Lymphadenitis caused by infection with an isoniazid- and rifampin-resistant strain of Mycobacterium bovis BCG in an infant with IFN-γ/IL-12 pathway defect

Diniz, Lílian Martins Oliveira; Guimarães, Tiago; Oliveira, Maria das Graças Rodrigues de; Pinto, Jorge; Miranda, Silvana Spíndola de

doi:10.1590/s1806-37132014000200014

Cited by 10 publications

(8 citation statements)

References 12 publications

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“…IL-12 plays an important role for the optimal production of IFN-γ by T cells and NK cells [ 19 ]. Patients with an inherited defect in the IFN-γ/IL-12 pathway show a decreased IFN-γ production due to a disturbed interaction between phagocytes and T lymphocytes and an increased susceptibility to infections with microorganisms of the genera Mycobacterium and Salmonella [ 20 – 22 ]. Severe S. aureus infections have not been documented so far in such patients or patients receiving ustekinumab.…”

Section: Discussionmentioning

confidence: 99%

Staphylococcus aureus bacteremia with iliac artery endarteritis in a patient receiving ustekinumab

et al. 2016

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BackgroundUstekinumab (Stelara®), a human monoclonal antibody targeting the p40-subunit of interleukin (IL)-12 and IL-23, is indicated for moderate to severe plaque psoriasis and psoriatic arthritis. In large multicenter, prospective trials assessing efficacy and safety of ustekinumab increased rates of severe infections have not been observed so far.Case presentationHere, we report the case of a 64-year old woman presenting with chills, pain and swelling of her right foot with dark maculae at the sole, and elevated inflammatory markers. She had received a third dose of ustekinumab due to psoriatic arthritis three days before admission. Blood cultures revealed growth of Staphylococcus aureus and imaging showed a thickening of the aortic wall ventral the bifurcation above the right internal iliac artery, resembling an acute bacterial endarteritis. Without the evidence of aneurysms and in absence of foreign bodies, the decision for conservative management was made. The patient received four weeks of antibiotic therapy with intravenous flucloxacillin, followed by an oral regime with levofloxacin and rifampicin for an additional four weeks. Inflammatory markers resolved promptly and the patient was discharged in good health.ConclusionTo our knowledge, this is the first report of a severe S. aureus infection in a patient receiving ustekinumab. Albeit ustekinumab is generally regarded as a safe drug, severe bacterial infections should always be included in the differential diagnosis of elevated inflammatory markers in patients receiving biologicals as these might present with nonspecific symptoms and fever might be absent. Any effort to detect deep-seated or metastatic infections should be made to prevent complications and to secure appropriate treatment. Although other risk factors for an invasive staphylococcal infection like psoriasis, recent corticosteroid injection, or prior hospitalisations were present, and therefore a directive causative link between the S. aureus bacteraemia and ustekinumab can not be drawn, we considered the reporting of this case worthwhile to alert clinicians as we believe that ongoing pharmacovigilance to detect increased risks for rare but severe infections beyond phase II and phase III trials in patients treated with biologicals is essential.

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Section: Discussionmentioning

confidence: 99%

Staphylococcus aureus bacteremia with iliac artery endarteritis in a patient receiving ustekinumab

et al. 2016

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“…Bugüne kadar bildirilen altı M.bovis BCG klinik izolatının ikisinde RIF ve INH'a birlikte direnç olduğu belirtilmiştir 10,11 . Bu suşlardan biri, bir hastanın balgam örneğinden, diğer suş ise BCG aşısının ardından süpüratif lenfadenit yakınmasıyla başvuran ve primer immün yetmezliği olan (IFN-γ/IL-12 yolağında defekt) 3.5 aylık bir kız çocuğundan izole edilmiştir 10,11 . Bu izolatın DNA dizi analizinde, RIF direncinden sorumlu rpoB geninde D516V mutasyonu ve INH direncinden sorumlu katG geninde S315T mutasyonu saptanmıştır 11 .…”

Section: Discussionunclassified

“…Bu suşlardan biri, bir hastanın balgam örneğinden, diğer suş ise BCG aşısının ardından süpüratif lenfadenit yakınmasıyla başvuran ve primer immün yetmezliği olan (IFN-γ/IL-12 yolağında defekt) 3.5 aylık bir kız çocuğundan izole edilmiştir 10,11 . Bu izolatın DNA dizi analizinde, RIF direncinden sorumlu rpoB geninde D516V mutasyonu ve INH direncinden sorumlu katG geninde S315T mutasyonu saptanmıştır 11 . Diğer dört RIF'e dirençli M.bovis BCG suşundan ikisi HIV ile enfekte 6 ve 9 aylık iki bebekten izole edilmiştir 12,13 .…”

Section: Discussionunclassified

Rifampicin-Resistant Mycobacterium bovis BCG Strain Isolated From an Infant With NEMO Mutation

