Meta-analysis to Assess Role of Systemic Antibiotics in Root Canal Treatment
Nouman Noor, Sadaf Humayoun, Humaira Zafar*, Noor Khan Lakhnana, Kiran Tauseef Bukhari
Al Nafees Med College, Isra University, Islamabad Campus, Pakistan
Received: 30-Jun-2017 , Accepted: 24-Oct-2017
Keywords: Root canal treatment, Antibiotics preference, Susceptibility, Oral pathogens
How To Cite
The role of systemic antibiotics in root canal treatment (RCT) always remained controversial. To exactly identify the state of affairs, regarding whether or not the usage of systemic antibiotics in RCT, the current meta analysis was carried out. To identify the frequency of discouraging or preferring the use of systemic antibiotics in RCT. Secondly to identify the efficacy of various antibiotics in post RCT infections. Department of Operative Dentistry, Rawal Dental College Islamabad and Pathology Department of Al Nafees Medical College & Hospital, Isra University Islamabad Campus, Pakistan. Total 41 published studies in 03 and a half decades were included in the study i.e 1981 – 2017. Various authentic electronic sources were used to gather adequate and authentic data by simple random sampling technique. 66.6%(n=08) studies from 1987 till 2011, were not in favour of using systemic antibiotics as a part of RCT. While 33.3% (n=04) preferred using systemic antibiotics for RCT. Regarding the local antibiotic preference, 33.3% (n=04) studies were in favour of using a combination of triple antibiotic paste comprising of metronidazole, minocycline and ciprofloxacin. There is no role of systemic/local antibiotics in endodontic management. However, the use of antibiotics is only recommended if deemed necessary by viewing the premorbid of patient.
The focal infection theory was established in early 1900s and hence restricted the evolvements in field of endodontics. The theory described that a foci of microorganisms or their enzymes and toxins can easily disseminate systemically. The resultant can manifest as either extensive tissue damage or systemic infection. The theory was rejected afterwards because of limited authentic supportive evidence. In year 2000 certain proven associations were established amongst dental infection with cardiovascular disorders, rheumatoid arthritis and many other systemic illnesses and complications. The documentary evidence was also provided to support that the cultivated bacteria from peripheral blood and the one present at the site of root canal treatment (RCT) were the same1. Jayakodhi H in 2012 also supplemented this finding that the involved bacteria are primarily the ones infecting root canals related with periradicular lesions2.The presence of Interappointment pain and swelling i.e flareups in pulp or periradicular tissues, are the initial symptoms following RCT to comprehend a microbial, mechanical or chemical etiology. The incidence of microbial etiology is on the top amongst all these2. The reason behind could be the incomplete or over instrumentation resulting in endodontic microbiota changes, apical extrusion of debris and could be secondary intraradicular infections3. Furthermore the management options for this includes premedication, relief of occlusion, drainage establishment, use of intracanal and systemic medication. The commonly involved bacteria for symptomatic periradicular lesions and flareups includes Porphyromonas gingivalis, Porphyromonas endodontalis, Fusobacterium nucleatum, Prevotella species, Porphyromonas species, Streptococcus mutans, Enterococcus feacalis4,5.
The use of systemic antibiotics always remained controversial. Fouad AF et al in 2002 concluded that usage of systemic antibiotics harbours no justification6. The observations was supplemented byNabavizadeh MR et al in 2011. He concluded the successful outcomes of RCT can well be achieved by intervening either through mechanical/chemical cleaning or via surgical procedure7. Weber JT et al in 2005 also discouraged the use of systemic antibiotics in RCT and preferred mechanical and chemical cleaning of root canal8-10. He also concluded that antimicrobial resistance, drug interaction, several side effects i.e nausea, vomiting, gastrointestinal upsets, allergic reactions and antibiotic associated colitis are the main reasons for discouraging systemic antibiotic usage in RCT7,8. Many other studies i.e by Palmer NA et al in 2001, Yingling NM et al in 2002 and Tabrizizade M et al in 2005 preferred using antibiotics for flareup reactions. The use of amoxil, penicillin V, clindamycin, erythromycin and metronidazole were preferred by them11-13.
