yes 2. No 3. Don t know

11 M. kansasii First-line regimen: This consists of rifampicin plus ethambutol plus isoniazid plus pyridoxine), with the treatment duration continuing until sputum culture results are negative for 12 months. In patients with no prior exposure to isoniazid, the drug is useful in the treatment of M kansasii infection, regardless of poor susceptibility results.

12 Multiple positive cultures: Mycobacterium Kansasii with increasing resistance profile. Sputum Sample 22/05/2009 Culture POSITIVE Mycobacterium Kansasii isolated after 13 days (HR) Clarithromycin and Rifampicin (R) Amikacin, Capreomycin and Kanamycin (S) Ethambutol, Ethionamide, Prothionamide, Moxifloxacin and Ofloxacin Cycloserine, Ethambutol, moxifloxacin, isoniazid and streptomycin. Managed by Respiratory Team with erratic adherence to medications. Despite this remained clinically well until.

13 May 2011 May 2011 Presented to QEH Fever Rigors Haemoptysis SOBOE Acute renal impairment Cr=132, Urea 5.9

14 Examination O/E: Temp 38 C Clubbed PR 105 BP 118/58 RR 20 Sats 99% OA AE & Dull L base

15 Investigations CXR complete opacification L Lung

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17 What does this CT show

18 L lung entirely collapsed + consolidation. Small L sided pleural effusion. Disease spreading to R lung: RLL ground glass and RUL atelectasis

19 QEH May 2011 Continued to become more unwell with disease progression. Sputum Sample from 08/04/2011 Culture POSITIVE Mycobacterium Kansasii isolated after 6 days (HR) Clarithromycin, Isoniazid, Rifampicin, Streptomycin (R) Azithromycin and Moxifloxacin (S) Amikacin, Ethambutol and Ofloxacin Treatment changed to: Cycloserine, Ethambutol, ofloxacin, ciprofloxacin, isoniazid and amikacin HAART: Atazanavir, Ritonavir and renally adjusted Lamivudine and Abacavir Tertiary referral to Chelsea and Westminster Hospital for management of M. Kansasii.

20 Chelsea & Westminster June 2011 Remained unwell spiking temperatures and malnourished weight 42kg. HIV disease CD4 = 47 (5.2%), VL 89 on Atazanavir, Ritonavir and Kivexa (No known baseline resistance). Bronchoscopy: completely obstructed LUL. Histopathology of biopsies: diffuse inflammatory infiltrate with no granulomas, AFBs not seen. Baseline bloods on admission: Urea 6.3 Cr 94 egfr 58 Hb 10.5 WCC 4.3 PLT 77 Bili 8 ALT 13 ALP 135

21 What do you do HIV & MDR M. Kansasii

22 Treatment Started 10/6/11 Amikacin 700mg OD Linezolid 600mg BD Rifabutin 300mg three time a week Isoniazid 900mg OM Ethambutol 1200mg OD Ciprofloxacin 500mg BD Cycloserine 250mg OD Co-trimoxazole 960mg OD to BD

23 Developed Tremors & Vomiting

24 What do you do next was this drug induced?

25 1. Linezolid 2. Rifabutin 3. Ciprofloxacin 4. Cycloserine 5. Other

26 Linezolid Oxazolidinone antibacterial Active against gram + bacteria Multiple Side Effects GI: diarrhoea, vomiting, abdominal pain, pancreatitis Systemic: fever, fatigue Haematological: anaemia, leucopenia, thrombocytopenia, eosinophilia. Renal failure Neurological: paraesthesia, tinnitus, blurred vision, peripheral and optic neuropathy and TREMOR

27 Treatment Changes Cycloserine STOPPED Linezolid Trough Level = 38.6mg/L (normal 6mg/L), dose reduction to 300mg BD Rpt level = 16mg/L dose reduction to 300mg OD Ciprofloxacin changed to ofloxacin

28 On Discharge 15/7/11 Clinically improved: Fevers resolved Gaining weight Well controlled HIV disease with undetectable VL on Atazanavir, Ritonavir and Kivexa.

29 Sudden DEAFNESS November 2011 What do you do next

30 Amikacin Aminoglycoside Renally excreted Impairs neuromuscular transmission Ototoxic

31 Currently-remains well After 6 months of treatment Linezolid and Isoniazid STOPPED Remains on Rifabutin, Ethambutol, Ofloxacin and Co-trimoxazole. Clinically stable and weight increasing = 54kg Jointly managed by both HIV teams (CD4=45, 10.2%, VL<40)

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33 What does this CT show

34 Consolidation of L lung with minimal parenchymal aeration in LMZ. R lung clear

35 Treatment Duration

36 Treatment Duration months since last culture positive? months since last culture positive 3. Depends on clinical scenario

37 Learning points Not all presumed TB is TB M kansasii MDR can occur due to poor adherence Appropriate tertiary referrals where combine HIV and mycobacterial experience Joint management can be successful Linezolid and other drug interaction and side effects complex and few data Deafness and amikacin-irreversible

38 Acknowledgments Dr Anton Pozniak Sheena Basnayake Dr Mark Nelson Prof Brian Gazzard Dr Judith Russell Dr Sayee Papineni Dr Keerti Gedela Sandra Mead Carol Annon NEXT CASE