Antimicrobial Stewardship
What is antimicrobial stewardship?
Antimicrobial stewardship is about safe and effective prescriptions of common antimicrobials.This involves minimising resistance, preventing hypersensitivity reactions and choosing the most evidence – based antimicrobial for the disease condition.
How to choose the right duration of antibiotic therapy?
For spreading odontogenic infections without severe or systemic features, infection following dentoalveolar surgery of necrotising gingivitis, less than 7 days is appropriate. Prolong length is asoscited with Clostridium difficile infection, candidiasis, and slection of antibiotic – resistant organisms, as well as increased costs.
What else can I do to optimise the antimicrobial dosage?
Seek specialist advice for patients with septic shock or who require intensive care support, patients with severe burns, [atoemts wotj f;uid sequestration into a third space (e.g. bleeding, ascites), patients with cystic fibrosis, pregnant women and obese patients.
Monitoring of antimicrobial blood concentration is important to improve efficacy, and minimise dose related toxicity of drugs.
Antibiotic Hypersensitivity
What are the common types of antimicrobial sensitivity?
Type A hypersensitivity
Type A hypersensitivity includes adverse drug reactions that are generally expected and predicted.
Type B hypersensitivity
Type B hypersensitivity includes adverse drug reactions that tare unpredictable, usually mediated by the immune system.
Immediate IgE mediated (allergic) hypersensitivity reaction
This is characterised by a range of conditions which could be mild urticaria, or immediate rash, to extensive urticaria, compromised airway, oedema, collapse of anaphylaxis, The reaction is expected within minutes to two hours. Although not all are severe, precautions should be taken, and specialist advice should be sought upon skin reactions.
For penicillin, immediate IgE mediated hypersensitivity reactions occur at an incidence of 1 – 4 per 100 000 course. |
Delayed immune – mediated (T cell) hypersensitivity reactions
Delayed immune – mediated hypersensitivity reactions are more common than immediate hypersensitivity reactions. Most are generally not severe. They mainly affect patients with a viral infection, as opposed to bacterial or fungal. They mainly affect individuals who have taken several courses of the drug. They can occur as rapidly as within 6 hours of receiving the antimicrobial. Symptoms include maculopapular rash (exanthem).
For penicillin induced delayed immune – mediated (T cell) hypersensitivity reactions, a mild maculopapular rath is not strongly predictive of future reaction. Often, patients will tolerate the drug if administed later. |
Delayed severe reactions
These are uncommon but serious. Severe cutaneous adverse reactions (SCAR) describes a group of T – cell mediated hypersensitivities with cutaneous plus internal organ or mucous membrane. Involvement.
· Drug rash with eosinophilia and systemic symptoms (DRESS) – typically characterised by fever, eosinophilia, desquamative gingivitis, and liver or kidney function
· Steven – Johnson syndrome / toxic epidermal necrolysis (SJS/ TEN) – a rare, acute, and potentially fatal skin reaction caused by acute keratinocyte death, resulting in fulminant epidermal skin and epithelial mucosal loss like burn injuries.
· Acute generalised exanthematous pustulosis (AGEP) – characterised by dozens to hundreds of pin – sized pustules on a background of erythema, often with fever and leucocytosis, and rarely, organ involvement; can have a quick onset following drug administration (e.g. one day)
· Acute intestinal nephritis (AIN) – a T cell mediated hypersensitivity reaction most associated with penicillins; causes kidney dysfunction and can include eosinophilia, fever and exanthamatous rash
· Serum sickness – characterised by vasculitic or urticarial rash, arthralgia/ arthritis, fever, hypocomplementemia and sometimes proteinuria. Serum sickness is triggered more commonly by cefaclor than other cephalosporins, and by sulphonamides. The onset is typically several days after starting treatment.
Antibiotics
Nitroimidazole Antibiotics
Mechanism of action: Nitroimidazoles work by disrupting microbial DNA which ultimately leads to cell death in bacteria and protozoa. They are particularly effective against anaerobes.
Targeted bacteria: The nitroimidazole, metronidazole, has activity against most anaerobic bacteria (e.g. Peptoniphilus [formerly Peptostreptococcus] species, P. gingivalise, P. oralis, B. fragilis).
