Nontuberculous Mycobacteria in Critical Care

Review Article

Austin Tuberc Res Treat. 2018; 3(1): 1010.

Nontuberculous Mycobacteria in Critical Care

Kassiri N and Reza Hashemian SM*

Clinical Tuberculosis and Epidemiology Research Center, Shahid Beheshti University of Medical Sciences, Iran

*Corresponding author: Seyed Mohammad Reza Hashemian, Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran

Received: January 04, 2018; Accepted: February 15, 2018; Published: February 23, 2018

Abstract

In critically ill patients infections is a common problem and their management is difficult because of some reasons such as delayed diagnosis, difficulties in recognizing causative microorganisms, and antibiotic-resistant strains. In this review article we briefly discussed Non Tuberculosis Mycobacterium (NTM) infections which have worldwide increasing in incidence and can lead to respiratory failure. Patients with NTM infection who experience lung disease are at high risk of respiratory failure and acute respiratory distress syndrome. Brief discussion about infections in burn and immune compromised patients is included.

Keywords: Non tuberculosis mycobacterium; Lung disease; NTM infection; Mycobacterium avium complex

Introduction

Recent studies inpatients, who are hospitalized in Intensive Care Unit (ICU), show that 51% of them have infections, and 71% are given treatment. Bacterial and some fungal infections, as opportunistic microorganism are the primary concern. Hospitalizing in ICU is associated with increasing in mortality rate and excess expenses. Pharmacokinetics, absorption, distribution, metabolism, and excretion of drugs experience many changes in critical illness [1].

NTM, are a group of mycobacteria which is not a causative organism of tuberculosis or leprosy, so they called as Mycobacteria Other Than Tuberculosis (MOTT). NTM bacteria are a family of small, rod-shaped bacilli which have more than 150 species. Atypical mycobacteria have different favor in choosing their environment and are identified as environmental mycobacteria [2,3]. NTM are the causative organisms in pulmonary diseases like tuberculosis, lymphadenitis, skin disease, or disseminated disease. Major clinical manifestations of NTM Infections are presented in Table 1 [4]. In 1950s, they were accepted as human pathogens [5]. Unlike tuberculosis and leprosy, spreading NTM infections from one person to another person is rare. Environmental exposure is the major way of contagion [6,7]. The risk of getting infected by a particular species of NTM is dependent on pathogenicity of microorganism, the method of exposure and frequency of exposure [8]. In the last decade, (NTM) infections have worldwide increasing in incidence and mortality [9,10]. The reasons for this increase are not obvious. But increasing incidence of acquired immune compromised syndrome, cancer, diabetes mellitus, chronic lung injuries, and continues supportive ventilation could be causative [11,12].

Table 1: Major clinical manifestations of NTM Infections [4].





  

    
Syndrome  

    
Frequent Causes  

    
Uncommon Causes  

  

  

    
Lung disease  

    
MAC, Mycobacterium kansasii, Mycobacteriumabscessus  

    
Mycobacterium fortuitum, Mycobacterium malmoense, Mycobacterium szulgai, Mycobacterium scrofulaceum, Mycobacterium smegmatis, Mycobacterium simiae, Mycobacterium xenopi Rare:  

      
Mycobacterium celatum, Mycobacterium asiaticum, Mycobacterium shimodei  

  

  

    
Cervical and    lymphadenitis  

    
MAC  

    
Mycobacterium scrofulaceum, Mycobacterium malmoense, Mycobacterium abscessus, Mycobacterium fortuitum  

  

  

    
soft tissue    manifestation  

    
Mycobacterium fortuitum, Mycobacterium chelonae, Mycobacterium abscessus, Mycobacterium marinum  

    
Mycobacterium haemophilum, Mycobacterium kansasi, Mycobacterium smegmatis, Mycobacterium ulcerans  

  

  

    
Skeletal (bones,    joints, tendons) disease  

    
Mycobacterium marinum, MAC,Mycobacterium kansasii, Mycobacterium fortuitum group, Mycobacterium abscessus, Mycobacterium chelonae  

    
Mycobacterium haemophilum, Mycobacterium scrofulaceum, Mycobacterium smegmatis, Mycobacterium terrae-nonchromogenicum complex  

