Read the following article about the role that dentists play in combating antibiotic resistance. briefly summarize the article and provide your thoughts of

CONCISE REV IEW

Antibiotics in dental practice: how justified are we

Sukhvinder S. Oberoi1, Chandan Dhingra1, Gaurav Sharma2 and Divesh Sardana3

1Department of Public Health Dentistry, Sudha College of Dental Sciences and Research, Faridabad, India; 2Department of Oral Medicine and Radiology, Sudha College of Dental Sciences and Research, Faridabad, India; 3Department of Pedodontics and Preventive Dentistry, Centre for Dental Education and Research, AIIMS, Delhi, India.

Antibiotics are prescribed by dentists in dental practice, during dental treatment as well as for prevention of infection. Indications for the use of systemic antibiotics in dentistry are limited because most dental and periodontal diseases are best managed by operative intervention and oral hygiene measures. The use of antibiotics in dental practice is character- ised by empirical prescription based on clinical and bacteriological epidemiological factors, resulting in the use of a very narrow range of broad-spectrum antibiotics for short periods of time. This has led to the development of antimicrobial resistance (AMR) in a wide range of microbes and to the consequent inefficacy of commonly used antibiotics. Dentists can make a difference by the judicious use of antimicrobials – prescribing the correct drug, at the standard dosage and appropriate regimen – only when systemic spread of infection is evident. The increasing resistance problems of recent years are probably related to the over- or misuse of broad-spectrum agents. There is a clear need for the development of prescribing guidelines and educational initiatives to encourage the rational and appropriate use of drugs in dentistry. This paper highlights the need for dentists to improve antibiotic prescribing practices in an attempt to curb the increas- ing incidence of antibiotic resistance and other side effects of antibiotic abuse. The literature provides evidence of inade- quate prescribing practices by dentists for a number of factors, ranging from inadequate knowledge to social factors.

Key words: Dental practice, periodontal disease, oral hygiene

INTRODUCTION

Antibiotics are routinely prescribed in dental practice for either prophylactic or therapeutic use. Prophylactic antibiotics are prescribed to prevent diseases caused by the introduction of members of the oral flora to distant sites or to a local, compromised, site in a host at risk1. In most cases, prophylaxis is used to prevent endocardi- tis, whereas therapeutic antibiotics are prescribed mostly to treat diseases of the hard and soft tissues in the oral cavity after local debridement has failed2. Dentists prescribe medications for the management

of a number of oral conditions, mainly orofacial infec- tions3. As most human orofacial infections originate from odontogenic infections, the prescription of anti- biotics by dental practitioners has become an impor- tant aspect of dental practice. For this reason, antibiotics account for the vast majority of medicines prescribed by dentists4. Dentists’ use of antibiotics is characterised by a num-

ber of particularities. In effect, antibiotic prescription is empirical; the clinician does not know what microor-

ganism is responsible for the infection because cultures are not commonly grown from the patient’s pus or exu- date. Based on clinical and bacterial epidemiological data, the types of microorganisms responsible for the infectious process are suspected, and treatment is decided on a presumptive basis, fundamental on proba- bilistic reasoning5. Antibiotic use may be associated with unfavourable

side effects, ranging from gastrointestinal (GI) distur- bances to fatal anaphylactic shock and development of resistance. The increasing antibiotic-resistance problems of recent years are probably related to the over- or misuse of broad-spectrum agents, such as cephalosporins and fluoroquinolones6. As a result, a new era has emerged in which some species of bacteria are resistant to the full range of antibiotics presently available, with methicillin-resistant Staphy- lococcus aureus being the most widely known exam- ple of this extensive resistance. These serious complications associated with antibiotic use have encouraged studies investigating the antibiotic- prescribing practices of dentists7–10.

4 © 2014 FDI World Dental Federation

International Dental Journal 2015; 65: 4–10

doi: 10.1111/idj.12146

The empirical and broad use of antibiotic prophy- laxis is clearly no longer acceptable, but details on responsible prescribing remain problematic. In the dental community, there has been a general trend towards over-prescribing11,12. One of the surveys in USA found that only 39% of dentists and 27% of physicians followed guidelines for antibiotic prophy- laxis appropriately13. Many practitioners rely on the recommendations of other practitioners — who often cite anecdotal evidence — or decide that, when in doubt, the wise and conservative course is to prescribed14. The present review discusses the specific prescribing

practices of general dentists with regard to antibiotic prophylaxis for dental procedures and the guidelines generally used in dental practice for the prescription of antibiotics.

