- Email: [email protected]
Associations between bacteremia from oral sources and distant-site infections: tooth brushing versus single tooth extraction
Vol. 119 No. 4 April 2015
Associations between bacteremia from oral sources and distant-site infections: tooth brushing versus single tooth extraction Farah K. Bahrani Mougeot, PhD,a Sabrina E. Saunders, BS,b Michael T. Brennan, DDS, MHS,c and Peter B. Lockhart, DDSd Objectives. To determine the impact of antibiotic prophylaxis (AP) on the incidence of bacteremia caused by oral bacterial species associated with infective endocarditis (IE) and prosthetic joint infections (PJIs) and to compare the incidence of following tooth brushing versus single tooth extraction. Study Design. Bacterial species in blood following single tooth extraction, with or without AP, and tooth brushing1 were compared with IE- and PJI-associated bacteria reported in the literature. Results. Of the 98 bacterial species identified in blood following single tooth extraction and tooth brushing, 321 and 12 were species were associated with IE and PJI, respectively. AP decreased the frequency of IE- and PJI-causing oral bacterial species in blood; however, single tooth extraction versus brushing resulted in bacteremia with IE- and PJI-causing species with similar frequencies: 65% versus 56% for IE, and 31% versus 28% for PJI. Conclusions. Although AP significantly decreased the incidence of bacteremia, the similarity between the incidence of bacteremia following brushing and extraction undermines AP as an effective strategy for the prevention of these distant-site infections. (Oral Surg Oral Med Oral Pathol Oral Radiol 2015;119:430-435)
Over 700 bacterial species have been identified in the human oral cavity.2 Some of these species cause local infections, such as periodontal disease (PD). Far more species, however, have been identified in bacteremia; after they enter the circulation, some have the potential to cause distant-site infections (DSI), such as infective endocarditis (IE) or prosthetic joint infections (PJIs).1,3-5 Bacteremia is common following invasive dental procedures as well as routine dental manipulations, such as tooth brushing.1,6 As a result, there has been a longstanding focus on preventing or reducing bacteremia with the use of antibiotic prophylaxis (AP) before dental procedures in patients at risk for DSIs.7-9 A previous study by our group reported the incidence, duration, and nature of bacteremia following tooth brushing versus single tooth extraction, and the impact of AP on these surrogate measures of risk for DSIs.1 The primary purpose of the present study was to determine the impact of AP on bacteremia caused by all oral bacterial species following tooth brushing and single tooth extraction,1 This work was supported by Carolinas HealthCare System (CHS) Research Fund. a Director of Oral Medicine Laboratory, Department of Oral Medicine, Carolinas Medical Center, Charlotte, NC, USA. b Cannon Research Summer Scholar, Department of Oral Medicine, Carolinas Medical Center, Charlotte, NC, USA. c Chairman, Department of Oral Medicine, Carolinas Medical Center, Charlotte, NC, USA. d Professor, Department of Oral Medicine, Carolinas Medical Center, Charlotte, NC, USA. Received for publication Nov 3, 2014; returned for revision Dec 30, 2014; accepted for publication Jan 15, 2015. Ó 2015 Elsevier Inc. All rights reserved. 2212-4403/$ - see front matter http://dx.doi.org/10.1016/j.oooo.2015.01.009
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as well as specific species reported to cause IE or PJI. Given that the most prevalent periodontal pathogens are anaerobes that thrive deep in the subgingival biofilm,3 it is assumed that anaerobic pathogens are less likely to be disturbed by tooth brushing than by more invasive procedures, such as tooth extraction. Another aim of this study was to determine if the bacterial species identified in blood after tooth brushing are different from those found after a single tooth extraction. These bacterial species were also compared on their reported causality for IE and PJI.
METHODS The detailed methods for subject recruitment and randomization to the three arms of this study have been published elsewhere.1 Briefly, patients enrolled in this study presented to our hospital-based dental clinic for dental extraction. Two hundred and ninety patients were randomized to one of three study arms: Tooth brushing (98 patients), single tooth extraction with AP (96 patients), or single tooth extraction with an identical placebo (96 patients). We collected demographic, baseline, and
Statement of Clinical Relevance Given the similar incidence of bacteremia caused by species associated with infective endocarditis and prosthetic joint infections following tooth brushing and single tooth extraction, poor oral hygiene may put patients at greater risk compared with dental office procedures.
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ORIGINAL ARTICLE Mougeot et al. 431
extensive oral disease and hygiene data parameters; the mean age of patients was 40 years; and 58% of patients were male and 73% African American. Patients randomized to the extraction groups were given 2.0 grams of amoxicillin or an identical placebo 1 hour before the procedure. Venous blood draws were obtained at six time points before, during, and after the procedure. Bacterial species cultured from blood were then identified by using the 16 S rRNA gene sequencing method.
56%, and 80% for tooth brushing, extractione amoxicillin, and extractioneplacebo, respectively.1 Of the 98 identified bacterial species, 32, and 12 are associated with IE1,10 and PJI, respectively (Tables I and II). The differences in the incidences of species associated with IE and PJI, as well as all oral species, were statistically significant for both the extractioneplacebo and the extractioneamoxicillin groups and the extractioneplacebo and tooth brushing groups (P < .0001).
