In 1928 Alexander Fleming’s chance discovery of Penicillium notatum growing on a discarded petri dish of Staphylococcus colonies has led to one of the greatest advances in modern medicine and for the benefit of mankind [1]. Antibiotics are commonly prescribed in dentistry and often for the management of endodontic infections. Arguably the greatest risk of hubris to human health comes in the form of antibiotic–resistant bacteria. We live in a bacterial world where we will never be able to stay ahead of the mutation curve [2]. The overprescribing of antibiotics in medicine and dentistry has selected for antibiotic-resistant bacteria. When bacteria become resistant to antibiotics, they gain the ability to exchange this resistance, making them nonsusceptible to antibiotics commonly prescribed [3]. Inappropriate use of antibiotics not only drives antibiotic resistance, but it increases the risk of potentially fatal anaphylactic reactions and exposes patients to unnecessary side effects [4]. Furthermore, antibiotic prescribing for common medical problems has been shown to increase expectations for antibiotics, whereby patients expect this as the standard of care and anything less is an indication that the clinician is somehow providing a disservice to the patient. This, in turn, leads to a vicious cycle of increased prescribing in order to meet patient expectations [5]. Several surveys over the last 18 years of both general dentists and endodontists have demonstrated the continued inappropriate prescribing habits when managing endodontic infections [6–9].

Endodontic pain is the result of an inflammatory process. Reversible pulpitis, resulting from a mild to moderate injury, has the potential for recovery provided the insult to the pulp is removed. Irreversible pulpitis, on the other hand, due to persistent or extensive damage will result in irreversible levels of inflammation within the pulpal tissues leading to necrosis and bacterial colonisation of the root canal system. Irreversible pulpitis, which is characterised by acute and intense pain, is one of the most frequent reasons that patients attend for emergency dental care. Apart from the removal of the tooth, the customary way of relieving the pain of irreversible pulpitis is by drilling into the tooth, removing the inflamed pulp (nerve) and cleaning the root canal. However, a significant minority of dentists continue to prescribe antibiotics to stop the pain of irreversible pulpitis [10]. A prospective, double-blind, placebo-controlled study was carried out to determine the effect of penicillin on pain in untreated teeth, diagnosed with moderate to severe irreversible pulpitis. The study showed without doubt that antibiotics gave the same response as an inert placebo tablet confirming that antibiotics are not indicated in pulpitis [11].

Systemic antibiotics may be indicated as an adjunct in patients with acute dentoalveolar infection resulting in a diffuse, spreading infection or evidence of systemic involvement (pyrexia, malaise, extra-oral swelling, fascial space involvement, submandibular or cervical lymphadenopathy, muscle trismus and pain during swallowing) [12–14]. A spreading infection of endodontic origin may be painful due to increasing pressure within the tissues. Interventions to reduce the inflammatory process, by either direct elimination of the microbial irritants within the root canal system (chemo-mechanical preparation), incision and drainage or extraction of an un-restorable tooth, are effective at reducing the pain by eliminating the inflammatory process [15]. Rarely patients may present with life-threatening Ludwig’s angina, a rapidly progressing poly-microbial cellulitis of the sublingual and submandibular spaces. These cases require urgent referral to the local oral maxillofacial unit for admission, extra-oral drainage if indicated and intravenous systemic antibiotics [16]. There is no question as to the necessity of antibiotics and their benefits in managing cases where systemic involvement is evident.

On the other hand, the effectiveness of antibiotics in the routine treatment of endodontic infections without systemic involvement is questionable. The systemic administration of antibiotics relies on patient compliance with the dosing regimens followed by absorption through the gastrointestinal tract and distribution via the circulatory system to bring the drug to the infected site. Hence, the infected area requires a normal intact blood supply, which is no longer the case for teeth with necrotic pulps and for teeth without vital pulp tissue [17].

A placebo-controlled, prospective, randomised, double-blind study was carried out to assess whether the routine administration of preoperative antibiotics was warranted for endodontic surgical procedures. The results showed that clindamycin had no effect on post-operative infections and as such did not warrant routine prophylaxis [18].

Prophylactic antibiotics, taken prior to endodontic procedures, have been advocated to reduce the likelihood of serious systemic complications like infective endocarditis (IE). Recent changes to guidelines from the British Society for Antimicrobial Chemotherapy, and the American Heart Association, recommend that only patients in the high-risk category require antibiotic coverage. This recommendation is based on a number of findings including the fact that there is no consistent association between having an intervention, dental or non-dental, and the development of IE. Regular tooth brushing/flossing and chewing almost certainly presents a greater risk of IE than a single dental procedure because of repetitive exposure to bacteraemia with oral flora. The clinical effectiveness of antibiotic prophylaxis is not proven. Antibiotic prophylaxis against IE for dental procedures may lead to a greater number of deaths through fatal anaphylaxis than would a strategy of no antibiotic prophylaxis. Finally antibiotic prophylaxis against IE is not cost-effective. Treatment decisions should be made in light of all circumstances presented by the patient. Treatments and procedures applicable to the individual patient rely on mutual communication between patient, physician, dentist and other healthcare practitioners [19–21].