RATIONALE FOR ANTIBIOTIC USAGE IN DENTAL PRACTICE

The human oral cavity contains a very broad range of microorganisms. Some authors speak of more than 500 different species, and Liebana et al.15 even reported that all known microorganisms associated with humans are at some time found in the oral cavity as either transient (the majority) or resident (only a few) species. The bacteria that cause odontogenic infections are

generally saprophytes. The microbiology in this sense is varied, and multiple microorganisms with different characteristics can be involved. Anaerobic and aerobic micro-organisms are usually present in the oral cavity, and numerous aerobic species cause odontogenic infections — the most common being Streptococcus spp. The microorganisms most com-

monly isolated from the oral and maxillofacial regions are listed in Table 1. In the course of dental caries, the bacteria that pen-

etrate the dentinal tubules are mainly facultative anaerobes (i.e. Streptococcus spp., Staphylococcus spp. and Lactobacillus spp.). When the pulp tissue becomes necrosed, the bacteria advance through the pulp canal and the process evolves towards periapical inflammation16. The peri-apical infection warrants the rationale for the systemic administration of the antibiotics.

WHEN ANTIBIOTICS SHOULD BE INDICATED

Antibiotic prophylaxis for infectious diseases of dental or oral origin is more prevalent than the antibiotic treatment of such infections. Antibiotics are not an alternative to dental intervention; rather they are adjunctive to clinical intervention. The major use of antibiotic prophylaxis in dental procedures is for proce- dures that cause bleeding in the oral cavity, and admin- istration of antibiotics for such cases has become common practice among dentists14. Antibiotics are also commonly indicated in dental practice for treating immunocompromised patients, patients with evident signs of systemic infection and if the signs and symp- toms of infection progress rapidly17. Antibiotics are typically prescribed in dental prac-

tice (i) for the treatment of acute and chronic infec- tions of odontogenic and non-odontogenic origins, (ii) as prophylactic treatment to prevent focal infection in patients at risk (as a result of systemic conditions such as endocarditis, artificial heart valves and congenital heart disease) and (iii) to prevent local infection and systemic spread among patients undergoing surgical oral or dental treatment.

Table 1 Types of bacteria, according to requirement of oxygen for growth, isolated from upper respiratory tract and head and neck infections23

Infection Aerobic and facultative anaerobic organisms Anaerobic organisms

Cervical lymphadenitis Staphylococcus aureus* Pigmented Prevotella Mycobacterium spp. Porphyromonas spp.*

Peptostreptococcus spp. Postoperative infection disrupting oral mucosa

Staphylococcus spp. Fusobacterium spp. Enterobacteriaceae* Bacteroides spp.* Staphylococcus spp.* Pigmented Prevotella

Porphyromonas spp. Peptostreptococcus spp.

Deep neck sites Streptococcus spp. Bacteroides spp.* Staphylococcus spp.* Fusobacterium spp.*

Peptostreptococcus spp. Odontogenic complications Streptococcus spp. Pigmented prevotella

Staphylococcus spp.* Porphyromonas spp.* Peptostreptococcus spp.

Ororpharyngeal: Vincent’s angina necrotic ulcerative gingivitis

Streptococcus spp. Fusobacterium necrophorum* Staphylococcus spp.* Spirochetes

Prevotella intermedia Fusobacterium spp.

*Organisms that have the potential to produce beta-lactamase.

