REVIEW ARTICLE
Infective Endocarditis Due to Neisseria elongata Amit Noheria, MBBS, SM, Peter W. Anderson, MD, Gino G. Tapia-Zegarra, MD, Larry M. Baddour, MD, and Walter R. Wilson, MD
Abstract: We present 2 cases of prosthetic valve endocarditis due to Neisseria elongata subspecies nitroreducens and elongata. Neisseria elongata is a fastidious, immotile, oxidase-positive, gram-negative bacillus found in the human oropharyngeal flora that is a rare cause of infective endocarditis. It is distinguished from Kingella kingae, Eikenella corrodens, and other organisms based on extended biochemical testing and 16S recombinant DNA sequencing. We review the literature on N. elongata endocarditis and highlight the similarities between N. elongata and HACEK organisms regarding their biochemical profiles and clinical features of infective endocarditis. (Infect Dis Clin Pract 2010;00: 00Y00)
eisseria elongata is a commensal human oropharyngeal organism first described in 1970.1 It is a nonmotile, oxidasepositive, short, and slender rod arranged as diplobacilli or short chains, with some coccoid forms. It is gram negative with a slight tendency to retain the first stain. It has limited ability to survive on blood agar at room temperature. Neisseria elongata is closely related to Kingella, Eikenella, Moraxella, Centers for Disease Control (CDC) group EF4, and a group of other difficult to identify organisms, apart from similarities with other Neisseria species.2 Although most Neisseria species are gramnegative diplococci, a few bacillary forms occur and include N. elongata, N. weaveri (formerly CDC group M5), N. bacilliformis, and group AK105. Although it is rare for N. elongata to cause infective endocarditis, it is the most common cause of infective endocarditis among all Neisseria species; others include N. mucosa, N. sicca, N. subflava, and occasionally N. cinerea, N. flavescens, N. gonorrhea, and group AK105.3,4 The subspecies nitroreducens (formerly CDC group M6) has been most frequently linked to infective endocarditis; it also can cause septicemia and osteomyelitis.2,5,6 Neisseria elongata subspecies elongata and glycolytica have been rarely reported to cause infective endocarditis.3,5 We present 2 cases of prosthetic valve endocarditis due to N. elongata subspecies nitroreducens and elongata and highlight the similarities between N. elongata
N
From the Division of Infectious Diseases, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN. Correspondence to: Dr. Walter R. Wilson, MD, Division of Infectious Diseases, Mayo Clinic, 200 First St. SW, Rochester, MN 55905. E-mail:
[email protected]. The authors have no funding or conflicts of interest to disclose. Ethics review/informed consent is not applicable. Copyright * 2010 by Lippincott Williams & Wilkins ISSN: 1056-9103
Infectious Diseases in Clinical Practice
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and HACEK organisms regarding their biochemical profiles and the clinical features of infective endocarditis.
CASE REPORTS Patient 1 A 65-year-old woman presented to the emergency department with a 4-day history of mild headache, malaise, moderategrade fever, and dyspnea. Levofloxacin was initiated after 2 sets of blood cultures grew gram-variable coccobacilli the next day. She had a history of bicuspid aortic valve endocarditis due to Haemophilus aphrophilus 24 years ago and had aortic valve homograft placement 15 years ago. Three years ago, she had mechanical mitral and composite aortic root replacement and tricuspid annuloplasty with subsequent anticoagulation and a single ventricular lead pacemaker implantation for atrial fibrillation and heart block. She was admitted to our hospital 2 days later. Medications included levofloxacin, warfarin, levothyroxine, aspirin, and multivitamins. She had a grade 3/6 midsystolic murmur at the left upper sternal border without any clinical evidence of embolic phenomenon. There was slight leukocytosis (10.7 109 leukocytes per liter, 83% neutrophils) with elevated erythrocyte sedimentation rate (75 mm/h) and C-reactive protein level (349 mg/L). Vancomycin, cefepime, rifampin, and gentamicin were started instead of levofloxacin. Rifampin and gentamicin were discontinued the next day when the blood culture isolate was reported to be a gram-negative oxidase-positive bacillus. A two-dimensional transesophageal echocardiogram (TEE) with Doppler imaging on day 2 of inpatient antibiotic therapy showed a homogenous crescentic echodensity (È1.4 3.6 cm) surrounding the aortic root consistent with perivalvular extension of infection and mobile echodensities on the pacing lead 1-cm proximal to the superior vena cavaYright atrial junction suggestive of thrombus or vegetation. Repeated TEE on day 7 showed the crescentic echodensity to be slightly smaller, pacing lead densities no longer seen, and no fistulous connections or vegetations. The culture isolate was procured. Preliminary report suggested it to be Kingella kingae but was later confirmed as N. elongata subspecies nitroreducens: nonmotile, biochemical profile positive for oxidase and nitrate reductase and negative for catalase, urease, lysine decarboxylase, arginine dihydrolase, ornithine decarboxylase, and oxidative fermentation of glucose, maltose, and xylose. The identification was confirmed by 16S recombinant DNA (rDNA) sequencing. Following in vitro antibiotic susceptibility results, vancomycin and cefepime were discontinued, and ceftriaxone was started to complete a total antibiotic course of 42 days. Repeated TEE on day 42 and blood cultures on days 50 and 72 were unremarkable, and the patient had no signs of endocarditis relapse.
