Mycobacterium abscessus: causing fatal endocarditis after cardiac catheterization.

Mycobacterium abscessus is an unusual cause of infection in immunocompetent patients. The intrinsic and acquired resistance of this organism to multiple antibiotics is a major issue in planning treatment regimens. We report a case of M. abscessus endocarditis of the native aortic valve in an immunocompetent patient following coronary angiography with a fatal outcome. The case highlights an unfortunate intervention-related nosocomial infection and the difficulties in chemotherapeutic options for this organism, particularly in the presence of renal failure.

Introduction

Mycobacterium abscessus is a highly pathogenic and chemotherapy-resistant organism.[12] It is very important to distinguish M. abscessus from other nontubercular mycobacteria (NTM) as antimycobacterial therapy is significantly more complex. Environmental mycobacteria are common postprocedure pathogens, especially when disposable equipment is recycled. Native valve endocarditis with NTM is rare and often missed. Appropriate diagnosis and timely intervention are necessary to manage this often fatal infection. The following case report highlights one such fatal and unusual case.

Case Report

A 53-year-old male patient from Gujarat (India), with a history of hypertension, diabetes mellitus, hypothyroidism, and a stable dilated cardiomyopathy was shifted to our hospital with a prolonged pyrexia, which had remained undiagnosed and unresponsive to standard antimicrobial treatment. A coronary angiography had been performed 8 weeks earlier, which showed normal coronary anatomy. Three weeks following the angiography, the patient developed moderate- to high-grade fever for which standard investigations, routine blood cultures, and imaging were performed and were inconclusive. He was transferred to our care 6 weeks into his febrile illness with no clear diagnosis. On examination, the patient was febrile, toxic, and had an early diastolic murmur in the aortic area. The investigations revealed hemoglobin 8.3 g/dL, white blood cells 9200 cells/mm3, platelets 2,23,000/mm3, serum creatinine level 2.2 mg/dL, and erythrocyte sedimentation rate 88 mm/h. Urine analysis showed 3-5 red blood cells (RBCs)/high power field (hpf) and a raised 24-h urine protein of 1527 mg/24 h was also noted. On ultrasonography, the kidney sizes were normal with no evidence of pyelonephritis or abscess. There was mild hepatosplenomegaly, but there was no evidence of focal lesions in the spleen or liver. Chest roentgenogram revealed mildly prominent pulmonary vasculature with cardiomegaly but no significant lung parenchymal pathology. The two-dimensional echocardiography (2D ECHO) done at previous hospital showed left ventricular ejection fraction (LVEF) of 30%, normal heart valves, and global hypokinesia. A repeat 2D echo at our center showed an evidence of mild aortic regurgitation with three discrete small mobile vegetations on the left and right coronary cusps of the aortic valve. There was no evidence of cusp perforation or any ring abscess. The other cardiac valves were normal. LVEF was 20%; a transesophageal echo confirmed the above findings. Choroidal infiltrates as a stigmata of infective emboli were noted, but there was no evidence of embolization to skin or any other organ. Antinuclear antibodies (anti-ANA), anti – double stranded antibody (anti-dsDNA), and anti–nucleophilic cytoplasmic antibodies (anti-ANCA) were negative and complement levels (C3 and C4) were within the normal range. The thyroid profile was normal. The patient was treated for heart failure and was started on ceftriaxone at a dose of 1 g twice daily intravenously as empirical treatment for infective endocarditis. Routine serial bacterial blood cultures did not show any growth. BACTEC Myco/F Lytic medium was then used, which demonstrated the rapidly growing organisms as NTM. Linezolid and clarithromycin were empirically added while awaiting the sensitivity and speciation of the NTM. Meanwhile, species identification using the Line probe assay technique revealed the organism to be M. abscessus and drug sensitivities were subsequently obtained. The organism was found to be sensitive to amikacin, clarithromycin, linezolid, and tobramycin, with intermediate sensitivity to cefoxitin but was found to be resistant to doxycycline, imipenem, cefepime, ceftriaxone, minocycline, and amox–clavulanic acid. The two antibiotics (linezolid and clarithromycin) were continued and the other sensitive drugs isoniazid, ethambutol, and cefoxitin were added to the treatment regimen. The patient defervesced for the first time after 7 weeks of continuous fever 1 week into the above treatment. Linezolid was withheld for 10 days in view of significant bone marrow suppression but was later reinstituted in lower doses. After 3 weeks of therapy with a combination of five antibiotics, the creatinine stabilized at 2.6 mg/dL having previously reached a peak of 3.6 mg/dL. Dyspnea improved and a repeat 2D echo showed an increase in LVEF to 40%. The valvular vegetations, however, were present and blood cultures still grew the same mycobacteria despite the patient having defervesced. Aortic valve replacement surgery was considered but was withheld in view of multiple comorbidities and patient's reluctance to undergo any procedure. A repeat 2D ECHO at 4 weeks post treatment showed no change in the vegetation size and the patient was discharged on request on all five antimycobacterial antibiotics. Subsequently, the patient developed worsening cardiac failure and died of pulmonary edema and renal dysfunction despite aggressive medical management in a local intensive care unit.