Literature review and analysis of bacterial species implicated in DSIs In a previous review of the literature, we had developed a list of 170 bacterial species that have been identified in blood cultures after dental procedures.1 This list was compared with another compiled list of 275 bacterial species reported to cause IE. The bacterial species that were common in both lists were then compared with the 98 oral bacterial species identified in blood in our prior study.1 In the present study, we extended our review of the literature to the past 25 years to find bacterial species reported to cause PJI by using the key words “prosthetic joint infections” and “bacterial species OR bacterium OR bacteremia.” A specific PubMed search was conducted by using the specific name of each bacterial species along with the key words “prosthetic joint infections” to determine whether that particular species was associated with PJI. The list of PJI bacterial species compiled from the published literature was used to determine which of the 98 oral bacterial species identified in blood in our prior study1 are associated with PJI. First, the frequency of bacterial species present in blood in either extraction group (i.e., with and without AP) was calculated to find the impact of amoxicillin on the bacterial species reported to cause IE and PJI or on all of the 98 oral bacterial species identified in our prior study. Second, the frequency of bacterial species in blood in the extractioneplacebo group was compared with that of the brushing group to determine the impact of these two dental manipulations on bacteremia caused by species associated with IE and PJI.
Impact of amoxicillin on bacterial species detected in blood and associated with IE and PJI AP with amoxicillin decreased the overall incidence of bacteremia after a single tooth extraction by 61% and the incidence of IE bacterial species by 68%, which is in keeping with the findings from our previous study.4 The IE bacterial species most significantly decreased in incidence by amoxicillin prophylaxis were Streptococcus spp., Fusobacterium nucleatum, and Peptostreptococcus micros (Table IIIA). However, F. nucleatum and P. micros are not common causes of IE.11-13 The bacterial species identified in blood to be associated with PJI were Actinomyces naeslundii, Granulicatella adiacens, Haemophilus aphrophilus, Peptostreptococcus micros, Prevotella melaninogenica, Propionibacterium acnes, Staphylococcus epidermidis, Streptococcus mitis, Streptococcus mutans, Streptococcus oralis, Streptococcus sanguinis, and Veillonella dispar/ parvulla.1 Overall, AP decreased the frequency of these 12 bacterial species by 81% (P < .0001) (Table IIIB).
Statistical analysis A subject was determined to be positive for bacteremia if any of the bacterial species identified from blood cultures matched the species reported in the published literature to cause IE or PJI. The incidence of bacterial species in each study arm was compared using chi-square tests. Statistical significance (P ¼ .05) was used in all cases.
RESULTS As reported previously, the overall incidence of any oral bacterial species detected from blood cultures was 32%,
Impact of dental manipulation on bacterial species detected in blood We compared the effects of the two dental manipulations and found a higher incidence of bacteremia from species associated with IE, PJI, and other oral bacterial species in the extractioneplacebo group than in the brushing group (i.e., 219 vs. 43). However, we found that the relative frequency of IE and PJI bacterial species in the extractioneplacebo group was not significantly different from the brushing group (Table IV). That is, of the 219 total instances in which oral bacterial species were detected in the extractioneplacebo group, IE bacterial species were identified 144 times (65%) and those associated with PJI were detected 68 times (31%). Also, of the 43 incidences of bacteremia in the brushing group, 24 (56%) were bacterial species associated with IE and 12 (28%) with PJI.
DISCUSSION In this study, we report for the first time the effects of dental manipulations (tooth brushing vs. tooth extraction) on bacteremia as a surrogate risk for DSIs (e.g., IE and PJI) and the impact of amoxicillin on PJI species.
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Table I. Comparison of infective endocarditis (IE) and prosthetic joint infections (PJIs) bacterial species detected in blood following tooth brushing versus single tooth extraction with or without antibiotic prophylaxis IE species detected in blood
Bacterial species
PJI species detected in blood
Single tooth Single tooth Tooth Single tooth extraction Single tooth extraction Tooth extraction with extraction with with amoxicillin with placebo brushing amoxicillin placebo brushing
Acinetobacter lwofii/calcoaceticus Actinobacillus actinomycetemcomitans Actinomyces meyeri/odontolyticus Actinomyces naeslundii Bifidobacterium longum/infantis Capnocytophaga oral clone X089 Eikonella corrodens Fusobacterium nucleatum Granulicatella adiacens Haemophilus aphrophilus Lactobacillus rhamnosus/casei Lactobacillus salivarius Neisseria elongate Neisseria flavescens Neisseria mucosa/sicca Peptostreptococcus micros Prevotella buccae Prevotella denticola Prevotella melaninogenica Prevotella oralis Propionibacterium acnes Staphylococcus epidermidis Staphylococcus warneri Stenotrophomonas maltophilia Streptococcus anginosus Streptococcus constellatus Streptococcus cristatus Streptococcus gordonii Streptococcus intermedius Streptococcus mitis/pneumoniae Streptococcus mutans Streptococcus oralis Streptococcus salivarius Streptococcus sanguinis Veillonella dispar/parvula
O O
O
O
O O O
O O O O O
O O O O O O
O O O O O O
O O O O
O O O O O
O O O O O O
O O O O O O
O O
O O O O
O
O
O
O
O
O
O O O O O O O O O O O O
O
O O
O
O O
O O
Table II. Comparison of the incidences of bacterial species associated with infective endocarditis (IE), prosthetic joint infections (PJIs), and all oral bacterial species detected in blood following tooth brushing and single tooth extractions with amoxicillin or placebo Incidence Bacterial species
Tooth brushing
Extractioneamoxicillin
Extractioneplacebo
IE (P < .0001) PJI (P < .0001) All oral species (P < .0001)*
23% 12% 32%
33% 14% 56%
60% 52% 80%
*
Total species N ¼ 32 N ¼ 12 N ¼ 98
*Results previously reported.1
Infective endocarditis IE-associated bacteria are often found in bacteremia resulting from invasive dental procedures, such as tooth extraction. Since tooth brushing disrupts only the (shallow) gingival pocket and tooth extraction disrupts both gingival and periodontal (deeper) pockets, one