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Infectious Diseases in Clinical Practice
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TABLE 1. Biochemical Properties of N. elongata Subspecies, K. kingae, and E. corrodens Biochemical Test
N. elongata Subspecies nitroreducens
N. elongata Subspecies elongata
N. elongata Subspecies glycolytica
Kingella kingae
Eikenella corrodens
+ j j
+ j j
+ + j
+ j j
+ j +
j
j
j
j
j
j +
j j
j j
j j
j +
j + j/weak +
j + j
j + weak +
j j +/j
j + j
Oxidase Catalase Ornithine decarboxylase Indole production Urease Nitrate reductase Gas from nitrate Nitrite reductase Acid from d-glucose
Patient 2 A 60-year-old woman on anticoagulation for mechanical aortic and mitral valves that were placed 10 years ago because of rheumatic heart disease developed nausea, emesis, chills, and a temperature of 102.5-F. She was treated for community-acquired pneumonia with levofloxacin for 7 days. A week after completing the antibiotic course, she presented to the emergency department with recurrent symptoms, a temperature of 103.5-F, and hypotension. She was fluid resuscitated and supported with dopamine; blood cultures were obtained, and she received a dose of ceftriaxone. Next day, a new cardiac murmur was noted, and the blood cultures grew gram-variable bacilli. She was started on vancomycin, gentamicin, and rifampin and the following day transferred to our hospital. On transfer, she was hemodynamically stable and afebrile and had no evidence of embolic phenomenon on physical examination or head computed tomography. She had necrotic teeth, mechanical S1 and S2, with a grade 2/6 midsystolic murmur at the left upper sternal border. Complete blood cell counts and electrolytes were unremarkable. A transthoracic echocardiogram showed no evidence of vegetations or regurgitation. Two-dimensional TEE with Doppler imaging the next day showed a mobile vegetation (0.7 0.3 cm) attached to the aortic surface of the prosthetic valve and no evidence of perivalvular extension. After 2 days, on confirmation of the isolate to be gram-negative diplobacilli, meropenem was started instead of vancomycin, gentamicin, and rifampin and changed 3 days later to ertapenem for ease of dosing. Ten days later, the patient was discharged on outpatient ceftriaxone. The organism was finally identified as N. elongata by 16S rDNA sequencing. This was consistent with the organism being nonmotile and the biochemical profile being positive for oxidase but negative for nitrate reductase, catalase, urease, lysine decarboxylase, arginine dihydrolase, and oxidative fermentation of glucose, maltose, xylose, sucrose, lactose, and mannitol. Negative catalase excluded subspecies glycolytica, and negative nitrate reductase excluded subspecies nitroreducens, and the identification was N. elongata subspecies elongata. On day 24 of antibiotic coverage, the patient was readmitted with a temperature of 102.6-F. Transesophageal echocardiogram showed new vegetations on the ventricular aspect of the aortic prosthesis. She was started on cefepime and gen-
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tamicin and underwent uncomplicated surgical aortic valve replacement. Operative cultures were negative. She was dismissed on an additional 6 weeks of cefepime and gentamicin. A week later, she presented with a renal toxic reaction that prompted discontinuation of gentamicin; cefepime was continued to complete 6 weeks of therapy.
