Successful Recovery After Disseminated Infection Due to Mycobacterium Abscessus in a Lung Transplant Patient: Subcutaneous Nodule as First Manifestation—A Case Report P. Morales, J.A. Ros, M. Blanes, D. Pérez-Enguix, V. Saiz, and M. Santos ABSTRACT Mycobacterium abscessus infection following lung transplantation (LT) has been described in a few cases. It is characterized by a variable initial location and subsequent course in this special risk group of patients, particularly those with cystic fibrosis (CF). Herein we have presented the case of a patient subjected to LT due to CF, who 1 year after transplantation developed a subcutaneous nodule produced by M abscessus, with subsequent hematogenous spread as well as bronchial and bone marrow involvement. Antecedents prior to LT included Staphylococcus aureus colonization and sputum positivity for Aspergillus fumigatus and Scedosporium apioespermum. Treatment with ciprofloxacin and linezolid was started on the basis of the antibiogram findings. The latter antibiotic was replaced by clarithromycin for 6 months. Two years later, the patient remains asymptomatic with respiratory function parameters in the normal range. The infected patient described herein was our only case with sepsis and multisystemic spread. The important mortality among such cases reported in the literature makes early diagnosis and treatment essential.
M
YCOBACTERIAL INFECTIONS in immune depressed patients are a frequent cause of mortality.1 Lung transplant (LT) patients constitute a special risk group in this sense, since the lungs are a preferential site for such infections. More specifically, Mycobacterium abscessus infection following LT has been described in a few cases.2,3 It is characterized by a variable initial location and subsequent course. On the other hand, nontuberculous mycobacteria are a growing problem among patients with cystic fibrosis (CF) and severe lung involvement.3,4 Infection in such cases is clinically indistinguishable from other common infections in these patients, though it may be evident after induction of immune suppression we have presented herein the case of a patient subjected to LT due to CF, who 1 year after transplantation developed a subcutaneous nodule produced by M abscessus, with subsequent hematogenous spread as well as bronchial and bone marrow involvement. Treatment led to resolution of the problem without sequelae. CASE REPORT An 18-year-old man diagnosed with CF included pancreatic, liver, and lung involvement required double LT. The main antecedents to transplantation were Staphylococcus aureus colonization and treatment with voriconazole (200 mg/12 hours) on two occasions,
due to the detection of Aspergillus fumigatus and Scedosporium apioespermum upon fungal culture of sputum. The treatment was maintained until negative conversion of two subsequent serial cultures spaced 15 days apart. Tuberculin testing and repeated sputum cultures in Lowenstein medium had proven negative for tuberculosis, before and after LT. The immunosuppressive regimen 1 year after transplantation was: tacrolimus prescribed at doses adjusted to blood concentrations of 10 to 15 ng/mL, azathioprine 50 mg/d, and prednisone 10 mg/d. The patient evolved without complications during the first year. At this point he presented with a small, nonadherent, painless nodule beneath the thoracotomy scar, with no accompanying clinical manifestations. The physical examination showed no alterations. Laboratory testing (complete blood count, liver and kidney function) were normal, with the exception of an erythrocyte sedimentation rate of 81 mm in the first hour. The chest X-ray findings were normal. Soft tissue echography revealed a hypoechoic nodule measuring 3 ⫻ 0.5 cm in the From the Unidad de Trasplante Pulmonar (P.M.), Hospital Universitario la Fe, Valencia, Spain; Servicio de Neumologı´a (J.A.R.), Hospital Virgen de la Arrixaca, Murcia, Spain; and Unidad de Infecciosas (M.B.), Servicio de Radiologı´a (D.P.-E., V.S.), and Servicio de Microbiologia (M.S.), Hospital Universitario La Fe, Valencia, Spain. Address reprint requests to Dra Pilar Morales, Unidad de Trasplante Pulmonar, Hospital Universitario La Fe, Avda Campanar 21, 46009 Valencia, España. E-mail:
[email protected]
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0041-1345/07/$–see front matter doi:10.1016/j.transproceed.2007.07.053
Transplantation Proceedings, 39, 2413–2415 (2007)
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2414 subcutaneous cellular tissue over a right rib. Puncture aspiration revealed abundant histiocytes with an acute lesion of polymorphonuclear leukocytes. The provisional microbiological study detected acid alcohol-fast bacteria, as a result of which specific treatment was started for M tuberculosis with four drugs: rifampicin, isoniazid, ethambutol, and pyrazinamide. On the fourth day, the patient developed a fever of 38.5°C, slight pain upon swallowing, and tenderness upon palpation of the nodule. A full-body computed tomography scan showed no significant alterations. The final microbiological result from puncture of the nodule indicated the presence of M abscessus. The treatment was then modified according to the findings of the antibiogram, replacing the antituberculosis medication with linezolid (600 mg/12 hours) and ciprofloxacin (750 mg/12 hours) via the oral route. The appearance of pancytopenia (hemoglobin 7.2 g/dL; leukocyte count 1500; platelet 125,000/mm3) led us to suspend linezolid after 30 days, replacing it with clarithromycin (500 mg/12 hours) and adjusting the tacrolimus because of the pharmacological interaction. Bone marrow aspiration likewise isolated M abscessus. The need for a blood transfusion was rejected by the patient for religious reasons. Thereafter, the same microorganism was simultaneously isolated from blood and a bronchial biopsy culture despite chest X-rays without alterations. Despite the spread, there was negative conversion of the cultures and correction of the hematological parameters. The patient was discharged 45 days after the diagnosis with withdrawal of the treatment 6 months later. After a year and a half follow-up, the patient remained asymptomatic, with laboratory tests and respiratory function parameters within reference limits.