Immunocompromised patients may not be able to tolerate a transient bacteraemia following invasive dental procedures. Consultation with the patient’s physician is recommended for nonsurgical and surgical endodontic treatments. Discussion of antibiotic prophylaxis for patients undergoing chemotherapy, irradiation, and hematopoietic cell transplantation is essential to prevent possible septicaemia [22].

Often in the past, prosthetic implants, such as total knee replacements, have resulted in dental prophylaxis being commonly recommended. Recent guidelines have suggested that the practitioner might consider discontinuing the practice of routinely prescribing prophylactic antibiotics for patients with hip and knee prosthetic joint implants undergoing dental procedures. Physicians, dentists and patients should work collaboratively to customise a treatment plan that is based on the evidence, clinical judgement and patient preferences [23].

There is limited evidence on the use of systemic antibiotics in the management of luxation injuries, and no evidence that antibiotic coverage improves outcomes for root fractured teeth, avulsed teeth and splinting. Antibiotic use remains at the discretion of the clinician as traumatic dental injuries are often accompanied by soft tissue and other associated injuries, which may require other surgical intervention. In addition, the patient’s medical status may warrant antibiotic coverage [24–28].

According to the BNF, amoxicillin is recommended for dental infections in doses ranging from 250 to 500 mg, every 8 h. The use of 3 g amoxicillin repeated after 8 h is also mentioned, as a short course of oral therapy. Another antibiotic that is also recommended by the BNF is co-amoxiclav, which can be used in doses ranging from 375 to 625 mg every 8 h. In patients allergic to penicillin, clindamycin can be used in doses ranging from 150 to 450 mg every 6 h. Another option for penicillin-allergic patients (as recommended by the BNF) is metronidazole, which can be used in a dose of 200–400 mg every 8 h for 3–7 days [29–31].

Whilst systemic antibiotics appear to be clinically effective as an adjunct in certain surgical and nonsurgical endodontic cases, their routine use in endodontics is not justified. On the other hand, local application of antibiotics in endodontics has been an effective mode of delivery. The first reported local use of an antibiotic in endodontic treatment was in 1951 when Grossman used a poly-antibiotic paste known as PBSC. This contained penicillin to target Gram-positive organisms, bacitracin for penicillin-resistant strains, streptomycin for Gram-negative organisms and sodium caprylate to target yeasts. The compounds were all suspended in a silicone vehicle. Although clinical evaluation suggested that the paste conferred a therapeutic effect, the composition was ineffective against anaerobic species, which are now appreciated as being the dominant organisms responsible for endodontic diseases [32].

Numerous inter-appointment antimicrobial medications have been used to further eliminate bacteria or bacterial products from within the root canal system locally as a topical application. The two most common antibiotic-containing commercial paste preparations currently available are Ledermix paste (Lederle Pharmaceuticals, Wolfratshausen, Germany) and Septomixine Fort paste (Septodont, Saint-Maur, France). Both of these preparations also contain corticosteroids as anti-inflammatory agents. Ledermix paste remains a combination of the same tetracycline antibiotic, demeclocycline HCl (at a concentration of 3.2 %) and a corticosteroid, triamcinolone acetonide (concentration 1 %), in a polyethylene glycol base. Septomixine Forte contains two antibiotics, neomycin and polymyxin B sulphate [33, 34].

A 50:50 mixture of Ledermix paste with calcium hydroxide was advocated as an intra-canal dressing in cases of infected root canals, pulp necrosis and infection with incomplete root formation (as an initial dressing prior to using calcium hydroxide alone for apexification), perforations, inflammatory root resorption and inflammatory peri-apical bone resorption and for the treatment of large peri-apical radiolucent lesions [13].

Clindamycin, which is effective against many commonly found endodontic pathogens, was found to offer no additional antimicrobial advantage over conventional root canal medicaments such as calcium hydroxide, and therefore, it has not been recommended for routine use in endodontic therapy [35].

Tetracyclines including tetracycline hydrochloride, minocycline, demeclocycline, and doxycycline are a group of broad-spectrum antibiotics that are effective against a wide range of bacteria. Tetracycline has been used in combination as an intra-canal antibacterial paste (Ledermix) or as a final irrigating solution (BioPure MTAD and Tetraclean) [36, 37].

A recent resurgence of using a triple antibiotic paste of ciprofloxacin, metronidazole and minocycline in regenerative case reports has demonstrated a favourable outcome provided careful case selection has been carried out. Due to the complexity of root canal infections, it is unlikely that any single antibiotic could result in effective and predictable complete disinfection of the canal. More likely, a combination would be needed to address the diverse flora encountered. A combination of antibiotics would also decrease the likelihood of the development of resistant bacterial strains.

The presence of antibiotic resistance genes in endodontic microorganisms has been investigated and proven. The question remains whether routine antibiotic prophylaxis is accounting for this and also brings to question how effective intra-canal medicaments containing antibiotics are in reality. If the existing endodontic flora within the confines of the root canal contains many of these resistant genes, are we simply creating further resistance and possible emergence of persistent strains that may be responsible for disease that does not respond to conventional therapy or re-treatment strategies? [38–41].