ABX 2 Flashcards
- Most beta-lactamases do not reduce activity
- Active against Gram negatives producing b-lactamase
- Several “Generations”
- Each successive generation includes more Gram-negative activity
- Limited side effect profile
- Safely tolerated in penicillin intolerance history
- Poor against anaerobes
Cephalosporins
- Excellent GRAM POSITIVE Coverage – Strep. spps. & Staph aureus
- some gram negative activity:
- Proteus, E. coli, and Klebsiella (PEcK)
- Limited oral gram negatives
1st gen cephalosporins
- Still excellent GRAM POSITIVE Coverage – Strep. spps.
- Some additional gram negatives:
- Morexella, Haemophilus, Enterobacter, Neisseria
(More HEN PEcK) - Still overall limited oral gram negative
2nd gen cephalosporins
Which gen of ceph have highest risk of C diff?
3rd gen ceph
What is the normal dose and frequency of ceflex?
500 4x a day for 5 days
Metronidazole is bactericidal against ____ bacteria
obligate anaerboes
●Bactericidal against all obligate ANAEROBES
Bacteroides spps. and Fusobacterium
●Breaks DNA structure directly through production of free radicals
●Antiprotozoal: amoeba (Entamoeba), Trichomonas, Giardia.
Metronidazole (flagyl)
What is the main bacteria that metronidazole acts against?
Bacteroides
Adverse Reactions:
●Metallic taste, dry mouth
●Dark urine
●Skin rashes
●Use of alcohol leads to “Antabuse”-type reaction: headache, flushing, NAUSEA
AVOID ALL ALCOHOL, incl. mouthwashes
CYP2C9 Inhibitor: DRUG INTERACTIONSWarfarin (Coumadin)
Lithium
Phenytoin (Dilantin)
Metronidazole
Bactrim, Metronidazole and Fluconazole all have what effect on warfarin?
Increase conc of active warfarin
●General Medical Uses:
Deep space abscesses
Gastrointestinal infections
●Resistance is not a problem. Given IV or orally.
DENTAL USES:
●Combined w/ -Lactams - 1st Line for serious orofacial
infections“poor man’s Augmentin”
●Management of refractory or progressive periodontitis.
●Rx: Metronidazole 500mg po Q8h x 5days, #15
Metronidazole
What are the 3 protein synthesis inhibitor ABX?
Clindamycin, macrolides, and tetracyclines
Activity for Gram Positives and Anaerobes
* Strep. & Staph. including MRSA
* Anaerobic gram negatives: Actinomyces, Bacillis, Bacteroides (increasing resistance)
* No aerobic gram-negatives
Clinical advantages
* PVL toxin inhibition
* Biofilm inhibition/penetration
Disadvantages
* C. difficile infection
* Clindamycin oral suspension unpleasant taste
* High doses of oral clindamycin (>450 mg Q6H) may cause esophagitis
Clindamycin
Is clinda recommended for ABX prophy for a dental procedure?
No
What is the dosage of clinda?
150 mg 2x a day for 5 days
What type of drug can enhace risk of c diff?
Proton pump inhibitors
- MOA: Bind to 30S subunit of Ribosome
● Bacteriostatic
● Broad spectrum activity but mostly for gram positives
● Requires active transport into cells- source of resistance
● Chelate/Bind divalent cations.
● Binds with Ca++, Mg++, antacids, iron or multivitamins.
● No renal or hepatic adjustment
● cleared totally unchanged in fecal excretion
Tetracyclines
●No longer used for odontogenic infections due to resistance:
■Management of localized juvenile periodontitis (Aggressive Periodontitis) – Aggregatibacter
actinomycetemcomitans (AA) –make -lactamase
■AA sensitive to Tetracyclines, Fluoroquinolones, Bactrim™… ?Augmentin.
■Additive Effects:Concentrates in the gingival crevice extremely well, 7–20 times more than any other drug
Anticollagenase
Anti-inflammatory
Inhibition of bone resorption
Promotes reattachment
Low-dose systemic doxycycline for refractory agg. periodontitis
● Periostat™ (100 mg daily)
● Local application in adjunctive tx for resistant periodontitis:
Atridox™ gel (doxycycline)
Arestin™ (minocycline microspheres)
Tetracyclines
What type of drug is azithromycin?
Macrolides
What macrolide is. not used?
●Narrow spectrum: LOTS of resistance
■ Adverse effects: Prokinetic, GI disturbances, diarrhea, cramping
■ Strong inhibitor of CYP3A –many drug interactions.
■ Highest QTc prolongation risk among antimicrobials
Erthryomycin
Which macrolide is not metabolized thru 3a4?
Azithromycin
● Improved infected tissue penetration and half life
● Concentrates in tissues, phagocytes, & fibroblasts giving it a long half-life.
● No phase I metabolism.
● Eliminated unmetabolized – no drug interactions - no cytochrome inhibition.
● CYP 3A4 interactions: ERY, Clarithromycin»_space;> Azithromycin
● Long half-life (60hrs) - qday dosing. Must use loading dose. (2x)
● Alternative agent for dental/perio infections
Orofacial Infection: 500mg, then 250mg PO Daily x 4 days.Perio Infection: 500mg PO Daily x 5 days
Side Effects:
* Possible reversible tinnitus with large doses
* Liver reports – jaundice, necrosis, failure
Azithromycin (zpack)
Dental uses: Used in odontogenic and periodontal infections in early, non-abscess
infections as 2nd alternative or in penicillin allergies
■ No activity against Bacteroides, common in dental abscesses
■ Alternative antibiotic in odontogenic infections.
■ Less effective than - Lactams (2nd choice)
■ Overall limit use due to already high resistance rates.
Macrolides
- MOA: Inhibit DNA gyrase and topoisomerases
– Blocks transcription/replication
– Bactericidal
– Concentration-dependent killing
TOns of side effects
Fluoroquinolones
