Pulmonary Cavity From Mycobacterium malmoense in an HIV-Infected Patient: Complicated by Bronchopleural Fistula

Pulmonary Cavity From Mycobacterium malmoense in an HIV-Infected Patient: Complicated by... Open Forum Infectious Diseases BRIEF REPORT CASE REPORT Pulmonary Cavity From The patient is a 63-year-old African American male with med- Mycobacterium malmoense in an ical history significant for long-standing HIV infection (most HIV-Infected Patient: Complicated by recently treated with raltegravir, emtricitabine, and tenofovir; Bronchopleural Fistula CD4 >600 and viral load undetectable), hepatitis C, and cirrho- sis. He presented with a 15–20-lb weight loss, nonproductive Eric Abston and Harrison Farber cough, and right-sided chest pain; he denied fever, chills, or Division of Pulmonary, Allergy, Sleep, and Critical Care Medicine, Boston University School of Medicine, Boston, Massachusetts night sweats. The remainder of review of systems was unre- markable. Chest imaging, including computed tomography We present a case of M. malmoense and HIV co-infection com- (CT), demonstrated a new 4.8-cm right upper lobe cavitary plicated by aspergilloma leading to bronchopleural s fi tula with lesion with multiple nodular cavitary foci as well as left-sided intractable pneumothorax and pleural aspergillosis, ultim- pulmonary nodules  (Figure  1). Samples from bronchoscopy ately requiring surgical intervention. Treatment guidelines for with broncheoalveolar lavage (BAL) and postbronchoscopy M. malmoense are reviewed, literature regarding M. malmoense sputum were all positive on acid fast bacilli (AFB) stain. Nucleic and HIV co-infection is reviewed, and the epidemiology of acid amplification testing (GeneXpert) on BAL and sputum M. malmoense in North America is discussed. samples was negative for Mycobacterium tuberculosis (MTB). Keywords. bronchopleural fistula; HIV; Mycobacterium Fungal cultures and serum galactomannin were negative. Given malmoense. the high negative predictive value of polymerase chain reaction for MTB infection on an AFB-positive sputum sample, MTB infection was thought to be unlikely. The patient was treated for Mycobacterium malmoense is an atypical mycobacterial nontuberculosis mycobacterium (NTM). Due to concerns for strain first discovered in Sweden in 1954. The incidence of drug interactions with his antiretroviral medication, a regimen M. malmoense infection has been rising since the 1980s; yet, of rifabutin, azithromycin, and ethambutol was selected after outside of northern Europe, infection is extremely rare. The discussions with several consulting services. This regimen was first case of pulmonary M.  malmoense infection in North initially complicated by gastric intolerance; however, this was America was reported in 1984 [1]. Most patients who de- abrogated by stepwise addition of these medications. velop M.  malmoense infections have structural lung disease Samples were sent to Charles River Laboratories (Newark, DE) that compromises immunity, such as chronic obstructive for culture and microbial identification via DNA sequencing. pulmonary disease (COPD). Infection is associated with All sputum and BAL samples were identified as Mycobacteria contaminated water or soil; no interpersonal communi- malmoense. Based on this, the rifabutin was changed to ri- cation of infection has been reported [2]. Disseminated fampin, and the other medications were continued (rifampin disease is rare and has only been observed in severely im- 600 mg, ethambutol 800 mg, and azithromycin 500 mg daily). munocompromised patients, such as those with AIDS. Due Hepatitis C treatment was deferred due to concern for hepato- to the progressive nature of the infection, timely diagnosis toxicity and side effects. Aer 15  ft months of therapy, sputum and appropriate management of M. malmoense infections are cultures were continually negative for M. malmoense; however, essential. However, because the clinical presentation is very the cavity persisted on chest imaging. similar to that of tuberculosis, patients can be easily misdi- Twenty-four months aer ft initial presentation, the patient agnosed and improperly treated. was admitted with a 4-day history of progressive dyspnea and nonproductive cough. Chest CT then demonstrated a right- sided hydropneumothorax. Placement of a chest tube yielded 400 cc of purulent fluid. Aer 2 w ft eeks, the air leak persisted; repeat chest CT demonstrated a tract fistula between the cavi- Received 21 June 2017; editorial decision 16 January 2018; accepted 17 January 2018. tary lesion and pleura. Pleural fluid from his chest tube grew Correspondence: E.  