In light of available literature, the current meta analysis was planned to identify the actual situation regarding whether or not the usage of systemic antibiotics in RCT.
2 Materials and Methods
2.1 Search methods A total 41 published studies in 03 and a half decades were included in the study i.e 1981 – 2017. Various authentic electronic sources were used to gather adequate and authentic data by simple random sampling technique. The National and Internationally published data was thoroughly reviewed for the current meta analysis.
To maintain the Quality Criteria, the published data was gathered from Pak Medinet.com, Medscape, Pubmed, Embase, Cochrane, Medline, Google search, British, and Canadian guidelines.
For quality criteria and based upon the study objectives, six aspects were identified and distributed amongst five authors of current manuscript. The MeSH terms were used for searching the relevant data. These six aspects are mentioned below;
- Published studies in favour of discouraging or preferring the use of systemic antibiotics in RCT.
- Published studies in favour of discouraging or preferring the use of local antibiotics in RCT.
- Sensitivity pattern of antibiotics for patients having post RCT infections.
- Resistant pattern of antibiotics for patients having post RCT infections.
- Sensitivity pattern of antibiotics for various bacteria/ pathogens in patients having post RCT infections.
- Resistant pattern of antibiotics for various bacteria/ pathogens in patients having post RCT infections.
The finally selected manuscripts were identified after the consensus of all five authors.
2.2 Inclusion criteria The published authentic guidelines, case reports, short communications, original and review articles were included in the study.
2.3 Exclusion criteriaLetters to editor, and editorials were excluded.
2.4 Data analysis The statistical analysis of published researches was done by using SPSS version 19. Frequencies were calculated in terms of percentages for quantitative variables.
Total 41(N) studies were included in the study. The statistics discouraging or preferring systemic/ local antibiotics for RCT are shown in table 1. Out of total 12 (n) published studies, 66.6%(n=08) from 1981 till 2011, were not in favour of using systemic antibiotics as a part of RCT. While 33.3% (n=04) preferred using systemic antibiotics for RCT. Regarding the local antibiotic preference, 33.3% (n=04) studies were in favour of using a combination of triple antibiotic paste comprising of metronidazole, minocycline and ciprofloxacin. The details are shown in table 1.
The studies supporting the sensitive pattern of systemic and local antibiotics in post RCT infections are shown in table 2. Regarding the penicillin group of antibiotics, statistic for four drugs were noticed i.e amoxil, amoxicillin, augmentin and penicillin V.
Nabavizadeh MR in 2011 and Palmer NA in 2001 concluded that amoxil is a drug of choice for any sort of post RCT infection. Palmer NA identified 47.3% sensitivity to amoxil. Yingling NM in 2002 and Roda R in 2007 concluded 67.8% each, sensitivity of amoxil. Roda R in 2007 concluded that amoxixillin harbours good sensitivity pattern for treating post RCT infections. Gamal M in 2015 declared augmentin a highly sensitive antibiotic. Yingling NM in 2002, Tabrizizade M in 2005, Morcillo E in 1997,and Skucaite N in 2010 concluded that penicillin V the drugs of choice for post RCT infections.
Regarding macrolide group, erythromycin was the commonly tested antibiotic. Tabrizizade M in 2005 (70.4% sensitivity), Morcillo E in 1997, Skucaite N in 2010, and Gamal M in 2015 concluded that erythromycin is the drug of choice for post RCT infections.
Regarding lincosamide group (bactericidal ones), clindamycin was the most commonly seen sensitive antibiotic. A study report by Yingling NM in 2002 showed 57.3% sensitivity. While other reported studies i.e Sobottka I in 2002, Swift JQ in 2002, Addy LD in 2005 and Skucaite N in 2010 also declared clindamycin a drug of choice for treating post RCT infections.
Regarding the local antibiotics, the study reports by Dhillon JS (2014), Taneja S (2011), Mohammadi Z (2009) and Sato I (1996) concluded a sensitive pattern for metronidazole, ciprofloxacin and minocycline (only when used in combination).
Amongst the list flouroquinolones, ciprofloxacin is the drug of choice declared sensitive by Sobottka I in 2002.
Roda R in 2007 declared linezolid (oxazolidinone i.e protein inhibitor) a sensitive one for post RCT infections.
