How can we ensure that patients with a rare disease get the best management? Drug resistant Tuberculosis shows a way Professor Peter D.O.Davies, Liverpool.

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Presentation transcript:

How can we ensure that patients with a rare disease get the best management? Drug resistant Tuberculosis shows a way Professor Peter D.O.Davies, Liverpool

Proportion of tuberculosis cases with first line drug resistance, UK, /10/2008 First line drugs: isoniazid, rifampicin, ethambutol & pyrazinamide (except Mycobacterium bovis) Multi-drug resistant: resistant to isoniazid and rifampicin (with or without other resistance) Source: Enhanced Tuberculosis Surveillance (ETS), UK Mycobacterial Surveillance Network (MycobNet), Enhanced Surveillance of Mycobacterial Infections (ESMI)

Multiple drug resistance DOTS-Plus in Latvia Lemaine V et al. Lancet 2005; 365:318-26

WHO report FEBRUARY 2008 WASHINGTON DC /GENEVA Multidrug-resistant tuberculosis (MDR-TB) has been recorded at the highest rates ever, according to a new report published today.

Warning A new plague is sweeping across the planet Soon multidrug resistant tuberculosis will kill one person in three The Constant Gardener November 2005

The management of MDRTB A rare disease no national guidelines. Little personal experience. Scattered occurrence What drugs and other care should the patient receive? How can we ensure that all patients get the best management?

Management of MDRTB DON’T

Estonia Very high rates of MDRTB Manageable annual numbers (75-100) Small country Single controller Several treatment supervisors Monthly progress meetings

England Low rate Manageable annual number (75-100) Central sensitivity testing Undesignated experts No co-ordination of therapy No central assessment No outcome data Need for co-ordination at National level

MDRTB service: Mission statement To provide advice from an expert group to suggest optimum treatment. To collect data on outcomes to build up a knowledge base to inform. Participation to be voluntary

National MDR-TB Service Agreement of relevant professional bodies e virtual committee of experts Give advice re: management Patient data and progress Follow up advice and management Voluntary Outcomes: bacteriological and clinical.

Proposal for the management of drug resistant tuberculosis All MDRTB specimens identified by reference lab. Clinician managing patient informed by lab director Clinician informed about MDRTB service Clinician invited to contact MDRTBS re management Asked to complete data entry form by MDRTBS Details entered onto blog by MDRTBS E committee informed of new case on Secure Blog. Advice entered onto blog and ed to managing clinician Three-monthly clinical updates from clinician to co- ordinator. Regular meetings convened by lead clinician

Composition of virtual e-committee Microbiologists/Lab directors 5 Chest Physicians 13 ID Physicians 5 HIV physicians 1 Paediatricians 5 Public Health Physicians 3 Respiratory Pharmacist 1 TB Specialist nurse 1 Surgeon 1 Total 35 Patient (1)

E mail message A reminder of how to log on to the new MDRTB secure web based discussion forum. (URL and log on details below, upper case essential):-

Activity from 1/1/08 to 31/12/09 Cases discussed (72) (55MDR, 4XDR 13 MDR not confirmed) Comments received 300 Most comments (15), fewest (2) Five most active repliers all Chest Physicians (75% of comments) ID repliers a/c for 12% of comments

Activity from 1/1/08 Questions asked Treatment recommended Problems with compliance Problems with infection control Problems with adverse reactions Preventive therapy for contacts

Problems in implementation Many opinions Delay in opinions Confused managing clinician “Secret” managing of patients Failure/inaccurate completion data entry forms Confidentiality

Problems in management of patients Achieving a consensus drugs, monitoring, adverse events. No designated MDRTB centres. Role of surgery not clear. Voluntary–need to add to guidelines?

“Political“ problems Different specialist bodies Chest Physicians ID Physicians Paediatricians Microbiologists Public health doctors Specialist TB nurses

Ethical problems Patient Confidentiality Ethical permission: Research or Audit? Physician liability. Who pays? Government: central or local? Private.

Conclusions Potential for best advice to be given Follow up advice available Outcomes recorded Advice modified as outcomes observed Collective wisdom A common sense approach Adaptable to other diseases

MDRTB the current problem (and solution) in the UK. Professor Peter Davies, Liverpool

Problems in implementation All MDRTB specimens identified by reference lab. Clinician managing patient informed. Clinician informed about MDRTB service Clinician invited to contact MDRTBS re management Asked to complete data entry form Three-monthly clinical updates from clinician to co- ordinator Regular monitoring of bacteriological results Regular input from MDRTBS. Regular meetings convened by lead clinician

March 02, 2010 MDRTB 77 I would appreciate your advice on the management of a Chinese student, dob She has been in the UK for the past 18 months, studying for a PhD. She comes from Beijing, and when there about 5 years ago had an episode of haemoptysis. She had few other symptoms. Apparently CXR and CT scan showed some abnormality on the left upper lobe. I understand that no organisms were cultured. She had had BCG as a child and gave no known TB contact history. Her University degree did involve her going in and out of the local hospital as she did a Radiology project. However there was very minimal contact with patients as she was not a medical student. Her physicians in Beijing elected to give her a 9 month daily course of rifapentine, isoniazid and ethambutol. She reports 100% adherence and tolerated the treatment well. She had no further haemoptysis, and with minimal symptoms at onset did not feel any different on treatment. At the end of her course she had the impression from her physicians that they were not sure if she had bronchiectasis or had had TB. About 2 years ago, still in Beijing, she recalls taking a week long course of ofloxacin for a gastrointestinal upset. Otherwise her only antibiotic exposure has been amoxicillin for sore throats. She has otherwise been fit and well and has no psychiatric history. After arriving in the UK, last February she had another haemoptysis. She was referred to the local Respiratory Clinic. (Sequential imaging is shown below). She is HIV negative. Three sputa were smear negative, but all three grew M.abscessus (sensitive to clarithromycin and co-trimoxazole, but resistant to amikacin, cefoxitin, tigecycline, tobramycin and linezolid). It was elected to give her treatment, but she went back to China over the summer period. On her return in the autumn she commenced treatment with clarithromycin, co-trimoxazole and amikacin (for 2 months) at the beginning of October. Clinic letters record that she had a mild cough and malaise, but she herself denies much in the way of symptoms. Subjectively she tolerated her treatment and with hardly any symptoms to begin with could not report any symptomatic improvement.

As discussed by phone regime should be Capreomycin, Pzi, Ethamb, Prothion, Cyclo, and probably PAS. One day we may know wherther PAS or linezolid is better. Also consider surgery early. Dont forget to check Vit D status Posted by: Peter Davies | March 10, 2010 at 01:08 PMMarch 10, 2010 at 01:08 PM