Abston, MD, PhD, 72 E.  Concord St, R-304, Boston, MA 02118 (eric.abston@bmc.org). Aspergillus fumigatus, as did bronchial washings obtained from Open Forum Infectious Diseases repeat bronchoscopy. Antifungal coverage with amphotericin Published by Oxford University Press on behalf of Infectious Diseases Society of America 2018. was begun initially because of concern for pleural aspergillosis This work is written by (a) US Government employee(s) and is in the public domain in the US. DOI: 10.1093/ofid/ofy023 and potential interaction with the antimycobacterial agents. BRIEF REPORT • OFID • 1 Downloaded from https://academic.oup.com/ofid/article-abstract/5/2/ofy023/4823228 by Ed 'DeepDyve' Gillespie user on 16 March 2018 positive culture obtained via bronchoscopy [3]. He responded well to therapy, only to develop a secondary fungal infection, which spread from his cavitary lesion to his pleura via a fis- tula that was responsible for a chronic pneumothorax. Despite several attempts to mitigate his condition with endobronchial valves and percutaneous plugging, definitive treatment ultim- ately required lobectomy and chest wall reconstruction. In this case, the patient had several concomitant infections that required simultaneous treatment and careful adjustment of treatment regimens. On initial presentation, we considered standard HRZE therapy to treat for active tuberculosis; how- ever, we instead chose rifabutin, azithromycin, and ethambutol as a second-line therapy to avoid drug interactions with his antiviral medications. Once cultures revealed M.  malmoense, we switched from rifabutin to rifampin, per British Thoracic Society guidelines [4]. The patient had been on his current HIV therapy (raltegravir, emtricitabine, and tenofovir) for years with good viral suppression (CD4  >600 and an undetectable viral load). Because rifampin increases the hepatic metabolism of raltegrivir, we increased the raltegrivir from 400 mg to 800 mg twice daily; this was well tolerated by the patient and main- tained viral suppression throughout treatment. Another im- portant consideration in this case was the chronic hepatitis C infection; again, with the input of several consulting services, we decided to defer treatment of the hepatitis C until antimyco- bacterial therapy was completed due to concern for hepatotox- icity and other side effects. Treatment of M. malmoense consists of a rifamycin and eth- ambutol, with the option of isoniazid [3]. Clarithromycin and ciprofloxacin have been studied as adjunctive therapies and have thus far demonstrated no benefit and potential extra side Figure 1. (A) Demonstrates right upper lobe cavitary lesion associated with initial effects [5]. An important caveat to current guidelines is that Mycobacterium malmoense infection in tissue previously known to be normal. (B) they are explicitly for HIV-negative patients; no studies have Shows the same right upper lobe cavitary lesion following mycobacterial therapy been performed in HIV-positive individuals. with interval development of aspergilloma. Pneumothorax and pleural effusion also seen. (C) Displays interval chest tube placement with bronchopleural fistula. Antibiotic resistance is an important concern given the Subcutaneous emphysema from chest tube also observed. prolonged course of treatment and slow progression of M.  malmoense infection. Drug susceptibility testing (DST)— However, as all mycobacterial cultures from this admission remains an area of ongoing research in M. malmoense infection, and during the previous nine months were negative, antimyco- with the potential to help guide appropriate antibiotic selection bacterial agents were discontinued and antifungal therapy was early in treatment. Within the DST literature, a distinction is changed to voriconazole. made between rapid-growing organisms (≤7  days for culture e b Th ronchopleural fistula ultimately failed to close with con- positivity) and slow-growing organisms (>7  days for culture servative measures. He underwent a right upper lobectomy and positivity). Time to culture positivity for M. malmoense