Journal Pre-proof Mycobacterium chelonae, an ‘atypical’ cause of an LVAD driveline infection Stefan Roest, Hannelore I. Bax, Nelianne J. Verkaik, Jasper J. Brugts, Alina A. Constantinescu, Chantal C. de Bakker, Ozcan Birim, Kadir Caliskan, Olivier C. Manintveld
PII:
S1201-9712(20)30004-7
DOI:
https://doi.org/10.1016/j.ijid.2020.01.002
Reference:
IJID 3893
To appear in:
International Journal of Infectious Diseases
Received Date:
11 December 2019
Revised Date:
27 December 2019
Accepted Date:
2 January 2020
Please cite this article as: Roest S, Bax HI, Verkaik NJ, Brugts JJ, Constantinescu AA, de Bakker CC, Birim O, Caliskan K, Manintveld OC, Mycobacterium chelonae, an ‘atypical’ cause of an LVAD driveline infection, International Journal of Infectious Diseases (2020), doi: https://doi.org/10.1016/j.ijid.2020.01.002
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier.
Mycobacterium chelonae, an ‘atypical’ cause of an LVAD driveline infection
Running title: M. chelonae LVAD driveline infection
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Stefan Roest1*, MD; Hannelore I. Bax2,3*, MD, PhD; Nelianne J. Verkaik2, MD, PhD; Jasper J. Brugts1, MD, PhD, MSc, FESC; Alina A. Constantinescu1, MD, PhD, Chantal C. de Bakker1, MSc; Ozcan Birim4, MD, PhD; Kadir Caliskan1, MD, PhD, FESC; Olivier C. Manintveld1, MD, PhD
Department of Cardiology, Thorax Center;
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Department of Medical Microbiology and Infectious Diseases;
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Department of Internal Medicine, Division of Infectious Diseases;
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Department of Cardio-Thoracic Surgery, Thorax Center, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
* Both authors contributed equally to this manuscript
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Corresponding author
O.C. Manintveld, MD, PhD, Dept. of Cardiology, Thorax Center Erasmus MC, University Medical Center Rotterdam Doctor Molewaterplein 40 3015 GD, Rotterdam, The Netherlands
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Room RG-431, Telephone: +31107035078, Fax: +31107035333,E-mail:
[email protected]
Highlights
First case of Mycobacterium chelonae driveline infection
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NTM infections should be considered in patients with LVAD driveline infection in case of negative routine bacterial cultures
Decontamination procedures hamper the detection of NTM
Multidisciplinary approach should be used to determine the optimal management of
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LVAD-associated NTM infections
Abstract
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We describe the first patient with a left ventricular assist device (LVAD) driveline infection
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caused by Mycobacterium chelonae presenting with persistent infection despite conventional antibiotics. Treatment was successful with surgical debridement, driveline exit relocation and a
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4-month-period of antibiotics. In case of culture negative LVAD driveline infection, nontuberculous mycobacteria should be considered. This case illustrates that multidisciplinary
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collaboration is essential in providing optimal care for LVAD patients.
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Keywords: Driveline infection, Left Ventricular Assist Device, Mycobacterium chelonae
Introduction
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In a selected group of patients with end-stage heart failure, a Left Ventricular Assist Device (LVAD) is implanted. The number of LVAD implantations is rising rapidly (de By, 2018, Kormos, 2019). One of the most common complications is a driveline infection. The incidence of LVAD-associated infections (including driveline infections) is around 28% in the first twelve months post-implantation (de By, 2018, Kormos, 2019). Early diagnosis and appropriate
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treatment is important in order to prevent ascending infection, including LVAD pump infections, which is associated with increased morbidity and mortality (de By, 2018, Kormos, 2019, Simeon, 2017). Here, we describe a patient with a rare cause of an LVAD driveline infection.
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Case Report A 56-year old Caucasian male with a history of ischemic cardiomyopathy, diabetes and an
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LVAD (HeartMate II, Abbott®) since 2015 as bridge-to-transplant, presented at the outpatient clinic with pain and purulent discharge at the driveline exit 3.5 years post-LVAD implantation.
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There was no fever or redness and a low C-reactive protein (CRP) of 0.6 mg/L. The patient was
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treated with oral levofloxacin 500 mg BID, after a bacterial culture of the wound fluid was obtained. As a consequence he was deemed not eligible for heart transplantation at that time.