would expect that the proportions of bacterial species found in blood after these two manipulations would be different. However, our data suggest that these two very different manipulations, in terms of perceived invasiveness, disrupted similar percentages of bacterial species that could cause IE. Although the load, or
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Table III. Impact of amoxicillin on bacterial species associated with distant-site infections detected in blood following dental extraction A. Most prevalent infective endocarditisecausing bacterial species Infective endocarditis (IE)ecausing bacterial species
Counts (extractioneplacebo)
Counts (extractioneamoxicillin)
Percentage change
P value
10 10 13 12 18 19
0 1 2 2 4 7
100% 90% 85% 83% 78% 63%
.0015 .0096 .0054 .0183 .0138 .0114
P value
Streptococcus mutans Fusobacterium nucleatum Peptostreptococcus micros Streptococcus intermedius Streptococcus mitis/pneumoniae Streptococcus anginosus
B. Prosthetic joint infectionecausing bacterial species Bacterial species
Counts (extractioneplacebo)
Counts (extractioneamoxicillin)
Percentage change
8
1
88%
.0168
37 4 19
6 1 6
84% 75% 68%
<.0001 .3122 .0088
68
14
79%
<.0001
Facultative anaerobes (Actinomyces naeslundi, Granulicatella adiacens, Propionibacterium acnes, Staphylococcus epidermidis) Viridans streptococci Aerobes (Haemophilus aphrophilus) Strict anaerobes (Peptostreptococcus micros, Prevotella melaninogenica, Veillonella dispar/parvulla) Total
Table IV. Incidence of total bacterial species associated with infective endocarditis and prosthetic joint infections detected in blood following tooth brushing or single tooth extraction with placebo
Bacterial species Infective endocarditis
Randomization (N)
Tooth brushing (43) Extractioneplacebo (219) Prosthetic joint infection Tooth brushing (43) Extractioneplacebo (219)
Total incidence of bacterial species (%) 24 144 12 68
(56) (65) (28) (31)
magnitude, of bacterial species in blood and the host immune response likely play important roles in the outcomes of bacteremia following dental office procedures, the much higher frequency of tooth brushing may put individuals at greater risk for DSIs annually compared with dental office procedures, which are far less frequent. The most prevalent bacteria found in blood following both tooth extraction and brushing were Streptococcus spp.,1 and most of the detected IE-causing bacterial species were Streptococcus spp. as well (see Table IIIA). For example, S. mitis, accounted for approximately 15% of the total frequency of IE bacterial species, and approximately 28% of the Streptococcus spp. (data not shown). Although the incidence of S. mitis in blood was reduced by 78% in the extractioneamoxicillin group (see Table IIIA),
amoxicillin did not completely eliminate these bacteria. Other studies have also reported the failure of AP to prevent IE caused by S. mitis and pointed out the increasing resistance of this species to blactam antibiotics, such as amoxicillin.14-17 Some early studies have suggested that amoxicillin has a lower, or no, significant effect on the incidence or magnitude of bacteremia during and up to 10 minutes after dental extractions.18 Non-streptococcal species that were significantly impacted by amoxicillin are rare causes of IE. For example, the frequency of bacteremia from Fusobacterium nucleatum was decreased by 90% (see Table IIIA), but we could find only six reported cases of IE caused by this organism.11,12 Another rare cause of IE is Peptostreptococcus micros, which was reduced by 85% by amoxicillin, but we found only 21 reported cases of IE caused by this species (see Table IIIA).13 Similar trends hold true for other anaerobic species detected in our study but which rarely cause IE.13,19-21 Therefore, the reduction in frequency of these bacterial species by amoxicillin may not be clinically significant in the prevention of IE. Prosthetic joint infections Our study suggests that amoxicillin decreased the frequency of PJI bacterial species in blood after single tooth extractions by 81% (see Table IIIB). These species belong to the diverse group of aerobic and anaerobic bacterial species inhabiting the oral cavity. However,
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the majority of these bacterial species was identified as viridans group streptococci rarely associated with PJIs.22 The longstanding practice of AP for PJIs is controversial for several reasons, largely because PJIs are rarely caused by species found in the mouth,23 for example, Staphylococcus aureus, which was not detected in our original study.1,10 Even if S. aureus entered the bloodstream through the oral cavity, this species is not significantly affected by amoxicillin.24 Additionally, the percentage of the total detected bacterial species that are associated with PJI is essentially the same between the extractioneplacebo and the brushing groups (see Table IV) (31% vs. 28%, respectively). Since tooth extraction and tooth brushing disrupted similar percentages of bacterial species that can cause PJIs, patients with prosthetic joints might also be at greater risk over time from such naturally occurring bacteremia. There are some limitations to this study. First, as we pointed out in our original paper,1 all participants in this study presented to our hospital-based urgent care dental clinic in need of an extraction and therefore may not represent the general population with regard to demographic characteristics and severity of dental disease. Additionally, the subanalysis in the present study relies heavily on published studies that used conventional culture-based approach, rather than the more sensitive 16 S rRNA gene sequencing approach, to identify bacterial species. Furthermore, although we have investigated the nature and incidence of IE- and PJIcausing bacteremia, we did not address such factors as bacterial load and host immune responses, which are likely to be important factors in the outcome of IE- and PJI- associated bacteremia. The molecular microbiology technology available at the time of our original study did not allow for determining the bacterial load for bacteremia. Although the use of AP before dental extraction decreased the frequency of bacterial species associated with IE and PJIs, clearly bacteremia incidence is a surrogate measure of risk for IE or PJIs. Our data support the current emphasis on the fact that tooth brushing likely causes a far greater incidence of bacteremia annually compared with office-based dental procedures. From a practical standpoint, since AP is not feasible before tooth brushing and the efficacy of AP has yet to be demonstrated, the benefits of AP before dental procedures may be outweighed by the risks, which include cost, antibiotic resistance, and drug reactions.
