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Mycobacterium Simiae Case report BMJ Case Rep: first published as 10.1136/bcr-2020-241037 on 28 May 2021. Downloaded from Disseminated Mycobacterium simiae and Mycobacterium avium infection causing an immune reconstitution inflammatory syndrome in a female patient with HIV infection Jacqueline Alexandra Bachofner,1 Kristian Ikenberg,2 Bettina Schulthess,3 Johannes Nemeth1 1Department of Infectious SUMMARY infections containing a macrolide (azithromycin or Diseases and Hospital This case study discusses the management of a clarithromycin), a fluorochinolone (eg, moxiflox- Epidemiology, University disseminated Mycobacterium simiae and Mycobacterium acin) and a third antibiotic class (eg, clofazimine, Hospital Zurich, Zurich, avium infection causing an immune reconstitution streptomycin or an amionglycoside such as amik- Switzerland acin) have been used, but standardised treatment 2Institute of Pathology and inflammatory syndrome in a 52- year- old woman with recommendations to this point are non- existent. Molecular Pathology, University HIV infection. Disseminated M. avium infections have Hospital Zurich, Zurich, extensively been described in HIV patients; however, Switzerland reports of infections with M. simiae are rare. Treatment of CASE PRESENTATION 3 Institute of Medical M. simiae infections is challenging due to its high rates A- 52- year old woman of African descent was newly Microbiology, University of of natural drug resistances, and thus far, no standard diagnosed with AIDS due to a HIV type 1 infection Zurich, Zurich, Switzerland treatment regimen exists. in December 2019. At that time, the CD4 count was 13 cells/ L, and the viral load was about 240 Correspondence to µ Dr Jacqueline Alexandra 000 copies/mL. In January 2020, an antiretroviral Bachofner; BACKGROUND therapy (ART) with Descovy (emtricitabin +teno- Jacqueline. bachofner@ hispeed. Mycobacterium avium has been described foviralafenamid) and Tivicay (dolutegravir) was ch frequently as a cause of pulmonary infection in initiated. Bactrim (cotrimoxazol) was prescribed for pneumocystis prophylaxis. As part of the initial Accepted 11 May 2021 patients with chronic pulmonary disease (eg, bron- chiectasis and cystic fibrosis) and disseminated evaluation, the patient was tested for other infec- infection in patients with HIV/AIDS.1 Treatment tious diseases: serological testing for hepatitis A recommendation for M. avium consists of a three- indicated a past infection, hepatitis B and hepatitis http://casereports.bmj.com/ C serological panels were negative, Cytomegalo- drug regimen including macrolide, rifamycin and virus (CMV) and Ebstein- Barr virus (EBV) PCR ethambutol.2 Mycobacterium simiae is a rare, were also negative. slowly growing non- tuberculous mycobacterium Two weeks after the beginning of ART, the patient (NTM), which was first discovered in monkeys in presented with new onset of fever (39°C), fatigue 1965 by Karassova et al (simia is the Latin word and weight loss. Personal history and family history for monkey).1–3 M. simiae has been reported in were unremarkable. No recent travel history. She several regions of the world, mainly the USA and reported regular medication intake. Physical exam- in the Middle East (Lebanon, Iran, Reunion Island, ination did not show any abnormal findings apart Israel and Texas).4–8 In the late 1990s, a nosoco- from the elevated axillary temperature. At this time, on October 2, 2021 by guest. Protected copyright. mial pseudo- outbreak in a hospital in Texas was leucocyte count was 1.74 G/L, haemoglobin was 67 documented; the reservoir was a contaminated 9 g/L and the platelet count was 217 G/L. C reactive water supply. In most published cases, M. simiae protein was 109 mg/L. Body mass index at presen- is reported to be an opportunistic pathogen- causing tation 17.2 kg/m2. Chest radiograph and chest CT infections in immunocompromised patients (espe- did not show any pulmonary infiltrates. Unspecific cially AIDS) or in patients with pre- existing pulmo- mediastinal lymphadenopathy was seen on chest 4 10 nary diseases. However, there are cases of CT. Urine analysis did not show signs of urinary infections reported in immunocompetent patients: tract infection. After another 2 weeks, the patient 11 © BMJ Publishing Group Cruz et al describe a case of a healthy child with developed bilateral, painful, inguinal lymphadenop- Limited 2021. Re- use M. simiae lymphadenitis. M. simiae skin infection is athy. A gynaecological infection or a gynaecological permitted under CC BY- NC. No reported in an immunocompetent adult due to an tumour as a cause of the lymphadenopathy were commercial re- use. See rights iatrogenic infection.12 Balkis et al13 describe a case and permissions. Published excluded after normal smear results and a