Mycobacterium abscessus causing native aortic valve endocarditis post stenting

Abstract

Native valve endocarditis owing to Mycobacterium abscessus (M. abscessus) is extremely rare and only a few cases have been reported in the literature. We present a case of a 44-year old male patient, a coronary artery disease (CAD) case with a stent in situ with pyrexia of unknown origin (PUO). He started becoming febrile following placement of stent and continued to remain febrile for duration of five months before coming to our centre. Echocardiogram showed vegetations on the aortic valve and paired blood cultures grew M. abscessus. Antibiotics including Clarithromycin were added to his treatment and a valve replacement was planned. The patient underwent valve replacement, however succumbed to the illness despite best efforts.

It is difficult to diagnose M. abscessus in Gram stain as they appear as diphtheroids and may be interpreted as contaminants. Even an accurate diagnosis makes this organism difficult to treat. Early surgical intervention along with aggressive antibiotic therapy is recommended for treatment.

Key Message

Mycobacterium abscessus is difficult to diagnose and on Gram stain they may appear as diphtheroids often being regarded as contaminants, thus missing the diagnosis.

Introduction

Mycobacterium abscessus is a clinically significant, rapidly growing Non tubercular Mycobacterium (NTM). It consists of three subspecies—Mycobacterium abscessus subspecies abscessus, Mycobacterium abscessus subspecies bolletii and Mycobacterium abscessus subspecies massiliense.¹ A wide variety of infections have been associated with it, in both immunocompetent and immune compromised individuals, which include skin, soft tissue, bone, lungs, prosthetic cardiac valves and disseminated infections. Mycobacterium abscessus is a pathogen isolated from pulmonary infections, longstanding chronic obstructive airway disease and cystic fibrosis. It has also been reported in long term intravenous catheter usage. Mycobacterium abscessus are ubiquitous in the environment—in water sources and in soil. These have been found in tap water and are increasingly being found as a contaminant in the hospital environment. Patients with mycobacteremia are at an increased risk of developing infective endocarditis, particularly, if they have prosthetic valve or valvular abnormalities. But native valve endocarditis as seen in our case is a rare presentation.²

Case report

A 44-year-old male patient, a known case of hypertension, coronary artery disease (CAD), non-diabetic, presented to our hospital with complaints of intermittent fever, recurrent episodes of chest pain, heartburn, progressive generalized weakness, myalgia, breathlessness on exertion of five months duration.

The patient had an anterolateral myocardial infarction six months back in the month of July 21, and was managed with percutaneous intervention (PCI) to left anterior descending (LAD) artery at a private tertiary care centre. After about six weeks of the procedure, he started developing fever. Patient was admitted to different hospitals as a case of Pyrexia of Unknown Origin (PUO). However, his fever persisted and he remained symptomatic. He was diagnosed as a case of infective endocarditis at a tertiary care centre, where vegetations were detected on his aortic valve (0.3 cm × 0.3 cm), along with mild aortic regurgitation (AR). However, blood culture reports from that centre did not reveal any growth. He was given empirical antibiotics (linezolid, amikacin and imipenem) to which he responded and became afebrile after two weeks of treatment. The antibiotics were continued for another four weeks. However, one week after discontinuation of antibiotics, he became febrile again. Cardiac computer tomography revealed LAD stent hypodensities (In stent restenosis or thrombosis), mild irregularity in aortic valve, changes suggestive of pulmonary edema. He was advised an aortic valve replacement (AVR) and coronary artery bypass graft (CABG). However, the patient did not undergo the advised treatment and reported to our hospital.

On examination, he was febrile (Temp-102 °F, had tachycardia (HR-114/min), had tachypnoea (RR-28/min). His BP was normal (130/84 mm Hg). His jugular venous pressure (JVP) was raised and he had pallor. Cardiovascular examination revealed an ejection systolic murmur at the aortic region. His laboratory investigations revealed Hb-7.8 g/dL, ESR-56 mm/h, total leucocyte count-2900/mm³, differential leucocyte count-P₆₀L₃₃E₀₆M₀₁, platelet count-63,000/mm³, blood urea-17 mg/dL, S creatinine-1.1 mg/dL, serum asparate transaminase and alanine transaminase (AST/ALT)-221/107 IU/L, serum lactate dehydrogenase (LDH)-404 IU/L.

