DENT 3005:Introduction to Pharmacology **Anti-infectives** Dr Thuy Linh Truong thuy.truong@uwa.edu.au # **DENT 3005: Introduction to Pharmacology** ## **Anti-infectives** Dr Thuy Linh Truong thuy.truong@uwa.edu.au **Acknowledgement** of country The University of Western Australia acknowledges that its campus is situated on Noongar land, and that Noongar people remain the spiritual and cultural custodians of their land, and continue to practise their values, languages, beliefs and knowledge. Artist: Dr Richard Barry Walley OAM The logo of the University of Western Australia # **Acknowledgement of country** The University of Western Australia acknowledges that its campus is situated on Noongar land, and that Noongar people remain the spiritual and cultural custodians of their land, and continue to practise their values, languages, beliefs and knowledge. Artist: Dr Richard Barry Walley OAM **Learning Outcomes** **Learning objectives** 1) Understand the different types of anti- infective drugs and their mechanism of action 1) Antibacterials 2) Antifungals 3) Antivirals 4) Antiprotozoals 5) Anthelminthics 2) Understand antimicrobial resistance and factors influencing antibiotic selection 3) Understand antimicrobial stewardship 4) Understand indication, dosing direction and regimen for antibacterial in the dental setting 5) Recognise oral and dental side effects of these drugs 6) Understand drugs interactions with dental medications 7) Applied knowledge to clinical scenarios # **Learning Outcomes** ## **Learning objectives** 1) Understand the different types of anti-infective drugs and their mechanism of action - 1) Antibacterials - 2) Antifungals - 3) Antivirals - 4) Antiprotozoals - 5) Anthelminthics 2) Understand antimicrobial resistance and factors influencing antibiotic selection 3) Understand antimicrobial stewardship 4) Understand indication, dosing direction and regimen for antibacterial in the dental setting 5) Recognise oral and dental side effects of these drugs 6) Understand drugs interactions with dental medications 7) Applied knowledge to clinical scenarios **Anti-infectives** * Definitions * Anti-infective = antimicrobial $\rightarrow$ broad term for anything combating infections * Anti-bacterial: fight bacteria! * Anti-viral: against viruses * Anti-fungal: against fungus etc, you get it $\bigodot$ * Indications: not comprehensive! * Based on clinical practice & evidence, may include non-marketed use * Drug groups * Antibacterials, Antifungals, Antivirals, Antiprotozoals, Anti-helminthics * Antimicrobial: empirical Vs prophylaxis * Non-Surgical Vs Surgical prophylaxis # **Anti-infectives** - **Definitions** - Anti-infective = antimicrobial → broad term for anything combating infections - Anti-bacterial: fight bacteria! - Anti-viral: against viruses - Anti-fungal: against fungus etc, you get it bigodot - **Indications: not comprehensive!** - Based on clinical practice & evidence, may include non-marketed use - **Drug groups** - Antibacterials, Antifungals, Antivirals, Antiprotozoals, Anti-helminthics - **Antimicrobial: empirical Vs prophylaxis** - Non-Surgical Vs Surgical prophylaxis RESISTANCE! * AMR = microbes evolve to resist drugs → undermines treatment, endangers global health * It's the microbe, not the drug, that changes * **Resistance Mechanisms (ABs)** * Limited uptake, target modification, drug inactivation, efflux pumps * **Spread:** Mutations, viral mutation, plasmid transfer * **Drivers:** Overuse/misuse in healthcare and agriculture, incomplete courses. * **Solutions:** Prescribe judiciously, follow guidelines, improve diagnostics, raise awareness An illustration shows a microbe with a shield deflecting an antibiotic thrown at it by a person. # **RESISTANCE!** - AMR = microbes evolve to resist drugs → undermines treatment, endangers global health - It's the microbe, not the drug, that changes - **Resistance Mechanisms (ABs)** - Limited uptake, target modification, drug inactivation, efflux pumps - **Spread:** - Mutations, viral mutation, plasmid transfer - **Drivers:** - Overuse/misuse in healthcare and agriculture, incomplete courses. - **Solutions:** - Prescribe judiciously, follow guidelines, improve diagnostics, raise awareness # Antimicrobial Stewardship (AMS) in Dental Practice * **AMS:** Optimize antibiotic use to reduce resistance * **Goal:** Right drug, dose, duration – only when needed * **Why:** Prevent AMR, toxicity, and high costs. * **Strategies** * Follow guidelines * Use narrow-spectrum drugs * Consider local resistance * **Complementary:** Infection control, hygiene, surveillance * **Tailored approach:** Adjust based on resources * **Key resource:** AMS in Australian Hospitals guide * **Your role:** Prescribe responsibly (A man throwing an antibiotic capsule at a shield-wielding bacterium. The bacterium is shown as a green microbe with angry eyes, holding a shield. The man is holding a large block labeled "ANTIBIOTIC"). </img> # **Antimicrobial Stewardship (AMS) in Dental Practice** - **AMS:** Optimize antibiotic use to reduce resistance - **Goal:** Right drug, dose, duration – only when needed - **Why:** Prevent AMR, toxicity, and high costs. - **Strategies** - Follow guidelines - Use narrow-spectrum drugs - Consider local resistance - **Complementary:** Infection control, hygiene, surveillance - **Tailored approach:** Adjust based on resources - **Key resource:** AMS in Australian Hospitals guide - **Your role:** Prescribe responsibly (A man throwing an antibiotic capsule at a shield-wielding bacterium. The bacterium is shown as a green microbe with angry eyes, holding a shield. The man is holding a large block labeled "ANTIBIOTIC"). </img> ## Antibacterials | **Bactericidal** | **Bacteriostatic** | | :--- | :--- | | Aminoglycosides | Lincosamides | | Carbapenems | Macrolides | | Cephalosporins | Tetracyclines | | Glycopeptides | Antimycobacterials | | Penicillins | Linezolid | | Quinolones | Nitrofurantoin | | Rifamycins | Sodium fusidate | | Antimycobacterials | Tigecycline | | Monbactams | Trimethoprim | | Colistin | Trimethoprim + sulfamethoxazole | | Macrocyclic antibacterial | | | Fosfomycin | | | Methenamine Hippurate | | | Metronidazole | | # **Antibacterials** | **Bactericidal** | **Bacteriostatic** | | :--- | :--- | | Aminoglycosides | Lincosamides | | Carbapenems | Macrolides | | Cephalosporins | Tetracyclines | | Glycopeptides | Antimycobacterials | | Penicillins | Linezolid | | Quinolones | Nitrofurantoin | | Rifamycins | Sodium fusidate | | Antimycobacterials | Tigecycline | | Monbactams | Trimethoprim | | Colistin | Trimethoprim + sulfamethoxazole | | Macrocyclic antibacterial | | | Fosfomycin | | | Methenamine Hippurate | | | Metronidazole | | Antibacterials: main class and MOA 4) Interference w/ metabolic processes 1) Inhibition of cell wall synthesis **NH₂** COOH p-Aminobenzoic acid **CH₂CH-CH-COOH** -NH- O Folic acid COOH Folic acid RNA Ribosome Peptide DNA 2) Inhibition of protein synthesis 3) Disruption of microbial cell membrane ## **Antibacterials: main class and MOA**  4) Interference w/ metabolic processes 1) Inhibition of cell wall synthesis **NH₂** COOH p-Aminobenzoic acid **CH₂CH-CH-COOH** -NH- O Folic acid COOH Folic acid RNA Ribosome Peptide DNA 2) Inhibition of protein synthesis 3) Disruption of microbial cell membrane | Class | Mechanism of Action | Examples | |---|---|---| | **Beta-lactams** | Inhibit cell wall synthesis (bind