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Septic arthritis due to Kingella kingae in an adult patient.

Introduction

Kingella kingae, a short Gram negative bacillus, is best known for being a constituent of the HACEK group of organisms; i.e. Aggregatibacter (formerly the aphrophilus group of Haemophilus and Actinobacillus), Cardiobacterium, Eikenella, and Kingella spp (1). It is part of the normal pharyngeal flora in children, and is well recognised as a cause of invasive bone and joint infections in this age group (2). However infections due to K. kingae in adult patients are much less common and the patients usually have a degree of immunocompromise. We report here an unusual case of ankle septic arthritis due to K. kingae in an adult patient.

Case Report

A 68 year old woman, with a 40 year history of rheumatoid arthritis, was admitted with a 2 day history of acute on chronic worsening of pain and swelling in her right ankle. Having undergone left total hip and bilateral knee joint replacements, she was awaiting a right ankle replacement. At presentation she was taking azathioprine, prednisone and celecoxib for her rheumatoid arthritis.

On examination she was febrile with a warm, swollen, erythematous right ankle, with pain on movement and tenderness over the medial and lateral malleoli. Blood tests showed a normal leucocyte count but raised inflammatory markers (CRP: 161mg/L, ESR: 72 mm/ hr). X-rays confirmed arthritic changes in the ankle and foot.

Aspiration of the ankle recovered 1.5ml of turbid fluid. A formal white cell count was not performed. A Gram stain demonstrated large numbers of white cells, which were predominantly neutrophils, but no organisms were visualised. The sample was of insufficient volume for biochemistry analysis. The aspirate was inoculated on to blood and chocolate agar (CO2 incubation at 37[degrees]C) and Fastidious Anaerobe Agar (anaerobic incubation at 37[degrees]C). There was insufficient aspirate to inoculate a blood culture bottle. After 48 hours incubation, small colonies were visualised on both the chocolate and blood agar plates. Gram stain of these colonies revealed a short, plump Gram negative bacillus. The colonies were slightly haemolytic with a strong positive oxidase reaction. Catalase testing was negative. Biochemical profile testing (Rapid NH, Remel) confirmed the identification of K. kingae (code 1120, 99.9% probability). The isolate was susceptible to penicillin with an MIC of 0.16mg/l. Peripheral blood cultures yielded no growth after 5 days incubation.

Empirical treatment with flucloxacillin (2g 6-hourly) and benzyl penicillin (1.2g 6-hourly) was rationalised to benzyl penicillin alone 1.2g 4-hourly. The patient improved rapidly on the antimicrobial therapy alone and washout of the joint was not undertaken. She was discharged to the community where she received a benzyl penicillin infusion of 8g over 24 hours via PICC line for 6 weeks. She continued to make an uneventful recovery and has subsequently gone on to have an arthrodesis of her ankle, which was preferred to replacement following the infection.

Discussion

Kingella kingae was originally placed under the Moraxella genus and named Moraxella kingii after Elizabeth O King of the US Centers for Disease Control(CDC) who isolated the bacterium in 1960 (3). It was later transferred to its own genus and renamed Kingella kingae in 1976 (4). K. kingae are facultative anaerobic Gram negative rods which lie together in small clusters and decolourise unevenly on Gram stain. Small colonies are seen after 48 hours and usually have a small zone of beta haemolysis on blood agar. They are oxidase positive.

K. kingae has been shown to be a commensal of the oropharyngeal tract in early childhood. Previously considered a rare cause of human infection, it is now recognised as an important cause of invasive infection in paediatric patients, predominantly under the age of 2 years (2). Infections have most commonly been reported in the bones and joints of children. K. kingae constitutes one of the HACEK group of organisms which are collectively responsible for 3-5% of cases of bacterial endocarditis (2). They are also known to cause lower-respiratory tract infections, meningitis, ocular infections and stomatitis. According to the literature, almost 90% of patients with invasive Kingella kingae infections are under the age of 5 years, with 60% of episodes occurring in the under 2 year age group (5). Based on studies on children in day-care centres it is thought Kingella kingae is transmitted from child to child via saliva particles (6). In contrast to the healthy children acquiring Kingella kingae infections, adults frequently have pre-disposing factors such as rheumatoid arthritis, Felty's syndrome, liver cirrhosis, systemic lupus erythematosus, renal disease, sickle cell anaemia, malignancies and HIV(2,7-9). The fact that relatively few invasive K. kingae infections occur in immunocompetent adults indicates that protection from colonisation and infection requires an acquired immune response (2).