CONCLUSIONS Antibiotic prophylaxis is currently recommended by the American Heart Association for patients at higher risk for developing IE and is often given to those with prosthetic joints. Although AP decreases the frequency
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of all oral bacterial species, including species associated with IE and PJIs, both tooth brushing and single tooth extractions disrupt similar bacterial species in similar proportions. Although more invasive dental procedures, such as multiple extractions, could yield different incidences of bacteremia compared with single tooth extractions, our data support the current trend away from the routine use of AP in these patient populations. Considering the much higher frequency of tooth brushing compared with dental office procedures and the significant incidence of bacteremia caused by bacterial species associated with IE and PJIs that results from tooth brushing, such routine daily activities in the presence of poor oral hygiene and periodontal disease may put patients at a greater risk for these two DSIs. This work was supported by Carolinas Health Care System (CHS) Research Fund. SS was the recipient of the CHS Summer Scholar Program Award.
REFERENCES 1. Lockhart PB, Brennan MT, Sasser HC, et al. Bacteremia associated with toothbrushing and dental extraction. Circulation. 2008;117:3118-3125. 2. Dewhirst FE, Chen T, Izard J, et al. The human oral microbiome. J Bacteriol. 2010;192:5002-5017. 3. Castillo DM, Sanchez-Beltran MC, Castellanos JE, et al. Detection of specific periodontal microorganisms from bacteraemia samples after periodontal therapy using molecular-based diagnostics. J Clin Periodontol. 2011;38:418-427. 4. Hoen B, Duval X. Clinical practice. Infective endocarditis. N Engl J Med. 2013;368:1425-1433. 5. Rethman MP, Watters W III, Abt E, et al. The American Academy of Orthopaedic Surgeons and the American Dental Association clinical practice guideline on the prevention of orthopaedic implant infection in patients undergoing dental procedures. J Bone Joint Surg Am. 2013;95:745-747. 6. Lockhart PB, Brennan MT, Thornhill M, et al. Poor oral hygiene as a risk factor for infective endocarditis-related bacteremia. J Am Dent Assoc. 2009;140:1238-1244. 7. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis. Guidelines from the American Heart Association. A guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2007;116:1736-1754. 8. Watters W III, Rethman MP, Hanson NB, et al. Prevention of orthopaedic implant infection in patients undergoing dental procedures. J Am Acad Orthop Surg. 2013;21:180-189. 9. Lockhart PB, Loven B, Brennan MT, Fox PC. The evidence base for the efficacy of antibiotic prophylaxis in dental practice. J Am Dent Assoc. 2007;138:458-474. 10. Bahrani-Mougeot FK, Paster BJ, Coleman S, et al. Diverse and novel oral bacterial species in blood following dental procedures. J Clin Microbiol. 2008;46:2129-2132. 11. Shammas NW, Murphy GW, Eichelberger J, et al. Infective endocarditis due to Fusobacterium nucleatum: case report and review of the literature. Clin Cardiol. 1993;16:72-75.
OOOO Volume 119, Number 4 12. Weber G, Borer A, Riesenberg K, Schlaeffer F. Infective endocarditis due to Fusobacterium nucleatum in an intravenous drug abuser. Eur J Clin Microbiol Infect Dis. 1999;18:655-657. 13. Pathak R, Ngwe A, Enuh H, Saverimuttu J. Peptostreptococcus induced native-valve endocarditis. 2013. Available at: http:// ispub.com/IJID/12/1/1478. Accessed September 3, 2014. 14. Masuda K, Nemoto H, Nakano K, et al. Amoxicillin-resistant oral streptococci identified in dental plaque specimens from healthy Japanese adults. J Cardiol. 2012;59:285-290. 15. Chunduri NS, Madasu K, Goteki VR, Karpe T, Reddy H. Evaluation of bacterial spectrum of orofacial infections and their antibiotic susceptibility. Ann Maxillofac Surg. 2012;2:46-50. 16. Smith A, Jackson MS, Kennedy H. Antimicrobial susceptibility of viridans group streptococcal blood isolates to eight antimicrobial agents. Scand J Infect Dis. 2004;36:259-263. 17. Hall GE, Baddour LM. Apparent failure of endocarditis prophylaxis caused by penicillin-resistant Streptococcus mitis. Am J Med Sci. 2002;324:51-53. 18. Hall G, Hedström SA, Heimdahl A, Nord CE. Prophylactic administration of penicillins for endocarditis does not reduce the incidence of postextraction bacteremia. Clin Infect Dis. 1993;17: 188-194. 19. Michaux-Charachon S, Lavigne JP, Le FA, et al. Endocarditis due to a new rod-shaped Neisseria sp. J Clin Microbiol. 2005;43:886889. 20. Oh S, Havlen PR, Hussain N. A case of polymicrobial endocarditis caused by anaerobic organisms in an injection drug user. J Gen Intern Med. 2005;20:C1-C2.