Metronidazole Contraindications: Metronidazole and alcohol should not be consumed together because of a possible interaction that can lead to unpleasant side effects. Metronidazole, an antibiotic, inhibits an enzyme involved in metabolizing alcohol. When combined with alcohol, it can cause a reaction like the "disulfiram reaction" (the reaction caused by the drug disulfiram, which is used to treat alcohol dependence). This reaction may include symptoms like nausea, vomiting, palpitations, flushing, rapid heart rate, and shortness of breath. It’s typically advised to avoid alcohol while taking metronidazole and for at least 24 hours after completing the course to prevent these adverse effects. Dosage, frequency: The 12 hourly dosing regimen is based on pharmacokinetic data and minimum inhibitory concentrations of the pathogens involved, in addition to limited clinical studies and extensive clinical experience with its use. |
Glycopeptide Antibiotics
Glycopeptide antibiotics inhibit bacterial wall synthesis by binding D-Ala-D-Ala units, again preventing cross linking.
Indication: The primary indication in dental practice for the parenteral glycopeptide vancomycin, is treatment of infection with MRSA. It is not as effective as beta lactams in the treatment of S. aureus infections that are susceptible to beta lactams.
Vancomycin Vancomycin is associated with selection of VRE (vancomycin – intermediate S. aureus [VISA[]. |
Beta Lactam Antibiotics
Mechanism of action: Beta lactams inhibit synthesis of the cell wall found in all bacteria. Bacteria are unable to do peptidoglycan rings after incorporating beta lactams. This wall is thicker in gram positive bacteria, compared to gram negative bacteria.
Contraindications:
· For patients with history of penicillin AND cephalosporin immune mediated hypersensitivity, avoid all beta lactams except for aztreonam. Subsequently refer to specialist clinic.
· For patients with delayed non-severe penicillin hypersensitivity (usually a maculopapular rash or benign childhood rash), no significant organ involvement and not severe cutaneous lesion, avoid penicillins, followed by prolonged provocation test. Can still administer cephalosporin, in these patients, carbapenem or aztreonam
· Avoid penicillins and cephalosporins for all patient with severe delayed hypersensitivity to penicillin. Only exception is when there is a significant reaction in which beta lactam is the preferred drug. (meningitis, endocarditis, sepsis)
Beta lactams - Narrow – spectrum penicillins: benzyl penicillin and phenoxymethylpenicillin
Targeted bacteria: Narrow spectrum penicillins are active against numerous oral pathogens, including Peptoniphilus (formerly Peptostreptococcus) species, Actinomyces species, most Streptococcus species and other oral anaerobes (e.g. Fusobacterium species). They are inactivated by strains that produce beta lactamase enzymes.
penicillin G/ benzylpenicillin Indications: For susceptible infections (e.g. spreading odotogenic infection with severe or systemic features), it the treatment of choice because of its narrow spectrum of activity. It is given parenterally. Contra-indications: Avoid in all patients with hypersensitivity of penicillin, with the exception of Type A reactions. Dosage · Surgical prophylaxis for patients with liver disease: single dose · Spreading odontogenic infection with severe or systemic features: Penicillin G intravenously, o Patients requiring intensive care support: 2.4g (child: 50mg/kg up to 2.4g) 4 hourly o Patients not requiring intensive care support: 1.8g (child: 50mg/kg up to 2.4g) 4 hourly § PLUS metronidazole |
penicillin V/ phenoxymethylpenicillin Mechanism: Penicillin V is a penicillin antibiotic used to treat bacterial infections such as throat infections, skin infections, and respiratory infections. It works by inhibiting the growth of bacteria through the prevention of cell wall synthesis. Given orally, phenoxymethylpenicillin is preferred to amoxicillin because of its narrower spectrum of activity. Food impairs the absorption of phenoxymethylpenicillin. Ideally, it should be dosed at 6 – hourly intervals, but for practical purposes four times daily dosing, evenly spaced during waking hours, is often used (e.g. half an hour before each meal and at bed time. Contra-indications: Avoid in all patients with hypersensitivity of penicillin, except for Type A reactions. Indications, dosage, frequency
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Beta lactams - Narrow – spectrum penicillins with antistaphylococcal activity: Dicloxacillin and flucloxacillin
Dixocloxacillin and flucloxacillin are active against streptococci and staphylococci, but inactive against MRSA. They are recommended as the first line treatment for many skin and soft tissue infections (e.g. acute suppurative sialadenitis).
Dosages: Food impairs the absorption of phenoxymethylpenicillin. Ideally, it should be dosed at 6 – hourly intervals, but for practical purposes four times daily dosing, evenly spaced during waking hours, is often used (e.g. half an hour before each meal and at bed time.