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Antibiotics for odontogenic infections

Despite the high incidence of odontogenic infections, there are no uniform criteria regarding the use of anti- biotics to treat them. A considerable percentage of pain of dental origin originates from acute and chronic infections of pulpal origin, which necessitates operative intervention, rather than antibiotics. Non- indicated clinical cases for antibiotic use, which are commonly practised by dentists, include acute periapi- cal infection, dry socket and pulpitis18. The clinical situations that require antibiotic ther-

apy on empirical basis are limited, and they include oral infection accompanied by elevated body tempera- ture and evidence of systemic spread, such as lymph- adenopathy and trismus19. Facial cellulitis, which may or may not be associated with dysphagia, is a serious disease that should be treated promptly by antibiotics because of the possibility of spread of infection via lymph and blood circulation, with the development of septicaemia. Chronic inflammatory periodontal conditions do

not require routine use of antibiotics; systemic antimi- crobials should only be used in acute periodontal con- ditions where drainage or debridement is impossible, where there is local spread of the infection or where systemic spread has occurred9. Whereas some authors consider the natural and

semisynthetic penicillins (amoxicillin) to be the options of first choice20, others prefer the combination of amoxicillin and clavulanic acid owing to the increase in resistance to the penicillins and low level of bacterial resistance to this combination, with a broad-spectrum action, pharmacokinetic profile, tolerance and dosing characteristics21. Penicillinase-resistant penicillin or an ampicillin-like

derivative is prescribed for infections caused by penicillinase-producing Staphylococcus spp. or those involving gram-negative bacteria. Patients allergic to penicillin are treated with clindamycin 300 mg (65%), which is the drug of choice, azithromycin (15%) or metronidazole-spiramycin combination (13%)22. Some authors have proposed clindamycin as the drug of choice in view of its good absorption, low incidence of bacterial resistance and the high antibi- otic concentrations reached in bone23. The antibiotics useful for treating patients with odontogenic infec- tions are listed in Table 2.

Antibiotics for non-odontogenic infection

Non-odontogenic infections require prolonged treat- ment. Such infections include tuberculosis (TB), syphi- lis, leprosy and non-specific infections of the mucosal membranes, muscles and fascia, salivary glands and bone.

New synthetic antibiotics, such as fluoroquinolones, are the drug of choice for management of non-odon- togenic infections and are indicated for bone and joint infections, genitourinary (GU) tract infections and respiratory tract infections and extend the bacterial spectrum to include gram-negative bacilli, gram-positive aerobic cocci and, in the case of third-generation flu- oroquinolones (moxifloxacin), anaerobic organisms24. Bone and anaerobic infections are managed by prescribing clindamycin (orally) or lincomycin (paren- terally)25. In the case of a primary oral tubercular lesion, an

empirical treatment given for TB can cure the oral tubercular lesion, even in the absence of histopatho- logical evidence26. The treatment of specific infections caused by mycobacteria requires the use of antibiotics for long periods of time (6 months to 2 years) and includes the administration of dapsone, clofazimine and rifampicin for leprosy, and associations of etham- butol, isoniazid, rifampicin, pyrazinamide and strepto- mycin for TB27.

Prophylactic use of antibiotics

Prophylactic antibiotics, taken before a number of dental procedures, have been advocated (i) to reduce the likelihood of postoperative local complications (such as infections or dry socket) or serious systemic complications (such as infective endocarditis), (ii) in surgical excision of benign tumours and (iii) in immu- nocompromised patients.

Prophylaxis against systemic spread

The use of antibiotics as prophylaxis for focal infec- tion is a common practice. Although the potential

Table 2 Antibiotics commonly used to treat odonto- genic infections

Antibiotic Administration route

Posology

Amoxicillin p.o. 500 mg/8 hours 1000 mg/12 hours

Amoxicillin/ clavulanic acid

p.o. or i.v. 500–875 mg/8 hours* 2000 mg/12 hours* 1000–2000 mg/8 hours†

Clindamycin p.o. or i.v. 300 mg/8 hours* 600 mg/8 hours†

Azithromycin p.o. 500 mg/24 hours, three consecutive days

Ciprofloxacin p.o. 500 mg/12 hours Metronidazole p.o. 500–750 mg/8 hours Gentamycin i.m. or i.v. 240 mg/24 hours Penicillin i.m. or i.v. 1.2–2.4 million IU/24 h‡

Up to 24 million IU/24 hours†

i.m., intramuscular; i.v., intravenous; p.o., per os (oral). *p.o. administration. †i.v. administration. ‡i.m. administration.