normal by BMJ. of disseminated M. simiae infection in an immuno- pelvis MRI. Despite an empiric treatment with competent 83- year-old man without pre- existing cefepime and doxycycline for 2 weeks, the patient To cite: Bachofner JA, pulmonary disease with immune senescence being was still febrile without clinical improvement. Ikenberg K, Schulthess B, et al. BMJ Case Rep a possible risk factor. Treatment of M. simiae infec- Repeated blood cultures were performed without 2021;14:e241037. tions is challenging because of multiple intrinsic signs of bacterial growth. No other cause of the fever doi:10.1136/bcr-2020- drug resistances, especially against tuberculo- could be identified. Multiple examinations were 241037 static drugs.14 15 Treatment regimen for M. simiae initiated but no viral, bacterial or fungal infection Bachofner JA, et al. BMJ Case Rep 2021;14:e241037. doi:10.1136/bcr-2020-241037 1 Case report BMJ Case Rep: first published as 10.1136/bcr-2020-241037 on 28 May 2021. Downloaded from Table 1 Antibiotic susceptibility patterns of M. simiae and M. avium M. simiae M. avium Drug MIC (mg/L) Interpretation MIC (mg/L) Interpretation Clarithromycin 4 S 4 S Ethambutol >16 na 16 na Rifampicin >8 R 1 S Rifabutin >8 R 0.25 S Amikacin 16 S 8 S Moxifloxacin 0.5 S 1 S Clofazimine ≤1 na ≤1 na Linezolid >64 R 16 I Doxycyline >16 R >16 R Trimethoprim/ 2/32 S 2/38 S sulfamethoxazole Isoniazid 8 na >8 na Minimal inhibitory concentrations (MIC) were determined by broth microdilution as Figure 1 Cell block preparation from the fine needle aspiration (FNA) recommendedby CLSI using Sensititre SLOWMYCOI plates (ThermoFisher, Waltham, MA).25 of an inguinal lymph node: granulomatous inflammation with typical ClofazimineMIC was measured by quantitiative MGIT testing.26 aggregation of epithelioid histiocytes (H&E stain; 400×). Interpretation according to species- independent CLSI breakpoints for slowly growing NTM.25 I, intermediate; M. avium, Mycobacterium avium; MIC, minimal inhibitory concentrations; M. simiae, Mycobacterium simiae; na, no breakpoints available; R, resistant; S, susceptible. was identified: CMV PCR and EBV PCR were still negative, EBV and toxoplasmosis serologies indicated a past infection, Crypto- coccus neoformans antigen was negative and sputum PCR for the temporal association of the beginning of the symptoms and atypical bacterial pneumonia was negative. Because of neutro- introduction of the ART, and the extent of disease, it is sugges- paenia, a bone marrow biopsy was performed, which showed tive that the patient suffered from disseminated M. simiae and M. reactive changes compatible with HIV infection. avium infection already at the time of HIV diagnosis. Therefore, After additional 2 weeks, M. simiae grew in citrate blood we hypothesise that the development of symptoms was mostly cultures, bone marrow, lymph node, sputum and stool cultures. due to beginning IRIS after successful suppression of the HI viral An inguinal lymph node biopsy confirmed granulomatous load and immune reconstitution. Mycobacterial cultures are not inflammation and copious acid-fast bacilli (figure 1). In one routinely performed at the time of diagnosis, and therefore, we blood culture and in the lymph node biopsy M. avium was cannot prove whether the mycobacterial infection was ongoing isolated in addition to M. simiae. at the time of HIV diagnosis or not. The treatment for presumptive IRIS encompasses first treat- http://casereports.bmj.com/ TREATMENT ment against the pathogen to reduce pathogen load and second Having diagnosed a disseminated mycobacterial infection with slowing the fulminant immune response, ideally without 16–18 M. simiae and M. avium, we started a treatment regimen with hampering the ‘normal’ recovery of the immune system. azithromycin (oral 500 mg once daily), moxifloxacin (oral 400 The pathogen- directed therapy against M. simiae is compli- mg once daily) and amikacin (intravenous 15 mg per kg ones cated since optimal treatment regimens have not been studied. daily). After 4 weeks, based on the drug susceptibility testing The standard treatment regimen for M. avium infections, results (table 1), we switched from intravenous amikacin to consisting of a macrolide, ethambutol and a rifamycine, is not clofazimine (oral 50 mg twice daily). Because of persistent recommended for M. simiae infections due to high rates of resis- tances. Overall, M. avium seems to be more susceptible than M. fever, we repeatedly performed additional diagnostic rounds on October 2, 2021 by guest. Protected copyright. searching for other infections, but to no avail. Therefore, we simiae to antibiotics. This is consistent with the results from our started treatment with prednisone 20 mg for a presumptive patient, shown in table 1. For M. simiae
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