PBPs) → cell lysis | Penicillins, Cephalosporins, Carbapenems | | **Aminoglycosides** | Bind 30S ribosome → misread mRNA → faulty proteins → cell death | Gentamicin, Amikacin | | **Macrolides** | Bind 50S ribosome → block peptide elongation (bacteriostatic) | Erythromycin, Azithromycin | | **Fluoroquinolones** | Inhibit DNA gyrase/topoisomerase IV → block DNA replication | Ciprofloxacin, Levofloxacin | | **Tetracyclines** | Bind 30S ribosome → block tRNA binding → inhibit protein synthesis | Doxycycline, Minocycline | | **Sulfonamides** | Inhibit folic acid synthesis (dihydropteroate synthase) → bacteriostatic | Sulfamethoxazole (+ trimethoprim) | | **Glycopeptides** | Bind D-Ala-D-Ala → block cell wall synthesis → lysis | Vancomycin | | **Polypeptides** | Disrupt cell membrane → leakage of contents → cell death | Bacitracin, Polymyxin B | | **Oxazolidinones** | Bind 23S RNA of 50S ribosome → inhibit initiation complex | Linezolid | | **Rifamycins** | Inhibit RNA polymerase → block transcription → cell death | Rifampin, Rifabutin | | **Nitrofurans** | Damage DNA, RNA, and proteins → broad metabolic inhibition → cell death | Nitrofurantoin | | Class | Mechanism of Action | Examples | |---|---|---| | **Beta-lactams** | Inhibit cell wall synthesis (bind PBPs) → cell lysis | Penicillins, Cephalosporins, Carbapenems | | **Aminoglycosides** | Bind 30S ribosome → misread mRNA → faulty proteins → cell death | Gentamicin, Amikacin | | **Macrolides** | Bind 50S ribosome → block peptide elongation (bacteriostatic) | Erythromycin, Azithromycin | | **Fluoroquinolones** | Inhibit DNA gyrase/topoisomerase IV → block DNA replication | Ciprofloxacin, Levofloxacin | | **Tetracyclines** | Bind 30S ribosome → block tRNA binding → inhibit protein synthesis | Doxycycline, Minocycline | | **Sulfonamides** | Inhibit folic acid synthesis (dihydropteroate synthase) → bacteriostatic | Sulfamethoxazole (+ trimethoprim) | | **Glycopeptides** | Bind D-Ala-D-Ala → block cell wall synthesis → lysis | Vancomycin | | **Polypeptides** | Disrupt cell membrane → leakage of contents → cell death | Bacitracin, Polymyxin B | | **Oxazolidinones** | Bind 23S RNA of 50S ribosome → inhibit initiation complex | Linezolid | | **Rifamycins** | Inhibit RNA polymerase → block transcription → cell death | Rifampin, Rifabutin | | **Nitrofurans** | Damage DNA, RNA, and proteins → broad metabolic inhibition → cell death | Nitrofurantoin | **Penicillins** * MOA: Bactericidal; interfere with bacterial cell wall peptidoglycan synthesis * **Drug interactions** * Methotrexate: increase MTX concN * Probenecid: decrease penicillin excretion * Allopurinol: increases risks of rash occurring * Warfarin : flucloxacillin & dicloxacillin decrease anticoagulant effect of warfarin * Voriconazole: flucloxacillin may decrease voriconazole concN * **ADR [common]:** immunological reactions * [rare]: black hairy tongue <table><thead><tr><th>Generic name</th></tr></thead><tbody><tr><td>Amoxicillin</td></tr><tr><td>Amoxicillin + Clavulanate acid</td></tr><tr><td>Ampicillin</td></tr><tr><td>Benzylpenicillin</td></tr><tr><td>Dicloxacillin</td></tr><tr><td>Flucloxacillin</td></tr><tr><td>Phenoxymethylpenicillin</td></tr><tr><th>Common ADR</th></tr><tr><td>Diarrhea, nausea, pain and inflammation at injection site (less common with benzylpenicillin), superinfection (including candidiasis) especially during prolonged treatment with broad-spectrum penicillin, allergy</td></tr></tbody></table> ## **Penicillins** - **MOA:** Bactericidal; interfere with bacterial cell wall peptidoglycan synthesis - **Drug interactions** - Methotrexate: increase MTX concN - Probenecid: decrease penicillin excretion - Allopurinol: increases risks of rash occurring - Warfarin : flucloxacillin & dicloxacillin decrease anticoagulant effect of warfarin - Voriconazole: flucloxacillin may decrease voriconazole concN - **ADR [common]:** immunological reactions - [rare]: black hairy tongue | Generic name | |---| | Amoxicillin | | Amoxicillin + Clavulanate acid | | Ampicillin | | Benzylpenicillin | | Dicloxacillin | | Flucloxacillin | | Phenoxymethylpenicillin | | Common ADR | |---| | Diarrhea, nausea, pain and inflammation at injection site (less common with benzylpenicillin), superinfection (including candidiasis) especially during prolonged treatment with broad-spectrum penicillin, allergy | # Cephalosporins * MOA: Interfere with bacterial cell wall peptidoglycan synthesis * Drug interactions * Probenecid: prolongs activity of cephalosporins * ADR [common]: immunological reactions <table> <thead> <tr> <th>Generic name</th> </tr> </thead> <tbody> <tr> <td>Cefaclor</td> </tr> <tr> <td>Cefalexin</td> </tr> <tr> <td>Cefazolin</td> </tr> <tr> <td>Cefapime</td> </tr> <tr> <td>Cefotaxime</td> </tr> <tr> <td>Cefoxitin</td> </tr> <tr> <td>Ceftaroline</td> </tr> <tr> <td>Ceftazidime</td> </tr> <tr> <td>Ceftriaxone</td> </tr> <tr> <td>Cefuroxime</td> </tr> </tbody> </table> <table> <thead> <tr> <th>Common ADR</th> </tr> </thead> <tbody> <tr> <td>Diarrhea, nausea, vomiting, pain and inflammation at injection site, rash, headache, dizziness, allergy, Clostridioides difficile-associated disease, superinfection (including Candida and Enterococcus spp., especially with broader-spectrum cephalosporins and prolonged treatment)</td> </tr> </tbody> </table> # **Cephalosporins** - **MOA:** Interfere with bacterial cell wall peptidoglycan synthesis - **Drug interactions** - Probenecid: prolongs activity of cephalosporins - **ADR [common]:** immunological reactions | Generic name | |---| | Cefaclor | | Cefalexin | | Cefazolin | | Cefapime | | Cefotaxime | | Cefoxitin | | Ceftaroline | | Ceftazidime | | Ceftriaxone | | Cefuroxime | | Common ADR | |---| | Diarrhea, nausea, vomiting, pain and inflammation at injection site, rash, headache, dizziness, allergy, Clostridioides difficile-associated disease, superinfection (including Candida and Enterococcus spp., especially with broader-spectrum cephalosporins and prolonged treatment) | # Lincosamides * MOA: Interfere with bacterial cell wall peptidoglycan synthesis by binding * Drug interactions * Lincosamides may prolong action of non-depolarising neuromuscular blockers * ADR [rare]: taste disturbances | **Generic name** | |---| | Clindamycin | | Lincomycin | | **Common ADR** | |---| | Diarrhea (mild-to-severe), nausea, vomiting, abdominal pain or cramps, rash, itch, contact dermatitis (with topical use) | # **Lincosamides** - **MOA:** Interfere with bacterial cell wall peptidoglycan synthesis by binding - **Drug interactions** - Lincosamides may prolong action of non-depolarising neuromuscular blockers - **ADR [rare]:** taste disturbances | **Generic name** | |---| | Clindamycin | | Lincomycin | | **Common ADR** | |---| | Diarrhea (mild-to-severe), nausea, vomiting, abdominal pain or cramps, rash, itch, contact dermatitis (with topical use) | # Metronidazole - MOA: Metabolised to active metabolites that are thought to interfere with DNA synthesis - **Drug interactions** - Alcohol: disulfiram like reaction - Busulfan: increase busulfan concN - Disulfiram: confusion & psychotic reactions - Fluorouracil: increase FU concN - Phenobarbital: reduce concN of metro. - InH metabolism of Warfarin - **ADR** - [common]: metallic taste - [infrequent]: furry tongue, glossitis, stomatitis, oral mucositis <table style="width:100%"> <thead> <tr> <th style="background-color:#007B9E; color:white;">Generic