Few previous cases of adult joint sepsis caused by K. kingae have been reported in the literature. Of these few, most involve the knee and one case involved a septic elbow (7, 10-13). As far as we are aware, this is the first reported case of adult septic arthritis caused by K. kingae, occurring in an ankle joint.

The subtle clinical manifestations of K. kingae have been noted previously with patients often presenting only with mild malaise and no or minimal fevers (2,7). K. kingae infections predominantly affect the large weight bearing joints such as hips, knees and ankles (2). Patients with osteo-articular infections due to K. kingae often have blood leucocyte counts, c-reactive proteins and erythrocyte sedimentation rates that are within normal limits or only mildly elevated. The bacterial count in the synovial fluid is often low. As with other HACEK organisms K. kingae is a fastidious bacterium. Recovery of K kingae from body fluids and pus can thus be problematic because these types of specimens seem to be inhibitory to the bacteria. Inoculating synovial fluid into blood culture medium has been shown to increase the likelihood of isolating the organism (2,10).

The technology available for rapid identification of bacteria from clinical samples is now rapidly evolving. Targeted PCR is currently the most sensitive method for detecting K. kingae directly from sterile site aspirates (14). However, this is not practical when looking for many potential pathogens in a clinical sample. 16S rRNA gene sequencing offers a more broad based approach, with the ability to look for many different potential pathogens at once, but is less sensitive at detecting K. kingae than targeted PCR (15). The recent introduction of MALDI-TOF (Matrix Associated Laser Desorption and Ionisation-Time of Flight) technology into many of the bigger diagnostic laboratories may expedite identification once K. kingae colonies are growing on the plate (16). However there has been no research done as yet on the ability of MALDI-TOF technology to detect HACEK organisms directly from patient samples. Other technology which may be of value here is PCR-Electrospray Ionisation/Mass Spectrometry, which combines both PCR and mass spectrometry technology to allow rapid and sensitive identification of a wide spectrum of pathogens directly from patient samples (17). Micro-array may also offer a sensitive and practical approach to the molecular diagnosis of K. kingae infections in the future; although at the time of writing there is little available commercially using microarray technology for bacterial identification.

There are no specific guidelines or optimal therapy for K. kingae. Patients are treated empirically until cultures reveal the isolate and its susceptibility pattern. The organism is usually susceptible to beta-lactams however beta-lactamase producing K. kingae isolates have been described (2). Intravenous penicillin is a standard treatment for those isolates which have tested susceptible (18).

Conclusion

This case demonstrates that K. kingae can occasionally cause septic arthritis in adults, particularly those with underlying immunocompromise. Inoculation of synovial fluid into blood culture media improves chances of isolating the organism and should be recommended as routine procedure to improve the recovery rate of these types of fastidious organisms. Newly emerging identification technologies may in the future assist with the more rapid and sensitive diagnosis of this organism.

References

(1.) J Versalovic (Editor). Manual of Clinical Microbiology, 10th Ed; American Society of Microbiology Press, USA. Vol 1: pg 1192.

(2.) Yagupsky P. Kingella kingae: from medical rarity to an emerging paediatric pathogen. Lancet Infect Dis 2004; 4: 358-367.

(3.) Henriksen SD, Bovre K. Moraxella kingii sp. Nov., a haemolytic saccharolytic species of the genus Moraxella. J Gen Microbiol 1968; 58: 377-385.

(4.) Henriksen SD, Bovre K. Transfer of Moraxella kingii Henriksen and Bovre to the genus Kingella gen. nov. in the family Neiseriaceae. Int J Syst Bacteriol 1976; 26: 44750.