Regarding tetracyclines, doxycycline and minocycline were the two tested drugs. Sobottka I in 2002 and Skucaite N (2010) declared doxycycline a sensitive one for treating post RCT infections.
Skucaite N in 2010, and Gamal M in 2015 concluded that vancomycin (glycopeptide group) is a sensitive drug for post RCT infections.
The studies supporting the resistant pattern of systemic and local antibiotics in post RCT infections are shown in table 3. Studies done by Roda R and Sobottka I in 2002 and 2007, concluded resistant pattern to amoxicillin. Penicillin V, Erythromycin and Clindamycin were declared resistant by Aracil B and Groppo FC in 2001 & 2005. The National UK formulary guidelines professed Clindamycin as having resistant pattern.
Metronidazole and Tetracyclines were declared resistant by Gamal M in 2015. Regarding the resistant pattern of metronidazole Skucaite N in 2010 also concluded the same resistant pattern for anaerobes.
The details of antibiotic susceptibility reported in various studies for oral microbes is shown in table 4. Vancomycin harbours 100% sensitivity for oral pathogens in post RCT. The findings were described in study carried out by Skucaite N in 2010. This finding was supported by Gamal M in 2015. He also declared vancomycin a drug of choice.
Penicillin G harbours 100% sensitivity for Porphyromona species. The findings were described in a study carried out by Skucaite N in 2010. Morcillo E in 1997 supported this observation.
Clindamycin harbours 100% sensitivity for anaerobes. The findings were described in a study carried out by Skucaite N in 2010. It was further strengthened by studies carried out by Canadian guidelines in 2001, Sobottka I in 2002, Swift JQ in 2002, Addy LD in 2005, and Skucaite N in 2010. All of those studies declared clindamycin a drug of choice for all oral pathogens.
Next in sequence are the Quinolones. Sobottka I in 2002 disclosed 98% sensitivity for oral pathogens in post RCT.
Roda R in 2007 concluded that linezolid was 95% sensitive for oral biofilm in post RCT infections.
The sensitivity details of augmentin, erythromycin and tetracycline/ doxcycline are also shown in table IV.
The details of resistant pattern of various antibiotics in relation to oral microbes are shown in table IV. UK guidelines for the year 2002 strongly discouraged the use of clindamycin. Whereas the statistics of different researches regarding resistant pattern of various antibiotics are also tabulated in table 4.
Out of total 12 (n) published studies i.e 66.6% studies from 1987 till 2011, were not in favour of using systemic antibiotics as a part of RCT. The recommended UK guidelines (2002) for systemic antibiotics usage in RCT are strongly discouraged. However it was clarified that the systemic antibiotics should only be used in patients at risk for infective endocarditis14. In the advancing era systemic antibiotics are recommended only if there are features for systemic infections or re-implantation of an avulsed tooth15-17.
Barnes J et al in 2011 described that in 1770s and 1980s increased understanding for the microbiology of infected root canal was identified18. Over the past two decades that knowledge was built upon and good understanding was established for microbial biofilm, etiological factors for infections, and the associated factors for successful outcome or failure of root canal19. Achievingsuccessful sterilization during RCT always remained a challenging task for the clinicians resulting in failure of RCT. The highlighted reasons includes presence of various microorganisms and the polymicrobial infections20.
Gamal M et al in 2015 conducted a study on patients having post RCT infection. The commonly detected isolates were Enterococcus faecalis 15%, Streptococcus mutans 9.5%, Streptococcus acidominimus 8.7% and Porphyromonas gingivalis 7.93%. The antimicrobial sensitivity for these microbes revealed amoxicillin-clavulanic acid, erythromycin and vancomycin the ideal choices. Resistant pattern to tetracycline was observed in 36.50 % cases21.
The injudicious use of systemic antibiotics by dental practitioners should be discouraged. They are adding up to the economical burden and emergence of drug resistance strains. Moreover a patient has to bear severe side effects22-25.
