Abx and infections pt.2 Flashcards
Why not use Augmentin for everything?
- Cost ($10/15 vs $50)
- 3x more side effects
- Resistance
- In the person exposed, primarily
- Stewardship
- Analogy – moving from studio/1BR apartment
Why risk using amoxicillin rather than clindamycin?
Risk of using amoxicillin:
* No risk if the reaction is?
* Any non-SJS rash history to amoxicillin? re-exposed?
* Risk of a severe reaction is ?
* Risk for sever reaction if initial ‘allergy’ was immediate onset, ?
Why risk using amoxicillin rather than clindamycin?
Risk of using amoxicillin:
* No risk if the reaction is GI, headache, yeast infection, family history
* Any non-SJS rash history to amoxicillin, re-exposed to amoxicillin 93-94% tolerate with no subsequent reactions
* Risk of a severe reaction is 0.001%
* Risk for sever reaction if initial ‘allergy’ was immediate onset, 0.29%
Risk of Clindamycin
Among oral antibiotics commonly prescribed by dentists, clindamycin has
the highest fatal (2.9/million prescriptions), serious (233.2/million
prescriptions), and overall (337.3/million prescriptions) ADR rates.
* Double any other dental antibiotic
* >15 times higher than amoxicillin
* Amoxicillin has the lowest fatal
(0.1/million prescriptions), serious
(11.9/million prescriptions), and overall
(21.5/million prescriptions) ADR rates
Risk of C. difficile Infection By Antibiotic
* Clindamycin
* Augmentin
* Cephalexin
* Amoxicillin
* Penicillin
- Clindamycin 25-fold increased risk (greatest risk)
- Augmentin 8.5-fold
- Cephalexin (Keflex) 3-fold
- Amoxicillin 2-fold
- Penicillin 1.8-fold
Recurrence and Mortality of c dif
Antibiotic Duration Impacts CDI Risk
use under 3 days to decrease risk
PPI and Abx
lower ph of stomach reduicing sporicidal emzyme ability
probiotic use with Abx?who can benefit?
May consider for higher risk individuals:
* 65yo+
* recent hospitalization or nursing home
* weak immune system (HIV/AIDS, cancer, or
taking immunosuppressive drugs)
* previous C. diff infection
* taking proton pump inhibitors
amox or clindamyacin?
amox when no contraindications for type 1 allergy
low risk signs for amoxicillin allergy
tree analogy
Why is the Penicillin Allergy Label Bad?
Cephalosporins
* beta-lactamases?
* Active against?
* generations?
* Each successive generation includes?
* side effects?
* Safely tolerated in?
* Poor against?
- Most beta-lactamases do not reduce activity of cephalosporins
- 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 (particularly gram-)
ceph moa
binds PBP
1st gen cephs names
1st Generation Cephalosporins
* Excellent coverage of?
* gram activity? spp?
* oral gram -?
- Excellent GRAM POSITIVE Coverage – Strep. spps. & Staph aureus
- some gram negative activity:
- Proteus, E. coli, and Klebsiella (PEcK)
- Limited oral gram negatives- NO P. gingivalis
kelfex Rx
RX: Cephalexin 500mg po QID x 5 days
2nd gen cephs names
2nd gen cephs
* gram coverages?
* oral gram -?
- Still excellent GRAM POSITIVE Coverage – Strep. spps.
- Some additional gram negatives:
- Morexella, Haemophilus, Enterobacter, Neisseria
(More HEN PEcK) - Still overall limited oral gram negative- YES P. gingivalis
when would 1st and 2nd gen cephs be used in dentistry
1st gen more used for prophylaxis/allergies where as 2nd gen can be used for infections due to increased gram - coverage, however amoxicillin is preferred
Cefuroxime rx
Cefuroxime 500mg po BID x 5 days
less doing with longer t1/2
how can we use 1st and 2nd gen ceph in mouth
: may be used for early odontogenic infections. (no perio indications)
ndividuals allergic to amoxicillin may receive cephalexin?
ndividuals allergic to amoxicillin may receive cephalexin as long as the reaction was not anaphylactic-like.