ORIGINAL ARTICLE Mougeot et al. 435 21. Haddow LJ, Mulgrew C, Ansari A, et al. Neisseria elongata endocarditis: case report and literature review. Clin Microbiol Infect. 2003;9:426-430. 22. Sollecito TP, Abt E, Lockhart PB, et al. The use of prophylactic antibiotics prior to dental procedures in patients with prosthetic joints: evidence-based clinical practice guideline for dental practitionersda report of the American Dental Association Council on Scientific Affairs. J Am Dent Assoc. 2015;146:11-16. 23. Berbari EF, Osmon DR, Carr A, et al. Dental procedures as risk factors for prosthetic hip or knee infection: a hospital-based prospective case-control study. Clin Infect Dis. 2010;50:8-16. 24. Peel TN, Cheng AC, Buising KL, Choong PF. Microbiological aetiology, epidemiology, and clinical profile of prosthetic joint infections: are current antibiotic prophylaxis guidelines effective? Antimicrob Agents Chemother. 2012;56:2386-2391.
Reprint requests: Peter B. Lockhart, DDS Department of Oral Medicine Carolinas Medical Center PO Box 32861 Charlotte NC 28232-2861 [email protected]
Associations between bacteremia from oral sources and distant-site infections: tooth brushing versus single tooth extraction Farah K. Bahrani Mougeot, PhD,a Sabrina E. Saunders, BS,b Michael T. Brennan, DDS, MHS,c and Peter B. Lockhart, DDSd Objectives. To determine the impact of antibiotic prophylaxis (AP) on the incidence of bacteremia caused by oral bacterial species associated with infective endocarditis (IE) and prosthetic joint infections (PJIs) and to compare the incidence of following tooth brushing versus single tooth extraction. Study Design. Bacterial species in blood following single tooth extraction, with or without AP, and tooth brushing1 were compared with IE- and PJI-associated bacteria reported in the literature. Results. Of the 98 bacterial species identified in blood following single tooth extraction and tooth brushing, 321 and 12 were species were associated with IE and PJI, respectively. AP decreased the frequency of IE- and PJI-causing oral bacterial species in blood; however, single tooth extraction versus brushing resulted in bacteremia with IE- and PJI-causing species with similar frequencies: 65% versus 56% for IE, and 31% versus 28% for PJI. Conclusions. Although AP significantly decreased the incidence of bacteremia, the similarity between the incidence of bacteremia following brushing and extraction undermines AP as an effective strategy for the prevention of these distant-site infections. (Oral Surg Oral Med Oral Pathol Oral Radiol 2015;119:430-435)
Over 700 bacterial species have been identified in the human oral cavity.2 Some of these species cause local infections, such as periodontal disease (PD). Far more species, however, have been identified in bacteremia; after they enter the circulation, some have the potential to cause distant-site infections (DSI), such as infective endocarditis (IE) or prosthetic joint infections (PJIs).1,3-5 Bacteremia is common following invasive dental procedures as well as routine dental manipulations, such as tooth brushing.1,6 As a result, there has been a longstanding focus on preventing or reducing bacteremia with the use of antibiotic prophylaxis (AP) before dental procedures in patients at risk for DSIs.7-9 A previous study by our group reported the incidence, duration, and nature of bacteremia following tooth brushing versus single tooth extraction, and the impact of AP on these surrogate measures of risk for DSIs.1 The primary purpose of the present study was to determine the impact of AP on bacteremia caused by all oral bacterial species following tooth brushing and single tooth extraction,1 This work was supported by Carolinas HealthCare System (CHS) Research Fund. a Director of Oral Medicine Laboratory, Department of Oral Medicine, Carolinas Medical Center, Charlotte, NC, USA. b Cannon Research Summer Scholar, Department of Oral Medicine, Carolinas Medical Center, Charlotte, NC, USA. c Chairman, Department of Oral Medicine, Carolinas Medical Center, Charlotte, NC, USA. d Professor, Department of Oral Medicine, Carolinas Medical Center, Charlotte, NC, USA. Received for publication Nov 3, 2014; returned for revision Dec 30, 2014; accepted for publication Jan 15, 2015. Ó 2015 Elsevier Inc. All rights reserved. 2212-4403/$ - see front matter http://dx.doi.org/10.1016/j.oooo.2015.01.009
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as well as specific species reported to cause IE or PJI. Given that the most prevalent periodontal pathogens are anaerobes that thrive deep in the subgingival biofilm,3 it is assumed that anaerobic pathogens are less likely to be disturbed by tooth brushing than by more invasive procedures, such as tooth extraction. Another aim of this study was to determine if the bacterial species identified in blood after tooth brushing are different from those found after a single tooth extraction. These bacterial species were also compared on their reported causality for IE and PJI.
