M. S. Jackson, J. Bagg, M. N. Gupta1 and R. D. Sturrock1. Infection ... ing parenteral nutrition [3]. source of ... allo
Rheumatology 1999;38:572–575
Oral carriage of staphylococci in patients with rheumatoid arthritis M. S. Jackson, J. Bagg, M. N. Gupta1 and R. D. Sturrock1 Infection Research Group, University of Glasgow Dental School and 1Centre for Rheumatic Diseases, Department of Medicine, Glasgow Royal Infirmary, University of Glasgow, Glasgow, UK Abstract Objective. To determine the prevalence of oral staphylococcal carriage in patients with rheumatoid arthritis compared with healthy controls. Methods. Fifty healthy adults, 25 healthy elderly volunteers and 25 patients with rheumatoid arthritis were studied. An oral rinse, tongue swab and nasal swab were collected for culture on blood agar and a range of selective agars. Isolates of staphylococci were identified and antibiotic sensitivity profiles determined by standard methods. Results. Staphylococci were isolated from the mouths of 94% of the healthy adults, 24% of whom carried Staphylococcus aureus. All the healthy elderly carried oral staphylococci and 36% were colonized with S. aureus. Staphylococci were isolated from 96% of the rheumatoid arthritis patients and this group had the highest carriage rate of S. aureus (56%), significantly higher than the healthy adults (P < 0.05). In all three groups, Staphylococcus epidermidis was isolated from the mouths of >80%. No methicillin-resistant strains of S. aureus were isolated. Conclusion. Oral carriage of S. aureus appears to be common in patients with rheumatoid arthritis and studies of the mouth as a source of infection in septic arthritis would be merited. K : Staphylococci, Oral cavity, Oral flora, Rheumatoid arthritis, Septic arthritis.
The oral flora contains >300 known species of bacteria [1], but surprisingly there have been no formal studies of staphylococci in the mouth. Staphylococcus aureus is implicated in some oro-facial infections, e.g. angular cheilitis [2] and oral mucositis in elderly patients receiving parenteral nutrition [3]. Oral bacteria can translocate to cause systemic infection, e.g. streptococcal infective endocarditis [4] or septicaemia in the immunocompromised [5]. By analogy, the mouth may also be an unrecognized source of staphylococci in septic arthritis. The annual incidence of bacterial arthritis in the rheumatoid arthritis population is 30–70/100 000 compared with 2–10/100 000 in the general population [6, 7]. Fifty per cent of patients develop joint damage and 10–16% of patients die during the acute episode [7–9]. Staphylococci are the commonest cause of bacterial arthritis in adults [10]. Staphylococcus aureus is the primary cause of bacterial arthritis in 40% of cases from England and Wales [9], and causes 80% of joint infections in patients with concurrent rheumatoid arthritis [10]. Coagulase-negative staphylococci have also emerged in recent years as important medical pathogens, particularly in relation to implanted biomaterials, and
Staphylococcus epidermidis is now responsible for 40% of all prosthetic joint infections [11]. In native joints, it is generally believed that bacterial arthritis is secondary to the haematogenous seeding of a joint during a bacteraemia [10], but at present the source of the bacteraemia cannot be identified in up to 30% of cases [12]. Many patients with rheumatoid arthritis have a reduced salivary flow rate, which may result in significant changes to the normal oral flora [13]. Furthermore, the drugs used in the treatment of rheumatoid arthritis, many of which are immunosuppressive or cytotoxic, may cause oral ulceration, providing a portal of entry for oral bacteria. The data reported in this paper demonstrate that the mouths of many patients with rheumatoid arthritis are colonized by both S. aureus and S. epidermidis, suggesting that the oral cavity should be given serious consideration as a source of infection in septic arthritis.
Materials and methods Patients Two control groups of healthy adults were studied. The first comprised 13 male and 37 female adults with ages ranging from 18 to 54 (mean 32) yr. The second control group of healthy elderly comprised 10 male and 15 female residents of a geriatric unit, all of whom were
Submitted 14 May 1998; revised version accepted 15 January 1999. Correspondence to: J. Bagg, Oral Microbiology Unit, Level 9, Glasgow Dental Hospital and School NHS Trust, 378 Sauchiehall Street, Glasgow G2 3JZ, UK.