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Azarsız³

et al. 2015

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ÖZİnterlökin (IL)-12/interferon (IFN)-γ yolaklarında yer alan genlerdeki mutasyonlar ve nükleer faktör kappa-B temel modülatörü (Nuclear factor-kB Essential Modulator; NEMO) mutasyonları gibi konjenital hücresel immün yetmezliği olan bebeklerde BCG aşısından sonra yaygın Mycobacterium bovis BCG enfeksiyonlarının geliştiği bilinmektedir. Bu raporda, NEMO defektli bir bebekten izole edilen rifampisine dirençli M.bovis BCG suşunun irdelenmesi amaçlanmıştır. NEMO defektli 8 aylık bir erkek bebek, ateş, yaygın lenfadenopati ve hepatosplenomegali semptomlarıyla hastanemizin pediatri kliniğine getirilmiştir. Hastanın lenf nodu ve karaciğer biyopsisi örneklerinden hazırlanan yaymanın mikroskopik incelemesinde yoğun olarak (3+) aside dirençli boyanan basil (ARB) pozitifl iği saptanmıştır. Gerçek zamanlı PCR (GeneXpert MTB/RIF; Cepheid, ABD) ile örneklerde rifampisine duyarlı Mycobacterium tuberculosis kompleks (MTC) varlığı tespit edilmiştir. Örneklerin MGIT960 (Becton Dickinson, ABD) besiyerinde yapılan kültürlerinde 20. günde üreme saptanmış ve izolat GenoType MTBC kiti (Hain Lifescience, Almanya) ile M.bovis BCG ve spoligotiplendirme ile M.bovis BCG [SIT 482 (BOV_1)] olarak tanımlanmıştır. MGIT960 sisteminde yapılan primer antitüberküloz ilaç duyarlılık testlerinde izolat rifampisin (RIF), izoniyazid (INH), streptomisin (STM) ve etambutol (EMB)'e duyarlı bulunmuş ve hastaya antitüberküloz tedavi başlanmıştır. Hasta 2 yaşında yeniden hepatosplenomegali yakınmasıyla başvurmuş ve deri altındaki nodüllerden direne olan apse materyalinden hazırlanan yaymada yine ARB pozitifl iği (3+) saptanmıştır. Örnekte GeneXpert ile RIF'e dirençli MTC tespit edilmiş; örnekten yapılan kültürde 13. günde üreme saptanmış ve izolat M.bovis BCG olarak tanımlanmıştır. Duyarlılık testinde izolatın INH, STM ve EMB'e duyarlı, ancak RIF'e dirençli olduğu tespit edilmiştir. Yapılan DNA dizi analizinde rpoB geninin 531. kodonunda RIF direnciyle ilişkili S531L mutasyonu saptanmıştır. Hasta yaygın BCG bovis enfeksiyonu ve çoklu

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“…Local or systemic side effects due to primary BCG vaccination are relatively uncommon, and are mostly seen in cases of overdose, fortuitous revaccination or poor injection techniques. Only a few cases have been reported in the literature (Cuchet et al, 2004;Diniz et al, 2014;Lussier et al, 1999;Murphy et al, 1989;Okazaki et al, 2005;Zaïem et al, 2014). In Italy, because the general population is at low risk for acquiring tuberculosis infection, BCG vaccination for the entire population is not presently recommended.…”

Section: Introductionmentioning

confidence: 99%

A case of abscess after BCG vaccine in an immunocompetent child without other clinical signs

et al. 2015

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Introduction: Bacille Calmette-Gué rin (BCG), an attenuated strain of Mycobacterium bovis, is a rare cause of infection, with few published cases in immunocompetent individuals. Case presentation: We present the case of a cutaneous abscess in an immunocompetent infant returning from Morocco, where he received a BCG vaccination. The abscess developed at the site of inoculation in the forearm (a non-recommended site) in the absence of lymphadenopathy or systemic signs. The lesion did not recur after aspiration of the abscess and further treatment was not required. Conclusion: Infections caused by M. bovis BCG may be difficult to diagnose without systemic signs or lymphadenopathy but should be suspected in children returning from regions where BCG vaccination is widely applied. The present report suggests that abscess formation after BCG vaccination is a continuing problem, particularly in tuberculosis-endemic areas and when recommendations concerning dosage or injection techniques are not followed. Moreover, we highlight here the importance of combining phenotypic and genotypic methods for quick identification of Mycobacterium bovis BCG in abscess drainage fluids.

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Lymphadenitis caused by infection with an isoniazid- and rifampin-resistant strain of Mycobacterium bovis BCG in an infant with IFN-γ/IL-12 pathway defect

Cited by 10 publications

References 12 publications

Staphylococcus aureus bacteremia with iliac artery endarteritis in a patient receiving ustekinumab

Staphylococcus aureus bacteremia with iliac artery endarteritis in a patient receiving ustekinumab

Rifampicin-Resistant Mycobacterium bovis BCG Strain Isolated From an Infant With NEMO Mutation

A case of abscess after BCG vaccine in an immunocompetent child without other clinical signs

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