METHODS The detailed methods for subject recruitment and randomization to the three arms of this study have been published elsewhere.1 Briefly, patients enrolled in this study presented to our hospital-based dental clinic for dental extraction. Two hundred and ninety patients were randomized to one of three study arms: Tooth brushing (98 patients), single tooth extraction with AP (96 patients), or single tooth extraction with an identical placebo (96 patients). We collected demographic, baseline, and
Statement of Clinical Relevance Given the similar incidence of bacteremia caused by species associated with infective endocarditis and prosthetic joint infections following tooth brushing and single tooth extraction, poor oral hygiene may put patients at greater risk compared with dental office procedures.
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extensive oral disease and hygiene data parameters; the mean age of patients was 40 years; and 58% of patients were male and 73% African American. Patients randomized to the extraction groups were given 2.0 grams of amoxicillin or an identical placebo 1 hour before the procedure. Venous blood draws were obtained at six time points before, during, and after the procedure. Bacterial species cultured from blood were then identified by using the 16 S rRNA gene sequencing method.
56%, and 80% for tooth brushing, extractione amoxicillin, and extractioneplacebo, respectively.1 Of the 98 identified bacterial species, 32, and 12 are associated with IE1,10 and PJI, respectively (Tables I and II). The differences in the incidences of species associated with IE and PJI, as well as all oral species, were statistically significant for both the extractioneplacebo and the extractioneamoxicillin groups and the extractioneplacebo and tooth brushing groups (P < .0001).
Literature review and analysis of bacterial species implicated in DSIs In a previous review of the literature, we had developed a list of 170 bacterial species that have been identified in blood cultures after dental procedures.1 This list was compared with another compiled list of 275 bacterial species reported to cause IE. The bacterial species that were common in both lists were then compared with the 98 oral bacterial species identified in blood in our prior study.1 In the present study, we extended our review of the literature to the past 25 years to find bacterial species reported to cause PJI by using the key words “prosthetic joint infections” and “bacterial species OR bacterium OR bacteremia.” A specific PubMed search was conducted by using the specific name of each bacterial species along with the key words “prosthetic joint infections” to determine whether that particular species was associated with PJI. The list of PJI bacterial species compiled from the published literature was used to determine which of the 98 oral bacterial species identified in blood in our prior study1 are associated with PJI. First, the frequency of bacterial species present in blood in either extraction group (i.e., with and without AP) was calculated to find the impact of amoxicillin on the bacterial species reported to cause IE and PJI or on all of the 98 oral bacterial species identified in our prior study. Second, the frequency of bacterial species in blood in the extractioneplacebo group was compared with that of the brushing group to determine the impact of these two dental manipulations on bacteremia caused by species associated with IE and PJI.
Impact of amoxicillin on bacterial species detected in blood and associated with IE and PJI AP with amoxicillin decreased the overall incidence of bacteremia after a single tooth extraction by 61% and the incidence of IE bacterial species by 68%, which is in keeping with the findings from our previous study.4 The IE bacterial species most significantly decreased in incidence by amoxicillin prophylaxis were Streptococcus spp., Fusobacterium nucleatum, and Peptostreptococcus micros (Table IIIA). However, F. nucleatum and P. micros are not common causes of IE.11-13 The bacterial species identified in blood to be associated with PJI were Actinomyces naeslundii, Granulicatella adiacens, Haemophilus aphrophilus, Peptostreptococcus micros, Prevotella melaninogenica, Propionibacterium acnes, Staphylococcus epidermidis, Streptococcus mitis, Streptococcus mutans, Streptococcus oralis, Streptococcus sanguinis, and Veillonella dispar/ parvulla.1 Overall, AP decreased the frequency of these 12 bacterial species by 81% (P < .0001) (Table IIIB).
Statistical analysis A subject was determined to be positive for bacteremia if any of the bacterial species identified from blood cultures matched the species reported in the published literature to cause IE or PJI. The incidence of bacterial species in each study arm was compared using chi-square tests. Statistical significance (P ¼ .05) was used in all cases.
RESULTS As reported previously, the overall incidence of any oral bacterial species detected from blood cultures was 32%,
Impact of dental manipulation on bacterial species detected in blood We compared the effects of the two dental manipulations and found a higher incidence of bacteremia from species associated with IE, PJI, and other oral bacterial species in the extractioneplacebo group than in the brushing group (i.e., 219 vs. 43). However, we found that the relative frequency of IE and PJI bacterial species in the extractioneplacebo group was not significantly different from the brushing group (Table IV). That is, of the 219 total instances in which oral bacterial species were detected in the extractioneplacebo group, IE bacterial species were identified 144 times (65%) and those associated with PJI were detected 68 times (31%). Also, of the 43 incidences of bacteremia in the brushing group, 24 (56%) were bacterial species associated with IE and 12 (28%) with PJI.
DISCUSSION In this study, we report for the first time the effects of dental manipulations (tooth brushing vs. tooth extraction) on bacteremia as a surrogate risk for DSIs (e.g., IE and PJI) and the impact of amoxicillin on PJI species.