Precautions: Rarely, flucloxacillin is associated with cholestatic jaundice, particularly in older patients on prolonged therap. Cholestatic jaundice can occur after oral or intravenous administration, and up to 6 weeks after treatment. Dicloxacillin appears to cause less irreversible hepatotoxicity, but causes more interstitial nerphritis.
flucloxacillin/ floxacillin Contra-indications: Flucloxacillin is used with caution in those with liver or kidney problems. Avoid in all patients with hypersensitivity of penicillin, except for Type A reactions. Indications, dosage, frequency
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Beta lactams - Moderate – spectrum penicillins: amoxicillin and ampicillin
Amoxicillin and ampicillin are active against the pathogens treated by benzyl pencillin and phenoxymethylpenicillin.; however, they have a broader spectrum of activity. They are inactivated by strains that produce beta – lactamase enzymes.
Amoxicillin Contra-indications: Avoid in all patients with hypersensitivity of penicillin, except for Type A reactions. Indications, dosage, frequency · Endocarditic prophylaxis: o Amoxicillin 2g (child: 50mg/ kg up to 2g), orally 60 minutes before procedure OR o Amoxicillin 2g (child: 50mg/ kg up to 2g), intramuscularly 30 minutes before procedure, or within 60 minutes before the procedure
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Ampicillin Contra-indications: Avoid in all patients with hypersensitivity of penicillin, except for Type A reactions. Indications, dosage, frequency · Endocarditic prophylaxis: o Amoxicillin 2g (child: 50mg/ kg up to 2g), orally 60 minutes before procedure OR o Amoxicillin 2g (child: 50mg/ kg up to 2g), intramuscularly 30 minutes before procedure, or within 60 minutes before the procedure
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Beta lactams - Moderate – spectrum cephalosporins: cefalexin and cefazolin
Cephalosporins are beta – lactam antibiotics (ie. They contain a beta lactam ring in their structure). In most patients, cephalosporins do not cause significant adverse effects; however, some patients are hypersensitive to one or more beta – lactam antibiotics. Widespread use of cephalosporins is linked to an increasing prevalence of infections caused by methicillin – resistant Staphylococcus aureus (MRSA), vancomycin resistant enterococci, multi-drug-resistant Gram-negative bacteria and Clostridium difficile.
Indications:
· For patients with immediate or delayed nonsevere penicillin hypersensitivity (usually a maculopapular rash or benign childhood rash)
· Patients with amxicillin or ampicillin allergy who receive cefalxin or cefaclor, is more likely to have cross reactivity, due to their seminal R1 side chains
Targeted bacteria: Cefalexin and cefazolin have a similar spectrum of antibacterial activity. They are active against streptococci and staphylococci (both are gram positive), but inactive against MRSA and some anaerobes. In some circumstances, cefalexin and cephazolin can be used as a penicillin alternative in patients hypersensitive to penicillins (delayed non – severe penicillin hypersensitivity). However, in general, for patients with amoxicillin or ampicillin allergy who receive cefalxin or cefaclor, is more likely to have cross reactivity, due to their seminal R1 side chains.
Cefalexin Contra-indications: Indications, dosage, frequency
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Cefazolin Indications: Cefazolin has no common side – chains with other beta lactams so are often tolerated in penicillin or cephalosporin allergy. Contra-indications: Indications, dosage, frequency
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Broad spectrum penicillins (beta – lactamase inhibitor combinations): amoxicillin + clavulanate
The beta – lactamase enzyme inhibitor, clavulanate, has little inferent antibacterial activity; it inhibits the beta – lactamase enzymes produced by several bacteria, including S. aureus and Bacteroides fragilis. beta lactamase enzymes to hydrolyse, break down beta lactam antibiotics, thus are resistant to beta lactams. Therefore, beta lactamase inhibitors are often given in conjunction with beta lactams, thus overcoming resistance mechanisms in bacteria. The spectrum of activity of amoxicillin (see above) is significantly broadened when combined with clavulanate.
Because of its broad spectrum of activity, amoxicillin + clavulanate has a limited role in the treatment of odontogenic infections. It is used when narrower – spectrum regiments are not suitable. Additional treatment for anaerobic bacteria (e.g. metronidazole) is sually not required with amoxicillin + clavulanate.
Intravenous amoxicillin + clavulanate has an emerging role in Australia and is recommended for a limited number of infections in the guidelines.
amoxicillin + clavulanate (augmentin) Contra-indications: Avoid in all patients with hypersensitivity of penicillin, except for Type A reactions. Indications, dosage, frequency in conjunction with beta lactams, thus overcoming resistance mechanisms in bacteria · Spreading odontogenic infection with severe or systemic features: augmentin containing amoxicillin + clavulanate intravenously, 1+0.2g 6 hourly |
Lincosamides Antibiotics
Mechanism of action: Lincosamides work by inhibiting bacterial protein chain elongation by binging to the 50S ribosomal unit. However, they are generally not effectively against gram negative, unable to bypass and be permeable through gram negative cell wall.