  

  

    
Catheter-related    infections  

    
Mycobacteriumfortuitum, Mycobacterium abscessus, Mycobacterium chelonae  

    
Mycobacterium mucogenicum  

  

  

    
Disseminated    infection  

    
Patient with HIV    infection: Mycobacterium    avium, Mycobacterium    kansasii  

    
Mycobacterium haemophilum, Mycobacterium genavense, Mycobacterium xenopi, Mycobacterium marinum, Mycobacterium simiae, Mycobacterium intracellulare, Mycobacterium scrofulaceum, Mycobacterium fortuitum  

  

  

    
Patient without HIV    infection: Mycobacterium    abscessus, Mycobacterium chelonae  

    
Mycobacterium marinum, Mycobacterium kansasii, Mycobacterium haemophilum, Mycobacterium fortuitum  

  










Table 1: Major clinical manifestations of NTM Infections [4].

Non Tuberculosis Mycobacterium Infection

A retrospective study in medical center of Taiwan from January 1999 to June 2007 was planned to evaluate medical ICU patients whose respiratory specimens were positive for NTM. They defined tree group of patients, one group with NTM pulmonary infection, the other with NTM colonization and a control group who have culture negative samples for mycobacteria. Clinical sign, symptoms and outcomes were compared. Their finally result was that, increment in mortality rate in patients who have NTM pulmonary. Suitable treatment against NTM would followed by better result [13].

Pulmonary Tuberculosis (TB) needs invasive workups or treatment, but NTM infection with minimal clinical manifestation and stable radiographic feature requires closely observation except patients who are immune compromised so appropriate method for diagnosing is necessary. Molecular gene analysis including sequencing of16S rRNA and hsp65 is recommended to be more accurate than conventional biochemical methods [14]. When the clinicians, according to patient condition, decide to initiate treatment against NTM infection, there are some considerable points such as side effects of drugs and high relapse rate [8]. So 12 months of culture negativity would be one of the noticeable goals in their management. It is also important that sputum sampling is required every 1-2 months. Macrolides (clarithromycin or azithromycin) have major role in management of Mycobacterium avium-intracellular lung disease. The standard elective regimen prolongs 18-24 months. The combination of rifamycin (rifampicinor mycobutin), myambutol and a macrolide is suggested in this regimen. Amino glycosides (amikacin or streptomycin) could be adjoining on regimen in severe cases. They usually added for the first 2 or 3 months of treatment period. The optional regimen recommended to cure mycobacterium kansasii infection is similar to anti TB drugs except for pyrazinamide [15].

Mortality among burn patients is mainly because of infections especially after recovery from the initial burn injury. Gram-positive cocci like Staphylococcus aureus, gram negative bacilli such as Pseudomonas aeruginosa, less commonly fungi and viruses are known as causative organisms. Risk factors such as loosing skin integrity, immune compromised condition, inhalation damage, and continuity in having vascular catheters would higher the risk of developing NTM infections. On the whole, NTM infections in burn patients appear to be rare so routine screening or exam for mycobacteria is not required. However, it is noticeable that in patients who are failing to clinically improvement despite suitable recognition and management of typical bacterial and fungal pathogens accompanied with burns infections with NTM should be in the differential diagnosis [16].

In a study, HIV-infected patients who have disseminated NTM infection between 2000 and 2013 were analyzed. Culture from several sterile specimens of blood and mesenteric lymph node caught. Mycobacterium Avium Complex (MAC) was the most frequent pathogen which is recognized in this study. They concluded that in patients who have acquired immune deficiency syndrome with low CD4 level have high mortality rate in disseminated NTM infection. Low level of CD4 is counted as a risk factor of this condition [17].

Increased Respiratory Failure has Association with NTM Infection

Exchange between blood gases including O2 and CO2 fulfill the need of metabolism. Any failure in this process result in hypoxemia, in the presence or absence of hypercarbia and finally Respiratory Failure (RF) happens. Acute Respiratory Failure (ARF) defines when these events occurred during several minutes to hours. In Chronic Respiratory Failure (CRF) happening events prolong many days [16,18]. Acute exacerbation of CRF can lead to a condition which is called ARF on CRF [19]. Measuring arterial blood gases including partial pressure of O2(PaO2) and partial pressure of CO2(PaCO2) is the way to diagnosis RF.RF is defined in a patient respiring at sea level and at rest, when PaO2 is lesser than 60 mmHg or PaCO2 is more than 50 mmHg [18,20,21].

