Fatal Pulmonary Infection Due to Multidrug-Resistant Mycobacterium abscessus in a Patient with Cystic Fibrosis

Abstract

We report a case of fatal pulmonary infection caused by Mycobacterium abscessus in a young patient with cystic fibrosis, who underwent bipulmonary transplantation after a 1-year history of severe lung disease. Fifteen days after surgery he developed septic fever with progressive deterioration in lung function. M. abscessus, initially isolated from a pleural fluid specimen, was then recovered from repeated blood samples, suggesting a disseminated nature of the mycobacterial disease. Drug susceptibility testing assay, performed on two sequential isolates of the microorganism, showed a pattern of multidrug resistance. Despite aggressive therapy with several antimycobacterial drugs, including clarithromycin, the infection persisted, and the patient died. CASE REPORTA 20-year-old man with cystic fibrosis (CF) underwent bilateral pulmonary transplantation in July of 1999. For approximately 1 year prior to admission he had been suffering from severe pulmonary disease with intermittent episodes of septic fever, and during this period he had been hospitalized several times. Sputum cultures had yielded Pseudomonas aeruginosa and Aspergillus fumigatus, whereas blood cultures (collected either via catheter and by venipuncture) were positive for Saccharomyces cerevisiae. On the basis of these microbiological findings, he had received several courses of antibiotic and antifungal therapy consisting of quinolones, third-generation cephalosporins, and amphotericin B, which had, however, produced only temporary remission of the symptoms. All cultures for mycobacteria (blood, sputum, urine, etc.) were repeatedly negative; sputum culture was contaminated by P. aeruginosa.Bilateral lung transplantation was performed on 20 July 1999. There were no intraoperative complications, and the patient was started on immunosuppressive therapy.On 5 August 1999, the patient developed a septic syndrome, and computed tomography (CT) performed on 7 August 1999 revealed a hyperdense lesion in the right paracardiac region with features of parenchymal involvement and a reactive pleural effusion. In light of the previous fungal recovery from clinical specimens, he was promptly started on intravenous amphotericin B therapy. On 6 August 1999 the pleural fluid was cultured for mycobacteria and was inoculated into Middlebrook 7H12 medium (BACTEC 12B; Becton Dickinson Diagnostic Instruments, Sparks, Md.) and Löwenstein-Jensen slant (BioMerieux, Marcy l'Etoile, France). On 8 August 1999, sputum and blood samples were also submitted for mycobacterial studies. A smear of respiratory samples showed many acid-fast bacilli.All three specimens yielded a rapidly growing mycobacterium identified as Mycobacterium chelonae and subsequently as M. abscessus, and on 20 August 1999 the patient was started on intravenous ciprofloxacin, amikacin, and clarithromycin. Sensitivity studies soon revealed, however, that the isolates were clearly resistant to all three drugs, as well as to all of the others tested (Table 1). In fact, after 1 month of antibiotic therapy the patient...

Deletion of the mmpL4b gene in the Mycobacterium abscessus glycopeptidolipid biosynthetic pathway results in loss of surface colonization capability, but enhanced ability to replicate in human macrophages and stimulate their innate immune response

“…The rough colony phenotype has been associated with fatal disseminated infection (Sanguinetti et al, 2001). Epidemiological data indicate that the rough M. abscessus colony phenotype is the predominant form isolated from patients with clinical lung disease and/or chronic colonization, whereas the smooth form is isolated from those who are transiently colonized without symptoms and/or from patients with wound infection secondary to contact with contaminated environmental sources (Jönsson et al, 2007).…”

Inhaled therapies, azithromycin andMycobacterium abscessusin cystic fibrosis patients

“…Finally, another disturbing finding is the extremely heterogeneous clinical presentation of MABSC disease, extending from totally asymptomatic infection to fulminant forms in some patients, whether or not they had undergone transplantation [7][8][9][10]. This observation suggests a particular susceptibility to MABSC infection in some patients.…”

“…MABSC can cause severe pseudotuberculous lung disease [8], in some cases after following an indolent course for a number of years [9]. It may cause disseminated, sometimes fatal infections in lung transplant recipients [10,11]. These mycobacteria are intrinsically resistant to most of the antibiotics currently available [12] and treatment failure is frequent despite aggressive antibiotic therapy.…”

galK-based suicide vector mediated allelic exchange in Mycobacterium abscessus

“…The organism can cause a plethora of infections, ranging from wound and subcutaneous infections to serious pulmonary infections, the latter of which are often seen in elderly, immunocompetent patients with underlying lung disease, or tall, elderly woman with low body mass [1][2][3]. M. abscessus is also an important pathogen in patients with cystic fibrosis and in patients receiving anti-tumour necrosis factor alpha therapy [4][5][6][7]. Environmental isolates typically form smooth colonies on solid media and isolates from deep tissue infections have a rough colony morphotype [8][9][10].…”