Antibacterial drugs used in dentistry

Beta lactams used in dentistry

Penicillins

The most common adverse effects of the penicillins are nausea, diarrhoea, rash, urticaria, pain and inflammation ( at the injection ( after prolonged treatment and / or with broad spectrum penicillins).

* Narrow spectrum penicillins

Narrow spectrum penicillins are active mainly against Gram positive organism, and they are inactivated by beta lactamases.

Phenoxymethylpenicillin ( penicillin V ) is acid stable , so it can be given orally, although food impairs absorption. It is intrinsically less active than bensylpenicillin. Phenoxymethylpenicillin is the drug of choice in acute odontogenic infections due to its narrow ( and appropriate) spectrum of activity, with 85% of oral bacteria susceptible. Although susceptibility to amoxycillin is marginally higher ( 91%), it use should be reserved to prevent the development of resistance in infections caused by Streptococcus pneumoniae. Phenoxymethylpenicillin has fewer has fewer gastroinestinal problems than amoxycillin and is less likely to cause a rash.

Benzylpenicillin ( penicillin G) is administered parenterally and is the treatment of choice for susceptible infections if parenteral if parenteral treatment is warranted.

* Narrow spectrum penicillins with antistaphylococcal activity

Dicloxacillin and flucoxacillin are stable to beta lactamases produced by staphylococci.They are reliably absorbed by the oral rout; however , food reduces absorption and they are best taken half to one hour before food. Ideally, they should be dosed at 6 hourly intervals, but for practical purposes9 eg in children) four times a day dosing, evenly spaced during waking hours, can given. They are rarely indicated in general dental practice.

Flucloxacillin is generally well toilerated but, rarely, is associated with cholestatic jaundice, particularly in oder patients on prolonged therapy. This may occur after oral or intravenous administration and up to 6 weeks after treatment. It may last for months, can be irreversible and, rarely, may be fatal. Dicloxacillin appears to cause less irreversible hepatotoxicity but results in more infusion phlebitis and interstitial nephritis. Dicloxacillin may be preferable to flucloxacillin for oral therapy or in patients requiring prolonged therapy.

In this guidelines, di/flucloxacillin refers to dicloxacillin or flucloxacillin.

note; The intravenous formulation of dicloxacillin was discontinued in Australi in April 2012.

Moderate spectrum penicillins.

The aminopenicillins, amoxycillin and ampicillin, have greater than benzylpenicillin againts some Gram negative organisms ( eg Escherichia coli, Haemophilus influenzae) , but are destroyed by beta lactamase producing strains. Amoxycillin is better absorbed orally than ampicillin, is not affected significantly by food and requires fewer oral doses per day, but when administraed parentally they are equivalent.

Amoxycillin and ampicillin can increase the likelihood of rash in patients taking allopurinol ( used in the prevention of gout).
In this guidelins, amoxycillin/ ampicillin refers to amoxycillin or ampicillin.

* Broad spectrum penicillins ( beta lactamase inhibitor combinations)

Amoxycillin + clavulanate should not be used as first line treatment for odontogenic infections.
The beta lactamase inhibitor clavulanate inhibits the enzymes producced by Staphylococcus aureus, Bacteroides fragilis and H. influenzae, and also most of the beta lactamase enzymes found in E.coli and Klebsiella species.
Clavulanate possesses litle inherent antibacterial activity, but significantly extends the spectrum of activity of amoxicillin when given with it. This comnination should be reversed for the treatment of beta lactamase producing organisms. Additional anaerobic cover ( eg metronidazole) is not required with beta lactamase inhibitor combinations.
Amoxicillin + clavulanate can cause diarrhoea and hepatotocity, which occur more frequently than with amoxycillin alone.

Cephasporins

Cephalexin and cephazolin are moderate spectrum cephalosprins with a similar range of antimicrobial activity. They are active against streptococci and staphylococci, including beta lactamase producing staphylococci. Their Gram negative spectrum includes E.coli and most Klebiella species, but they are inactive against many Gram negative aerobes ( eg Serratia, Enterobater and Pseudomonas species) .
They are not useful against the Gramnegative anaerobe.

Bacteroides fragilis and related species.

The common adverse effcts are diarrhoea, nausea, rash, eosinophilia, drug fever, electrolyte disturbances, and pain and inflammation ( at the injection site).

* Glycopeptides.

Lincosamides and lincomycin are active against Gram positive aerobes and most anaerobes. They are used as second line therapy in those intolaerant to conventional therapy or where resistance is of concern.
Oral clindamycin and intravenous formulations of t=both clindamycine and lincomycin are available.
There is no oral liquid formulation of clindamycin currently marketed in Australia; however, a 50 capsule in 2 mL of water. Draw this solution into a syringe and make the volume up to 3 mL ( if necessary ) . The required volume of solution should be mixed with juice or sorft food to disguise the tast before administration.