in liq- right chest reconstruction with latissimus and serrated anterior uid medium with a standard protocol optimized to detect atyp- muscle flaps. He recovered slowly from these interventions and ical mycobacterial isolates is ~15 days [6]. er Th e is a clear role required long-term voriconazole treatment. for DST in M. tuberculosis; however, DST in NTM remains an area of active research [3–5]. Current guidelines recommend DISCUSSION DST for selected rapid-growing species, including M. abscessus, M. chelonae, and M. fortuitum [3]. However, in many NTM spe- This case describes a rare mycobacterial infection cies, especially slow-growing NTM (including M. malmoense), (M. Malmoense) and subsequent cavitary lesion in an immuno- a significant divergence between phenotype in vitro and in vivo compromised host. The infection was clinically significant per has been appreciated [3, 7]. A  recent meta-analysis showed American Thoracic Society guidelines, based on imaging and 2 • OFID • BRIEF REPORT Downloaded from https://academic.oup.com/ofid/article-abstract/5/2/ofy023/4823228 by Ed 'DeepDyve' Gillespie user on 16 March 2018 a poor treatment response rate, at 54%, with a high all-cause and its clinical similarity to tuberculosis, especially as appro- mortality rate (34%–54%) in patients treated for M. Malmoense priate diagnosis is essential for proper treatment. [8]. The difficulty in determining susceptibility in NTM stems Acknowledgments from the lack of a universally accepted laboratory protocol that Financial support. e Th authors volunteered their time and received no is optimized for slow-growing organisms. For this reason, a funding for work on this manuscript. recent study of M. malmoense did not include DST in its study Potential coni fl cts of interest. e a Th uthors have no conflicts to declare. All authors have submitted the ICMJE Form for Disclosure of Potential design. In our case, DST was not performed but would have Conflicts of Interest. Conflicts that the editors consider relevant to the con- been considered had the patient not improved clinically. Our tent of the manuscript have been disclosed. patient received rifampin, ethambutol, and azithromycin for a total of 24  months (negative sputum cultures for >9  months); References 1. Warren NG, Body BA, Silcox VA, Matthews JH. Pulmonary disease due to in this individual, antimycobacterial therapy was successful, as Mycobacterium malmoense. J Clin Microbiol 1984; 20:245–7. there was no evidence of mycobacterial species on subsequent 2. Hoefsloot W, Boeree MJ, van Nieuwkoop C, et  al. No human transmission of Mycobacterium malmoense in a perfect storm setting. Eur Respir J 2012; sputum samples or from excised lung tissue. 40:1576–8. In this case, the patient had long-standing HIV infection 3. Griffith DE, Aksamit T, Brown-Elliott BA, et  al; ATS Mycobacterial Diseases that was well controlled on antiretroviral medications. Little Subcommittee; American Thoracic Society; Infectious Diseases Society of America. An official ATS/IDSA statement: diagnosis, treatment, and prevention is known about what role, if any, HIV infection plays in the of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007; pathogenesis of M.  malmoense infection. Despite the preva- 175:367–416. 4. Murray MP, Laurenson IF, Hill AT. Outcomes of a standardized triple-drug reg- lence of M.  malmoense in northern Europe, few cases of HIV imen for the treatment of nontuberculous mycobacterial pulmonary infection. and M.  malmoense co-infections have been reported; several Clin Infect Dis 2008; 47:222–4. 5. Jenkins PA, Campbell IA, Banks J, et  al. Clarithromycin vs ciprofloxacin as case reports published in the 1990s described patients with ful- adjuncts to rifampicin and ethambutol in treating opportunist mycobacterial lung minant HIV infection (CD4 counts <100) and co-infection with diseases and an assessment of Mycobacterium vaccae immunotherapy. Thorax 2008; 63:627–34. M. malmoense [9–12]. In each of these cases (6 total), M. mal- 6. Hoffner SE, Henriques B, Petrini B, Källenius G. Mycobacterium malmoense: an moense was identified on culture, but all had other identified easily missed pathogen. J Clin Microbiol 1991; 29:2673–4. infections. Two of the 6 improved with treatment. Only 1 pa- 7. Research Committee of the British Thoracic Society. First randomised trial of treatments for pulmonary disease caused by M avium intracellulare, M mal- tient had pulmonary symptoms and met criteria for clinically moense, and M xenopi in HIV negative patients: rifampicin, ethambutol and iso- significant infection. With the advent of antiretroviral med- niazid versus rifampicin and ethambutol. Thorax 2001; 56: 167–72. 