name</th> </tr> </thead> <tbody> <tr> <td style="background-color:#CCCCCC;">Metronidazole</td> </tr> </tbody> </table> <table style="width:100%"> <thead> <tr> <th style="background-color:#007B9E; color:white;">Common ADR</th> </tr> </thead> <tbody> <tr> <td style="background-color:#CCCCCC;">Nausea, anorexia, abdominal pain, vomiting, diarrhea, metallic taste, CNS effects (eg dizziness, headache), thrombophlebitis (IV)</td> </tr> </tbody> </table> # **Metronidazole** - **MOA:** Metabolised to active metabolites that are thought to interfere with DNA synthesis - **Drug interactions** - Alcohol: disulfiram like reaction - Busulfan: increase busulfan concN - Disulfiram: confusion & psychotic reactions - Fluorouracil: increase FU concN - Phenobarbital: reduce concN of metro. - InH metabolism of Warfarin - **ADR** - [common]: metallic taste - [infrequent]: furry tongue, glossitis, stomatitis, oral mucositis <table style="width:100%"> <thead> <tr> <th style="background-color:#007B9E; color:white;">Generic name</th> </tr> </thead> <tbody> <tr> <td style="background-color:#CCCCCC;">Metronidazole</td> </tr> </tbody> </table> <table style="width:100%"> <thead> <tr> <th style="background-color:#007B9E; color:white;">Common ADR</th> </tr> </thead> <tbody> <tr> <td style="background-color:#CCCCCC;">Nausea, anorexia, abdominal pain, vomiting, diarrhea, metallic taste, CNS effects (eg dizziness, headache), thrombophlebitis (IV)</td> </tr> </tbody> </table> <center>Tetracyclines</center> * MOA: Broad-spectrum, bacteriostatic antibiotics * Inhibit protein synthesis via 30S ribosomal subunit * Drug interactions * Anticoagulants: Tetracyclines can lower plasma prothrombin activity → May require reduced anticoagulant dose (e.g., warfarin) * Dental implications * Binds calcium → incorporated into developing teeth * Causes permanent discoloration (yellow-grey/brown bands) * Affects enamel formation, increases susceptibility to decay <table><thead><tr><th><center>**Generic name**</center></th></tr></thead><tbody><tr><td>Demeclocycline</td></tr><tr><td>Doxycycline</td></tr><tr><td>Minocycline</td></tr><tr><td>Tetracycline</td></tr></tbody></table> <table><thead><tr><th><center>**Common ADR**</center></th></tr></thead><tbody><tr><td>Gastrointestinal symptoms and hypersensitivity reactions such as rashes and photosensitivity. Long-term use can cause superinfections. Doxycycline may irritate the esophagus if taken improperly, potentially leading to ulcers.</td></tr></tbody></table> # **Tetracyclines** - **MOA:** Broad-spectrum, bacteriostatic antibiotics - Inhibit protein synthesis via 30S ribosomal subunit - **Drug interactions** - Anticoagulants: Tetracyclines can lower plasma prothrombin activity → May require reduced anticoagulant dose (e.g., warfarin) - **Dental implications** - Binds calcium → incorporated into developing teeth - Causes permanent discoloration (yellow-grey/brown bands) - Affects enamel formation, increases susceptibility to decay | **Generic name** | |---| | Demeclocycline | | Doxycycline | | Minocycline | | Tetracycline | | **Common ADR** | |---| | Gastrointestinal symptoms and hypersensitivity reactions such as rashes and photosensitivity. Long-term use can cause superinfections. Doxycycline may irritate the esophagus if taken improperly, potentially leading to ulcers. | **Therapeutic guidelines** * **Management of Odontogenic Infections** * **Primary treatment:** Always address the source (e.g. extraction, root canal, periodontal debridement); antibiotics do **not** replace dental treatment * **Localized infections** (no facial swelling/systemic signs): * Include periapical, peri coronal, and periodontal abscesses * Present as dental pain, pus, or gum swelling * Treat with dental procedures to drain pus—antibiotics usually **not required** * If treatment is delayed >24h or fragments remain post-extraction, start antibiotics * Provide analgesia and warm saline or chlorhexidine rinses for peri coronal infections # **Therapeutic guidelines** ## **Management of Odontogenic Infections** - **Primary treatment:** Always address the source (e.g. extraction, root canal, periodontal debridement); antibiotics do **not** replace dental treatment - **Localized infections** (no facial swelling/systemic signs): - Include periapical, peri coronal, and periodontal abscesses - Present as dental pain, pus, or gum swelling - Treat with dental procedures to drain pus—antibiotics usually **not required** - If treatment is delayed >24h or fragments remain post-extraction, start antibiotics - Provide analgesia and warm saline or chlorhexidine rinses for peri coronal infections **Therapeutic guidelines** * **When to Refer or Prescribe Antibiotics** * Refer patients promptly to a dentist if presenting to a medical practitioner * Begin antibiotics only if dental treatment is delayed >24h or systemic signs are present * Recurrent infections despite antibiotics indicate missed dental intervention—seek expert advice * Common pathogens are polymicrobial; **amoxicillin** + **clavulanate** is effective monotherapy * Combine **metronidazole** with **penicillin** if anaerobic coverage needed # **Therapeutic guidelines** ## **When to Refer or Prescribe Antibiotics** - Refer patients promptly to a dentist if presenting to a medical practitioner - Begin antibiotics only if dental treatment is delayed >24h or systemic signs are present - Recurrent infections despite antibiotics indicate missed dental intervention—seek expert advice - Common pathogens are polymicrobial; **amoxicillin** + **clavulanate** is effective monotherapy - Combine **metronidazole** with **penicillin** if anaerobic coverage needed **Therapeutic guidelines** * **Spreading Odontogenic Infections (No Severe/Systemic Features)** * Can be managed outpatient with: * Drainage of pus * Source control via dental treatment * Antibiotics started after culture, if possible * Local anaesthesia may fail; consider sedation or GA * Analgesia is essential * Reassess at 48–72 hours—adjust antibiotics based on culture, check for unresolved abscesses via CT * Escalate care if not improving or worsening # **Therapeutic guidelines** ## **Spreading Odontogenic Infections (No Severe/Systemic Features)** - Can be managed outpatient with: - Drainage of pus - Source control via dental treatment - Antibiotics started after culture, if possible - Local anaesthesia may fail; consider sedation or GA - Analgesia is essential - Reassess at 48–72 hours—adjust antibiotics based on culture, check for unresolved abscesses via CT - Escalate care if not improving or worsening # **Therapeutic guidelines** - Indication: spreading odontogenic infection w/o severe/systemic features, infection following dentoalveolar surgery - **Metronidazole 400 mg** (child: 10 mg/kg up to 400 mg) orally, 12-hourly for 5 days - PLUS EITHER - **Phenoxymethylpenicillin 500 mg** (child: 12.5 mg/kg up to 500 mg) orally, 6-hourly for 5 days OR - **Amoxicillin 500 mg** (child: 15 mg/kg up to 500 mg) orally, 8-hourly for 5 days - OR (as a single preparation) - **Amoxicillin + clavulanate 875+125 mg** (child 2 months or older: 22.5+3.2 mg/kg up to 875+125 mg) orally, 12-hourly for 5 days - OR (penicillin hypersensitivity): **clindamycin 300 mg** (child: 7.5 mg/kg up to 300 mg) orally, 8-hourly for 5 days # **Therapeutic guidelines** ## **Regimen for Spreading Odontogenic Infection (No Severe/Systemic Features)** - **Indication:** spreading odontogenic