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Case Report |
1 Department of Clinical Microbiology, Nottingham University Hospitals NHS Trust, Queen's Medical Centre, Nottingham NG7 2UH, UK
2 Laboratory of HealthCare Associated Infection, Centre for Infections, Health Protection Agency, Colindale, London, UK
3 Institute of Infections, Immunity and Inflammation, School of Molecular Medical Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK
Correspondence
David P. J. Turner
david.turner{at}nottingham.ac.uk
Received 8 January 2007
Accepted 19 February 2007
Abbreviations: LHCAI, Laboratory of HealthCare Associated Infection.
The GenBank/EMBL/DDBJ accession no. for the 16S rRNA gene sequence of the isolate of Neisseria elongata is DQ914524.
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Case report |
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On examination, no murmurs were detected, but chest examination revealed bi-basal crepitations. A fever of 38.8 °C was noted 1 day after admission. A chest radiograph showed a heart at the upper limits of normal size, but no evidence of consolidation. Urinalysis demonstrated 3+ protein and 2+ blood; microscopic haematuria was present, but mid-stream urine culture was sterile. Abnormal blood results included: 127 mmol sodium l–1, 11.6 mmol urea l–1, 103 mmol creatinine l–1, 11.1 g haemoglobin dl–1, 113x109 platelets l–1, 170 mg C-reactive protein l–1, and an erythrocyte sedimentation rate of 31 mm h–1. The aerobic bottles (BD BACTEC Plus Aerobic/F) from each of three independently taken sets of blood cultures subsequently grew a Gram-negative bacillus after 1 day of incubation on the BACTEC 9240 instrument (BD Microbiology Systems), which proved difficult to identify. The anaerobic bottles (BD BACTEC Lytic/10 Anaerobic/F) remained negative after 5 days incubation. Antibiotic sensitivity tests (using the British Society for Antimicrobial Chemotherapy disc diffusion methodology) showed the organism was resistant to trimethoprim, but sensitive to amoxicillin, cefuroxime, ceftriaxone, ceftazidime, gentamicin, ciprofloxacin and meropenem. The patient was treated with 1 g intravenous ceftazidime twice a day and gentamicin. Over the next 5 days, he deteriorated and developed acute renal failure, metabolic acidosis and atrial fibrillation. Transthoracic echocardiography showed that the aortic valve replacement was thickened, which was confirmed by transoesophageal echocardiography.
Based on the Gram stain appearance and the initial biochemical profile, the blood culture isolate was provisionally identified as belonging to the genus Kingella, but was formally identified at the Laboratory of HealthCare Associated Infection (LHCAI) as Neisseria elongata subsp. elongata based on biochemical reactions (oxidase positive, catalase negative, lysine and ornithine negative, indole negative, glucose acid production negative, nitrate reduction negative, nitrite reduction positive) and the sequence of the 16S rRNA gene (GenBank accession no. DQ914524). The 16S rRNA gene was 99.6 % identical to both the N. elongata subsp. elongata and N. elongata subsp. glycolytica type strain sequences, but the organism was differentiated from the latter by the negative reaction in the catalase test. A negative reaction for nitrate reduction differentiated the organism from N. elongata subsp. nitroreducens.
A diagnosis of prosthetic aortic valve endocarditis was made, and antibiotic therapy was changed to 2 g intravenous amoxicillin 4 hourly and gentamicin. After 3 weeks, therapy was continued with 2 g intravenous ceftriaxone daily to complete 6 weeks treatment in total. The patient recovered fully.
