[CIS PIDD] [cis-pidd] Long term Azithromycin for IgA deficiency & recurrent bronchitis

Wed Aug 30 16:03:58 EDT 2017

Thanks to Jason & Karl for your very helpful suggestions on management and monitoring. Richard raises a highly pertinent question on Azithromycin dose and frequency. Based on the pharmacokinetics of the drug with activity lasting  7-10 days, over the past 5 years pulmonologists here have successfully treated cystic fibrosis patients and selected cases of bronchiectasis with 1 gram weekly (for adult > 50 kg body weight). I am told that some CF centres in Australia have adopted the same regimen.

Stan

From: cis-pidd at lyris.dundee.net [mailto:cis-pidd at lyris.dundee.net] On Behalf Of CIS-PIDD
Sent: 29 August 2017 11:41 PM
To: CIS-PIDD
Subject: Re: [cis-pidd] Long term Azithromycin for IgA deficiency & recurrent bronchitis

What is the prophylactic regimen? I have seen 5mg/kg/d, 5 or 10mg/kg M-W-F and 20mg/kg once a week. I suspect that both dose and frequency play a role in the potential for toxicity. There is little or no data on either safety or efficacy. It is too bad that there is not enough money in antibiotic prophylaxis for a drug company to take on a study.
Richard Wasserman
Dallas

On Tue, Aug 29, 2017 at 5:34 PM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>> wrote:

Dr. Ress:

I have yet to see any formal protocols or guidance for monitoring for long-term azithromycin.  The ATS/IDSA guidelines on nontuberculous mycobacteria do mention monitoring for toxicity, but they’re not really specific on the details.

That said, in my (relatively short) career, I’ve had one kid get tinnitus on treatment-dosed azithromycin (he was on the drug for 2 - 3 months, for what it’s worth), where we did find out that he was indeed supratherapeutic.  I also had one previously healthy kid get in Torsades after a single dose of ondansetron.  While it’s not my usual practice to ask for an EKG before prescribing short-term azithromycin or ondansetron to healthy kids, I’ve ended up glancing at the cardiopulmonary monitor to just make sure the QT looks normal.

A professor of mine went by the adage, “the punishment should fit the crime.”  My 2 cents – the longer or higher the dosing, or if the patient is on other QTc-prolonging agents , the more monitoring they’ll  get.  EKG, LFTs, hearing, drug levels – probably in that order of priority.  I concede this is probably a high number-needed-to-treat scenario.

       - Karl

Karl O. A. Yu, M.D., Ph.D., F.A.A.P.
Scientist II and Assistant Director, Center for Infectious Diseases and Immunology
RGH Research Institute | Rochester General Hospital | Rochester Regional Health
1425 Portland Ave., Room R-403, Rochester, NY   14621
Tel  585-922-3709<tel:(585)%20922-3709>  |  Fax  585-922-2415<tel:(585)%20922-2415>

From: cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net> [mailto:cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>] On Behalf Of CIS-PIDD
Sent: Tuesday, August 29, 2017 4:45 PM
To: CIS-PIDD
Subject: Re: [cis-pidd] Long term Azithromycin for IgA deficiency & recurrent bronchitis

Hi Stan,

Admittedly I am a 'low-but-not-undetectable-IgA-deficiency' skeptic.  In other words, in these situations I believe there are other factors contributing as much or moreso than the IgA.  Truth be told, even with undetectable serum IgA, I am always searching for additional contributing factors rather than looking to antibiotics to solve all.

My approach to these patients is to thoroughly re-evaluate things from an allergic rhintis, chronic rhinosinusitis and asthma standpoint and maximize therapy based on history, exam and diagnostics (PFTs, , allergy testing, sinus CT if applicable).  Once this has been re-visited and a consistent management plan (e.g. nasal saline irrigation, intranasal steroids, ICS, AIT, etc.) is in place I will work to discontinue the azithromycin or other prophylactic antibiotics.

I am not sure if anyone has determined a finite length of azithromycin prophylaxis at which adverse events start to occur.   I have seen children and adults on azithromycin fpr years.  Admittedly I do not routinely do hearing tests or ECGs.  Perhaps I should?  I alos would like to hear others' approaches.

-j

jason raasch, md

Midwest Immunology Clinic

Minnesota

________________________________
From: cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net> <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>> on behalf of CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
Sent: Tuesday, August 29, 2017 2:14:48 PM
To: CIS-PIDD
Subject: [cis-pidd] Long term Azithromycin for IgA deficiency & recurrent bronchitis

Dear Colleagues,

I've followed a 16 year-old adolescent since 2014 with mild IgA deficiency 0.36 (0.6-3.0) & low IgG4 (0.01). She had severe bronchitis aged 9 years and thereafter she has had recurrent annual viral infections with bronchitis. She has allergic rhinitis treated with nasal steroids and recently has been on a steroid MDI for asthma under the care of a pulmonologist. Prior to steroid therapy for the asthma she was on prophylactic Azithromycin from January to November 2015. In February 2016 she developed bronchitis requiring 2 antibiotic courses,  and went back on Azithromycin 3 times a week thereafter. In May 2016 she had normal lymphocyte subsets and total memory B-cells, but class-switched B-cells were low at 6.4%. Serum MBL, classical & alternate complement pathways, and lymphocyte proliferation were all normal, and there was a strong response to vaccination with tetanus & pneumovax 23 with protective specific IgG levels. I have not seen her since May 2016 but I understand she has now been diagnosed clinically with bacterial tonsillitis by her family physician (but no lab evidence), and is still on Azithromycin AB 3 times a week.

My concern is for how long can one continue AB prophylaxis in this scenario? I usually prescribe it only for 6 months over winter in young scholars with IgA deficiency and recurrent infections, to help them cope with school.  Also, what sort of routine precautions are advisable (annual hearing tests? 6 monthly ECG for QT interval prolongation?)

I’d appreciate any advice and hearing what others do & about routine monitoring protocols.

Thanks,

Stan

Stanley Ress
Emeritus Associate Professor of Medicine, UCT
Specialist physician & Clinical Immunologist,
UCT Private Academic hospital, Anzio Road, Observatory,
Cape Town, 7925 South Africa
TEL:INTERN. + 2721-4421966<tel:+27%2021%20442%201966> or 4421816 FAX:   "    + 2721-(0)865173095
Cell: 0833115482
email: stan.ress at uct.ac.za<mailto:stan.ress at uct.ac.za>

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