infection w/o severe/systemic features, infection following dentoalveolar surgery - **Metronidazole 400 mg** (child: 10 mg/kg up to 400 mg) orally, 12-hourly for 5 days - **PLUS EITHER** - **Phenoxymethylpenicillin 500 mg** (child: 12.5 mg/kg up to 500 mg) orally, 6-hourly for 5 days **OR** - **Amoxicillin 500 mg** (child: 15 mg/kg up to 500 mg) orally, 8-hourly for 5 days - **OR (as a single preparation)** - **Amoxicillin + clavulanate 875+125 mg** (child 2 months or older: 22.5+3.2 mg/kg up to 875+125 mg) orally, 12-hourly for 5 days - **OR (penicillin hypersensitivity):** - **clindamycin 300 mg** (child: 7.5 mg/kg up to 300 mg) orally, 8-hourly for 5 days **Therapeutic guidelines** * **Spreading Infection with Severe or Systemic Features** * Urgently transfer to hospital with oral/maxillofacial support * Symptoms: facial swelling, trismus, dysphagia, dyspnoea, fever >38°C, pallor, sepsis signs * Airway management, IV fluids, pus drainage, and surgical source control are critical * Collect cultures before starting antibiotics—do not delay treatment * **AB Regimen (IV)** * **Benzylpenicillin IV + metronidazole IV** * **OR Amoxicillin + clavulanate IV** (dose based on weight and ICU status) * **Penicillin allergy:** * Non-severe: cefazolin + metronidazole * Severe: clindamycin monotherapy * Switch to oral therapy once clinically stable, drains are dry, and patient is afebrile # **Therapeutic guidelines** ## **Spreading Infection with Severe or Systemic Features** - Urgently transfer to hospital with oral/maxillofacial support - Symptoms: facial swelling, trismus, dysphagia, dyspnoea, fever >38°C, pallor, sepsis signs - Airway management, IV fluids, pus drainage, and surgical source control are critical - Collect cultures before starting antibiotics—do not delay treatment - **AB Regimen (IV)** - **Benzylpenicillin IV + metronidazole IV** - **OR Amoxicillin + clavulanate IV** (dose based on weight and ICU status) - **Penicillin allergy:** - Non-severe: cefazolin + metronidazole - Severe: clindamycin monotherapy - Switch to oral therapy once clinically stable, drains are dry, and patient is afebrile # Therapeutic guidelines - **Postoperative Dental Infections** - Rare; exclude dry socket and inflammation before diagnosing infection - Symptoms: cellulitis, purulent discharge, persistent/worsening pain after 48h - Mild infections: manage with drainage, fragment removal, analgesia, rehydration - Add antibiotics only if systemic features or immunocompromised - Use same oral regimens as for spreading odontogenic infections - Review at 48–72 hours to assess response # **Therapeutic guidelines** ## **Postoperative Dental Infections** - Rare; exclude dry socket and inflammation before diagnosing infection - Symptoms: cellulitis, purulent discharge, persistent/worsening pain after 48h - Mild infections: manage with drainage, fragment removal, analgesia, rehydration - Add antibiotics only if systemic features or immunocompromised - Use same oral regimens as for spreading odontogenic infections - Review at 48–72 hours to assess response **Therapeutic guideline: periodontal** * Gingivitis: not indicated * Periodontitis: rarely indicated * Necrotizing gingivitis: metronidazole 400 mg orally, 12-hourly for 3 to 5 days * Periodontal abscess: treat as spreading odontogenic infections only in profound immunocompromised * Peri-mucositis: not indicated * Peri-implantitis: amoxicillin 500 mg orally, 8-hourly PLUS metronidazole 400mg orally, 12-hourly for 7 days # **Therapeutic guideline: periodontal** - **Gingivitis:** not indicated - **Periodontitis:** rarely indicated - **Necrotizing gingivitis:** metronidazole 400 mg orally, 12-hourly for 3 to 5 days - **Periodontal abscess:** treat as spreading odontogenic infections only in profound immunocompromised - **Peri-mucositis:** not indicated - **Peri-implantitis:** amoxicillin 500 mg orally, 8-hourly PLUS metronidazole 400mg orally, 12-hourly for 7 days **Antibacterials: prophylaxis** * **Indications** * Surgical: rarely indicated, role of surgical antibiotic prophylaxis for patients with profound immune compromise who are undergoing an invasive dental procedure is uncertain * Infective endocarditis: in patients w/ specific cardiac conditions * **Not indicated** * Prevention of alveola osteitis * Tooth extractions * Third molar surgery * Procedures involving insertion of dental implants * Periodontal surgery * Periapical surgery * Soft and hard tissue removal # **Antibacterials: prophylaxis** - **Indications** - Surgical: rarely indicated, role of surgical antibiotic prophylaxis for patients with profound immune compromise who are undergoing an invasive dental procedure is uncertain - Infective endocarditis: in patients w/ specific cardiac conditions - **Not indicated** - Prevention of alveola osteitis - Tooth extractions - Third molar surgery - Procedures involving insertion of dental implants - Periodontal surgery - Periapical surgery - Soft and hard tissue removal **Infective endocarditis Prophylaxis** **Figure 2.40 Cardiac conditions for which endocarditis prophylaxis is recommended for patients undergoing a procedure listed in the figure below** Endocarditis prophylaxis is recommended *only* for patients with the following cardiac conditions (that are associated with an increased risk of developing infective endocarditis and the highest risk of adverse outcomes from endocarditis) who are undergoing a procedure listed *below* [NB1] [NB2]: * prosthetic cardiac valve, including transcatheter-implanted prosthesis or homograft * prosthetic material used for cardiac valve repair, such as annuloplasty rings and chords * previous infective endocarditis * congenital heart disease *but only if it involves*: * unrepaired cyanotic defects, including palliative shunts and conduits * repaired defects with residual defects at or adjacent to the site of a prosthetic patch or device (which inhibit endothelialisation) * rheumatic heart disease [NB3]. NB1: Endocarditis prophylaxis is not recommended for patients with forms of valvular or structural heart disease not listed in this box, including patients with mitral valve prolapse, septal defects or cardiac implantable electronic devices. NB2: Patients with a heart transplant who have developed cardiac valvulopathy may also be at high risk of adverse outcomes from endocarditis; consult the patient's cardiologist for specific recommendations. NB3: See text below for discussion of patients with rheumatic heart disease. ## **Infective endocarditis Prophylaxis** ### **Figure 2.40 Cardiac conditions for which endocarditis prophylaxis is recommended for patients undergoing a procedure listed in the figure below** Endocarditis prophylaxis is recommended *only* for patients with the following cardiac conditions (that are associated with an increased risk of developing infective endocarditis and the highest risk of adverse outcomes from endocarditis) who are undergoing a procedure listed *below* [NB1] [NB2]: - prosthetic cardiac valve, including transcatheter-implanted prosthesis or homograft - prosthetic material used for cardiac valve repair, such as annuloplasty rings and chords - previous infective endocarditis - congenital heart disease *but only if it involves*: - unrepaired cyanotic defects, including palliative shunts and conduits - repaired defects with residual defects at or adjacent to the site of a prosthetic patch or device (which inhibit