Lincosamides are active against most anaerobic bacteria (e.g. Peptoniphilus [formerly Peptostreptococcus’ species], Porphyromonas gingivalis, Prevotella oralis, B. fragilis), and some aerobic bacteria (e.g. S aureus, most Streptococcus species).
Indications: In dental practice, lincosamides is reserved for the treatment of susceptible infections in patients with hypersensitivity to penicillins.
Although clindamycin is inherently more activity than lincomycin, for most indications the sae dosage is appropriate. In these guidelines, clindamycin is ranked preferentially to lincomycin because there are more clinical data to support its use.
Adverse effects: Clindamycin and lincomycin have similar adverse effects; they can both cause antibiotic – associated diarrhoea.
Dosages: There is no oral liquid formulation of clindamycin currently marketed bin Australia, however, a 10 mg/ mL clindamycin solution can be made by dispersing the contents of a 150mg capsule in 15mL of water. The solution should be taken or stirred until an even dispersion is formed and the required volume should be measured immediately. The dose can be mixed with juice or soft food to disguise the taste before administration. The solution should be prepared immediately before administering each dose, and any remaining solution should be discarded.
Clindamycin Contra-indications: in patients with a history of gastrointestinal issues, particularly those with a history of infection (C. diff), as clindamycin can disrupt the normal gut flora and increase the risk of C. diff-associated diarrhea, which can be severe. Indications, dosage, frequency · Endocarditic prophylaxis for patients with immediate (severe, or non severere) or delayed hypersensitivities to penicillins o Clindamycin 600mg (child: 20mg/ kg up to 600mg), orally 60 – 120 minutes before procedure OR if oral administration not possible o Clindamycin 600mg (child: 20mg/ kg up to 600mg), intravenously within 120 minutes before the procedure · Spreading odontogenic infection with immediate (severe, or non severere) or delayed hypersensitivities to penicillins o Clindamycin 600mg (child: 15mg/ kg up to 600mg), 8 hourly o |
lincomycin · Spreading odontogenic infection with immediate (severe, or non severere) or delayed hypersensitivities to penicillins o lincomycin 600mg (child: 15mg/ kg up to 600mg), 8 hourly
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Beta Lactams - Carbapenems
Indications:
· For patients with immediate or delayed severe/ nonsevere penicillin hypersensitivity
· In patients with penicillin allergy confirmed on testing, the rate of immune – mediated cross – reactivity with carbapenams is approximately 1%.
Imipenam |
meropenem |
erta penam |
Monobactams
· There is no cross – reactivity between penicillins and monobactams.
Contraindications: Avoid in patients with ceftriaxone allergy
Azetreonam
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Tetracyclines used in dentistry
Tetracyclines have a broad-spectrum of antibacterial activity. Doxycycline is the preferred tetracycline for dental indications. Doxycycline has not been associated with tooth discolouration, enamel hypoplasia or bone deposition, even in children younger than 8 years, so is increasingly used in this age group. However, use is limited by the lack of a suitable commercially available formulation. (e.g. oral liquid formulation).
Oesophagitis can occur with oral doxycycline. Oral doxycycline should be taken with food and a large glass of water, and the patient should remain upright after administration. Photosensitivity reactions can occur with tetracyclines warn patients to avoid sun exposure.
Bacteria
Commensal Bacteria
| Pathogenic Bacteria
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Below are some commensal gram positive bacteria. · Actinomyces spp · Lactobacillus spp · Streptococcus spp
| Most pathogenic bacteria are gram negative anaerobes. · Aggregatibacter actinomycetemcomitans · Campylobacter rectus · Eikenella corrodens · Fusobacterium nucleatum · Porphyromonas gingivalis · Prevotella intermedia · Streptococcus mutans · Tannerella forsynthia · Treponema denticola
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Dental Conditions and Dosages
· Necrotising gingivitis: Metronidazole 400mg orally 12 hourly for 3-5 days. If pain and inflammation restrict, oral hygiene practices, recommend short term use of a mouth wash to reduce plaque formation.
· Spreading odontogenic infection without systemic features: Metronidazole 400mg orally 12 hourly 5 days
· Peri-implantitis: Metronidazole 400mg orally 12 hourly for 7 days
· Spreading odontogenic infection with systemic features: Metronidazole 500mg (child: 12.5mg/kg up to 500mg) intravenously 12 hourly on top of Penicillin G, plus EITHER:
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