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Discussion |
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Isolates of subspecies N. elongata subsp. nitroreducens from blood cultures have been described to be frequently in association with endocarditis (Grant et al., 1990). In contrast, there are only two previous reports of endocarditis due to N. elongata subsp. elongata (Apisarnthanarak et al., 2001; Nawaz et al., 1996) and one due to N. elongata subsp. glycolytica (Andersen et al., 1995). It is unclear whether the pathogenic potential of the latter two subspecies is lower than that of N. elongata subsp. nitroreducens or whether N. elongata subsp. nitroreducens is more readily isolated from blood culture systems. Since 2003, the LHCAI has identified N. elongata subsp. elongata and N. elongata subsp. glycolytica from three and two blood cultures, respectively, although the source of infection was unknown. Interestingly, no isolates of N. elongata subsp. nitroreducens were identified during this period. Overall, N. elongata is the most common of the opportunistic Neisseria spp. reported as the aetiological cause of endocarditis. The other reported species include: Neisseria mucosa (20 cases), Neisseria sicca (14 cases), Neisseria subflava (12 cases), Neisseria cinerea (1 case) and Neisseria flavescens (1 case).
The patient described in this report had previously undergone aortic valve replacement surgery for valvular heart disease in association with Klinefelter's syndrome. Patients with Klinefelter's syndrome are recognized to have an increased risk of such disease (principally mitral valve prolapse, but also aortic valve disease), which is associated with increased mortality. Given the relatively high incidence of valvular disease in patients with Klinefelter's syndrome, we were surprised at the apparent absence of reports of endocarditis in association with this syndrome. The importance of good dental care needs to be emphasized in these patients.
The isolate of N. elongata subsp. elongata in this report proved difficult to formally identify. The isolate grew rapidly in the aerobic bottles on the BACTEC 9240 instrument, but failed to grow in the three anaerobic bottles. The commercially available identification system, API NH (BioMérieux) was unable to assign the organism to a specific genus. Based on the Gram-stain morphology and initial biochemical tests, the organism was tentatively identified as Kingella sp., and referred to the LHCAI for further analysis. At the LHCAI, long-chain cellular fatty acid analysis revealed a profile that was closest to that of N. weaveri. However, as the latter is catalase-positive, the sequence of the 16S rRNA gene was determined. The sequence closely matched that of N. elongata, and biochemical tests were subsequently able to assign the organism to N. elongata subsp. elongata. Sequencing of the 16S rRNA gene has previously been reported as useful in the identification of N. elongata (Hombrouck-Alet et al., 2003).
We have reviewed the English-language reports of endocarditis due to all the subspecies of N. elongata. Eighteen cases of endocarditis due to N. elongata (including this case) have been described in detail (Andersen et al., 1995; Apisarnthanarak et al., 2001; Dominguez & Smith, 1998; Grant et al., 1990; Haddow et al., 2003; Hoshino et al., 2005; Imperial et al., 1995; Kaplan & Flaherty, 1991; Kociuba et al., 1993; Meuleman et al., 1996; Nawaz et al., 1996; Perez, 1986; Picu et al., 2003; Rose et al., 1990; Simor & Salit, 1983; Struillou et al., 1993). The reported age range is 7–82 years. Five (28 %) of the cases affected prosthetic valves, and prior dental infection (or treatment) was reported in eight (44 %) cases. All cases were treated with a third generation cephalosporin, benzylpenicillin or ampicillin/amoxicillin, usually combined with gentamicin in the initial phase. The total length of treatment varied between 4 and 7 weeks. Notably, a high proportion of patients (9/18, 50 %) required valvular surgery, but all patients for whom the outcome was stated (17/18) survived.
In conclusion, we describe what is believed to be the third case of endocarditis due to N. elongata subsp. elongata. Clinical microbiologists and physicians should be alert to the possibility of endocarditis when opportunistic Neisseria spp. (particularly N. elongata) are isolated from blood cultures. The possibility that rod-shaped isolates, biochemically resembling the genus Kingella, may belong to the genus Neisseria should also be considered. We suggest that the acronym, ‘HACEK’, which is widely used to describe a miscellaneous group of Gram-negative coccobacilli that colonize the oropharynx and are rarely associated with endocarditis, should be changed to ‘HACNEK’ (the ‘N’ representing N. elongata) as an aide-mémoire for clinical practice and future studies.
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