endothelialisation) - rheumatic heart disease [NB3]. **NB1:** Endocarditis prophylaxis is not recommended for patients with forms of valvular or structural heart disease not listed in this box, including patients with mitral valve prolapse, septal defects or cardiac implantable electronic devices. **NB2:** Patients with a heart transplant who have developed cardiac valvulopathy may also be at high risk of adverse outcomes from endocarditis; consult the patient's cardiologist for specific recommendations. **NB3:** See text below for discussion of patients with rheumatic heart disease. # Antibacterials: prophylaxis - Infective endocarditis - Endocarditis prophylaxis only for patients with a cardiac condition(s) - Dental procedures —only those involving manipulation of the gingival or periapical tissue or perforation of the oral mucosa (eg extraction, implant placement, biopsy, removal of soft tissue or bone, subgingival scaling and root planning, replanting avulsed teeth) - Drug regimen - [oral] amoxicillin 2 g (child: 50 mg/kg up to 2 g) orally, 60mins before procedure - **Delay non severe penicillin hypersensitivity:** Cefalexin 2 g (child: 50 mg/kg up to 2 g) orally, 60 mins before procedure - **Immediate (severe or non-severe) or delayed severe hypersensitivity to penicillins:** clindamycin 600 mg (child: 20 mg/kg up to 600 mg) orally, 60 to 120 minutes before the procedure # **Antibacterials: prophylaxis** ## **Infective endocarditis** - Endocarditis prophylaxis only for patients with a cardiac condition(s) - Dental procedures —only those involving manipulation of the gingival or periapical tissue or perforation of the oral mucosa (eg extraction, implant placement, biopsy, removal of soft tissue or bone, subgingival scaling and root planning, replanting avulsed teeth) - **Drug regimen** - [oral] amoxicillin 2 g (child: 50 mg/kg up to 2 g) orally, 60mins before procedure - **Delay non severe penicillin hypersensitivity:** Cefalexin 2 g (child: 50 mg/kg up to 2 g) orally, 60 mins before procedure - **Immediate (severe or non-severe) or delayed severe hypersensitivity to penicillins:** clindamycin 600 mg (child: 20 mg/kg up to 600 mg) orally, 60 to 120 minutes before the procedure Diagram showing mechanisms of antifungal drugs acting on fungal cell structures including disruption of transcription, inhibition of mitosis, ergosterol synthesis, and interference with the cell membrane and wall. # **Antifungals** | Organism | Azoles | Echinocandins | Amphotericin B | Flucytosine | Griseofulvin | Terbinafine | | :--- | :--- | :--- | :--- | :--- | :--- | :--- | | **Yeasts** | Susceptible | Susceptible | Susceptible | Susceptible | Resistant | Varying susceptibility | | **Dermatophytes** | Susceptible | No data | No data | No data | Susceptible | Susceptible | | **Dimorphic moulds** | Susceptible | No data | Susceptible | Resistant | Resistant | Susceptible | | **Moulds** | Fluconazole resistant | Varying susceptibility | Varying susceptibility | Mostly Resistant | Resistant | Varying susceptibility | | **Mucorales** | Fluconazole & itraconazole resistant | Resistant | Susceptible | Resistant | Resistant | Resistant | # **Antifungals** | Organism | Azoles | Echinocandins | Amphotericin B | Flucytosine | Griseofulvin | Terbinafine | | :--- | :--- | :--- | :--- | :--- | :--- | :--- | | **Yeasts** | Susceptible | Susceptible | Susceptible | Susceptible | Resistant | Varying susceptibility | | **Dermatophytes** | Susceptible | No data | No data | No data | Susceptible | Susceptible | | **Dimorphic moulds** | Susceptible | No data | Susceptible | Resistant | Resistant | Susceptible | | **Moulds** | Fluconazole resistant | Varying susceptibility | Varying susceptibility | Mostly Resistant | Resistant | Varying susceptibility | | **Mucorales** | Fluconazole & itraconazole resistant | Resistant | Susceptible | Resistant | Resistant | Resistant | **Azoles** * MOA: Azoles impair the synthesis of ergosterol in fungal cell membranes leading to their breakdown * Drug interactions * Many drug interactions * Remember all our drug interactions because these are CYP3A4 inhibitors * Oral candidiasis: fluconazole, miconazole * Oral candidiasis in **immunocompromised or other tx failed**: itraconazole, ketoconazole, posaconazole, voriconazole <table> <thead> <tr> <th>Generic name</th> </tr> </thead> <tbody> <tr> <td>Fluconazole</td> </tr> <tr> <td>Itraconazole</td> </tr> <tr> <td>Ketoconazole (only thru SAS)</td> </tr> <tr> <td>Miconazole</td> </tr> <tr> <td>Posaconazole</td> </tr> <tr> <td>Voriconazole</td> </tr> </tbody> </table> <table> <thead> <tr> <th>Common ADR</th> </tr> </thead> <tbody> <tr> <td>Rash, headache, dizziness, nausea, vomiting, abdominal pain, diarrhoea, elevated liver enzymes</td> </tr> </tbody> </table> ## **Azoles** - **MOA:** Azoles impair the synthesis of ergosterol in fungal cell membranes leading to their breakdown - **Drug interactions** - Many drug interactions - Remember all our drug interactions because these are CYP3A4 inhibitors - **Oral candidiasis:** fluconazole, miconazole - **Oral candidiasis in immunocompromised or other tx failed:** itraconazole, ketoconazole, posaconazole, voriconazole | Generic name | |---| | Fluconazole | | Itraconazole | | Ketoconazole (only thru SAS) | | Miconazole | | Posaconazole | | Voriconazole | | Common ADR | |---| | Rash, headache, dizziness, nausea, vomiting, abdominal pain, diarrhoea, elevated liver enzymes | ```html <table> <thead> <tr> <th><b>Drug</b></th> <th><b>Indication</b></th> <th><b>Dosing Regimen</b></th> </tr> </thead> <tbody> <tr> <td><b>Fluconazole</b></td> <td>Oropharyngeal/ esophageal candidiasis</td> <td>Oral/IV, 50–200 mg once daily (the lower doses are usually used for oropharyngeal candidiasis). Up to 400 mg once daily can be used in oesophageal candidiasis. Treat for 7–14 days in oropharyngeal candidiasis and for 14–21 days in oesophageal candidiasis.</td> </tr> <tr> <td><b>Miconazole</b></td> <td>Oropharyngeal candidiasis</td> <td>Adult, child >2 years, oral, half a spoonful (2.5 mL) using the measure provided 4 times daily (for 7–14 days for treatment). Birth (at term) – 2 years, oral, quarter of a spoonful (1.25 mL) using the measure provided 4 times daily (for 7–14 days for treatment)</td> </tr> <tr> <td><b>Itraconazole</b></td> <td>Oropharyngeal/ oesophageal candidiasis in immunocompromised</td> <td>Oral liquid, 200 mg daily. Treat oropharyngeal candidiasis for at least 7–14 days and oesophageal candidiasis for 14–21 days. 50 mg capsule (Lozanoc®), 50–100 mg once daily for 28 days. 100 mg capsule (eg Itracap®), 100–200 mg once day</td> </tr> <tr> <td><b>Posaconazole</b></td> <td>Oropharyngeal candidiasis nf immunocompromised</td> <td>Oral liquid, 200 mg once daily for 1 day, then 100 mg once daily. Refractory to fluconazole or itraconazole, oral liquid 400 mg twice daily.</td> </tr> </tbody> </table> ``` ## **Antifungal Dosing Regimens** ```html <table> <thead> <tr> <th><b>Drug</b></th> <th><b>Indication</b></th> <th><b>Dosing Regimen</b></th> </tr> </thead> <tbody> <tr> <td><b>Fluconazole</b></td> <td>Oropharyngeal/ esophageal candidiasis</td> <td>Oral/IV, 50–200 mg once daily (the lower doses are usually used for oropharyngeal candidiasis). Up to 400 mg once daily can be used in oesophageal candidiasis. Treat for 7–14 days in oropharyngeal candidiasis and for 14–21 days in oesophageal candidiasis.