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Two weeks later, the patient returned to the outpatient clinic with persistent purulent discharge from the driveline exit without systemic symptoms and negative bacterial cultures. The patient
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was admitted and treated with intravenous antibiotics. Bacterial, mycobacterial and fungal cultures were obtained and incubated for a prolonged period of time (14 days) for identification of potential fastidious and/or slowly growing micro-organisms. An ultrasound was performed
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demonstrating a fluid collection around the driveline over a length of 15 centimeters. Subsequently, a PET-CT scan was performed to evaluate the extent of the infection (Akin, 2018) and showed uptake in the subcutaneous tissue surrounding the LVAD driveline compatible with the ultrasound findings (Figure 1A). Since regular microbial cultures remained negative, the patient was discharged without antibiotics.
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After 6 days, routine bacterial cultures became positive (Figure 1B). Matrix-assisted Laser Desorption/Ionization (MALDI) identified Mycobacterium chelonae and acid fast staining showed the presence of mycobacteria (Figure 1C). Reverse line blot hybridization confirmed the MALDI findings showing a banding pattern fitting Mycobacterium chelonae/Mycobacterium abscessus complex/Mycobacterium immunogenum. Further molecular identification with partial gene sequencing of the 16S-23S rRNA internal transcribed spacer (ITS) region confirmed M.
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chelonae as the cause of the driveline infection. The patient was readmitted and started on
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imipenem 500 mg QID intravenously and clarithromycin 500 mg BID orally, based on
susceptibility results. After two weeks of adequate antimicrobial treatment, surgical debridement
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was performed with relocation of the driveline exit to the right side of the abdomen. Negative
infected exit site (Figure 1D, 1E).
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pressure wound therapy (Vacuum Assisted Closure) was initiated at the location of the old,
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After surgical exploration, imipenem and clarithromycin were continued for one additional week, after which clarithromycin was combined with doxycycline 100 mg BID orally. Total
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duration of antibiotic therapy was 4 months. Until this date (8.5 months after stopping antibiotics), no infection recurrence has occurred and the patient is considered eligible for heart
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transplantation again.
Discussion
LVAD-associated infections are serious infections associated with high morbidity and mortality (de By, 2018, Kormos, 2019, Simeon, 2017). LVAD-associated infections can be divided into driveline infections and ascending or pump infections. Early diagnosis is important in order to 4
initiate appropriate antimicrobial therapy with or without surgical debridement to prevent disease progression. Causative pathogens of LVAD-associated infections are mainly Staphylococcus aureus and coagulase negative staphylococci, causing approximately 50% of infections, but also Pseudomonas aeruginosa and Enterobacteriaceae have been described (Simeon, 2017, Nienaber, 2013, Kusne, 2017). LVAD infections caused by nontuberculous mycobacteria (NTM) are extremely rare. Recently, Breton et al. reported two cases of driveline infections caused by M.
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abscessus (Nunez Breton, 2018). Mycobacterium chimaera was reported in 2 patients in the
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context of a worldwide outbreak of infected heater cooler units (Balsam, 2017). Here, we describe the first patient with an LVAD driveline infection caused by M. chelonae.
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NTM are ubiquitous environmental organisms found in soil, dust and water. Together with M.
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abscessus complex and Mycobacterium fortuitum, M. chelonae is the most clinically relevant species within the group of rapidly growing NTM (RGM). RGM are characterized by the ability
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to grow on solid culture media within seven days as opposed to the slowly growing NTM, usually requiring more than seven days for growth. In general, it is recommended to obtain
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cultures in specific liquid as well as solid media when there is a clinical suspicion of NTM infection (Griffith, 2007). Furthermore, it is recommended to include low temperature settings as for several NTM, including M. chelonae, the optimal growth temperature is 30°C. Interestingly, in our case the pus culture from the exit site on routine bacterial medium was positive at day 6
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while the liquid and solid cultures on specific mycobacterial culture media remained negative. This might be due to the decontamination procedure, which is routinely performed when nonsterile specimens are prepared for mycobacterial diagnostics. Although this procedure is important for reducing contamination with other micro-organisms, it may hamper the detection of NTM and RGM in particular (Griffith, 2007). Therefore, including prolonged incubation on
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non-specific bacterial culture media might increase the detection rate of NTM as was the case in our patient. Once a mycobacterial culture is positive, proper species identification is crucial, since susceptibility and optimal treatment regimens differs between different NTM and between different RGM. In general, treatment requires a combination of antibiotic agents based on susceptibility results for at least 4 months in case of skin and soft tissue infections (Griffith, 2007). Our patient was successfully treated with a 4-month combination antibiotic regimen,
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surgical debridement and driveline relocation. Since NTM including RGM have the tendency to
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form biofilms, removing the foreign material in case of NTM infections of prosthetic material seems prudent whenever feasible (Sousa, 2015).