8. Diel R, Ringshausen FC, Richter E, et al. Microbiological and clinical outcomes of ications, there has only been 1 report of an HIV-infected pa- treating non-MAC NTM pulmonary disease: a systematic review and meta-anal- tient with concomitant M.  malmoense infection (disseminated ysis. Chest 2017; 152:120–42. 9. Zaugg M, Salfinger M, Opravil M, Lüthy R. Extrapulmonary and disseminated cutaneous disease) [13]; this patient had a CD4 count of 477 infections due to Mycobacterium malmoense: case report and review. Clin Infect with antiviral therapy and responded well to treatment. Clearly, Dis 1993; 16:540–9. 10. Willocks L, Leen CL, Brettle RP, et al. Isolation of Mycobacterium malmoense from further study is needed to determine the effect of HIV and HIV-positive patients. J Infect 1993; 26:345–6. M. malmoense co-infection on disease pathogenesis. 11. Chocarra A, Gonzalez Lopez A, Breznes MF, et al. Disseminated infection due to M.  malmoense remains a rare infection in the United Mycobacterium malmoense in a patient infected with human immunodeficiency virus. Clin Infect Dis 1994; 19:203–4. States, despite its increasing prevalence in northern Europe. 12. Claydon EJ, Coker RJ, Harris JR. Mycobacterium malmoense infection in HIV Determining the true prevalence of M.  malmoense infections positive patients. J Infect 1991; 23:191–4. 13. Pigem R, Cairó M, Martínez-Lacasa X, et  al. Disseminated infection with cuta- in the United States has been difficult. In 1979 and 1980, 2 and neous involvement caused by Mycobacterium malmoense in an immunocompro- 12 cases, respectively, were reported in the United States [14]. mised patient. J Am Acad Dermatol 2013; 69:e192–3. 14. Good RC; for the Centers for Disease Control. Isolation of nontuberculous myco- Another survey demonstrated 11 in 1992, 35 in 1993, and 27 in bacteria in the United States, 1979. J Infect Dis 1980; 142:779–83. 1994 [15]. A recent study reviewed 1865 patients identified with 15. Buchholz UT, McNeil MM, Keyes LE, Good RC. Mycobacterium malmoense infections in the United States, January 1993 through June 1995. Clin Infect Dis nontuberculous mycobacterium identified 1 M.  malmoense 1998; 27:551–8. isolate [16]. Since these earlier surveys, the prevalence of pul- 16. Prevots DR, Shaw PA, Strickland D, et al. Nontuberculous mycobacterial lung dis- monary NTM has exploded, increasing by 135% from 1997 to ease prevalence at four integrated health care delivery systems. Am J Respir Crit Care Med 2010; 182:970–6. 2007 [17]. This has been primarily attributed to M.  avium in- 17. Adjemian J, Olivier KN, Seitz AE, et al. Prevalence of nontuberculous mycobacte- fection; however, there has been no effort to quantify rates of rial lung disease in U.S. Medicare beneficiaries. Am J Respir Crit Care Med 2012; 185:881–6. M.  malmoense inflection. For example, in Canada, 18. Al Houqani M, Jamieson F, Chedore P, et  al. Isolation prevalence of pulmo- M. malmoense had not been previously reported, and no isolates nary nontuberculous mycobacteria in Ontario in 2007. Can Respir J 2011; 18:19–24. were found in 2400 samples positive for NTM over 10  years 19. C owan CD, Hawboldt JJ, Bader M. Pulmonar y infection due to Mycobacterium [18]; however, 3 cases of M.  malmoense have recently been malmoense in a patient with Crohn disease. Can J Hosp Pharm 2009; 62:496–9. reported [19, 20]. These findings suggest that M.  malmoense 20. McCrossin C, Mailman T. First Canadian reports of cervical adenitis due to infection is either increasing and/or it is being identified more Mycobacterium malmoense and a 10-year review of nontuberculous Mycobacterial frequently. In either case, practitioners should be aware of NTM adenitis. Can J Infect Dis Med Microbiol 2006; 17:123–7. BRIEF REPORT • OFID • 3 Downloaded from https://academic.oup.com/ofid/article-abstract/5/2/ofy023/4823228 by Ed 'DeepDyve' Gillespie user on 16 March 2018 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Open Forum Infectious Diseases Oxford University Press