The results extracted from current meta analysis revealed that out of total 16 (n) studies, 12(n) were in favour of using systemic antibiotics, while 04(n) supported the use of local triple antibiotic paste. This is supported by a study report by Dhillon JS et al in 2014, which revealed successful outcome by applying triple antibiotic paste locally. This paste comprises a combination of metronidazole, ciprofloxacin, and minocycline26. Tracing back, the studies done by Taneja S et al in 2011, Mohammadi Z et al in 2011 and Sato I et al in 1996 were aligned with conclusions of Dhillon JS et al. They also found this triple antibiotic paste a very effective modality to eliminate endodontic pathogens.
However, because of impending risks of side effects by systemic antimicrobial, their use is discouraged. All these three studies narrated, that because of diversity in micro flora i.e aerobic and anaerobic, missing anyone of three above mentioned antibiotics will reduce the efficacy of treatment27-29. Swathi PA et al in 2014 conducted a study on diabetic patients undergone RCT, he concluded that infection rate was negligible in the group of patients where triple antibiotic paste as intercanal medication was used30.
Contrary the study by Roda R et al in 2007 for Valencian community (Spain) showed that augmentin (amoxixillin plus clavunic acid) is the most commonly prescribed drug. He also described that there 10% of all antibiotic prescriptions are because of dental infections31.
The current meta analysis concluded that vancomycin, flouroquinolones, linezolid, and penicillin G were the ideal drugs for managing post RCT infections. This finding is supported by the published data. Sobottka et al in 2002 concluded that flouroquinolones, doxycycline and clindamycin are the drugs of choices for successful management of dental infection. However, amoxicillin is having high resistant pattern for oral bacteria 32.
Swift JQ, et al (2002) described that clindamycin because of it specific pharmacokinetic and pharmacodynamics properties, harbours excellent tissue and bone penetration properties. Therefore it can be an ideal drug for managing all dental infection33.
Addy LD et al in 2005 concluded from his study that clindamycin is a drug of choice for endodontic procedures34. Contrary Dental Practitioner`s Formulary (DPF) of UK discourages the use of clindamycin because of a serious side effect i.e pseudomembranous colitis35, 36. However the Canadian guidelines recommends the use of clindamycin36,37. Morcillo E et al in 1997 concluded that despite the advancement in antimicrobials, none is worth enough to replace the penicillin group for managing dental infections38.
Like many other microbes for systemic infections, a trend of resistant pattern emergence is seen for the pathogenic oral bacteria39. Penicillins, macrolides and clindamycin are the reported drugs showingresistant pattern toPorphyromona apecies, Prevotella species, Streptoccocus viridans40,41.
The thorough literature review for this meta analysis showed that the use of systemic antibiotics followed by RCT should be discouraged. Necessitating the adoption of strict sterilization and disinfection protocols for successful outcomes of RCT.
There is no role of systemic/local antibiotics in endodontic treatment. It is discouraged, unnecessary and inappropriate. However, the use of antibiotics is only recommended if deemed necessary by viewing the premorbid of patient. Flouroquinolones, linezolid, penicillin G and vancomycin harbours good susceptibility for endodontic infections. While metronidazole, macrolides and tetracyclines are resistant to oral pathogens.
- Strict protocols/guidelines for sterilization/ disinfection, to be followed for RCT
- The prescription protocols/ guidelines to be reviewed for endodontic procedures.
- The justification of choice and dose of antibiotics should be appropriate to avoid emergence of drug resistance strains.
- If deemed necessary a paste of tripple local antibiotics i.e metronidazole, ciprofloxacin and minocycline should be used for RCT before starting systemic antibiotics.
- Elaborated studies should be carried out for assessing the sensitivity patterns of carbapenams, cephalosporins, and aminoglycosides to manage serious endodontic infection.
7 Limitations of study
Data was limited for the susceptibility pattern of carbapenams, cephalosporins, and aminoglycosides
8 Conflicts of interests
There are no conflicts of interests regarding publication of this manuscript.
9 Author`s contributions
NN: Provoking the idea of manuscript, Gathering and compiling the data for Published studies in favour of discouraging or preferring the use of systemic antibiotics in RCT.
SH: Gathering and compiling the data for Published studies regarding sensitivity & resistant pattern of antibiotics for patients having post RCT infections.
HZ: Compiling and formulating the entire manuscript by summarizing abstract, introduction, methodology, results and discussion.