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exists for oral microorganisms to seed and infect dis- tant tissues after oral procedures, there is no substan- tiated evidence that this occurs. Consequently, the issue of when and for what conditions systemic pro- phylactic antibiotics are necessary is controversial. Infective endocarditis is an uncommon, but serious

and often life-threatening, condition. Some studies have shown that dental procedures are trigger fac- tors for few cases of endocarditis28. Lockhart reported an increased incidence of infective endocar- ditis following dental extraction and periodontal sur- gery29. Ottent et al. reported that bacteraemia was associated with 74% of patients following tooth extraction30. The American Heart Association (AHA) 2007

guideline31 recommends infective endocarditis prophy- laxis only for those whose underlying cardiac condi- tions are associated with the highest risk of an adverse outcome. Such conditions include: the pres- ence of prosthetic heart valves; previous history of infective endocarditis; unrepaired cyanotic congenital heart disease; in the 6-month period following complete repair of a congenital heart defect with pros- thetic material or a device; repaired congenital heart disease with residual defects or adjacent to the site of a prosthetic patch or device; and cardiac transplanta- tion recipients who develop valvulopathy. Even if all patients at risk of developing infective

endocarditis were given antibiotic prophylaxis, it might only prevent 5.3% of cases28. There is a larger likelihood of bacteraemia related to normal daily activities than from dental procedures32; therefore, some argue that the era of antibiotic prophylaxis is over33. In the case of bacterial endocarditis (infective endocarditis), the absolute risk rate after dental treat- ment, even in at-risk patients, is considered very low34. This is consistent with recent guidelines from the British Society for Antimicrobial Chemotherapy35, which recommended that only patients in the high- risk category require coverage with Antibiotics. Recently, the AHA36 has also provided the follow-

ing new talking points for clinicians: infective endo- carditis is much more likely to occur following frequent exposure to random bacteraemias associated with daily activities than from bacteraemia caused by a dental, GI tract or GU tract procedure; prophylaxis may prevent an exceedingly small number of cases of infective endocarditis, if any, in people who undergo a dental, GI tract or GU tract procedure; the risk of antibiotic-associated adverse events exceeds the bene- fit, if any, from prophylactic antibiotic therapy; and maintenance of optimal oral health and hygiene may reduce the incidence of bacteraemia from daily activi- ties and is more important than prophylactic antibiot- ics for a dental procedure to reduce the risk of infective endocarditis.

Prophylaxis against local infection

Prophylaxis of local infection is taken to comprise the administration of antibiotics on a pre-, intra- or postoperative basis, to prevent the proliferation and dissemination of bacteria within and from the surgi- cal wound. Various surgical procedures are routinely covered by administration of systemic antimicrobials, including impacted third molars, orthognathic sur- gery, implant surgery and periapical surgery. The evidence for antibiotics acting to prevent

infection of surgical wounds in the mouth is poor to non-existent, indicating that pre-operative parenteral antibiotic prophylaxis for routine third-molar surgery in medically fit patients is unwarranted37. For most dentoalveolar surgical procedures in fit, non-medically compromised patients, antibiotic prophylaxis is not required or recommended35. Immunocompromised patients represent a special

category of patients for dental professionals because such patients are more prone to bacteraemia, which may rapidly lead to septicaemia. Therefore, antibiotic prophylaxis may be given in such cases. Antibiotic coverage is also mandatory in patients with uncon- trolled diabetes, who have to undergo invasive dental treatment38. There is no scientific basis for recommending sys-

temic antibiotic prophylaxis before invasive dental treatment in patients with total joint prostheses39. According to the American Dental Association and the American Academy of Orthopedic Surgeons, eval- uation is required of antibiotic prophylaxis in patients with total joint prostheses in the presence of immune deficiency40. The use of antibiotics in endodontics should be indicated for those patients with signs of local infection and fever41.