572
© 1999 British Society for Rheumatology
Oral staphylococci in rheumatoid arthritis
well at the time of sampling. Their ages ranged from 65 to 92 (mean 82) yr. The study group comprised three male and 22 female out-patients receiving treatment for rheumatoid arthritis. Their ages ranged from 21 to 82 (mean 60) yr. Sampling The mouths of all subjects were sampled by the concentrated oral rinse technique [14] and a tongue swab. A swab was also collected from the anterior nares. For the patients with rheumatoid arthritis, a SalivetteB (Sarstedt Ltd, Leicester, UK ) specimen was collected to allow assessment of the degree of oral dryness [15]. Culture and identification All specimens were inoculated onto Columbia blood agar with 5% defibrinated horse blood (Prolab Diagnostics, Merseyside, UK ), mannitol salt agar (Prolab Diagnostics, Merseyside, UK ), milk agar [16 ] with no added methicillin and P agar [17], and incubated at 37°C for 72 h. This extended incubation enhanced colony pigmentation and therefore visualization of different species. Blood agar purity plates of the different morphological colony types were established. Catalase-positive Gram-positive cocci were tested for coagulase production by slide agglutination (Staphaurex, Murex Diagnostics Ltd, Dartford, UK ) and all positive isolates checked by a tube coagulase test using rabbit plasma (Medical Wire & Equipment Co. Ltd, Corsham, UK ). Strains positive in both of these tests were identified as S. aureus. Staphylococcus epidermidis was identified on the basis of a set of eight sugar fermentation tests and susceptibility to novobiocin and polymyxin B [18] on P agar [17]. Other coagulase-negative staphylococci were speciated by a two-step procedure [19] utilizing Rosco Diagnostica tablets (Bioconnections, Barnsley, UK ). Antibiotic sensitivity testing Staphylococcus aureus isolates were tested against penicillin, ampicillin, co-amoxiclav, methicillin, erythromycin, cephradine, fusidic acid and vancomycin according to Stokes and Ridgway [20]. Statistical analysis Where appropriate, differences between groups were analysed by the x2 test. A value of P < 0.05 was accepted as indicative of a statistically significant difference.
Results Isolation rates of Staphylococcus species These are summarized in Table 1. The weight of growth varied widely, but in most cases was light to moderate. Staphylococci were isolated from the mouths of 47/50 (94%) healthy adults. Staphylococcus aureus was present in the mouths of 12 (24%), of whom 8 (67%) were also nasal carriers of S. aureus. Conversely, six adults were nasal carriers in the absence of oral carriage. Coagulase-
573
negative staphylococci were isolated from the mouths of 46/50 (92%) of the adults, predominantly S. epidermidis and S. warneri. Staphylococci were isolated from the mouths of all the healthy elderly. Staphylococcus aureus was present in the mouths of 9/25 (36%). This was not significantly greater than the rate of colonization among the younger adult controls. Forty per cent of those with oral S. aureus were nasal carriers. None were nasal carriers in the absence of oral carriage. Coagulase-negative staphylococci were isolated from the mouths of 23/25 (92%) of the healthy elderly adults, predominantly S. epidermidis, S. warneri and S. haemolyticus. Overall, staphylococci were isolated from the mouths of 24/25 (96%) of the adults with rheumatoid arthritis. Staphylococcus aureus was present in the mouths of 14 (56%) of this group, a significantly greater rate of colonization than the healthy adults (P < 0.01). Eleven (78%) of those with oral carriage of S. aureus were also nasal carriers of the organism. Three patients in this group were nasal carriers in the absence of oral carriage. Coagulase-negative staphylococci were isolated from the mouths of 22/25 (88%) of those with rheumatoid arthritis, predominantly S. epidermidis, S. haemolyticus and S. warneri. Salivary flow rates The mean volume of saliva collected in the SalivetteA specimens from the rheumatoid arthritis patients was 117 ml (range 0–570 ml ). This compares with a mean value of 250 ml quoted for healthy controls [15]. Antibiotic sensitivity profiles All of the isolates from the three groups were sensitive to methicillin, vancomycin and cephradine. With the exception of one isolate from the healthy adults, they were also sensitive to erythromycin and fusidic acid. Very few of the strains were sensitive to penicillin, ampicillin or co-amoxiclav.
