[CIS PIDD] [cis-pidd] Multi drug resistant Campylobacter jejuni infection in RAG1 SCID

Tue Aug 16 00:50:47 EDT 2016

Hi, Dr. Parikh --

I have no experience with such an MDR strain as such ... but I would suggest a few boxes worth checking ...

#  Mayo's micro lab is very good, in my experience.  They will test whatever you ask them to test (and even some we should NOT asking them to test for).  If you don't have the data, in addition to what's mentioned before, ask for amox/clav, minocycline, and chloramphenicol.

#  The best paper I've seen on MDR Campy would be Lehtopolku et al., Antimicrob Agent Chemother 2010.  It looks like they didn't even bother checking for amikacin since 99% of the MDR isolates are gentamicin sensitive.  *If* the bug is gentamicin- or tobramycin- sensitive, I would STRONGLY recommend using this instead of amikacin.  It is fairly difficult to get therapeutic blood levels of amikacin.  Gent or tobra ... peanuts.  I am hesitant to say one is failing therapy if the patient is not getting adequate levels of therapy to begin with.  Go with once-daily extended interval dosing to ensure one reaches the ultrahigh peaks with whatever aminoglycoside with the lowest MIC.  (If the bug is gent/tobra resistant ... this will not be pretty)

#  Treat as if the patient has osteomyelitis.  (For all I know, she might).  It would not surprise me if we would need >= 5 months.  At least 2 active IV drugs -- hopefully, not tigecycline.  (My experience with kids saved by tigecycline versus died despite tigecycline is very lopsided).

#  For that matter, do you have evidence that the Campylobacter is in the gut (stool culture / mucosal biopsy, etc.) -- rather than somewhere else (bone, heart, liver / spleen, skin / soft tissue)?  If not yet done, I would insist that the patient get a TEE.

#  As to what Dr. Vinh suggested with paromomycin ... there is one clinical report out there (at least), Okada et. al., Int Med 2008, that used kanamycin (another non-orally bioavailable aminooglycoside -- though, yes, they are all nonbioavailable) in addition to 2 IV agents to finally get the patient's fevers to stop.  (Cool case ... 31 y/o M with XLA).  Problem is, kanamycin is not available as a proper pharmaceutical in the U.S.  (Though most microbiology research laboratories have a half a kilo of kanamycin sitting in their chemical shelf).  A doable alternative may be oral gentamicin, which has been shown to decontaminate gut against KPC (Tascini et al., Antimicrob Agents Chemother 2014).

#  For the granulocyte transfusions -- I doubt they would help.  The patient it not getting recurrent Campylobacter due to neutrophil dysfunction.  So long as she is on active antibiotics, the Campylobacter is controlled.  It's when one thinks of turning them off in which I will get nervous.  Going with what (little) is known about host/pathogen relationships with Campylobacter (Jannsen et. al., Clin Micr Rev, 2009), I suspect the carriage / recurrent infection will not stop until the patient has good levels of her own nascent IgM and IgA.

Good luck in your case.

  - Karl

Karl O. A. Yu, M.D., Ph.D., F.A.A.P.
Instructor of Pediatrics (Pediatric Infectious Diseases)
University of Chicago - Comer Children's Hospital
5841 S Maryland Ave, MC 6054, Chicago IL 60637
Pager:  773-702-6800   x1744
Fax:  773-702-1196
Lab phone (Bubeck Wardenburg laboratory): 773-834-6976
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From: CIS-PIDD [cis-pidd at lists.clinimmsoc.org]
Sent: Monday, August 15, 2016 9:36 PM
To: CIS-PIDD
Subject: Re:[cis-pidd] Multi drug resistant Campylobacter jejuni infection in RAG1 SCID

Hello Suhag,

With respect to the Campy, you may also want to consider testing for Fosfomycin, cefepime, and ceftolazone/tazo, although it may be hard to interpret some of these results.

Disk diffusion (Kirby Bauer) method may be a sufficient start to screen; if there is no zone of inhibition (i.e. growth right up to the disk), it's likely resistant. However, if there is a zone of inhibition, an MIC-based method would be required. The etest is a common MIC method, but historically, can be variable for some of the tested antibiotics. There is less information about test comparative performances for the newer antibiotics. Alternatively, the lab can consider agar dilution or broth microdilution method, but those are more laborious and may not be available.

An older article had also suggested paromomycin as a potential agent (Freydiere et al., Eur J Clin Microbiol. 1984), although this appears to be only in vitro testing and I could not find any clinical reports. Given that it is a non-absorbable aminoglycoside, it may be worth considering prior to transplant as an attempt for gut decolonization. It will obviously do nothing for the line-bacteremia, and it may need to be used in combination with other agents for decolonization.

Don

Donald C. Vinh, MD, FRCP(C)
Director, Infectious Disease Susceptibility Program
Assistant Professor, FRQS Clinician-Scientist
Dept of Medicine (Division of Infectious Diseases; Division of Allergy & Clinical Immunology)
Dept of Medical Microbiology; Dept of Human Genetics

McGill University Health Centre - Research Institute
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From: CIS-PIDD <cis-pidd at lists.clinimmsoc.org>
Sent: August-15-16 9:40 PM
To: CIS-PIDD
Subject: [cis-pidd] Multi drug resistant Campylobacter jejuni infection in RAG1 SCID

Dear Colleagues:

I am seeking advice for a 20 year old female with RAG1 SCID with recurrent and multi drug resistant Campylobacter jejuni infection (in vitro resistance to macrolides, fluoroquinolones,  doxycycline; sensitive to meropenem and aminoglycosides). Patient has had multiple recurrences of campylobacter jejuni bacteremia over the past 5 months, and has responded to meropenem and amikacin.  She was maintained on meropenem and was asymptomatic. CT scans of chest, abdomen were unremarkable;  A central line was placed a day prior to start of conditioning for matched unrelated donor BMT. A surveillance culture done few hours after placement of the central line is growing campylobacter. She also developed fever  5 days later.

Thus, this is  concerning for lack of efficacy of meropenem. We have added amikacin and due to persistence of fevers, added tigecycline today.

We plan to send the new culture isolates for sensitivity testing with extended panel of antibiotics, such as tigecycline, colistin, rifaximin, ceftazidime-avibactam. Can you recommend a lab experienced with campylobacter sensitivity testing for more comprehensive testing. We had sent the previous test to Mayo.

Any other supportive care recommendations? We are considering granulocyte transfusions during the neutropenic phase.

I am very concerned about our ability to control this infection in the post-transplant phase. I will appreciate if anyone can share experience with MDR campylobacter jejuni bacteremia in immune compromised patients and advice on management of this infection.

Regards,

Suhag

Suhag H. Parikh, M.D.
Associate Professor of Pediatrics
Duke University School of Medicine
Attending Physician
Pediatric Blood and Marrow Transplant Program
Duke University Medical Center
Box 3350, Durham, NC 27710
Tel: 919-668-1121
Fax: 919-668-1180
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