RF can cause patients to hospitalize in intensive care unit and make them dependent to mechanical ventilation. Tuberculosis, cardiogenic or non-cardiogenic pulmonary edema, pulmonary hemorrhage, pneumonia, diabetes, drug toxicity, neuromuscular disorders, chest wall deformities, Chronic Obstructive Pulmonary Disease (COPD), emphysema, refractory asthma, End-Stage Renal Disease (ESRD), malnutrition and acquired immune deficiency syndrome are several etiologies of RF [22-25]. In several studies the rule of RF etiologies as predisposing factors of NTM infection is mentioned [26-28]. A nationwide cohort study was designed to estimate the chance of developing RF in patients who have NTM infection, in comparison with the ordinary people. In this study they followed up a great group of patients with NTM infection for 4 years. They conclude that these patients have a greater risk to develop RF in comparison with the general population, especially in the first 6 months after diagnosis. Another finding was that, patients with other comorbidities particularly COPD and diabetes are in higher risk for developing RF. Mycobacterium avium complex infection is known as a great risk factor for respiratory failure. Finally they suggest that in order to prevent RF, an early diagnosis of NTM disease is necessary [29]. Recommended criteria suggested for diagnosing NTM lung disease are present in Table 2.

Table 2: Guidelines for diagnosing NTM pulmonary disease [29].





  

    
Clinical and radiologic features indicative of mycobacterial    disease  

  

  

    
Positive Acid Fast Bacilli smear and/or moderate to heavy    growth on medium in two clinical specimens (e.g., sputum or BAL)  

  

  

    
Absence of other pathogens (e.g., tuberculosis, aspergillosis)  

  

  

    
Underlying host conditions such as alcoholism,    immunosuppressive conditions, chronic lung disease, cystic fibrosis, lung    cancer  

  

  

    
Failure of clearance of the NTM in sputum within 2 weeks after    initiation of anti-mycobacterial therapy  

  

  

    
When sputum evaluation in cavitary or non cavitary disease is    negative:  

      
1) Trans bronchial or open lung biopsy has histopathologic    features of mycobacterial disease and NTM grows on culture  

      
2) Trans bronchial or open lung biopsy does not grow the    organism but has histopathologic features of mycobacterial disease and other    probable causes for granulomatous disease have been ruled out.  

  










Table 2: Guidelines for diagnosing NTM pulmonary disease [29].

Acute Respiratory Distress Syndrome and NTM Infection

Acute Respiratory Distress Syndrome (ARDS) is a medical syndrome identified with generalized lung inflammation, severe dyspnea and hypoxia [30]. Diffuse lung injury is the main reason for ARDS. Toxic inhalation, pneumonia are some examples of direct injuries. For indirect damages sepsis could be a good example [31]. The diagnosis of ARDS is based on Berlin ARDS Definition which is presented in Table 3.

Table 3: The Berlin definition of ARDS [31].





  

    
Timing  

    
Initiate of within 7 days of    insult, or progression of respiratory symptoms  

  

  

    
Chest imaging  

    
Bilateral chest opacities on    chest radiograph or computed tomography which cannot justified by other    pathologies.  

  

  

    
Origin of edema  

    
The origin of edema is not    because of cardiac failure or volume overload.  

  

  

    
Oxygenation  

    
Mild : 200 mmHg < PaO2 /FIO2 <300 mmHg with PEEP or    CPAP >5 cmH2O  

      
Moderate: 100 mmHg < PaO2 /FIO2 <200 mmHg with PEEP >5    cmH2O  

      
Severe: PaO2 /FIO2 <100 mmHg with PEEP >5    cmH2O  

  










Table 3: The Berlin definition of ARDS [31].

The Large Observation a cohort study designed in 50 countries from 5 continents to evaluate patients experience mechanical ventilation against non invasive ventilation. The samples gained from 459 medical ICUs. They concluded that this syndrome have association with a great mortality rate and appeared to be under identified, under managed and needing advancement in ARDS patients management [32].