Pulmonary Cavity From Mycobacterium malmoense in an HIV-Infected Patient: Complicated by Bronchopleural Fistula

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Abstract

Open Forum Infectious Diseases BRIEF REPORT CASE REPORT Pulmonary Cavity From The patient is a 63-year-old African American male with med- Mycobacterium malmoense in an ical history significant for long-standing HIV infection (most HIV-Infected Patient: Complicated by recently treated with raltegravir, emtricitabine, and tenofovir; Bronchopleural Fistula CD4 >600 and viral load undetectable), hepatitis C, and cirrho- sis. He presented with a 15–20-lb weight loss, nonproductive Eric Abston and Harrison Farber cough, and right-sided chest pain; he denied fever, chills, or Division of Pulmonary, Allergy, Sleep, and Critical Care Medicine, Boston University School of Medicine, Boston, Massachusetts night sweats. The remainder of review of systems was unre- markable. Chest imaging, including computed tomography We present a case of M. malmoense and HIV co-infection com- (CT), demonstrated a new 4.8-cm right upper lobe cavitary plicated by aspergilloma leading to bronchopleural s fi tula with lesion with multiple nodular cavitary foci as well as left-sided intractable pneumothorax and pleural aspergillosis, ultim- pulmonary nodules  (Figure  1). Samples from bronchoscopy ately requiring surgical intervention. Treatment guidelines for with broncheoalveolar lavage (BAL) and postbronchoscopy M. malmoense are reviewed, literature regarding M. malmoense sputum were all positive on acid fast bacilli (AFB) stain. Nucleic and HIV co-infection is reviewed, and the epidemiology of acid amplification testing (GeneXpert) on BAL and sputum M. malmoense in North America is discussed. samples was negative for Mycobacterium tuberculosis (MTB). Keywords. bronchopleural fistula; HIV; Mycobacterium Fungal cultures and serum galactomannin were negative. Given malmoense. the high negative predictive value of polymerase chain reaction for MTB infection on an AFB-positive sputum sample, MTB infection was thought to be unlikely. The patient was treated for Mycobacterium malmoense is an atypical mycobacterial nontuberculosis mycobacterium (NTM). Due to concerns for strain first discovered in Sweden in 1954. The incidence of drug interactions with his antiretroviral medication, a regimen M. malmoense infection has been rising since the 1980s; yet, of rifabutin, azithromycin, and ethambutol was selected after outside of northern Europe, infection is extremely rare. The discussions with several consulting services. This regimen was first case of pulmonary M.  malmoense infection in North initially complicated by gastric intolerance; however, this was America was reported in 1984 [1]. Most patients who de- abrogated by stepwise addition of these medications. velop M.  malmoense infections have structural lung disease Samples were sent to Charles River Laboratories (Newark, DE) that compromises immunity, such as chronic obstructive for culture and microbial identification via DNA sequencing. pulmonary disease (COPD). Infection is associated with All sputum and BAL samples were identified as Mycobacteria contaminated water or soil; no interpersonal communi- malmoense. Based on this, the rifabutin was changed to ri- cation of infection has been reported [2]. Disseminated fampin, and the other medications were continued (rifampin disease is rare and has only been observed in severely im- 600 mg, ethambutol 800 mg, and azithromycin 500 mg daily). munocompromised patients, such as those with AIDS. Due Hepatitis C treatment was deferred due to concern for hepato- to the progressive nature of the infection, timely diagnosis toxicity and side effects. Aer 15  ft months of therapy, sputum and appropriate management of M. malmoense infections are cultures were continually negative for M. malmoense; however, essential. However, because the clinical presentation is very the cavity persisted on chest imaging. similar to that of tuberculosis, patients can be easily misdi- Twenty-four months aer ft initial presentation, the patient agnosed and improperly treated. was admitted with a 4-day history of progressive dyspnea and nonproductive cough. Chest CT then demonstrated a right- sided hydropneumothorax. Placement of a chest tube yielded 400 cc of purulent fluid. Aer 2 w ft eeks, the air leak persisted; repeat chest CT demonstrated a tract fistula between the cavi- Received 21 June 2017; editorial decision 16 January 2018; accepted 17 January 2018. tary lesion and pleura. Pleural fluid from his chest tube grew Correspondence: E.  