On echocardiography, his ejection fraction was 40%. A thickened mass (1.07 cm × 1.02 cm) was seen on the aortic valve right coronary cusp (RCC), which was homogenous and hyperechoic. There was severe eccentric AR impinging on the anterior mitral leaflet (AML), mild to moderate mitral regurgitation (MR). Positron emission tomography (PET) scan showed increased myocardial and aortic valve uptake indication inflammation (Fig. 1). Blood cultures were sent twice, but were flagged positive only second time after 48 h of incubation. Subcultures on blood and MacConkey agar were done. Gram stain from the growth showed gram variable bacilli. Some were faintly stained and gave ghost appearance with occasional beaded structures. On Ziehl Neelsen (ZN) stain the organism was acid fast. Blood agar showed minute, dry, white non hemolytic colonies (Fig. 2). Lowenstein Jensen (LJ) medium showed smooth pale colonies after three days of incubation. Growth from blood agar and LJ medium were identified as Mycobacterium abscessus by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). The same was also confirmed by Hains line probe assay. Patient was thus diagnosed as a case of native aortic valve endocarditis caused by Mycobacterium abscessus post cardiac intervention. Clarithromycin was added to his antibiotics, which included meropenem, teicoplanin and ceftriaxone plus sulbactam. Patient improved and became afebrile. However, his renal functions kept deteriorating. Blood urea rose from 17 mg/dL on admission to 54 mg/dL, and serum creatinine rose from 1.1 mg/dL to 3 mg/dL within 10 days of admission.

Fig. 1.

Axial fludeoxyglucose positron emission tomography scan showing increased uptake of the injected dye in the aortic valve (arrow) indicating inflammation.

Fig. 2.

Blood agar showing minute, dry, white non haemolytic colonies after 48 h of incubation at 37 °C.

After three weeks of antimicrobial treatment, a repeat coronary angiogram was done which showed right dominant circulation with ostial LAD 100% occlusion. He underwent CABG and AVR. LAD showed no signs of inflammation. Left Internal Mammary Artery (LIMA) graft to distal LAD was placed, right aortic sinus abscess was drained and repaired with a pericardial patch and 21  mm St. Jude Medical AV replacement was done. Patient consent was obtained for inclusion in the study.

Histopathology of the aortic root vegetation revealed necrotic inflammatory infiltrate, myxoid degeneration of the vessel wall. ZN stain of the tissue showed numerous acid fast bacilli (Fig. 3). Culture of the tissue of the suspected vegetation, removed during the surgery showed growth of Mycobacterium abscessus. Post operatively patient's general condition remained critical. He subsequently developed hypotension, acute renal failure with anuria. He was managed with continuous renal replacement therapy and vasopressors, but despite aggressive management the patient succumbed to the illness on Day 41 of admission.

Fig. 3.

Ziehl Neelsen stain of the tissue section from surgically resected aortic vegetation showing numerous acid fast bacilli.

Discussion

Mycobacterium abscessus is a rapidly growing mycobacterium (RGM) and has now been recently emerging in unfamiliar settings with varied clinical manifestations, infecting immunocompetent individuals, which was previously known to cause disseminated disease only in immune suppressed conditions. After exposure to M. abscessus, immune cells like macrophages, phagocytose the invading bacteria. However, rough strain, which is more virulent, can evade phagocytosis, induce production of cytokines like interferon-γ causing formation of extracellular bacterial cords that may lead to disseminated infection. M. abscessus has a hydrophobic outer surface leading to biofilm formation and is also resistant to disinfectants, high temperature and acidic conditions. It is one of the most resistant organisms to chemotherapeutic agents and is perceived as huge threat to humans due to its high multidrug resistance.^3,4 Many cases of prosthetic valve endocarditis by Mycobacterium abscessus have been reported before, but native valve infective endocarditis post catheterization is an extremely rare entity.^4,5 Mycobacterium abscessus is easily cultivable in common media like blood and MacConkey agar in two to three days. On Gram stain M. abscessus can easily be confounded with diphtheroids.^6,7 Diagnosing these requires a high index of suspicion in PUO cases with blood cultures showing gram variable bacilli. ZN smears of such cases with suspected NTM may show AFB along with rapid growth in LJ media may clinch the diagnosis as seen in our case and can be further confirmed by molecular tests.

Early diagnosis and timely intervention can help saving such patients as Mycobacterium abscessus is a difficult organism to treat as it is notoriously resistant to standard antitubercular agents. The Clinical and Laboratory Standard Institute (CLSI) recommends testing RGM for susceptibility to clarithromycin, aminoglycosides, cefoxitin, fluoroquinolones, tigecycline, cotrimoxazole, linezolid, and imipenem.⁸ The recommended drug susceptibility testing method is by microbroth dilution method. The resistant rates for clarithromycin, cefoxitin, and amikacin are low as compared to fluoroquinolones and imipenem as seen in most studies. The presence of erm gene in M abscessus complex confers macrolide resistance through methylation of 23S ribosomal RNA. As there are limited case reports, there are no recommended guidelines for treatment of M abscessus and is mostly based on retrospective case series. The treatment of disseminated disease usually involves treatment with macrolide in combination with amikacin plus cefoxitin/imipenem plus surgical debridement in case of focal point. In hospital setting, contamination of medical devices, water supply and failure of disinfection procedures is the main cause of spread of M abscessus complex. Though NTM have always been present in environment, they were considered rare causes of infections. However, with improved diagnostic modalities, it has proven to be a myth and the prevalence in clinical scenarios has been on rise.

Disclosure of competing interest

The authors have none to declare.