ARDS caused by bilateral pneumonia or sepsis due to NTM infection is not common. Patients in these cases need intensive medical management and respiratory support, so recognizing these organisms as a cause of RF is significant [33-35].

Conclusion

NTM are opportunistic pathogens with increasing incidence in recent years. Patients with NTM infection who experience lung disease are at high risk of respiratory failure. In critically ill patients infections is a common problem and their management is difficult because of some reasons such as delayed diagnosis, difficulties in recognizing causative microorganisms, and antibiotic-resistant strains. Newer antimicrobial combinations and clinical trials are recommended.

References

  1. Martin SJ, Yost RJ. Infectious diseases in the critically ill patients. J Pharm Pract. 2011; 24: 35-43.
  2. Cassidy PM, Hedberg K, Saulson A, McNelly E, Winthrop KL. Nontuberculous mycobacterial disease prevalence and risk factors: a changing epidemiology. Clin Infect Dis. 2009; 49: e124-129.
  3. Falkinham JO 3rd. Surrounded by mycobacteria: nontuberculous mycobacteria in the human environment. J Appl Microbiol. 2009; 107: 356-367.
  4. Daley CL, Griffith DE. Pulmonary non-tuberculous mycobacterial infections. Int J Tuberc Lung. 2010; 14: 665-671.
  5. Velayati AA, Farnia P, Mozafari M, Malekshahian D, Seif S, Rahideh S, et al. Molecular Epidemiology of Nontuberculous Mycobacteria Isolates from Clinical and Environmental Sources of a Metropolitan City. PLoS One. 2014; 9: e114428.
  6. Mirsaeidi M, Farshidpour M, Ebrahimi G, Aliberti S, Falkinham JO 3rd. Management of nontuberculous mycobacterial infection in the elderly. Eur J Intern Med. 2014; 25: 356-363.
  7. Bryant JM, Grogono DM, Greaves D, Foweraker J, Roddick I, Inns T, et al. Whole-genome sequencing to identify transmission of Mycobacterium abscessus between patients with cystic fibrosis: a retrospective cohort study. Lancet. 2013; 381: 1551-1560.
  8. Halstrom S, Price P, Thomson R. Environmental mycobacteria as a cause of human infection. Int J Mycobacteriol. 2015; 4: 81-91.
  9. Rahideh S, Derakhshaninezhad Z, Farnia P, Mozafari M, Seif S, Malekshahian D, et al. Review and meta-analysis of nontuberculous mycobacteria in the Middle East. Int J Mycobacteriol. 2015; 4: 149.
  10. Velayati A, Farnia P, Mozafari M, Mirsaeidi M. Nontuberculous Mycobacteria Isolation from Clinical and Environmental Samples in Iran: Twenty Years of
  11. Velayati AA, Rahideh S, DerakhshaniNezhad Z, Farnia P, Mirsaeidi M. Nontuberculous mycobacteria in Middle East: Current situation and future challenges. Int J Mycobacteriol. 2015; 4: 7-17
  12. D’Antonio S, Rogliani P, Paone G, Altieri A, Alma MG, Cazzola M, et al. An unusual outbreak of nontuberculous mycobacteria in hospital respiratory wards: Association with nontuberculous mycobacterial colonization of hospital water supply network. Int J Mycobacteriol. 2016; 5: 244-247.
  13. Shu CC, Lee CH, Wang JY, Jerng JS, Yu CJ, Hsueh PR, et al. Nontuberculous mycobacteria pulmonary infection in medical intensive care unit: the incidence, patient characteristics, and clinical significance. Intensive Care Med. 2008; 34: 2194-2201.
  14. Joao I, Cristovao P, Antunes L, Nunes B, Jordao L. Identification of nontuberculous mycobacteria by partial gene sequencing and public databases. Int J Mycobacteriol. 2014; 3: 144-151.
  15. Ryu YJ, Koh WJ, Daley CL. Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease: Clinicians’ Perspectives. Tuberc Respir Dis (Seoul). 2016; 79: 74-84.