NKL: Gathering and compiling the data for Published studies regarding sensitivity pattern of antibiotics for various bacteria/ pathogens in patients having post RCT infections.
KTB: Gathering and compiling the data for Published studies regarding resistant pattern of antibiotics for various bacteria/ pathogens in patients having post RCT infections.
10 Funding resources
None to disclose
- Murray CA, Saunders WP. Root canal treatment and general health: a review of the literature. Int Endod J. 2000;33(1):1-18.
- Jayakodi H, Kailasam S, Kumaravadivel K, Thangavelu B, Mathew S. Clinical and pharmacological management endodontic flare-up. J Pharm Bioallied Sci. 2012; 4(2): 294–298.
- Siqueira JF. Microbial causes of endodontic flare-ups. Int Endod J. 2003;36(3):453–63.
- Roças IN, Siqueira JF, Andrade AF, Uzeda M. Oral treponemes in primary root canal infections as detected by nested PCR. Int Endod J. 2003;36(1):20–6.
- Jacinto RC, Gomes BP, Ferraz CC, Zaia AA, Filho SFJ. Microbiological analysis of infected root canals from symptomatic and asymptomatic teeth with periapical periodontitis and the antimicrobial susceptibility of some isolated anaerobic bacteria. Oral Microbiol Immunol. 2003;18(4):285–292.
- Fouad AF. Are antibiotics effective for endodontic pain? Endod Top. 2002;3(2):52–6.
- Nabavizadeh MR, Sahebi S, Nadian I. Antibiotic Prescription for Endodontic Treatment: General Dentist Knowledge + Practice in Shiraz . Iran Endod J. 2011; 6(2): 54–59.
- Weber JT, Courvalin P. An emptying quiver: antimicrobial drugs and resistance. Emerg Infect Dis. 2005;11(4):791–793.
- Barker GR, Qualtrough AJ. An investigation into antibiotic prescribing at a dental teaching hospital. Br Dent J. 1987;162(3):303–306.
- Palmer N, Martin M. An investigation of antibiotic prescribing by general dental practitioners: a pilot study. Prim Dent Care. 1998;5(1):11–14.
- Palmer NA, Dailey YM, Martin MV. Can audit improve antibiotic prescribing in general dental practice? Br Dent J. 2001; 191(6):253–255.
- Yingling NM, Byrne BE, Hartwell GR. Antibiotic use by members of the American Association of Endodontists in the year 2000: report of a national survey. J Endod. 2002;28(3):396–404.
- Tabrizizade M, Alijani T. Antibiotic prescribing habits among general dental practitioners in Yazd. J Islam Dental Assoc Iran. 2005;17(1):23–29.
- National Institute for Health and Clinical Excellence. Prophylaxis against infective endocarditis: antimicrobial prophylaxis against infective endocarditis in adults and children undergoing interventional procedures. London, UK: National Institute for Health and Clinical Excellence, 2008. Clinical Guideline 64.
- Joint Formulary Committee. British National Formulary. 60th ed. London, UK: British Medical Association and Royal Pharmaceutical Society, 2010.
- Flores MT, Andersson L, Andreasen JO. International Association of Dental Traumatology. Guidelines for the management of traumatic dental injuries. II. Avulsion of permanent teeth. Dent Traumatol. 2007; 23(2): 130–136.
- Sato I, Kurihara AN, Kota K, Iwaku M, Hoshino E. Sterilization of infected root- canal dentine by topical application of a mixture of ciprofloxacin, metronidazole and minocycline in situ. Int Endod J. 1996;29 (2):118-124.
- Möller A J, Fabricius L, Dahlén G, Ohman A E, Heyden G. Influence on periapical tissues of indigenous oral bacteria and necrotic pulp tissue in monkeys. Scand J Dent Res. 1981; 89(3): 475–484.
- Barnes J, Patel S. Contemporary endodontics. Brit Dent J. 2011;211(6): 463 – 468.
- Leonardo MR, Hemandez ME, Silva LA, Filho TM. Effect of a calcium hydroxide-based root canal dressing on periapical repair in dogs: A histological study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102(12):680-5
- Gamal M, Sherbiny E. Antimicrobial Susceptibility of Bacteria Detected from the Root Canal Infection (Before and After). Int J Dent Sci Res. 2015; 3 (1): 4-9.