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Table I. Comparison of infective endocarditis (IE) and prosthetic joint infections (PJIs) bacterial species detected in blood following tooth brushing versus single tooth extraction with or without antibiotic prophylaxis IE species detected in blood
Bacterial species
PJI species detected in blood
Single tooth Single tooth Tooth Single tooth extraction Single tooth extraction Tooth extraction with extraction with with amoxicillin with placebo brushing amoxicillin placebo brushing
Acinetobacter lwofii/calcoaceticus Actinobacillus actinomycetemcomitans Actinomyces meyeri/odontolyticus Actinomyces naeslundii Bifidobacterium longum/infantis Capnocytophaga oral clone X089 Eikonella corrodens Fusobacterium nucleatum Granulicatella adiacens Haemophilus aphrophilus Lactobacillus rhamnosus/casei Lactobacillus salivarius Neisseria elongate Neisseria flavescens Neisseria mucosa/sicca Peptostreptococcus micros Prevotella buccae Prevotella denticola Prevotella melaninogenica Prevotella oralis Propionibacterium acnes Staphylococcus epidermidis Staphylococcus warneri Stenotrophomonas maltophilia Streptococcus anginosus Streptococcus constellatus Streptococcus cristatus Streptococcus gordonii Streptococcus intermedius Streptococcus mitis/pneumoniae Streptococcus mutans Streptococcus oralis Streptococcus salivarius Streptococcus sanguinis Veillonella dispar/parvula
O O
O
O
O O O
O O O O O
O O O O O O
O O O O O O
O O O O
O O O O O
O O O O O O
O O O O O O
O O
O O O O
O
O
O
O
O
O
O O O O O O O O O O O O
O
O O
O
O O
O O
Table II. Comparison of the incidences of bacterial species associated with infective endocarditis (IE), prosthetic joint infections (PJIs), and all oral bacterial species detected in blood following tooth brushing and single tooth extractions with amoxicillin or placebo Incidence Bacterial species
Tooth brushing
Extractioneamoxicillin
Extractioneplacebo
IE (P < .0001) PJI (P < .0001) All oral species (P < .0001)*
23% 12% 32%
33% 14% 56%
60% 52% 80%
*
Total species N ¼ 32 N ¼ 12 N ¼ 98
*Results previously reported.1
Infective endocarditis IE-associated bacteria are often found in bacteremia resulting from invasive dental procedures, such as tooth extraction. Since tooth brushing disrupts only the (shallow) gingival pocket and tooth extraction disrupts both gingival and periodontal (deeper) pockets, one
would expect that the proportions of bacterial species found in blood after these two manipulations would be different. However, our data suggest that these two very different manipulations, in terms of perceived invasiveness, disrupted similar percentages of bacterial species that could cause IE. Although the load, or
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ORIGINAL ARTICLE Mougeot et al. 433
Table III. Impact of amoxicillin on bacterial species associated with distant-site infections detected in blood following dental extraction A. Most prevalent infective endocarditisecausing bacterial species Infective endocarditis (IE)ecausing bacterial species
Counts (extractioneplacebo)
Counts (extractioneamoxicillin)
Percentage change
P value
10 10 13 12 18 19
0 1 2 2 4 7
100% 90% 85% 83% 78% 63%
.0015 .0096 .0054 .0183 .0138 .0114
P value
Streptococcus mutans Fusobacterium nucleatum Peptostreptococcus micros Streptococcus intermedius Streptococcus mitis/pneumoniae Streptococcus anginosus
B. Prosthetic joint infectionecausing bacterial species Bacterial species
Counts (extractioneplacebo)
Counts (extractioneamoxicillin)
Percentage change
8
1
88%
.0168
37 4 19
6 1 6
84% 75% 68%
<.0001 .3122 .0088
68
14
79%
<.0001
Facultative anaerobes (Actinomyces naeslundi, Granulicatella adiacens, Propionibacterium acnes, Staphylococcus epidermidis) Viridans streptococci Aerobes (Haemophilus aphrophilus) Strict anaerobes (Peptostreptococcus micros, Prevotella melaninogenica, Veillonella dispar/parvulla) Total
Table IV. Incidence of total bacterial species associated with infective endocarditis and prosthetic joint infections detected in blood following tooth brushing or single tooth extraction with placebo
Bacterial species Infective endocarditis
Randomization (N)
Tooth brushing (43) Extractioneplacebo (219) Prosthetic joint infection Tooth brushing (43) Extractioneplacebo (219)
Total incidence of bacterial species (%) 24 144 12 68
(56) (65) (28) (31)
magnitude, of bacterial species in blood and the host immune response likely play important roles in the outcomes of bacteremia following dental office procedures, the much higher frequency of tooth brushing may put individuals at greater risk for DSIs annually compared with dental office procedures, which are far less frequent. The most prevalent bacteria found in blood following both tooth extraction and brushing were Streptococcus spp.,1 and most of the detected IE-causing bacterial species were Streptococcus spp. as well (see Table IIIA). For example, S. mitis, accounted for approximately 15% of the total frequency of IE bacterial species, and approximately 28% of the Streptococcus spp. (data not shown). Although the incidence of S. mitis in blood was reduced by 78% in the extractioneamoxicillin group (see Table IIIA),
amoxicillin did not completely eliminate these bacteria. Other studies have also reported the failure of AP to prevent IE caused by S. mitis and pointed out the increasing resistance of this species to blactam antibiotics, such as amoxicillin.14-17 Some early studies have suggested that amoxicillin has a lower, or no, significant effect on the incidence or magnitude of bacteremia during and up to 10 minutes after dental extractions.18 Non-streptococcal species that were significantly impacted by amoxicillin are rare causes of IE. For example, the frequency of bacteremia from Fusobacterium nucleatum was decreased by 90% (see Table IIIA), but we could find only six reported cases of IE caused by this organism.11,12 Another rare cause of IE is Peptostreptococcus micros, which was reduced by 85% by amoxicillin, but we found only 21 reported cases of IE caused by this species (see Table IIIA).13 Similar trends hold true for other anaerobic species detected in our study but which rarely cause IE.13,19-21 Therefore, the reduction in frequency of these bacterial species by amoxicillin may not be clinically significant in the prevention of IE. Prosthetic joint infections Our study suggests that amoxicillin decreased the frequency of PJI bacterial species in blood after single tooth extractions by 81% (see Table IIIB). These species belong to the diverse group of aerobic and anaerobic bacterial species inhabiting the oral cavity. However,