DISCUSSION Both patients had prosthetic valve endocarditis due to nonmotile gram-negative indistinct bacilli that initially retained the Gram stain. In addition, the biochemical profiles, including presence of oxidase, were similar to Kingella and Eikenella, although key differences allowed identification of the organisms as N. elongata subspecies (Table 1).2 The identification was confirmed by 16S rDNA sequencing, although this technique does not allow verification of the subspecies. Grant et al2 in their 1990 review of the N. elongata subspecies nitroreducens isolates analyzed at the Special Bacteriology Reference Laboratory, CDC, Atlanta, reported 15 cases of endocarditis between 1964 and 1988. Similarly, Wong and Janda6 in their 1992 review of N. elongata subspecies nitroreducens isolates at the Microbial Diseases Laboratory, California Department of Health, Berkeley, reported 9 cases of endocarditis due to this organism between 1974 and 1990. Reviewing the descriptive clinical case reports in the literature and including our 2 cases, we summarize 23 cases of endocarditis due to N. elongata, 17 due to nitroreducens, 4 due to elongata, and 2 due to glycolytica (Table 2).2,3,5,7 Of the 23 total cases, 16 were native valve endocarditis, and 7 involved prosthetic valves. Nine of the 16 native valve endocarditis cases had a known cardiac abnormality including 7 with a valvular anomaly. Nearly all cases presented with insidious onset of nonspecific symptoms such as fever, malaise, arthralgias, and headache for 1 to 3 weeks, often relapsing after a course of antibiotics. Vegetations were visualized in 12 of these 23 cases including 3 of 4 elongata and both glycolytica cases. At least 4 patients developed a myocardial abscess, and 7 patients had heart failure. Systemic embolization occurred in 7 of the 23 cases, including 4 strokes. Cardiac surgery was performed in 11 cases. All patients were treated with penicillin, ampicillin, or a third-generation cephalosporin, with or * 2010 Lippincott Williams & Wilkins
Copyright © 2010 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
* 2010 Lippincott Williams & Wilkins
1996
1998
2001
2003
2005
2008
Nawaz et al
Hofstad et al
Apisarthanarak et al
Haddow et al
Hoshino et al
Hsiao et al
Prosthetic valve endocarditis Mauleman et al 1996
2003
1995 1995
Anderson et al Imperial et al
Picu et al
1993
Struillou et al
79
50
7
54
65
30
29
57 31
27
33
M
M
F
M
M
M
F
M
M
M F
M
M
M M
N
N
N
G
N
N
E
N
E
G N
N
N
N N N
N
N
N
MV vegetation, MR AV vegetation, AR, abscess Thick echolucent PTFE PV MV vegetation, MR
None
MV vegetation, MR
AV vegetation MV vegetation
AV vegetation, AR, abscess None
MR AR, MR MV vegetation, MR
MV vegetation
None
MV vegetation
Prosthetic AV, None dental infection, pacemaker Prosthetic AV AV vegetation, abscess Prosthetic AV, Sub-valvular dental infection stenosis
TGA, status post Rastelli repair None
Bicuspid AV
None
HoCM
None
MVP, dental infection None None
Bicuspid AV
None None Myxomatous MV
MVP
RHD, AR
MVP
New Echo Findings
1 major, 3 minor
1 major, 4 minor
1 major, 2 minor
2 major
1 major, 2 minor
2 major
1 major, 2 minor
1 major, 2 minor
2 major
2 major 1 major, 2 minor
1 major, 3 minor
2 major
2 major 3 minor 2 major
1 major, 3 minor
1 major, 2 minor
2 major
Duke Criteria
Stroke, SAH, abscess AKI
None
Stroke
None
CHF, abscess
Surgical Treatment
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AVR
None
(Continued on next page)
Vancomycin, gentamicin, ampicillin 4 wk Ceftriaxone 6 wk; gentamicin 2 wk
Ampicillin 6 wk; gentamicin 2 wk
Ceftazidime 7 wk; AVR gentamicin 4 wk Ampicillin, gentamicin 2 wk; None ceftriaxone 6 wk Penicillin, gentamicin 1 wk; Debridement, ceftriaxone 8 wk MV repair
None
None
None
None None
Penicillin, gentamicin 2 wk; MVR ampicillin 4 wk Ampicillin 43 d; AVR tobramycin 26 d Nafcillin, gentamicin, Debridement penicillin 65 d Nafcillin, gentamicin, penicillin MVR Ceftriaxone 4 wk None Ceftazidime 10 d; MVR gentamicin 16 d; ampicillin 4wk Penicillin 9 d; ampicillin, AVR gentamicin 4 wk Ceftriaxone 6 wk MVR
Antibiotic Treatment
Penicillin, gentamicin 5 wk Ampicillin, gentamicin, ceftriaxone 4 wk Brachial Ampicillin, vancomycin pseudoaneurysm 3 d; ceftriaxone, gentamicin 6 wk None Benzylpenicillin, netilmicin, ceftriaxone 2 wk None Ceftriaxone 6 wk
Abscess, systemic embolization Splenic infarct, CHF None None
CHF, AKI TTP, stroke CHF, AKI
Stroke
Abscess, AKI, CHF CHF
Complications
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1998
74
1993
Kociuba et al
25 65 82
M
M
F
Risk Factors
&
Dominiguez et al
42
1990 1990 1991
Grant et al Rose et al Kaplan et al
31
1990
Grant et al
57
1986
Perez et al
31
Year Age Sex Subspecies
Native valve endocarditis Simor et al 1983
Author
TABLE 2. Case Reports of Infective Endocarditis Due to N. elongata
Infectious Diseases in Clinical Practice Neisseria elongata Endocarditis
3
Infectious Diseases in Clinical Practice
4
AKI 1 major, 3 minor E F 60 Noheria et al
2010
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AKI indicates acute kidney injury; AR, aortic regurgitation; AV, aortic valve; AVR, aortic valve replacement; CHF, congestive heart failure; E, elongate; F, female; G, glycolytica; HoCM, hypertrophic obstructive cardiomyopathy; M, male; MR, mitral regurgitation; MV, mitral valve; MVP, mitral valve prolapse; MVR, mitral valve replacement; N, nitroreducens; PV, pulmonic valve; RHD, rheumatic heart disease; SAH, subarachnoid hemorrhage; TGA, transposition of great arteries; TTP, thrombotic thrombocytopenic purpura.