(5.) Yagupsky P, Dagan R, Howard CB, Einhorn M, Kassis I, Simu A. Clinical features and epidemiology of invasive Kingella kingae infections in southern Israel. Pediatrics 1993; 92: 800-804.

(6.) Slonim A, Walker ES, Mishori E, Porat N, Dagan R, Yagupsky P. Person-to-person transmission of Kingella kingae among day care center attendees. J Infect Dis 1998; 178: 1843-1846.

(7.) Lewis DA, Settas L. Kingella kingae causing septic arthritis in Felty's syndrome. Postgrad Med J 1983; 59: 525-526.

(8.) Wolak T, Abu-Shakra M, Flusser D, Liel-Cohen N, Buskila D, Sukenik S. Kingella endocarditis and meningitis in a patient with SLE and associated antiphospholipid syndrome. Lupus 2000; 9: 393-396.

(9.) Urs S, D'Silva BS, Jeena CP, Sona CP, Beena K, Shetty KR. Kingella kingae septicemia in association with HIV disease. Trop Doct 1994; 24: 127.

(10.) Elyes B, Mehdi G, Haj Slama Kamel B, Hela Z, Smida Imen B. Kingella kingae septic arthritis with endocarditis in an adult. Joint Bone Spine 2006; 73: 472-473.

(11.) Esteve V, Porcheret H, Clerc D, Dorfmann H, Le Pennec MP. Septic arthritis due to Kingella kingae in an adult. Joint Bone Spine 2001; 68: 85-86.

(12.) Vincent J, Podewell C, Franklin GW, Korn JH. Septic arthritis due to Kingella (Moraxella) kingae: case report and review of literature. J Rheumatol 1981; 8: 501-503.

(13.) Salminen I, Von Essen R, Koota K, Nissinen A. A pitfall in purulent arthritis brought out in Kingella kingae infection of the knee. Ann Rheum Dis 1984; 43: 656-657.

(14.) Moumile K, Merckx J, Glorion C, Berche P, Ferroni A. Osteoarticular infections caused by Kingella kingae in children: contribution of polymerase chain reaction to the microbiologic diagnosis. Paediatr Infect Dis J 2003; 22: 837-839.

(15.) Cherkaoui A, Ceroni D, Emonet S, Lefevre Y, Schrenzel J. Molecular diagnosis of Kingella kingae osteoarticular infections by specific real-time PCR assay. J Med Microbiol 2009; 58: 65-68.

(16.) Couturier MR, Mehinovic E, Croft AC, Fisher MA. Identifcation of HACEK clinical isolates by matrix-assisted laser desorption-time of flight mass spectrometry. J Clin Microbiol 2011; 49: 1104-1106.

(17.) Kaleta EJ, Clark AE, Cherkaoui A, Wysocki VH, Ingram EL, Schrenzel J, et al. Comparative analysis of PCR-electrospray ionization/mass spectrometry (MS) and MALDI-TOF/MS for the identification of bacteria and yeast from positive blood culture bottles. Clin Chem 2011; 57: 1057-1067.

(18.) Sordillo EM, Rendel M, Sood R, Belinfanti J, Murray O, Brook D. Septicaemia due to beta-lactamase-positive Kingella kingae. Clin Infect Dis 1993; 17: 818-819.

Author information

Ajay Sanghvi, BSc MBChB [1] Michael Addidle, MBChB MRCP DTM&H FRCPath [2] Kate Grimwade, MBChB MRCP PhD DTM&H [3]

[1] John Radcliffe Hospital, Oxford, UK [2] Pathlab Bay of Plenty, Tauranga, New Zealand [3] Tauranga Hospital, Tauranga, New Zealand

Author contributions

AS: substantive drafting of the main article. MA: revision of article and literature review. KG: clinical care of patient and revision of article. The authors declare no conflicts of interest.

Author for correspondence

Michael Addidle, Pathlab Bay of Plenty, PO Box 130, Tauranga 3140. Email: Michaela@pathlab.co.nz
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Author:Sanghvi, Ajay; Addidle, Michael; Grimwade, Kate
Publication:New Zealand Journal of Medical Laboratory Science
Article Type:Case study
Date:Aug 1, 2012
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