Download JMM CASE REPORTS Case report template Achromobacter

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JMM CASE REPORTS
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Case report template
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Achromobacter Xylosoxidans Endocarditis and Septic Arthritis in an
Infant Affected by Generalized Arterial Calcification of Infancy
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Craig S. Levoy1, MD, David J. Hall2, MD, and David Berman3, DO, MS
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Address:
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Department of Family Medicine, Bayfront Health, 700 Sixth Street South, St.
Petersburg, FL, USA, 33701
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Division of General Pediatrics and Adolescent Medicine, Johns Hopkins
University School of Medicine and All Children's Hospital Johns Hopkins
Medicine, 601 Fifth Street South, St. Petersburg, FL, USA 33701
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Division of Pediatric Infectious Diseases, All Children's Hospital Johns Hopkins
Medicine, 601 Fifth Street South, St. Petersburg, FL, USA 33701
Corresponding author:
Craig S. Levoy, MD
Corresponding author email address:
[email protected]
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In order to assist us in choosing the correct editor to handle your paper, please choose one box in each of the
following categories:
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Field:
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Subject:
X Human ☐Dental ☐Veterinary/Fisheries
X Bacteriology ☐Virology
☐ Mycology
☐ Parasitology
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Keywords: Please provide at least one keyword for each of the following categories:
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Disease/Indication: Achromobacter xylosoxidans, Generalized Arterial Calcification of Infancy
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Pathology/Symptoms: endocarditis, septic arthritis
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Treatment: Colistin
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ABSTRACT
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Introduction: Achromobacter xylosoxidans is a non-fermentative aerobic Gram-negative bacillus,
which most frequently causes nosocomial infections. Endocarditis from the pathogen has only rarely
been reported, and has a near-fatal outcome without surgical intervention.
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Case Presentation: We present a case of Achromobacter xylosoxidans endocarditis and septic arthritis
in an infant affected by Generalized Arterial Calcification of Infancy (GACI). The patient was
successfully treated with six weeks of intravenous colistin, meropenem, and trimethoprimsulfamethoxazole.
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Conclusion: This is the first reported case of colistin used to treat A. xylosoxidans endocarditis. We
discuss the antibiotic challenges of treating multi-drug resistant (MDR) A. xylosoxidans endocarditis
in a patient who is not a surgical candidate.
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INTRODUCTION
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Achromobacter xylosoxidans is a non-fermentative aerobic Gram-negative bacillus, which most
frequently causes nosocomial infections. Taxonomy has changed several times since its original
description in 1971, including the nomenclature Alcaligenes xylosoxidans, but most recent studies
have classified the bacterium as Achromobacter xylosoxidans (Yabuuchi & Oyama, 1971; Yabuuchi et
al., 1998). Infections with the pathogen vary and are traditionally noted in immunocompromised
patients. A. xylosoxidans is well-described among cystic fibrosis patients, presenting as an
opportunistic lung infection that readily acquires drug resistance (Jeukens et al., 2015; Tokuyasu et
al., 2012). A. xylosoxidans endocarditis has only rarely been described in the literature, and has a near
fatal outcome without surgical intervention (Derber et al., 2011).
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Generalized Arterial Calcification of Infancy (GACI, OMIM 208000) is a rare autosomal recessive
disorder, most attributed to mutations of the ENPP1 gene, characterized by calcification of the internal
elastic lamina of muscular arteries (Chong & Hutchins, 2008; Edouard et al., 2011; Farquhar et al.,
2005; Kalal et al., 2012; Ramjan et al., 2009; Rutsch et al., 2008; Rutsch et al., 2003; Shaireen et al.,
2013; van der Sluis et al., 2006). GACI is often fatal within the first 6 months of life, usually
secondary to myocardial ischemia resulting in refractory heart failure (Chong & Hutchins, 2008;
Rutsch et al., 2008; Rutsch et al., 2003). Recent studies, however, have demonstrated survival of
patient’s with GACI beyond the infancy period when treated with bisphosphonate therapy (Edouard et
al., 2011; Ramjan et al., 2009; Rutsch et al., 2008; van der Sluis et al., 2006). No formalized
treatment plan exists in the literature for patients affected by GACI. Drug choice, dosing, duration,
and route remain controversial (Ramjan et al., 2009).
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Colistin, also known as polymyxin E, is an antibiotic that has been used in the Cystic Fibrosis
population as a drug of “last resort” for multi-drug resistant (MDR) gram-negative bacterial
pneumonia (Biswas et al., 2013). A recent study demonstrated that intravenous colistin was safe and
effective in the treatment of severe nosocomial infections caused by MDR gram-negative bacteria in
the pediatric population (Karl et al., 2013).