AVR
None 3 minor 65 Noheria et al
2010
F
N
Prosthetic AV/MV, AV collection, pacemaker pacer lead density Prosthetic AV/MV, AV vegetation, dental infection increased gradient
None 70 Evans et al
2007
M
E
Prosthetic AV
AV thickening
1 major, 3 minor
Cefepime, gentamicin 1 wk; cefepime 5 wk
None
None
None
Cefepime 4 wk; amikacin 2 wk Amoxicillin, gentamicin 3 wk; ceftriaxone 2 wk Vancomycin, cefepime 1 wk; ceftriaxone 6 wk AKI 1 major, 2 minor 67 Cervera et al
2004
M
N
Prosthetic AV
None
Complications Author
TABLE 2. (Continued)
Year Age Sex Subspecies
Risk Factors
New Echo Findings
Duke Criteria
Antibiotic Treatment
Surgical Treatment
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without an aminoglycoside. Our case with nitroreducens is the third report of infective endocarditis due to a Neisseria species in a patient with a pacemaker (previous reports due to N. elongata subspecies nitroreducens and Neisseria species group AK105).4,8 She was treated with antibiotics alone. The case with elongata had vegetations and ultimately required surgical valve replacement. Neisseria elongata is similar to the HACEK group organisms that are also gram-negative coccobacillary organisms found in normal oropharyngeal flora, grow slowly, prefer a carbon dioxideYenriched atmosphere, and have an enhanced propensity to cause endocarditis. Neisseria elongata can be easily mistaken for Kingella and occasionally Eikenella in the preliminary microbiologic reports but can be distinguished on full biochemical profile (as opposed to N. elongata, K. kingae is nitrate reductase negative, and E. corrodens is ornithine decarboxylase positive) and rDNA sequencing. Similar to infective endocarditis with the HACEK organisms, N. elongata endocarditis presents as a subacute course is often cured with medical therapy alone, has a significant embolic risk, and is associated with low mortality. In summary, N. elongata is an organism that is fastidious and difficult to identify with characteristics similar to some organisms in the HACEK group. Rarely, it can cause infective endocarditis. We question whether the term HANCEK is a better acronym that includes N. elongata and other Neisseria species. If HANCEK were so designated, then the isolation of N. elongata in blood cultures would serve as a major Duke criterion in defining the syndrome of infective endocarditis.9
REFERENCES 1. Bovre K, Holten E. Neisseria elongata sp.nov., a rod-shaped member of the genus Neisseria. Re-evaluation of cell shape as a criterion in classification. J Gen Microbiol. 1970;60(1): 67Y75. 2. Grant PE, Brenner DJ, Steigerwalt AG, et al. Neisseria elongata subsp. nitroreducens subsp. nov., formerly CDC group M-6, a gram-negative bacterium associated with endocarditis. J Clin Microbiol. 1990;28(12):2591Y2596. 3. Evans M, Yazdani F, Malnick H, et al. Prosthetic valve endocarditis due to Neisseria elongata subsp. elongata in a patient with Klinefelter’s syndrome. J Med Microbiol. 2007;56(Pt 6): 860Y862. 4. Michaux-Charachon S, Lavigne JP, Le Fle`che A, et al. Endocarditis due to a new rod-shaped Neisseria sp. J Clin Microbiol. 2005;43(2):886Y889. 5. Hsiao JF, Lee MH, Chia JH, et al. Neisseria elongata endocarditis complicated by brain embolism and abscess. J Med Microbiol. 2008;57(Pt 3):376Y381. 6. Wong JD, Janda JM. Association of an important Neisseria species, Neisseria elongata subsp. nitroreducens, with bacteremia, endocarditis, and osteomyelitis. J Clin Microbiol. 1992;30(3): 719Y720. 7. Cervera JI, Todolı´ JA, Sauquillo JM, et al. Endocarditis due to the Neisseria elongata subspecies nitroreducens [in Spanish]. Enferm Infecc Microbiol Clin. 2004;22(9):556Y557. 8. Meuleman P, Erard K, Herregods MC, et al. Bioprosthetic valve endocarditis caused by Neisseria elongata subspecies nitroreducens. Infection. 1996;24(3):258Y260. 9. Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis. 2000;30(4):633Y638.
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