Discussion

Postprocedure mycobacterial infections have been often reported, especially in India where glutaraldehyde is used as a sterilizing solution for surgical and other equipments.[3] Cardiac catheterization is now increasingly performed in smaller centers. Risk factors for bacteremia following catheterization include obesity, duration of the procedure, the number of balloons used, and the number of skin punctures performed.[4] Infections complicating coronary angiography include sepsis, endocarditis, suppurative pancarditis, stent infection, septic arthritis, epidural abscess, necrotizing fasciitis, and groin wound infection.[5] The most common causative organism of bacteremia following cardiac catheterization is Staphylococcus aureus, particularly in the obese. Native valve endocarditis with NTM such as M. abscessus is rare and often missed without appropriate blood cultures. In cases of postprocedure endocarditis, the aortic valve is predominantly affected (as was seen in our case).[5] Early diagnosis and prolonged combination therapy are obligatory to minimize mortality, as M. abscessus is inherently resistant to multiple antibiotics. Although there are no specific drug protocols for treatment of pulmonary M. abscessus disease, a macrolide-based regimen is often used combined with surgical debridement for successful therapy. Evidence-based management for other nonpulmonary diseases and specifically for M. abscessus endocarditis is lacking due to sheer rarity of the condition and treatment is based on in vitro drug susceptibility.[6] Typically, antibiotics with maximum in vitro activity against M. abscessus isolates include amikacin, clarithromycin, tigecycline, and cefoxitin. To a lesser extent, linezolid and imipenem are also effective against nearly 50% of clinical isolates. Combination therapy is mandatory and should be administered for at least 2-4 months. Tigecycline and linezolid are newer antibiotics with efficacy against M. abscessus and the recommended treatment length with these drugs is 6-12 months. Among the carbapenems, only imipenem is useful in some cases.[7]

In our patient, clarithromycin and linezolid were used in combination as aminoglycosides were contraindicated due to renal failure. The cause of the raised creatinine was thought to be multifactorial, secondary to diabetic nephropathy, hypertension, and congestive cardiac failure. The possibility of septic emboli causing nephritis seems low owing to only 3-5 RBCs/hpf in urine. Linezolid could not be used in its maximal dose due to bone marrow suppression. Isoniazid and ethambutol were added as standard antituberculous therapy with the hope of some benefit in such a desperate situation. M. abscessus infection is not always considered a medically curable condition, but prolonged antibiotic therapy may result in chronic suppression of the disease. In vitro drug susceptibility patterns do not always correlate with clinical responses and measurements of minimum inhibitory concentrations of antibiotics do not always predict their therapeutic effects.[1] Endocarditis caused by M. abscessus generally has a very poor prognosis despite combination antimicrobial therapy, as only two of the 10 documented cases described in the literature have survived after treatment.[8] Surgical intervention to replace the infected valve would have been worth attempting if the patient had been willing. However, in view of the dismal treatment outcomes shown by previous studies,[8] it remains uncertain if early institution of appropriate therapy or valve replacement would have altered the ultimately fatal outcome with this pathogen.[18] Nosocomial infection control needs to be strengthened particularly at smaller centres where complex interventions are increasingly being conducted.