Discussion This study demonstrates clearly that staphylococci are part of the normal oral flora in most humans. Staphylococci were isolated from the mouths of >90% of the healthy adults and we have recently shown that 92% of a group of healthy children carried staphylococci in their mouths, 64% of which were S. aureus (submitted ). The mouths of most of the healthy adults were colonized with coagulase-negative staphylococci, predominantly S. epidermidis and S. warneri. However, S. haemolyticus, S. schleiferi and S. lugdunensis were also identified. Twenty-four per cent of the healthy adults were colonized with S. aureus, an unexpectedly high oral carriage rate. Among the healthy elderly patients, the distribution of coagulase-negative staphylococci was similar to that of the healthy adult group, with S. epidermidis by far the commonest isolate, followed by S. warneri and S. haemolyticus. Whilst more
M. S. Jackson et al.
574
T 1. Carriage of Staphylococcus spp. in the oral cavity of healthy adults, healthy elderly and patients with rheumatoid arthritis Oral carriage Study group
S. aureus
S. epidermidis
S. warneri
S. haemolyticus
Healthy adults (n = 50) Healthy elderly (n = 25) Rheumatoid arthritis (n = 25)
12 (24%)
44 (88%)
14 (28%)
7 (14%)
9 (36%)
23 (92%)
9 (36%)
10 (40%)
14 (56%)
21 (84%)
4 (16%)
7 (28%)
of the elderly patients (36%) were found to have oral colonization with S. aureus, the difference between the two control groups was not statistically significant. A wide range of coagulase-negative staphylococci was isolated from the mouths of the patients with rheumatoid arthritis. Staphylococci are the most important cause of prosthetic joint infections and S. epidermidis is responsible for a large percentage of late or chronic infections [21]. Such joints are frequently placed in patients with rheumatoid arthritis and the possibility of a bacteraemia from an oral source resulting in a late prosthetic joint infection merits consideration. The potential pathogenic importance of the less common species that were isolated should not be underestimated. For example, a recent case study [22] showed that a previously healthy 26-yrold male developed endocarditis caused by S. lugdunensis after a tooth extraction. A significantly higher proportion (56%) of the patients with rheumatoid arthritis carried oral S. aureus than the adult controls (24%) (P < 0.01). This is not a purely age-related effect, since there was no significant difference between colonization rates for the two control groups and the rheumatoid arthritis patients were significantly younger than the healthy elderly individuals. It is more likely to reflect other disease-associated factors such as the oral dryness indicated by the SalivetteA readings. Since S. aureus is a significant pathogen in septic arthritis [9, 10], this finding is potentially important. At present, the source cannot be identified in up to 30% of cases [12] and all possible sites, including the mouth, should be given consideration. The antimicrobial susceptibility patterns of the strains of S. aureus isolated from the patients with rheumatoid arthritis and the controls were very similar and mirrored the typical sensitivity profile of S. aureus strains currently isolated in the community. In summary, these results have demonstrated that staphylococci are frequently isolated from the oral cavity and that S. aureus is present in the mouths of significantly more patients with rheumatoid arthritis than healthy controls. There is a very real possibility that these organisms could translocate to cause disease at distant sites and may, therefore, be of relevance to the pathogenesis of septic arthritis.
Other species S. S. S. S. S. S. S. S.
schleiferi (4%) lugdunensis (2%) schleiferi (8%) capitis (4%) lugdunensis (8%) kloosii (8%) saccharolyticus (4%) hominis (4%)
Acknowledgement We acknowledge the support of the Arthritis Research Campaign. MG is the Mary Miller Clinical Research Fellow.
