[PAGID] CGD patient

[Vinh, Donald (NIH/NIAID) [F]]

I think the levofloxacin is an interesting point. I guess it depends what you believe is going on here.

The 'standard 4-drug' regimen (isoniazid, rifampin, pyrazinamide, ethambutol) is recommended during the intensive phase for tuberculous meningitis due to M. tuberculosis. If you think that this is BCG/M. bovis, though, clearly the PZA is not necessary.

Additionally, the recommendation to use 4 drugs is based on the possibility of drug resistance (especially if the prevalence of drug-resistance is 4% or more, although local guidelines may vary). So while 4-drugs is safest for M. tuberculosis, I am not aware that the commercial BCG strains (which would be the most likely source here, if this is BCG meningitis) have demonstrated acquired resistance (a few strains have low level in vitro resistance to INH and ethionamide, but I don't know what that means clinically).

It is hard to comment from a distance on whether or not to continue amphotericin. Is there evidence of yeast disease (e.g. Candida) elsewhere (e.g. blood, retinal spots)? If there evidence of mould (e.g. sinus images). Is there anything that could be biopsied to give you an answer? Waiting for CSF cultures may not yield much. Even in true TB meningitis, a good volume of CSF (e.g. 5 mL) is usually required to make a diagnosis by culture - a volume typically hard to get, especially in children. For molds, the best sample is tissue.


Donald C. Vinh, MD
Infectious Disease specialist & Medical Microbiologist
Visiting Post-doctoral Fellow, LCID
NIH / NIAID
9000 Rockville Pike
Bldg 10CRC, Rm B3-4141
Bethesda, MD     USA
20892
Ph: 301-496-2473
Fax: 301-480-4507
e-mail: vinhd at niaid.nih.gov<mailto:vinhd at niaid.nih.gov>

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From: pagid-bounces at list.clinimmsoc.org [pagid-bounces at list.clinimmsoc.org] On Behalf Of Nacho Gonzalez [nachgonzalez at gmail.com]
Sent: Wednesday, August 19, 2009 6:12 AM
To: pagid at list.clinimmsoc.org
Subject: Re: [PAGID] CGD patient

Why not add levofloxacin? It has a blood brain barrier penetration and antiTB efficacy may be considered as first line therapy. Furthermore, 4 antiTB drugs is a standard regimen in tuberculous meningitis

Luis Ignacio Gonzalez Granado. Immunodeficiencies and Pediatric infectious diseases division. Hospital 12 octubre. Madrid.

2009/8/19 <grumach at usp.br<mailto:grumach at usp.br>>
Dear Donald,

Thanks for your comment. My first hypothesis is BCG meningitis but should I leave without antifungal drugs? Dexamethasone was used for one week just after the seizures. Should i introduce it again with ethambutol?

Anete S Grumach

Citando "Vinh, Donald (NIH/NIAID) [F]" <vinhd at niaid.nih.gov<mailto:vinhd at niaid.nih.gov>>:


If you believe this is BCG meningitis, then the pyrazinamide will  not be useful since M. bovis/BCG produces pyraziminidase and is  intrinsically resistant to pyrazinamide. Ethambutol has decent blood  brain barrier penetration. Streptomycin does not. If there is  paradoxical worsening on treatment, you may consider concomitant  dexamethasone.

Donald C. Vinh, MD
Infectious Disease specialist & Medical Microbiologist
Visiting Post-doctoral Fellow, LCID
NIH / NIAID
9000 Rockville Pike
Bldg 10CRC, Rm B3-4141
Bethesda, MD     USA
20892
Ph: 301-496-2473
Fax: 301-480-4507
e-mail: vinhd at niaid.nih.gov<mailto:vinhd at niaid.nih.gov>

********************************************************************************************

Disclaimer:

The information in this e-mail and any of its attachments is  confidential and may contain sensitive information.  It should not  be used by anyone who is not the original intended recipient.  If  you have received this e-mail in error please inform the sender and  delete it from your mailbox or any other storage devices.  The  National Institute of Allergy and Infectious Diseases (NIAID)  shall  not accept liability for any statement made that are the sender's  own and not expressly made on behalf of the NIAID by one of its  representatives.

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From: pagid-bounces at list.clinimmsoc.org<mailto:pagid-bounces at list.clinimmsoc.org>  [pagid-bounces at list.clinimmsoc.org<mailto:pagid-bounces at list.clinimmsoc.org>] On Behalf Of grumach at usp.br<mailto:grumach at usp.br>  [grumach at usp.br<mailto:grumach at usp.br>]
Sent: Tuesday, August 18, 2009 9:10 PM
To: pagid at list.clinimmsoc.org<mailto:pagid at list.clinimmsoc.org>
Subject: [PAGID] CGD patient

Dear


I have just diagnosed CGD in a 3 month old male. He had prolonged
fever with unknown origin and BCG vaccination was not looking well. He
developed seizures and liquor showed about 600 cells, predominantly
lymphomono, high protein and low sugar. No positivity was obtained in
the cultures (for BCG still going on).
He received drugs for all possibilities: Amphotericin, Isoniazide,
Pirazinamide, ryphampicin, co-trimoxazole and antibiotics. The fever
and seizures disapeared after the 3rd day. BCG lesion is still present
(same aspect). The cerebrospinal fluid (after 30 days) presents 73
cells, lymphomono, high protein, low glucose and a previous positive
ADA.
I would suggest to change pirazinamide for ethambutol.
Do you have any suggestion?

Thanks a lot

Best regards

Anete S Grumach, MD, PhD
Outpatient group of Primary Immunodeficiencies,
Dept of Dermatology, University of São Paulo
Dept of Immunization, Adverse Events, Secretary of Health, São Paulo