Abston, MD, PhD, 72 E.  Concord St, R-304, Boston, MA 02118 (eric.abston@bmc.org). Aspergillus fumigatus, as did bronchial washings obtained from Open Forum Infectious Diseases repeat bronchoscopy. Antifungal coverage with amphotericin Published by Oxford University Press on behalf of Infectious Diseases Society of America 2018. was begun initially because of concern for pleural aspergillosis This work is written by (a) US Government employee(s) and is in the public domain in the US. DOI: 10.1093/ofid/ofy023 and potential interaction with the antimycobacterial agents. BRIEF REPORT • OFID • 1 Downloaded from https://academic.oup.com/ofid/article-abstract/5/2/ofy023/4823228 by Ed 'DeepDyve' Gillespie user on 16 March 2018 positive culture obtained via bronchoscopy [3]. He responded well to therapy, only to develop a secondary fungal infection, which spread from his cavitary lesion to his pleura via a fis- tula that was responsible for a chronic pneumothorax. Despite several attempts to mitigate his condition with endobronchial valves and percutaneous plugging, definitive treatment ultim- ately required lobectomy and chest wall reconstruction. In this case, the patient had several concomitant infections that required simultaneous treatment and careful adjustment of treatment regimens. On initial presentation, we considered standard HRZE therapy to treat for active tuberculosis; how- ever, we instead chose rifabutin, azithromycin, and ethambutol as a second-line therapy to avoid drug interactions with his antiviral medications. Once cultures revealed M.  malmoense, we switched from rifabutin to rifampin, per British Thoracic Society guidelines [4]. The patient had been on his current HIV therapy (raltegravir, emtricitabine, and tenofovir) for years with good viral suppression (CD4  >600 and an undetectable viral load). Because rifampin increases the hepatic metabolism of raltegrivir, we increased the raltegrivir from 400 mg to 800 mg twice daily; this was well tolerated by the patient and main- tained viral suppression throughout treatment. Another im- portant consideration in this case was the chronic hepatitis C infection; again, with the input of several consulting services, we decided to defer treatment of the hepatitis C until antimyco- bacterial therapy was completed due to concern for hepatotox- icity and other side effects. Treatment of M. malmoense consists of a rifamycin and eth- ambutol, with the option of isoniazid [3]. Clarithromycin and ciprofloxacin have been studied as adjunctive therapies and have thus far demonstrated no benefit and potential extra side Figure 1. (A) Demonstrates right upper lobe cavitary lesion associated with initial effects [5]. An important caveat to current guidelines is that Mycobacterium malmoense infection in tissue previously known to be normal. (B) they are explicitly for HIV-negative patients; no studies have Shows the same right upper lobe cavitary lesion following mycobacterial therapy been performed in HIV-positive individuals. with interval development of aspergilloma. Pneumothorax and pleural effusion also seen. (C) Displays interval chest tube placement with bronchopleural fistula. Antibiotic resistance is an important concern given the Subcutaneous emphysema from chest tube also observed. prolonged course of treatment and slow progression of M.  malmoense infection. Drug susceptibility testing (DST)— However, as all mycobacterial cultures from this admission remains an area of ongoing research in M. malmoense infection, and during the previous nine months were negative, antimyco- with the potential to help guide appropriate antibiotic selection bacterial agents were discontinued and antifungal therapy was early in treatment. Within the DST literature, a distinction is changed to voriconazole. made between rapid-growing organisms (≤7  days for culture e b Th ronchopleural fistula ultimately failed to close with con- positivity) and slow-growing organisms (>7  days for culture servative measures. He underwent a right upper lobectomy and positivity). Time to culture positivity for M. malmoense in liq- right chest reconstruction with latissimus