APPROPRIATE SELECTION OF ANTIBIOTIC: DOSAGE AND DURATION

Oral antibiotics that are effective against odontogenic infections include penicillin, clindamycin, erythromy- cin, cefadroxil, metronidazole and the tetracyclines42. The type of antibiotic chosen and its dosage are dependent on the severity of infection and the pre- dominant type of causative bacteria. The most commonly used antibiotics in dental prac-

tice, penicillins in general, were found to be the most commonly prescribed antibiotics by dentists43; the most popular antibiotic was amoxicillin7, followed by penicillin V10, metronidazole and the combination of amoxicillin and clavulanic acid44. Patients who are allergic to penicillin should benefit

from clindamycin; which is active against some oral anaerobic and facultative bacteria and has the advan- tage of good bone penetration. However, increasing

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the dose of this antibiotic may increase the possibility of serious side effects such as neutropenia and pseudo- membranous colitis45. The ideal duration of antibiotic treatment is the

shortest cycle capable of preventing both clinical and microbiological relapse. Most acute infections are resolved within 3–7 days. When oral antibiotics are used, a high dose should be considered to help achieve therapeutic levels more rapidly46. In recent years, more attention has been given to

short courses of antibiotic. Rubenstein explained that short-course antibiotic therapy requires antibiot- ics to have certain characteristics, such as: rapid onset of action; bactericidal activity; lack of propen- sity to induce resistant mutants; ease of penetration into tissues; activity against non-dividing bacteria; unaffected by adverse infection conditions (low pH, anaerobiasis, presence of pus, etc.); administration at an optimal dose; and an optimal dosing regi- men47.

CONDITIONS NOT WARRANTING/ CONTRAINDICATIONS FOR THE USE OF ANTIBIOTICS

Consideration for antibiotic prophylaxis should be given in patients with kidney and/or liver failure and in pregnant or lactating mothers (as antibiotics may have an indirect effect on their infants). Dose adjust- ments are required for dental procedures in patients with kidney failure to avoid an increased plasma con- centration of the drug. Almost all antibiotics, except cloxacillin, clindamycin, metronidazole and macro- lides, require dose modification in patients with renal insufficiency48. Dose adjustment can be carried out by reducing the amount administered in each dose or by increasing the interval between doses (without modi- fying the amount of drug)49. Patients with liver failure require a dose reduction

of erythromycin, clindamycin, metronidazole and anti-tuberculosis drugs. Oral zinc supplementation is effective in hepatic encephalopathy and consequently improves patients’ health-related quality of life50. Almost all antibiotics are contraindicated during

pregnancy as a result of their major side effects. Risk of having a spontaneous abortion during the early pregnancy are associated with gestational use of dic- lofenac, naproxen, celecoxib, ibuprofen and rofecox- ib, alone or in combination51. In general, all antibiotics can cause three potential

problems for nursing infants. First, they can modify the bowel flora and alter gut defence mechanisms; this can result in diarrhoea and malabsorption of nutri- ents. Second, they may have direct effects that may or may not be dose related. Lastly, and often ignored, is that antibiotics can alter and interfere with microbio-

logical culture, resulting in babies being investigated for sepsis52.

DISCUSSION AND CONCLUSION

Antibiotic therapy is mandatory and essential in medi- cine and dentistry. Dentists are not always aware of the most current clinical guidelines regarding antibi- otic prophylaxis, even though guidelines are available. This is the reason for the empirical prescription of antibiotics and the adverse consequences of antibiotic use. Antibiotic use may be associated with unfavour- able side effects, ranging from gastrointestinal distur- bances to fatal anaphylactic shock and development of anti-microbial resistance. Minimising the occur- rence of antibiotic misuse and abuse has global impli- cations for the containment of antibiotic-resistant strains of bacteria. Development of resistance to drugs by microbes is a

natural phenomenon but is enhanced by the inap- propriate use of antimicrobials. A few strains that are naturally resistant and those with acquired resistance emerge as the dominant forms as a result of the selec- tive pressure exerted following exposure to antimicro- bials53. The antibiotic sensitivity of the bacteria found within the oral cavity is gradually decreasing, and a growing number of resistant strains have been detected – particularly Porphyromonas and Prevotel- la54 – although the phenomenon has also been reported for Streptoccocus viridans and for drugs such as the macrolides, penicillin and clindamycin55. Resis- tance has been reported against all beta-lactam antibi- otics (including penicillin derivatives and cephalosporins), clindamycin, ciprofloxacin, erythro- mycin and tetracycline56. The proper use of antibiotics is related to the prin-

ciples of infection management, microbiology of infectious agent and host response, and the pharma- cology of the particular agent. In the clinical setting, these principles are modulated by a number of factors. These factors need to be understood to ensure appro- priate prescribing of antibiotics.

Acknowledgement

None declared.

Conflicts of interest

None declared.

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