</td> </tr> <tr> <td><b>Miconazole</b></td> <td>Oropharyngeal candidiasis</td> <td>Adult, child >2 years, oral, half a spoonful (2.5 mL) using the measure provided 4 times daily (for 7–14 days for treatment). Birth (at term) – 2 years, oral, quarter of a spoonful (1.25 mL) using the measure provided 4 times daily (for 7–14 days for treatment)</td> </tr> <tr> <td><b>Itraconazole</b></td> <td>Oropharyngeal/ oesophageal candidiasis in immunocompromised</td> <td>Oral liquid, 200 mg daily. Treat oropharyngeal candidiasis for at least 7–14 days and oesophageal candidiasis for 14–21 days. 50 mg capsule (Lozanoc®), 50–100 mg once daily for 28 days. 100 mg capsule (eg Itracap®), 100–200 mg once day</td> </tr> <tr> <td><b>Posaconazole</b></td> <td>Oropharyngeal candidiasis nf immunocompromised</td> <td>Oral liquid, 200 mg once daily for 1 day, then 100 mg once daily. Refractory to fluconazole or itraconazole, oral liquid 400 mg twice daily.</td> </tr> </tbody> </table> ``` # Echinocandins * **MOA:** inhibiting synthesis of 1,3-beta-D-glucan in the fungal cell wall * **Drug interactions:** limited data * Invasive candidiasis * Caspofungin & Micafungin are also indicated for oesophageal candidiasis | Generic name | |---| | Anidulafungin inj | | Caspofungin inj | | Micafungin inj | | Common ADR | |---| | Nausea, vomiting, diarrhoea, rash, hypokalaemia, increased liver enzymes, injection site reactions (uncommon with anidulafungin) | # **Echinocandins** - **MOA:** inhibiting synthesis of 1,3-beta-D-glucan in the fungal cell wall - **Drug interactions:** limited data - Invasive candidiasis - Caspofungin & Micafungin are also indicated for oesophageal candidiasis | Generic name | |---| | Anidulafungin inj | | Caspofungin inj | | Micafungin inj | | Common ADR | |---| | Nausea, vomiting, diarrhoea, rash, hypokalaemia, increased liver enzymes, injection site reactions (uncommon with anidulafungin) | # Other - **Amphotericin B**: oral & perioral candidiasis [10mg qid 7-14 days] - Drug interaction: Azoles (antagonistic effect) - **Nystatin**: oropharyngeal candidiasis - Adult, child, oral liquid 100 000 units 4 times daily for 7–14 days for treatment. Higher doses, e.g. 500 000 units 4 times daily, can be used - **Terbinafine**: fungal skin infections (including head and neck region) - **Drug interaction** - inH metabolism of tramadol to the active metabolite - inH metabolism of some TCAs $\rightarrow$ increase ADR - Rifampicin increases the metabolism of terbinafine $\rightarrow$ reduce antifungal effect | Generic name | | :--- | | Amphotericin B | | Flucytosine | | Griseofulvin | | Nystatin | | Pentamidine inj | | Terbinafine | # **Other Antifungals** - **Amphotericin B**: oral & perioral candidiasis [10mg qid 7-14 days] - Drug interaction: Azoles (antagonistic effect) - **Nystatin**: oropharyngeal candidiasis - Adult, child, oral liquid 100 000 units 4 times daily for 7–14 days for treatment. Higher doses, e.g. 500 000 units 4 times daily, can be used - **Terbinafine**: fungal skin infections (including head and neck region) - **Drug interaction** - inH metabolism of tramadol to the active metabolite - inH metabolism of some TCAs → increase ADR - Rifampicin increases the metabolism of terbinafine → reduce antifungal effect | Generic name | | :--- | | Amphotericin B | | Flucytosine | | Griseofulvin | | Nystatin | | Pentamidine inj | | Terbinafine | **Antivirals** * Viruses are non-cellular, obligate intracellular parasites * Cause diseases like influenza, herpes, hepatitis, and HIV/AIDS * Made of DNA/RNA in a protein shell (lack cytoplasm or membranes) * Replicate by hijacking host cell machinery * Hard to treat without harming host cells * Antivirals aim for **selective toxicity**— target viral-specific enzymes or replication steps A drawing of a bottle labeled COVID-13 and some pills and blister packs with stylized viruses in the background. # **Antivirals** - Viruses are non-cellular, obligate intracellular parasites - Cause diseases like influenza, herpes, hepatitis, and HIV/AIDS - Made of DNA/RNA in a protein shell (lack cytoplasm or membranes) - Replicate by hijacking host cell machinery - Hard to treat without harming host cells - Antivirals aim for **selective toxicity**— target viral-specific enzymes or replication steps **Antivirals** | Class | Drug | Primary indications | | :--- | :--- | :--- | | guanine analogues | aciclovir, famciclovir | herpes simplex, shingles | | | valaciclovir | herpes simplex, shingles, CMV | | | ganciclovir, valganciclovir | CMV | | neuraminidase inhibitors | oseltamivir, peramivir, zanamivir | influenza A and B | | HCV NS3/4A inhibitors | glecaprevir, voxilaprevir | hepatitis C | | HCV NS5A inhibitors | ledipasvir, pibrentasvir, velpatasvir | hepatitis C | | HCV NS5B nucleotide inhibitors | sofosbuvir | | | other antivirals | amantadine | influenza A | | | adefovir, entecavir, peginterferon alfa-2a | hepatitis B | | | cidofovir, foscarnet, letermovir, maribavir | CMV | | | nirsevimab, palivizumab | respiratory syncytial virus | | | molnupiravir, nirmatrelvir and ritonavir, remdesivir | coronavirus disease 2019 (COVID-19) | | | ribavirin | hepatitis C | ## **Antivirals** | Class | Drug | Primary indications | | :--- | :--- | :--- | | guanine analogues | aciclovir, famciclovir | herpes simplex, shingles | | | valaciclovir | herpes simplex, shingles, CMV | | | ganciclovir, valganciclovir | CMV | | neuraminidase inhibitors | oseltamivir, peramivir, zanamivir | influenza A and B | | HCV NS3/4A inhibitors | glecaprevir, voxilaprevir | hepatitis C | | HCV NS5A inhibitors | ledipasvir, pibrentasvir, velpatasvir | hepatitis C | | HCV NS5B nucleotide inhibitors | sofosbuvir | | | other antivirals | amantadine | influenza A | | | adefovir, entecavir, peginterferon alfa-2a | hepatitis B | | | cidofovir, foscarnet, letermovir, maribavir | CMV | | | nirsevimab, palivizumab | respiratory syncytial virus | | | molnupiravir, nirmatrelvir and ritonavir, remdesivir | coronavirus disease 2019 (COVID-19) | | | ribavirin | hepatitis C | **Guanine Analogues** * **MOA:** inhibit viral DNA polymerase and DNA synthesis * **Drug interactions** * Impair renal excretion of mycophenolate * Probenecid impair renal secretion of guanine analogues * **ADR:** check individual monograph <table> <thead> <tr> <th>Generic name</th> </tr> </thead> <tbody> <tr> <td>Aciclovir</td> </tr> <tr> <td>Famciclovir</td> </tr> <tr> <td>Ganciclovir</td> </tr> <tr> <td>Valaciclovir</td> </tr> <tr> <td>Valganciclovir</td> </tr> </tbody> </table> ## **Guanine Analogues** - **MOA:** inhibit viral DNA polymerase and DNA synthesis - **Drug interactions** - Impair renal excretion of mycophenolate - Probenecid impair renal secretion of guanine analogues - **ADR:** check individual monograph | Generic name | |---| | Aciclovir | | Famciclovir | | Ganciclovir | | Valaciclovir | | Valganciclovir | ```html <table> <thead> <tr> <th style="text-align: left;"><strong>Drug (brand)</strong></th> <th style="text-align: left;"><strong>Indication & drug regimen</strong></th> <th style="text-align: left;"><strong>Selected ADR</strong></th> </tr> </thead> <tbody> <tr> <td style="text-align: left;">Aciclovir (Aciclovir)</td> <td style="text-align: left;">Orolabial herpes simplex Oral 400 mg 5 times daily for 5 days in selected cases, eg severe infection, immunocompromised patient. A dose of 400 mg 3 times daily for 5–10 days can be used in HIV infection</td> <td style="text-align: left;">[infrequent] vertigo, dizziness, sore throat</td> </tr> <tr> <td style="text-align: left;">Famciclovir (Famvir)</td> <td style="text-align: left;">Recurrent orolabial herpes simplex [immunocompetent adult]: Oral, 1500 mg as a single dose in selected patients, eg with severe infection [immunocompromised adult]: Oral, 500 mg twice daily for 5–10 days in HIV patients</td> <td style="text-align: left;">[infrequent] confusion in elderly, dizziness</td> </tr> <tr> <td style="text-align: left;">Ganciclovir (Cymevine inj)</td> <td style="text-align: left;">Not dental related</td> <td style="text-align: left;">[infrequent] mouth ulceration, dry mouth, drowsiness</td> </tr> <tr> <td style="text-align: left;">Valaciclovir (Valtrex)</td> <td style="text-align: left;">Recurrent oral labial herpes simplex Oral, 2 g every 12 hours for 2 doses in selected patients, eg with severe infection. HIV-positive, oral 1 g twice daily for 5–10 days. Prevention, immunocompromised, oral 500 mg twice daily</td> <td style="text-align: left;">[infrequent] vertigo, dizziness, sore throat</td> </tr> <tr> <td style="text-align: left;">Valganciclovir</td> <td style="text-align: left;">Not dental related</td> <td style="text-align: left;">[common] oral candidiasis, cough, headache, dizziness</td> </tr> </tbody> </table> ``` ## **Antiviral Drug Summary** ```html <table> <thead> <tr> <th style="text-align: left;"><strong>Drug (brand)</strong></th> <th style="text-align: left;"><strong>Indication & drug regimen</strong></th> <th style="text-align: left;"><strong>Selected ADR</strong></th> </tr> </thead> <tbody> <tr> <td style="text-align: left;">Aciclovir (Aciclovir)</td> <td style="text-align: left;">Orolabial herpes simplex Oral 400 mg 5 times daily for 5 days in selected cases, eg severe infection, immunocompromised patient. A dose of 400 mg 3 times daily for 5–10 days can be used in HIV infection</td> <td style="text-align: left;">[infrequent] vertigo, dizziness, sore throat</td> </tr> <tr> <td style="text-align: left;">Famciclovir (Famvir)</td> <td style="text-align: left;">Recurrent orolabial herpes simplex [immunocompetent adult]: Oral, 1500 mg as a single dose in selected patients, eg with severe infection [immunocompromised adult]: Oral, 500 mg twice daily for 5–10 days in HIV patients</td> <td style="text-align: left;">[infrequent] confusion in elderly, dizziness</td> </tr> <tr> <td style="text-align: left;">Ganciclovir (Cymevine inj)</td> <td style="text-align: left;">Not dental related</td> <td style="text-align: left;">[infrequent] mouth ulceration, dry mouth, drowsiness</td> </tr> <tr> <td style="text-align: left;">Valaciclovir (Valtrex)</td> <td style="text-align: left;">Recurrent oral labial herpes simplex Oral, 2 g every 12 hours for 2 doses in selected patients, eg with severe infection. HIV-positive, oral 1 g twice daily for 5–10 days. Prevention, immunocompromised, oral 500 mg twice daily</td> <td style="text-align: left;">[infrequent] vertigo, dizziness, sore throat</td> </tr> <tr> <td style="text-align: left;">Valganciclovir</td> <td style="text-align: left;">Not dental related</td> <td style="text-align: left;">[common] oral candidiasis, cough, headache, dizziness</td> </tr> </tbody> </table> ``` **Antimalarial** * Caused by *Plasmodium* via mosquito bite * *P. falciparum* is most dangerous * Not endemic in Australia/NZ, but travel-related cases occur * Risk of local spread in northern Australia * Affects liver $\rightarrow$ red blood cells $\rightarrow$ fever, chills * Relapses possible with *P. vivax*/*P. ovale* * Relevant due to drug interactions & medical history # **Antimalarial** - Caused by *Plasmodium* via mosquito bite - *P. falciparum* is most dangerous - Not endemic in Australia/NZ, but travel-related cases occur - Risk of local spread in northern Australia - Affects liver → red blood cells → fever, chills - Relapses possible with *P. vivax*/*P. ovale* - Relevant due to drug interactions & medical history Anti- protozoals: Antimalarials | Drug | **Prophylaxis of malaria** | **Treatment of malaria$^{1}$** | | :--- | :--- | :--- | | artemether with lumefantrine | no | first line for uncomplicated malaria$^{2}$ | | artesunate (SAS) | no | first line for severe malaria | | atovaquone with proguanil | yes | alternative for uncomplicated malaria$^{2}$ | | clindamycin | no | used with quinine for uncomplicated malaria$^{2}$ | | doxycycline | yes | used with quinine for uncomplicated malaria$^{2}$ | | mefloquine | yes | chloroquine-resistant malaria$^{2}$; due to risk of severe neuropsychiatric effects, use only when other options are not available or unsuitable (seek specialist advice) | | primaquine | no | used to eradicate liver stages of *P. vivax* or *P. ovale* malaria to prevent relapse months or years later | | quinine | no | used with clindamycin or doxycycline as an alternative for uncomplicated malaria$^{2}$; used for severe malaria if artesunate is unavailable | | tafenoquine | yes | used to eradicate liver stages of *P. vivax* or *P. ovale* malaria to prevent relapse months or years later | $^{1}$ a drug used for prophylaxis should not be used as treatment $^{2}$ for *P. vivax* or *P. ovale* malaria, add primaquine or tafenoquine (confirm G6PD status before starting treatment) # **Anti-protozoals: Antimalarials** | Drug | **Prophylaxis of malaria** | **Treatment of malaria$^{1}$** | | :--- | :--- | :--- | | artemether with lumefantrine | no | first line for uncomplicated malaria$^{2}$ | | artesunate (SAS) | no | first line for severe malaria | | atovaquone with proguanil | yes | alternative for uncomplicated malaria$^{2}$ | | clindamycin | no | used with quinine for uncomplicated malaria$^{2}$ | | doxycycline | yes | used with quinine for uncomplicated malaria$^{2}$ | | mefloquine | yes | chloroquine-resistant malaria$^{2}$; due to risk of severe neuropsychiatric effects, use only when other options are not available or unsuitable (seek specialist advice) | | primaquine | no | used to eradicate liver stages of *P. vivax* or *P. ovale* malaria to prevent relapse months or years later | | quinine | no | used with clindamycin or doxycycline as an alternative for uncomplicated malaria$^{2}$; used for severe malaria if artesunate is unavailable | | tafenoquine | yes | used to eradicate liver stages of *P. vivax* or *P. ovale* malaria to prevent relapse months or years later | $^{1}$ a drug used for prophylaxis should not be used as treatment $^{2}$ for *P. vivax* or *P. ovale* malaria, add primaquine or tafenoquine (confirm G6PD status before starting treatment) # Other * [Atovaquone] * **MOA**: inhibit protozoal mitochondrial electron transport * **Drug interactions** * Impair renal excretion of mycophenolate * Probenecid impair renal secretion of guanine analogues * **ADR**: check individual monograph <table> <thead> <tr> <th>Generic name</th> </tr> </thead> <tbody> <tr> <td>Atovaquone</td> </tr> <tr> <td>Metronidazole</td> </tr> <tr> <td>Paromomycin *SAS*</td> </tr> <tr> <td>Pyrimethamine *SAS</td> </tr> </tbody> </table> This drug is not marketed in Australia but may be available through the SAS # **Other Anti-protozoals** - **[Atovaquone]** - **MOA**: inhibit protozoal mitochondrial electron transport - **Drug interactions** - Impair renal excretion of mycophenolate - Probenecid impair renal secretion of guanine analogues - **ADR**: check individual monograph | Generic name | |---| | Atovaquone | | Metronidazole | | Paromomycin *SAS* | | Pyrimethamine *SAS | This drug is not marketed in Australia but may be available through the SAS **Antihelmintics** **Worm Infestations (Helminthiasis)** * Caused by helminths e.g. Nematodes, trematodes, cestodes * Complex life cycles, some require intermediate hosts **Anthelmintic Treatment** * Drugs disrupt energy metabolism, neuromuscular function, or membrane permeability * Mechanisms lead to paralysis or death of the worm * Rare in Australia/NZ, but important for patients with relevant travel history **Would you love me if I was a worm?