DISCUSSION
M abscessus is an ubiquitous microorganism, found in soil, water, and dust. It can also be found colonizing body secretions and surfaces. It has been reported in up to 83% of water supplies of dialysis units.5 Infection caused by this microorganism was first described by Moore and Frerichs6 in 1953, in a woman with chronic osteoarthritis who developed a gluteal abscess. It has also been reported after trauma, injections, or surgery, though without posing a threat to the life of the patient.5–9 M abscessus occasionally produces respiratory infection in patients with chronic lung diseases, such as bronchiectasis, chronic obstructive pulmonary disease, pneumoconiosis, or CF.3 Because the symptoms are similar these are underdiagnosed among patients with CF, due to overgrowth in culture of other microorganisms3,4,10: Pseudomona aeruginosa, Staphylococcus aureus, Candida albicans, and Aspergillus fumigatus. When the microorganism is suspected, molecular techniques should therefore be used for detection.3 M abscessus, M chelonae, and M fortuitum are the most frequently isolated species.4,10 Infection by these bacteria should be suspected in young patients with unexplained impairment of lung function, systemic corticotherapy and/or allergic bronchopulmonary aspergillosis.4 Immunodepressed patients constitute a risk population for opportunistic infections, involving both spread within a single organ and systemic involvement.2,11,12 The immunosuppression induced in transplant patients constitutes a special situation; patients with different types of grafts
MORALES, ROS, BLANES ET AL
(kidney, liver, heart) have been reported to show skin involvement.13–17 The increased immunosuppression and contact with the exterior through the airway causes LT patients to be more vulnerable.11,12 Mycobacterial infections, which are generally infrequent, are particularly caused by M tuberculosis18 and, to a lesser extent, by atypical mycobacteria. They have been reported mainly in patients with CF. Among 261 patients described by Malouf and Glanville,1 M abscessus was isolated in three patients; one showed only skin involvement, while the other two were diagnosed from bronchoalveolar lavage and sputum culture. Sanguinetti et al3 reported the case of a patient with LT due to CF who developed sepsis with parenchymal lung infiltration and pleural effusion due to M abscessus 1 month after transplantation. Prior to transplantation, P aeruginosa and A fumigatus have been isolated; as a result, the same therapeutic scheme was repeated. Following isolation of the germ from the pleural fluid and the sputum, treatment was started with ciprofloxacin, clarithromycin, and amikacin, without success possibly due in part to the increased immune suppression, since the patient was in the postoperative period, or because of a delay in establishing the diagnosis. Taylor and Palmer19 described infections of the chest wall and lungs due to M abscessus at 15 months after LT in a patient with CF and infected bilateral breast prostheses. The patient died despite treatment on several occasions for repeated prior M abscessus infections and the adoption of peroperative prophylactic measures. The authors raised the question whether prior colonization by this microorganism in CF patients should be considered to be a contraindication for transplantation. The candidate for LT described in our report likewise showed CF with bacterial colonization by S aureus, with repeated respiratory infections and prior isolation of fungi: A fumigatus and S apiospermum. Unlike the case described by Sanguinetti et al,3 the infection due to M abscessus developed at 1 year after transplantation when there were lower dosages of immunosuppressants. The skin was initially involved, with no alterations of the lungs or any other organ. A review of the literature yielded no other case with skin, lung, blood, and bone marrow involvement. Chernenko et al20 recently published the result of a retrospective multicenter review of 5200 patients. In 17 subjects (0.33%), M abscessus was isolated (12 in the lungs), and intercurrent infections by other germs detected in over half of these patients. In conclusion, infections due to M abscessus are presently infrequent among LT patients. The presentations vary from self-limited conditions or isolated lesions to disseminated presentations with a poor prognosis. Rapid detection as well as early treatment are essential.4,18 Screening is moreover required prior to transplantation, particularly in patients with CF.3,21 Clarithromycin (500 mg twice a day) for 6 months has been shown to be effective,22 though as monotherapy it may give rise to resistance.16 It is therefore advisable to administer two antibiotics,16,22 for example,