Clindamycin is well absorbed orally. Intravenous doses should be administered slowly to avoid producing serious arrhythmias.

The most common adverse effects of lincosamides are diarrhoea, nausea, vomiting, abdominal cramps, abdominal pain, metallic taste( with intravenous administration) , itch and rash.

Macrolides used in dentistry

Macrolides are rarely indicated in dental practice, although roxithromycin may be used to treat acute odontogenic infections in patients with penicillin hypersensitivity. In vitro, roxithromycine has reasonable activity against some oral organism, such as viridans group streptococci and Gram positive anaerobes . However, its activity against Gram negative anaerobic organism is more variable; Bacteroides fragilides and Fuosbacterium species are resistant.

Roxithromycin is prefered to erythromycine because it has a more benign adverse effect profile , fewer drug interactions and better activity against oral pathogens.

The most common adverse effects of macrolides are nausea, vomiting, diarrhoea, abdominal pain, cramps, headache, dyspnoea, cough and candial infections.

* Nitromidazoles used in dentistry

Metronidazole and tinidazole have a spectrum of activity that encompasses Gram negative anaerobes such as Bacteroides fragilis, gram positive anaerobes such as Clostridium species,and anaerobic protozoa. Metronidazole is the drug of choice for spreading neck infectins and acute ulcerative gingivitis.

Metronidazole is available as an intravenous preparation; however, excellent absorption means that tablets or suppositories can often be used instead. In these guidelines, for the treatment of mixed aerobic and anaerobic infection, metronidazole is recommended at dose of 400mg orally and 500mg intravenously, with a 12 hourly dosing schedule to increase patient adherence.
This dosing regimen is based on pharmacokinetic data and minimum inhibitory concentrations of the pathogens involved, rather than formal clinical studies.

Tinizole is avalable only as an oral preparation. It has a long er half life than metronidazole so it can be administered less frequently or as a single dose .
The most common adverse effects of nitromidazoles are nausea, diarrhoea and a meltallic taste.
Nitromidazoles can interact with alcohol causing a disuliram like reaction ( severe intestinal cramping, flushing, tachycardia, nausea and vomiting).
Patients should be counselled to avoid alcohol during treatment, and for at least 24 hours after treatment with metronidazole or 72 hours after treatment with tinidazole. Metronidazole also inhibits the metabolism of warfarin, increaseing its concentration and the risk of bleeding, so patients taking warfarin should have their international normalised ratio ( INR) monitored.

* Tetracyclines used in dentistry

Tetracylines are usually bacteriostatic and a broad spectrum of activity, which includes Gram positive and gram negative bacteria, Chlamydia, Rickettsia, Mycoplasma, spirochaetes, some nontuberculous mycobacteria and some protozoa . Tetracyclines are rarely indicated in general dental practice, but may be used in management of tooth avulsion to help prevent root resorption.

Doxycycline is the preferred tetracycline in most situations, as once daily dosing enhances patient adherence and dosage adjustment is not required in patient with renal impairment.
Demeclocycline is available in combination with triamcinolone acetonide as an intracanal paste .

Tetracyclines are contraindicated in children 8 years of age or less as they chelate calcium ions and are incorporated into the hydroxyapatite of the developing enamel and dentine, leading to tooth discoloration and enamel dysplasia. They are also deposited in bone , causing deformities and inhibiting bone growth. As dentine development may continue beyond 8 years of age, some practitioners avoid tetracyclines in children up to 12 years of age . Tetracyclines are safe for use during the first 18 weeks of pregnancy ( 16 weeks postconception) after which they may affect the formation of the baby's teeth and cause discoloration. There have been rare occurrences of hepatic necrosis in pregnant women. Tetracyclines may be used for short courses ( eg 7 to 10 days)in breastfeeding women if there are no appropriate alternatives.
All tetracyclines cause soem gastrointestinal symptoms. Oesophagitis can occur with any tetracycline so they should be taken sfter food with a full glass of water and the patient should be instructed to remain upright for at least 30 minutes after oral administration. Photosensitivityreaction should be recommened . Candidal overgrowth can also occur with any tetracycline.

There are several important interactions with tetracyclines. Antacids decrease the absorption of tetracyclines, and oral doses of tetracyclines and antacids should be seperated by 2 hours. Some drugs ( eg carbamazepine, phenytoin) reduce the plasma concentration of doxycycline. Tetracyclines can enhance the activity of warfarin so patients taking warfarin should have their international normalized ratio ( INR) monitored.