References 1. Wilson MJ, Weightman AJ, Wade WG. Applications of molecular ecology in the characterization of uncultured microorganisms associated with human disease. Rev Med Microbiol 1997;8:91–101. 2. MacFarlane TW, Helnarska S. The microbiology of angular cheilitis. Br Dent J 1976;140:403–6. 3. Bagg J, Sweeney MP, Harvey Wood K, Wiggins A. Possible role of Staphylococcus aureus in severe oral mucositis among elderly dehydrated patients. Microb Ecol Health Dis 1995;8:51–6. 4. Franklin CD. The aetiology, epidemiology, pathogenesis and changing pattern of infective endocarditis, with a note on prophylaxis. Br Dent J 1992;172:369–73. 5. Bergmann OJ. Oral infections and septicaemia in immunocompromised patients with haematologic malignancies. J Clin Microbiol 1988;26:2105–9. 6. Kaandorp CJE, van Schaardenburg D, Krijnen P, Habbema JDF, van de Laae MAFJ. Risk factors for septic arthritis in patients with joint disease: a prospective study. Arthritis Rheum 1995;38:1819–25. 7. Morgan DS, Fisher D, Merianos A, Currie BJ. An 18 year clinical review of septic arthritis from tropical Australia. Epidemiol Infect 1996;117:423–8. 8. Le Dantec L, Maury F, Flipo RM et al. Peripheral pyogenic arthritis. A study of one hundred and seventy nine cases. Rev Rheum 1996;63:103–10. 9. Ryan MJ, Kavanaugh R, Wall PJ, Hazelman BL. Bacterial joint infections in England and Wales: analysis of bacterial isolates over a four year period. Br J Rheumatol 1997;36:370–3. 10. Goldenberg DL. Septic arthritis. Lancet 1998;351: 197–202. 11. Brause BD. Infections associated with prosthetic joints. Clin Rheum Dis 1986;12:523–35. 12. Kaandorp CJE, Dinant HJ, van de Laar MAFJ, Moens HJB, Prins APA, Dijkmans BAC. Incidence and source of native and prosthetic joint infection: a communitybased prospective survey. Ann Rheum Dis 1997;56:470–5.
Oral staphylococci in rheumatoid arthritis
13. MacFarlane TW. The oral ecology of patients with severe Sjogren’s syndrome. Microbios 1984;41:99–106. 14. Samaranayake LP, MacFarlane TW, Lamey PJ, Ferguson MM. A comparison of oral rinse and imprint sampling techniques for the detection of yeast, coliform and Staphylococcus aureus carriage in the oral cavity. J Oral Pathol 1986;15:386–8. 15. Sweeney MP, Bagg J, Baxter WP, Aitchison TC. Oral disease in terminally ill cancer patients with xerostomia. Oral Oncol ( Eur J Cancer Part B) 1998;34:123–6. 16. Allen JL, Cowan ME, Cockroft PM. A comparison of three semi-selective media for the isolation of methicillinresistant Staphylococcus aureus. J Med Microbiol 1994;40:98–101. 17. Kloos WE, Schleifer KH. Simplified scheme for routine identification of human staphylococcus species. J Clin Microbiol 1975;1:82–8.
575
18. Kloos WE, Lambe DW. Staphylococcus. In: Balows A, Hausler WJ Jr, Herrmann KL, Isenberg HD, Shadomy HJ, eds. Manual of clinical microbiology, 5th edn. Washington, DC: American Society for Microbiology, 1991:222–37. 19. Ieven M, Verhoeven J, Pattyn SR, Goosens H. Rapid and economical method for species identification of clinically significant coagulase negative staphylococci. J Clin Microbiol 1995;33:1060–3. 20. Stokes EJ, Ridgway GL. Clinical bacteriology, 5th edn. London: Arnold, 1980:215. 21. An YH, Friedman RJ Prevention of sepsis in total joint arthroplasty. J Hosp Infect 1996;33:93–108. 22. Kralovic SM, Melin-Aldana H, Smith KK, Linnemann CC Jr. Staphylococcus lugdunensis endocarditis after tooth extraction. Clin Infect Dis 1995;20:715–6.