** # **Antihelmintics** ## **Worm Infestations (Helminthiasis)** - Caused by helminths e.g. Nematodes, trematodes, cestodes - Complex life cycles, some require intermediate hosts ## **Anthelmintic Treatment** - Drugs disrupt energy metabolism, neuromuscular function, or membrane permeability - Mechanisms lead to paralysis or death of the worm - Rare in Australia/NZ, but important for patients with relevant travel history **Would you love me if I was a worm?** ## Antihelmintics | Drug | Pregnancy | Breastfeeding | Children | Adverse effects | |---|---|---|---|---| | **Benzimidazoles** | | | | | | albendazole | avoid use | appears safe | may use if >6 months | well tolerated | | mebendazole | avoid in first trimester | may use | may use if >6 months | well tolerated | | **Other anthelminitics** | | | | | | ivermectin | avoid use | may use | may use if >5 years and/or >15 kg | mild adverse effects when used for strongyloidiasis | | praziquantel | appears safe | safe | may use | well tolerated in short courses | | pyrantel | safe | safe | may use | well tolerated | ## **Antihelmintics** | Drug | Pregnancy | Breastfeeding | Children | Adverse effects | |---|---|---|---|---| | **Benzimidazoles** | | | | | | albendazole | avoid use | appears safe | may use if >6 months | well tolerated | | mebendazole | avoid in first trimester | may use | may use if >6 months | well tolerated | | **Other anthelminitics** | | | | | | ivermectin | avoid use | may use | may use if >5 years and/or >15 kg | mild adverse effects when used for strongyloidiasis | | praziquantel | appears safe | safe | may use | well tolerated in short courses | | pyrantel | safe | safe | may use | well tolerated | **Benzimidazoles** * MOA: Inhibit microtubule polymerisation by binding to beta tubulin in parasite * Drug interactions: **not dental related** * ADR [common]: headache <table> <thead> <tr> <th>Generic name</th> <th>Brand Name</th> </tr> </thead> <tbody> <tr> <td>Albendazole</td> <td>Zentel</td> </tr> <tr> <td>Mebendazole</td> <td>Combantrin</td> </tr> </tbody> </table> <table> <thead> <tr> <th>ADR</th> </tr> </thead> <tbody> <tr> <td>**Common or infrequent**</td> </tr> <tr> <td>headache, nausea, vomiting, diarrhoea, abdominal pain, increased liver function tests, dizziness, fever</td> </tr> <tr> <td>**Infrequent or rare**</td> </tr> <tr> <td>hypersensitivity (itch, rash, urticaria), alopecia, bone marrow depression, hepatitis</td> </tr> </tbody> </table> ## **Benzimidazoles** - **MOA:** Inhibit microtubule polymerisation by binding to beta tubulin in parasite - **Drug interactions:** **not dental related** - **ADR [common]:** headache | Generic name | Brand Name | |---|---| | Albendazole | Zentel | | Mebendazole | Combantrin | | ADR | |---| | **Common or infrequent** | | headache, nausea, vomiting, diarrhoea, abdominal pain, increased liver function tests, dizziness, fever | | **Infrequent or rare** | | hypersensitivity (itch, rash, urticaria), alopecia, bone marrow depression, hepatitis | # Other * Ivermectin (also in dermatological lecture) * **MOA**: binding to glutamate-gated chloride ion channels and acting as a GABA agonist in parasite * **ADR**: fatigue, dizziness * Praziquantel * **MOA**: depending on concN can increase muscular activity or cause integumental damage * **ADR**: dizziness, drowsiness * Pyrantel * **MOA**: depolarising neuromuscular blocking agent * **ADR**: headache <table><thead><tr><th>Generic name</th></tr></thead><tbody><tr><td>Ivermectin</td></tr><tr><td>Praziquantel</td></tr><tr><td>Pyrantel</td></tr></tbody></table> # **Other Antihelmintics** - **Ivermectin** (also in dermatological lecture) - **MOA**: binding to glutamate-gated chloride ion channels and acting as a GABA agonist in parasite - **ADR**: fatigue, dizziness - **Praziquantel** - **MOA**: depending on concN can increase muscular activity or cause integumental damage - **ADR**: dizziness, drowsiness - **Pyrantel** - **MOA**: depolarising neuromuscular blocking agent - **ADR**: headache | Generic name | |---| | Ivermectin | | Praziquantel | | Pyrantel | References * Ritter JM, Flower RJ, Henderson G, Loke YK, MacEwan D, Robinson E, editors. *Rang & Dale’s pharmacology*. 10th ed. Edinburgh: Elsevier; 2023 * Australian Medicines Handbook Online [Internet]. Adelaide (AU): Australian Medicines Handbook Pty Ltd;2000. Anti-infectives; [updated 2025; cited 2025]. Available from: UWA Onesearch * Australian Commission on Safety and Quality in Health Care. *Antimicrobial stewardship* [Internet]. Sydney: ACSQHC; [cited 2025 Apr 30]. Available from: https://www.safetyandquality.gov.au/standards/nsqhs-standards/preventing-and-controlling-infections-standard/antimicrobial-stewardship * Oral and Dental Expert Group. Therapeutic *Guidelines Oral and Dental* (Version 3). Therapeutic Guidelines Ltd:2019 * Pharmaceutical Society of Australia. *Australian Pharmaceutical Formulary and Handbook: A Guide to Best Practice*. 25th ed. Canberra: Pharmaceutical Society of Australia; 2021 * Ali K. *Clinical dental pharmacology*. 1st ed. Oxford: Wiley-Blackwell; 2023 * Bullock S, Manias E. *Fundamentals of pharmacology*. 8th ed. Frenchs Forest, NSW: Pearson Australia; 2017 * MIMS Australia. *eMIMSelite: Consumer medicine information, specific clinical monograph* [Internet]. Sydney: MIMS Australia; [updated 2025; cited 2025 Apr 17]. Available from: UWA Onesearch * Kaya CT, Erol C. How to achieve infective endocarditis prophylaxis. *Eur Heart J Cardiovasc*. 2018 Dec 12;16(33) # **References** - Ritter JM, Flower RJ, Henderson G, Loke YK, MacEwan D, Robinson E, editors. *Rang & Dale’s pharmacology*. 10th ed. Edinburgh: Elsevier; 2023 - Australian Medicines Handbook Online [Internet]. Adelaide (AU): Australian Medicines Handbook Pty Ltd;2000. Anti-infectives; [updated 2025; cited 2025]. Available from: UWA Onesearch - Australian Commission on Safety and Quality in Health Care. *Antimicrobial stewardship* [Internet]. Sydney: ACSQHC; [cited 2025 Apr 30]. Available from: https://www.safetyandquality.gov.au/standards/nsqhs-standards/preventing-and-controlling-infections-standard/antimicrobial-stewardship - Oral and Dental Expert Group. Therapeutic *Guidelines Oral and Dental* (Version 3). Therapeutic Guidelines Ltd:2019 - Pharmaceutical Society of Australia. *Australian Pharmaceutical Formulary and Handbook: A Guide to Best Practice*. 25th ed. Canberra: Pharmaceutical Society of Australia; 2021 - Ali K. *Clinical dental pharmacology*. 1st ed. Oxford: Wiley-Blackwell; 2023 - Bullock S, Manias E. *Fundamentals of pharmacology*. 8th ed. Frenchs Forest, NSW: Pearson Australia; 2017 - MIMS Australia. *eMIMSelite: Consumer medicine information, specific clinical monograph* [Internet]. Sydney: MIMS Australia; [updated 2025; cited 2025 Apr 17]. Available from: UWA Onesearch - Kaya CT, Erol C. 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