  16. Boyer J, Blatz P, Akers K, Okulicz J, Chung K, Rentz E, et al. Nontuberculous mycobacterium infection in a burn ICU patient. US Army Research. 2010; 36: 136-139.
  17. Kobayashi T, Nishijima T, Teruya K, Aoki T, Kikuchi Y, Oka S, et al. High Mortality of Disseminated Non-Tuberculous Mycobacterial Infection in HIVInfected Patients in the Antiretroviral Therapy Era. PLoS One. 2016; 11: e0151682.
  18. Behrendt CE. Acute respiratory failure in the United States: incidence and 31-day survival. Chest. 2000; 118: 1100-1105.
  19. Roussos C, Koutsoukou A. Respiratory failure. Eur Respir J Suppl. 2003; 47: 3s-14s.
  20. Sue DYLD, editor. Respiratory failure. 3rd Edn. New York, NY: Lange Medical Books/McGraw Hill. 2008; 247-313.
  21. Kohno S, Seki M, Takehara K, Yamada Y, Kubo K, Ishizaka A, et al. Prediction of requirement for mechanical ventilation in community-acquired pneumonia with acute respiratory failure: a multicenter prospective study. Respiration. 2013; 85: 27-35.
  22. Gong MN, Thompson BT, Williams P, Pothier L, Boyce PD, et al. Clinical predictors of and mortality in acute respiratory distress syndrome: potential role of red cell transfusion. Crit Care Med. 2005; 33: 1191-1198.
  23. Lewandowski K. Contributions to the epidemiology of acute respiratory failure. Crit Care. 2003; 7: 288-290.
  24. Franca SA, Toufen C Jr, Hovnanian AL, Albuquerque AL, Borges ER, Pizzo VR, et al. The epidemiology of acute respiratory failure in hospitalized patients: a Brazilian prospective cohort study. J Crit Care. 2011; 26: 330 e331-338.
  25. Orsini J, Ahmad N, Butala A, Flores R, Tran T, Llosa A, et al. Etiology and Outcome of Patients with HIV Infection and Respiratory Failure Admitted to the Intensive Care Unit. Interdiscip Perspect Infect Dis. 2013; 2013: 732421.
  26. Erasmus JJ, McAdams HP, Farrell MA, Patz EF Jr. Pulmonary nontuberculous mycobacterial infection: radiologic manifestations. Radiographics. 1999; 19: 1487-1505.
  27. Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007; 175: 367-416.
  28. Andrejak C, Nielsen R, Thomsen VO, Duhaut P, Sorensen HT, Thomsen RW, et al. Chronic respiratory disease, inhaled corticosteroids and risk of non-tuberculous mycobacteriosis. Thorax. 2013; 68: 256-262.
  29. Yeh JJ, Wang YC, Lin CL, Chou CYT, Yeh TC, Wu BT, et al. Nontuberculous mycobacterial infection is associated with increased respiratory failure: a nationwide cohort study. PLoS One. 2014; 9: e99260.
  30. Kassiri N, Hashemian SM. ARDS Definition Evolution: Past and Future Quotes. J Anesth Clin Res. 2014; 5: 464.
  31. Hashemian SM, Mortaz E, Tabarsi P, Jamaati H, Maghsoomi Z, Khosravi A, et al. Elevated CXCL-8 expression in bronchoalveolar lavage correlates with disease severity in patients with acute respiratory distress syndrome resulting from tuberculosis. J Inflamm. 2014; 11: 21.
  32. Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, et al. Epidemiology, patterns of care and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016; 315: 788-800.
  33. John SG, Zangeneh TT, Parthasarathy S. Acute respiratory distress syndrome secondary to Mycobacterium abscessus lung infection - a case report. F1000 Research. 2014; 3: 111.
  34. The ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin definition. JAMA. 2012; 307: 2526-2533.
  35. Ioachimescu OC, Tomford JW. Nontuberculous mycobacterial disorders. Carey W, Editor. In: Disease Management Project; Cleveland Clinic-Centre for Continuing Education: Cleveland, OH, USA. 2015.

Citation: Kassiri N and Reza Hashemian SM. Nontuberculous Mycobacteria in Critical Care. Austin Tuberc Res Treat. 2018; 3(1): 1010.