- Skucaite N. Susceptibility of Endodontic Pathogens to Antibiotics in Patients with Symptomatic Apical Periodontitis. J Endod. 2010; 36(10):1611–1616.
- Nunez RA, Cabello CR, Ortega VE. Antibiotic use by members of the Spanish Endodontic Society. J Endod. 2009; 35(6): 1198–1203.
- Ocek Z, Sahin H, Baksi G, Apaydin S. Development of a rational antibiotic usage course for dentists. Eur J Dent Educ. 2008; 12(1): 41–47.
- Maslamani AMJ, Sedeqi FA, Moule AJ. Prescription pattern of antibiotic and analgesic in endodontic treatment in Kuwaiti population: A self-administered Survey. Saudi Endod J 2014;4(3):128-34
- Hinckfuss SE, Messer LB. An evidence-based assessment of the clinical guidelines for replanted avulsed teeth. Part II: prescription of systemic antibiotics. Dent Traumatol. 2009; 25(2): 158–164.
- Dhillon JS, AmitaL, Saini SK, Bedi HS, Ratol SS, Gill B etal. Healing of a large periapical lesion using triple antibiotic paste and intracanal aspiration in nonsurgical endodontic retreatment. J Endod. 2014; 5(3): 161-165.
- Taneja S, Kumari M. Use of triple antibiotic paste in the treatment of large periradicular lesions. J Investig Clin Dent. 2011;3(2):72-6
- Mohammadi Z, Abbott PV. On the local applications of antibiotics and antibiotic-based agents in endodontics and dental traumatology. Int Endod J. 2009;42(2):555-567.
- Pai S, Pai ARV, Thomas MS, Bhat V. Effect of calcium hydroxide and triple antibiotic paste as intracanal medicaments on the incidence of inter-appointment flare-up in diabetic patients: An in vivo study. J Conserv Dent. 2014; 17(3): 208-211
- Roda R, Bagán JV, Bielsa SJM, Pastor CE. Antibiotic use in dental practice. A review. Med Oral Patol Oral Cir Bucal. 2007;12(3):186-192.
- Sobottka I, Cachovan G, Sturenburg E, Ahlers MO, Laufs R, Platzer U, et al. In vitro activity of moxifloxacin against bacteria isolated from odontogenic abscesses. Antimicrob Agents Chemother. 2002;46(6):4019-4021.
- Swift JQ, Gulden WS. Antibiotic therapy--managing odontogenic infections. Dent Clin North Am. 2002;46(4):623-633.
- Addy LD, Martin MV. Clindamycin and dentistry. Brit Dent. 2005;199(5): 23 - 26
- Dental Practitioner`s Formulary 2002-2004 British National Formulary No 44. London: The Royal Pharmaceutical Society of Great Britain and the British Medical Society, 2002
- Littler WA. Clindamycin suspension and endocarditis prophylaxis. Br Dent J. 2001;190(1): 407.
- Bombassaro AM, Wetmore SJ, John MA. Clostridium difficile colitis following antibiotic prophylaxis for dental procedures. J Can Dent Assoc. 2001; 67(1): 20–22.
- Morcillo E. Fundamentos farmacológicos de la terapéutica antimicrobiana. Av Odontoestomatol. 1997; 1(1):29-35.
- Salinas BM, Riu CN, Aytes BL, Escoda GC. Susceptibilidad antibiótica de las bacterias causantes de infecciones odontogénicas. Med Oral Patol Oral Cir Bucal. 2006;11(1):51-6.
- Aracil B, Minambres M, Oteo J, Torres C, Garces GJL, Alos JI etal. High prevalence of erythromycin-resistant and clindamycin-susceptible (M phenotype) viridans group streptococci from pharyngeal samples: a reservoir of mef genes in commensal bacteria. J Antimicrob Chemother. 2001;48(6):592-594.
- Groppo FC, Castro FM, Pacheco AB, Motta RH, Filho TR, Ramacciato JC. Antimicrobial resistance of Staphylococcus aureus and oral streptococci strains from high-risk endocarditis patients. Gen Dent. 2005;53(2):410-413.