MYCOBACTERIUM ABSCESSUS IN LUNG RECIPIENT
amikacin and imipenem, or clarithromycin and ciprofloxacin.22 Due to the common use of antibiotics and thus an increased risk of resistance in patients with CF, triple therapy is advised.2 The suggested duration of treatment is 6 months, as with other mycobacteria.22 The regimen prescribed in our case was combined antibiotherapy according to the results of the antibiogram. Two years later, the patient remained asymptomatic. REFERENCES 1. Malouf MA, Glanville AR: The spectrum of mycobacterial infection after lung transplantation. Am J Respir Crit Care Med 160:1611, 1999 2. Morales P, Pemán J, Solé A, et al: Lung transplantation and emerging fungal infections: another challenge for late survival. Eur Respir J 28:777s, 2006 3. Sanguinetti M, Ardito F, Fiscarelli E, et al: Fatal pulmonary infection due to multidrug-resistant Mycobacterium abscessus in a patient with cystic fibrosis. J Clin Microbiol 39:816, 2001 4. Mussaffi H, Rivlin J, Shalit I, et al: Nontuberculous mycobacteria in cystic fibrosis associated with allergic bronchopulmonary aspergillosis and steroid therapy. Eur Respir J 25:324, 2005 5. Morris-Jones R, Fletcher C, Morris-Jones S, et al: Mycobacterium abscessus: a cutaneus infection in a patient on renal replacement therapy. Clin Exp Dermatol 26:415, 2001 6. Moore M, Frerichs JB: An unusual acid-fast infection of knee with subcutaneus, abscess-like lesions of the gluteal region. J Invest Dermatol 20:133, 1953 7. Galil K, Miller LA, Yakrus A, et al: Abscessus due to Mycobacterium abscessus linked to injection of unapproved alternative medication. Emerg Infect Dis 5:681, 1999 8. Ryu HJ, Kim WJ, Oh CH, et al: Iatrogenic Mycobacterium abscessus infection associated with acupuncture: clinical manifestations and its treatment. Int J Dermatol 44:846, 2005 9. Newman MI, Camberos AE, Ascherman J: Mycobacteria abscessus outbreak in US patients linked to offshore surgicenter. Ann Plast Surg 55:107, 2005
2415 10. Bange FC, Brown BA, Smaczny C, et al: Lack of transmission of Mycobacterium ascessus among patients with cystic fibrosis attending a single clinic. Clin Infect Dis 32:1648, 2001 11. Sole A, Morant P, Salavert M, et al: Aspergillus infections in lung transplant recipients: risk factors and outcome. Clin Microbiol Infect 11:359, 2005 12. Morales P, Torres JJ, Salavert M, et al: Visceral leishmaniasis in lung transplantation. Transplant Proc 35:2001, 2003 13. Scholze A, Loddenkemper C, Grünbaum M, et al: Cutaneus Mycobacterium abscessus infection after kidney transplantation. Nephrol Dial Transplant 20:1764, 2005 14. Freudenberger RS, Simafranca SM: Cutaneous infection with rapidly-growing mycobacterial infection following heart transplant: a case report and review of the literature. Transplant Proc 38:1526, 2006 15. Schmekal B, Janko O, Zazgornik J, et al: Skin tuberculosis with atypical mycobacterium 8 years after combined pancreaskidney transplantation. Am J Nephrol 22:566, 2002 16. Prinz BM, Michalis S, Kettelhack, et al: Subcutaneus infection with Mycobacterium abscessus in renal transplant recipient. Dermatology 208:259, 2004 17. Chastain MA, Buckley J, Russo GG: Mycobacterium chenolae/abscessus complex infection in a liver transplant patient. Int J Dermatol 40:769, 2001 18. Morales P, Briones A, Torres JJ, et al: Pulmonary tuberculosis in lung and heart-lung transplantation: fifteen years of experience in a single center in Spain. Transplant Proc 37:4050, 2005 19. Taylor JL, Palmer SM: Mycobacterium abscessus chest wall and pulmonary infection in a cystic fibrosis lung transplant recipient. J Heart Lung Transplant 25:985, 2006 20. Chernenko SM, Humar A, Hutcheon M, et al: Mycobacterium abscessus infections in lung transplant recipients: the international experience. J Heart Lung Transplant 25:1447, 2006 21. Chalermskulrat W, Sood N, Neuringer IP, et al: Nontuberculous mycobacteria in end stage cystic fibrosis: implications for lung transplantation. Thorax 61:507, 2006 22. Jogi R, Tyring SK: Therapy of nontuberculous mycobacterial infections. Dermatol Ther 17:491, 2004