and serrated anterior uid medium with a standard protocol optimized to detect atyp- muscle flaps. He recovered slowly from these interventions and ical mycobacterial isolates is ~15 days [6]. er Th e is a clear role required long-term voriconazole treatment. for DST in M. tuberculosis; however, DST in NTM remains an area of active research [3–5]. Current guidelines recommend DISCUSSION DST for selected rapid-growing species, including M. abscessus, M. chelonae, and M. fortuitum [3]. However, in many NTM spe- This case describes a rare mycobacterial infection cies, especially slow-growing NTM (including M. malmoense), (M. Malmoense) and subsequent cavitary lesion in an immuno- a significant divergence between phenotype in vitro and in vivo compromised host. The infection was clinically significant per has been appreciated [3, 7]. A  recent meta-analysis showed American Thoracic Society guidelines, based on imaging and 2 • OFID • BRIEF REPORT Downloaded from https://academic.oup.com/ofid/article-abstract/5/2/ofy023/4823228 by Ed 'DeepDyve' Gillespie user on 16 March 2018 a poor treatment response rate, at 54%, with a high all-cause and its clinical similarity to tuberculosis, especially as appro- mortality rate (34%–54%) in patients treated for M. Malmoense priate diagnosis is essential for proper treatment. [8]. The difficulty in determining susceptibility in NTM stems Acknowledgments from the lack of a universally accepted laboratory protocol that Financial support. e Th authors volunteered their time and received no is optimized for slow-growing organisms. For this reason, a funding for work on this manuscript. recent study of M. malmoense did not include DST in its study Potential coni fl cts of interest. e a Th uthors have no conflicts to declare. All authors have submitted the ICMJE Form for Disclosure of Potential design. In our case, DST was not performed but would have Conflicts of Interest. Conflicts that the editors consider relevant to the con- been considered had the patient not improved clinically. Our tent of the manuscript have been disclosed. patient received rifampin, ethambutol, and azithromycin for a total of 24  months (negative sputum cultures for >9  months); References 1. Warren NG, Body BA, Silcox VA, Matthews JH. Pulmonary disease due to in this individual, antimycobacterial therapy was successful, as Mycobacterium malmoense. J Clin Microbiol 1984; 20:245–7. there was no evidence of mycobacterial species on subsequent 2. Hoefsloot W, Boeree MJ, van Nieuwkoop C, et  al. No human transmission of Mycobacterium malmoense in a perfect storm setting. Eur Respir J 2012; sputum samples or from excised lung tissue. 40:1576–8. In this case, the patient had long-standing HIV infection 3. Griffith DE, Aksamit T, Brown-Elliott BA, et  al; ATS Mycobacterial Diseases that was well controlled on antiretroviral medications. Little Subcommittee; American Thoracic Society; Infectious Diseases Society of America. An official ATS/IDSA statement: diagnosis, treatment, and prevention is known about what role, if any, HIV infection plays in the of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007; pathogenesis of M.  malmoense infection. Despite the preva- 175:367–416. 4. Murray MP, Laurenson IF, Hill AT. Outcomes of a standardized triple-drug reg- lence of M.  malmoense in northern Europe, few cases of HIV imen for the treatment of nontuberculous mycobacterial pulmonary infection. and M.  malmoense co-infections have been reported; several Clin Infect Dis 2008; 47:222–4. 5. Jenkins PA, Campbell IA, Banks J, et  al. Clarithromycin vs ciprofloxacin as case reports published in the 1990s described patients with ful- adjuncts to rifampicin and ethambutol in treating opportunist mycobacterial lung minant HIV infection (CD4 counts <100) and co-infection with diseases and an assessment of Mycobacterium vaccae immunotherapy. Thorax 2008; 63:627–34. M. malmoense [9–12]. In each of these cases (6 total), M. mal- 6. Hoffner SE, Henriques B, Petrini B, Källenius G. Mycobacterium malmoense: an moense was identified on culture, but all had other identified easily missed pathogen. J Clin Microbiol 1991; 29:2673–4. infections. Two of the 6 improved with treatment. Only 1 pa- 7. Research Committee of the British Thoracic Society. First randomised trial of treatments for pulmonary disease caused by M avium intracellulare, M mal- tient had pulmonary symptoms and met criteria for clinically moense, and M xenopi in HIV negative patients: rifampicin, ethambutol and iso- significant infection. With the advent of antiretroviral med- niazid versus rifampicin and ethambutol. Thorax 2001; 56: 167–72. 