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Measures to prevent recurrence of NTM infection could not be established as specific risk factors
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(e.g. hot tub exposure or sauna visits) were not identified. Furthermore, such exposures are not allowed in this patient population. In conclusion, in patients with a an LVAD driveline infection
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unresponsive to conventional antibiotic regimens and with negative bacterial cultures on nonselective culture media NTM and RGM in particular should be considered as a cause. Besides
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the use of selective culture media including prolonged incubation in non-selective culture media at different temperatures might increase the yield. The combination of prolonged antibiotic therapy and surgical debridement and driveline relocation seems a prudent approach. Nevertheless, in each case a multidisciplinary approach should be used to determine the optimal
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management of LVAD-associated NTM infections. Funding
None of the authors received funding for this case report. Ethical Approval No ethical approval was needed. Written consent was signed by the patient.
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Conflict of interest
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All authors declare no conflict of interest.
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References 1.
de By T, Mohacsi P, Gahl B, Zittermann A, Krabatsch T, Gustafsson F, Leprince P, Meyns B, Netuka I, Caliskan K, Castedo E, Musumeci F, Vincentelli A, Hetzer R, Gummert J, members E. The European Registry for Patients with Mechanical Circulatory Support (EUROMACS) of the European Association for Cardio-Thoracic Surgery
2.
of
(EACTS): second report. Eur J Cardiothorac Surg 2018;53:309-16. Kormos RL, Cowger J, Pagani FD, Teuteberg JJ, Goldstein DJ, Jacobs JP, Higgins RS,
ro
Stevenson LW, Stehlik J, Atluri P, Grady KL, Kirklin JK. The Society of Thoracic
-p
Surgeons Intermacs database annual report: Evolving indications, outcomes, and scientific partnerships. J Heart Lung Transplant 2019;38:114-26. Simeon S, Flecher E, Revest M, Niculescu M, Roussel JC, Michel M, Leprince P,
re
3.
Tattevin P. Left ventricular assist device-related infections: a multicentric study. Clin
4.
lP
Microbiol Infect 2017;23:748-51.
Akin S, Muslem R, Constantinescu AA, Manintveld OC, Birim O, Brugts JJ, Maat A,
ur na
Froberg AC, Bogers A, Caliskan K. 18F-FDG PET/CT in the Diagnosis and Management of Continuous Flow Left Ventricular Assist Device Infections: A Case Series and Review of the Literature. Asaio J 2018;64:e11-e9. Nienaber JJ, Kusne S, Riaz T, Walker RC, Baddour LM, Wright AJ, Park SJ, Vikram
Jo
5.
HR, Keating MR, Arabia FA, Lahr BD, Sohail MR, Mayo Cardiovascular Infections Study G. Clinical manifestations and management of left ventricular assist deviceassociated infections. Clin Infect Dis 2013;57:1438-48.
6.
Kusne S, Mooney M, Danziger-Isakov L, Kaan A, Lund LH, Lyster H, Wieselthaler G, Aslam S, Cagliostro B, Chen J, Combs P, Cochrane A, Conway J, Cowger J, Frigerio M, 8
Gellatly R, Grossi P, Gustafsson F, Hannan M, Lorts A, Martin S, Pinney S, Silveira FP, Schubert S, Schueler S, Strueber M, Uriel N, Wrightson N, Zabner R, Huprikar S. An ISHLT consensus document for prevention and management strategies for mechanical circulatory support infection. J Heart Lung Transplant 2017;36:1137-53. 7.
Nunez Breton JD, Hernandez G, Simkins J, Chaparro SV. Mycobacterium abscessus Left Ventricle Assist Device Driveline Infections: An Emerging Pathogen? Transpl Infect Dis
Balsam LB, Louie E, Hill F, Levine J, Phillips MS. Mycobacterium chimaera left
ro
8.
of
2018;20:e12957.
ventricular assist device infections. J Card Surg 2017;32:402-4.
Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, Holland
-p
9.
re
SM, Horsburgh R, Huitt G, Iademarco MF, Iseman M, Olivier K, Ruoss S, von Reyn CF, Wallace RJ, Jr., Winthrop K, Subcommittee ATSMD, American Thoracic S, Infectious
lP
Disease Society of A. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med
10.
ur na
2007;175:367-416.
Sousa S, Bandeira M, Carvalho PA, Duarte A, Jordao L. Nontuberculous mycobacteria
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pathogenesis and biofilm assembly. Int J Mycobacteriol 2015;4:36-43.
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Figure legend
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Figure 1
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Figure 1A: transverse PET-CT view showing clear 18F-FDG uptake in the subcutaneous tissue surrounding the driveline
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Figure 1B: growth of Mycobacterium chelonae on chocolate agar
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Figure 1C: acid fast acid staining showing the presence of mycobacteria
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Figure 1D: driveline relocation procedure. * marks the infected part of the LVAD driveline
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Figure 1E: negative pressure wound therapy after driveline relocation
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