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the majority of these bacterial species was identified as viridans group streptococci rarely associated with PJIs.22 The longstanding practice of AP for PJIs is controversial for several reasons, largely because PJIs are rarely caused by species found in the mouth,23 for example, Staphylococcus aureus, which was not detected in our original study.1,10 Even if S. aureus entered the bloodstream through the oral cavity, this species is not significantly affected by amoxicillin.24 Additionally, the percentage of the total detected bacterial species that are associated with PJI is essentially the same between the extractioneplacebo and the brushing groups (see Table IV) (31% vs. 28%, respectively). Since tooth extraction and tooth brushing disrupted similar percentages of bacterial species that can cause PJIs, patients with prosthetic joints might also be at greater risk over time from such naturally occurring bacteremia. There are some limitations to this study. First, as we pointed out in our original paper,1 all participants in this study presented to our hospital-based urgent care dental clinic in need of an extraction and therefore may not represent the general population with regard to demographic characteristics and severity of dental disease. Additionally, the subanalysis in the present study relies heavily on published studies that used conventional culture-based approach, rather than the more sensitive 16 S rRNA gene sequencing approach, to identify bacterial species. Furthermore, although we have investigated the nature and incidence of IE- and PJIcausing bacteremia, we did not address such factors as bacterial load and host immune responses, which are likely to be important factors in the outcome of IE- and PJI- associated bacteremia. The molecular microbiology technology available at the time of our original study did not allow for determining the bacterial load for bacteremia. Although the use of AP before dental extraction decreased the frequency of bacterial species associated with IE and PJIs, clearly bacteremia incidence is a surrogate measure of risk for IE or PJIs. Our data support the current emphasis on the fact that tooth brushing likely causes a far greater incidence of bacteremia annually compared with office-based dental procedures. From a practical standpoint, since AP is not feasible before tooth brushing and the efficacy of AP has yet to be demonstrated, the benefits of AP before dental procedures may be outweighed by the risks, which include cost, antibiotic resistance, and drug reactions.
CONCLUSIONS Antibiotic prophylaxis is currently recommended by the American Heart Association for patients at higher risk for developing IE and is often given to those with prosthetic joints. Although AP decreases the frequency
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of all oral bacterial species, including species associated with IE and PJIs, both tooth brushing and single tooth extractions disrupt similar bacterial species in similar proportions. Although more invasive dental procedures, such as multiple extractions, could yield different incidences of bacteremia compared with single tooth extractions, our data support the current trend away from the routine use of AP in these patient populations. Considering the much higher frequency of tooth brushing compared with dental office procedures and the significant incidence of bacteremia caused by bacterial species associated with IE and PJIs that results from tooth brushing, such routine daily activities in the presence of poor oral hygiene and periodontal disease may put patients at a greater risk for these two DSIs. This work was supported by Carolinas Health Care System (CHS) Research Fund. SS was the recipient of the CHS Summer Scholar Program Award.
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OOOO Volume 119, Number 4 12. Weber G, Borer A, Riesenberg K, Schlaeffer F. Infective endocarditis due to Fusobacterium nucleatum in an intravenous drug abuser. Eur J Clin Microbiol Infect Dis. 1999;18:655-657. 13. Pathak R, Ngwe A, Enuh H, Saverimuttu J. Peptostreptococcus induced native-valve endocarditis. 2013. Available at: http:// ispub.com/IJID/12/1/1478. Accessed September 3, 2014. 14. Masuda K, Nemoto H, Nakano K, et al. Amoxicillin-resistant oral streptococci identified in dental plaque specimens from healthy Japanese adults. J Cardiol. 2012;59:285-290. 15. Chunduri NS, Madasu K, Goteki VR, Karpe T, Reddy H. Evaluation of bacterial spectrum of orofacial infections and their antibiotic susceptibility. Ann Maxillofac Surg. 2012;2:46-50. 16. Smith A, Jackson MS, Kennedy H. Antimicrobial susceptibility of viridans group streptococcal blood isolates to eight antimicrobial agents. Scand J Infect Dis. 2004;36:259-263. 17. Hall GE, Baddour LM. Apparent failure of endocarditis prophylaxis caused by penicillin-resistant Streptococcus mitis. Am J Med Sci. 2002;324:51-53. 18. Hall G, Hedström SA, Heimdahl A, Nord CE. Prophylactic administration of penicillins for endocarditis does not reduce the incidence of postextraction bacteremia. Clin Infect Dis. 1993;17: 188-194. 19. Michaux-Charachon S, Lavigne JP, Le FA, et al. Endocarditis due to a new rod-shaped Neisseria sp. J Clin Microbiol. 2005;43:886889. 20. Oh S, Havlen PR, Hussain N. A case of polymicrobial endocarditis caused by anaerobic organisms in an injection drug user. J Gen Intern Med. 2005;20:C1-C2.
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Reprint requests: Peter B. Lockhart, DDS Department of Oral Medicine Carolinas Medical Center PO Box 32861 Charlotte NC 28232-2861 [email protected]