8. Diel R, Ringshausen FC, Richter E, et al. Microbiological and clinical outcomes of ications, there has only been 1 report of an HIV-infected pa- treating non-MAC NTM pulmonary disease: a systematic review and meta-anal- tient with concomitant M.  malmoense infection (disseminated ysis. Chest 2017; 152:120–42. 9. Zaugg M, Salfinger M, Opravil M, Lüthy R. Extrapulmonary and disseminated cutaneous disease) [13]; this patient had a CD4 count of 477 infections due to Mycobacterium malmoense: case report and review. Clin Infect with antiviral therapy and responded well to treatment. Clearly, Dis 1993; 16:540–9. 10. Willocks L, Leen CL, Brettle RP, et al. Isolation of Mycobacterium malmoense from further study is needed to determine the effect of HIV and HIV-positive patients. J Infect 1993; 26:345–6. M. malmoense co-infection on disease pathogenesis. 11. Chocarra A, Gonzalez Lopez A, Breznes MF, et al. Disseminated infection due to M.  malmoense remains a rare infection in the United Mycobacterium malmoense in a patient infected with human immunodeficiency virus. Clin Infect Dis 1994; 19:203–4. States, despite its increasing prevalence in northern Europe. 12. Claydon EJ, Coker RJ, Harris JR. Mycobacterium malmoense infection in HIV Determining the true prevalence of M.  malmoense infections positive patients. J Infect 1991; 23:191–4. 13. Pigem R, Cairó M, Martínez-Lacasa X, et  al. Disseminated infection with cuta- in the United States has been difficult. In 1979 and 1980, 2 and neous involvement caused by Mycobacterium malmoense in an immunocompro- 12 cases, respectively, were reported in the United States [14]. mised patient. J Am Acad Dermatol 2013; 69:e192–3. 14. Good RC; for the Centers for Disease Control. Isolation of nontuberculous myco- Another survey demonstrated 11 in 1992, 35 in 1993, and 27 in bacteria in the United States, 1979. J Infect Dis 1980; 142:779–83. 1994 [15]. A recent study reviewed 1865 patients identified with 15. Buchholz UT, McNeil MM, Keyes LE, Good RC. Mycobacterium malmoense infections in the United States, January 1993 through June 1995. Clin Infect Dis nontuberculous mycobacterium identified 1 M.  malmoense 1998; 27:551–8. isolate [16]. Since these earlier surveys, the prevalence of pul- 16. Prevots DR, Shaw PA, Strickland D, et al. Nontuberculous mycobacterial lung dis- monary NTM has exploded, increasing by 135% from 1997 to ease prevalence at four integrated health care delivery systems. Am J Respir Crit Care Med 2010; 182:970–6. 2007 [17]. This has been primarily attributed to M.  avium in- 17. Adjemian J, Olivier KN, Seitz AE, et al. Prevalence of nontuberculous mycobacte- fection; however, there has been no effort to quantify rates of rial lung disease in U.S. Medicare beneficiaries. Am J Respir Crit Care Med 2012; 185:881–6. M.  malmoense inflection. For example, in Canada, 18. Al Houqani M, Jamieson F, Chedore P, et  al. Isolation prevalence of pulmo- M. malmoense had not been previously reported, and no isolates nary nontuberculous mycobacteria in Ontario in 2007. Can Respir J 2011; 18:19–24. were found in 2400 samples positive for NTM over 10  years 19. C owan CD, Hawboldt JJ, Bader M. Pulmonar y infection due to Mycobacterium [18]; however, 3 cases of M.  malmoense have recently been malmoense in a patient with Crohn disease. Can J Hosp Pharm 2009; 62:496–9. reported [19, 20]. These findings suggest that M.  malmoense 20. McCrossin C, Mailman T. First Canadian reports of cervical adenitis due to infection is either increasing and/or it is being identified more Mycobacterium malmoense and a 10-year review of nontuberculous Mycobacterial frequently. In either case, practitioners should be aware of NTM adenitis. Can J Infect Dis Med Microbiol 2006; 17:123–7. BRIEF REPORT • OFID • 3 Downloaded from https://academic.oup.com/ofid/article-abstract/5/2/ofy023/4823228 by Ed 'DeepDyve' Gillespie user on 16 March 2018

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Open Forum Infectious DiseasesOxford University Press

Published: Feb 1, 2018

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