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Our case describes a six-month-old Hispanic male with GACI, found to have MDR A. xylosoxidans
endocarditis and septic arthritis/myositis, who was successfully treated with six weeks of intravenous
colistin, meropenem, and trimethoprim-sulfamethoxazole.
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CASE REPORT
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A six-month-old Hispanic male with a medical history of GACI presented with fever and a two-day
history of right hip pain with decreased range of motion. The patient was receiving long-term weekly
intravenous bisphosphonate therapy via a tunnelled central venous catheter for treatment of his GACI.
The patient had a rectal temperature of 38.6° C on presentation. There was no cardiac murmur on the
initial physical examination. His right hip was held in a flexed position and he cried with passive hip
movement. Magnetic Resonance Imaging of the right hip demonstrated a small right joint effusion
with synovial and adjacent muscle enhancement. The patient subsequently underwent incision and
drainage of the right hip. Culture of the hip joint aspirate, as well as blood cultures from peripheral
and central venous line sites ultimately grew Achromobacter xylosoxidans. Identification of the
organism was accomplished using Microscan Walk-Away combo ID and MIC panel (Beckman
Coulter, Brea, CA) The initial isolate was susceptible to ceftazidime, levofloxacin, meropenem,
piperacillin/tazobactam, imipenem-cilastatin, trimethoprim-sulfamethoxazole, and
ticarcillin/clavulanate; intermediate to ceftriaxone; and resistant to amikacin, aztreonam, cefepime,
ciprofloxacin, gentamicin, and tobramycin. Antimicrobial susceptibility testing to these antibiotics
was performed using both MicroScan Walk-Away and Etest (bioMérieux, Durham, NC) with CLSI
(Clinical and Laboratory Standards Institute) interpretation. The patient’s tunnelled central line was
removed and he was started on intravenous piperacillin/tazobactam (300 mg kg–1 day–1).
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Despite central line removal, the patient remained persistently bacteremic and ultimately a systolic
murmur was auscultated on physical exam. A transthoracic echocardiogram revealed a hyperechoic
lesion on the anterior mitral leaflet measuring 5 mm x 6 mm, increased in size from a calcification
previously noted as a sequela of the patient’s underlying GACI in the same position several months
prior during routine outpatient care.
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After three days of antimicrobial therapy, the patient persisted with fever and bacteremia. At the
recommendation of specialist consultation, piperacillin/tazobactam was discontinued and triple
antibiotic therapy was instituted with intravenous meropenem (60 mg kg–1 day–1), levofloxacin (20 mg
kg–1 day–1), and trimethoprim-sulfamethoxazole (18 mg kg–1 day–1). Following fourteen days of this
antibiotic regimen, daily blood cultures continued to grow A. xylosoxidans. Additional susceptibility
testing demonstrated the development of resistance to levofloxacin, identified using the described
antimicrobial susceptibility testing. Using the disk-diffusion method for colistin susceptibility, the
disk diffusion zone was measured at 11 mm, considered susceptible by most standards (Biswas et al.,
2013). Levofloxacin was therefore discontinued and substituted with intravenous colistin (7 mg kg–
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day–1). Repeat susceptibility testing obtained one day following colistin administration demonstrated
resistance to all antibiotics tested (ceftazidime, levofloxacin, meropenem, piperacillin/tazobactam,
imipenem-cilastatin, trimethoprim-sulfamethoxazole, ticarcillin/clavulanate, ceftriaxone, amikacin,
aztreonam, cefepime, ciprofloxacin, gentamicin, and tobramycin). However, as the patient had been
afebrile after starting colistin, the regimen was continued. Blood cultures obtained three days after the
initiation of colistin demonstrated no bacterial growth.
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Repeat transthoracic echocardiogram, however, demonstrated progression of the hyperechoic lesion
on the anterior mitral valve leaflet with a hypermobile vegetation measuring 7 mm x 8 mm prolapsing
into the left atrium during ventricular systole. Surgical intervention was considered. Specialist
consultation and pediatric team meetings, however, determined that cardiothoracic surgery posed too
high of a risk of mortality given the patient’s underlying GACI.
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The patient was therefore continued on intravenous meropenem, trimethoprim-sulfamethoxazole, and
colistin for a total of six weeks after the first set of negative blood cultures were obtained. Subsequent
blood cultures over the six weeks showed no bacterial growth. Towards the latter part of the hospital
course, one blood culture from a peripherally inserted central catheter (PICC) grew Candida
parapsilosis. The PICC line was immediately removed and the patient was treated with intravenous
fluconazole (12 mg kg–1 day–1), with repeat peripheral blood cultures demonstrating no growth.
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To avoid the need for placement of a new central venous line, the patient was transitioned to oral
bisphosphonate therapy (risedronate 5 mg once per week) for treatment of his GACI. Six months
following hospital discharge, the patient remained afebrile with negative blood cultures. Outpatient
follow-up transthoracic echocardiogram showed no significant change. The patient did not develop
any neurotoxic or nephrotoxic side effects as a result of colistin therapy.
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DISCUSSION
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To our knowledge, this is the only pediatric case report of a patient with GACI diagnosed with leftsided native valve A. xylosoxidans endocarditis and right hip septic arthritis/myositis. This is also the
only report of a patient with A. xylosoxidans endocarditis treated, successfully or otherwise, with
colistin as part of the antibiotic regimen.
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No formalized therapeutic plan exists in the literature for patients affected by GACI. In our case, the
patient presented with a treatment regimen consisting of long-term weekly low-dose (0.1 mg kg–1)
intravenous pamidronate. The probable source of infection in our patient was the indwelling tunnelled
central venous line. The patient’s pre-existing mitral valve calcification secondary to his underlying
GACI likely acted as a nidus for the opportunistic A. xylosoxidans bacterium. Using the Modified
Duke criteria for infective endocarditis, the patient met two major (positive blood culture and
evidence of endocardial involvement) and two minor criteria (predisposing heart condition and fever
>38 C) (Li et al., 2000).
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A MEDLINE search of the English language literature resulted in only two case reports of A.
xylosoxidans septic arthritis (San Miguel et al., 1991; Suryavanshi & Lalwani 2015). Broadening the
search to include cases of osteomyelitis resulted in a total of seven reported cases (Dubey et al., 1988;
Fort et al. 2014; Hoddy & Barton, 1991; Pamuk et al. 2015; Ozer et al., 2012; Stark, 2007; Walsh et
al., 1993).
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A MEDLINE search of the English language literature for infective endocarditis secondary to A.
xylosoxidans resulted in only fourteen reported cases (Ahn et al., 2004; Davis et al., 1982; Derber et
al., 2011; Lofgren et al., 1981; Malek-Marin et al., 2009; Martino et al., 1990; McKinley et al., 1990;
Nanuashvili et al., 2007; Olson & Hoeprich, 1982; Rafael et al. 2014; Sasaki et al., 1993; Storey et
al., 2010; Tokuyasu et al., 2012; van Hal et al., 2008). A review of those cases demonstrated a greater
than fifty-percent mortality rate (Derber et al., 2011; Tokuyasu et al., 2012). Of the surviving patients,
only one case series reported survival in a patient who did not undergo surgical intervention
(McKinley et al., 1990).
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Based on expert medical opinion, our patient was not a surgical candidate. Additionally, resistance to
antibiotic therapy developed during treatment. Given the near certain risk of fatality without surgical
intervention, we explored additional antibiotic options.
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Little is known about optimal antibiotic therapy for A. xylosoxidans infections. Neither the CLSI nor
the EUCAST (The European Committee on Antimicrobial Susceptibility Testing) provide specific
guidance beyond nonspecies-related breakpoints. Intrinsic antibiotic resistance patterns and acquired
resistance has been widely reported (Abbott & Peleg 2015). It has been suggested that the most active
antibiotic agents against A. xylosoxidans are piperacillin-tazobactam, meropenem, and trimethoprimsulfamethoxazole, with tetracyclines having variable activity (Abbott & Peleg 2015). In the CF patient
population, the use of concurrent inhaled colistin has been reported as effective (Abbott & Peleg
2015; Jacquier et al. 2012; Biswas et al. 2013; Karl et al. 2013). The use of intravenous colistin, in
conjunction with meropenem and trimethoprim-sulfamethoxazole, led to resolution of bacteremia in
our patient.
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This case demonstrates two important, but separate, findings: the first specifically for patients affected
by GACI, and the second for patients with difficult to clear A. xylosoxidans infections. First, while
inherently limited, the current literature on GACI treatment has demonstrated similar efficacy of
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short-term intravenous bisphosphonate therapy followed by transition to oral bisphosphonate therapy
when compared to long-term intravenous bisphosphonate therapy alone (Ramjan et al., 2009). Our
case highlights the importance of the former approach over the latter, secondary to the risk of line
infection associated with long-term intravenous therapy. Second, this is the first known case report of
A. xylosoxidans infective endocarditis treated with intravenous colistin. Clearance of the bacteria was
noted within three days of starting colistin therapy. Our case is one of only two known reports of
survival in a patient with A. xylosoxidans endocarditis who did not undergo surgical intervention. In
cases of non-operable MDR A. xylosoxidans endocarditis, we propose the consideration of colistin as
part of an extended intravenous antibiotic regimen.
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Figure/Table Captions
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Abbreviations
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Ethical Statement
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Acknowledgements/Declaration of Interest
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Signature:
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Date:
13 September 2015
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