Metronidazole (Flagyl)
●Bactericidal against all?
spp?
●MOA
●additional targets?
●Bactericidal against all obligate ANAEROBES
Bacteroides spps. and Fusobacterium
●Breaks DNA structure directly through production of free radicals via redox rxns
●Antiprotozoal: amoeba (Entamoeba), Trichomonas, Giardia.
metro ADRs
- Metallic taste, dry mouth
- Dark urine
- Skin rashes
- Disulfiram reaction? (headache, flushing, N/V) avoidance of alcohol no longer required
metro interactions
other antimicrobials increasing warfarin con./ INR
TMP-SMX and fluconazole
warfarin interactions
majority activtity from s isomer which is increased due to CYP2C9 inhib= INR increased
Empiric Warfarin Dose Reduction with metro
Metronidazole (Flagyl)
●General Medical Uses:
●Resistance ?
●General Medical Uses:
Deep space abscesses
Gastrointestinal infections
●Resistance is not a problem. Given IV or orally.
Metro DENTAL USES:
●Combined with? used when?
nickname
●Management of?
●Rx:
●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
metro coverage
General Antibiotic Mechanisms of Action: cell wall action vs non-cell wall active
Protein Synthesis Inhibitors
- Clindamycin – STATIC
- Macrolides - STATIC
- Tetracyclines – STATIC
- Clindamycin, Macrolides, Tetracyclines MOA
inhibits RNA to stop pro synthesis (30s/50s subunit)
Clindamycin (Cleocin™) – IV and PO
Activity for?
* gram + spp?
gram- spp? Problem?
* No cover of?
Activity for Gram Positives and Anaerobes
* Strep. & Staph. including MRSA
* Anaerobic gram negatives: Actinomyces, Bacillis, Bacteroides (increasing resistance)
* No aerobic gram-negatives
clindamyacin clinical adv
- PVL toxin inhibition
- Biofilm inhibition/penetration
clindamyacin Disadvantages
* infection?
* oral suspension?
* High doses of oral clindamycin (>450 mg Q6H) may cause?
- C. difficile infection
- Clindamycin oral suspension unpleasant taste
- High doses of oral clindamycin (>450 mg Q6H) may cause esophagitis
Clindamycin (Cleocin™) – IV and PO Additional Dental Advantages
●penetration?
●Minimal concerns with?
●In dentistry:
●High penetration into saliva, gingival tissues, and bone
●Minimal renal concerns
●In dentistry: Late or severe endodontic infections & abscesses
with severe PCN allergy
clindamyacin rx
clinda coverage
is clindamyacin used as dental prophylaxis?
no longer recomended
Greater Reliance on Cephalosporins in Allergies
Fatal anaphylaxis from a single dose of a cephalosporin in patients
with no history of a serious reaction <1 per 1 million doses
not common so yes used in allergy cases
tetracycline moa
Bind to 30S subunit of Ribosome
tetracyclines
● Bacteriostatic/cidal?
● spectrum? mostly for?
● Requires? how can this cause resistance?
● Chelate?
● renal and hepatic adjustment
● cleared ?
● 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
tetracycline cover
good aggrebacter acitivity= used for perio dx
tetracycline and c dif as respiratory agent
- Tetracyclines demonstrated no increased risk (OR, 0.92) vs no antibiotic
exposure
safe agent for those with hx of CDI
which tetracycline does not discolor peds teeth
doxy
Doxycycline Considerations
* Tooth Discoloration? recomendations?
* Avoid during?
* GI? More common with? which form is better tolerated?
* esophogus?
* Peak plasma concentration may be reduced ~20% by?
* skin?
* Renal/hepatic disease?
Doxycycline Considerations
* Tooth Discoloration: Updated recommendations from the American
Academy of Pediatrics permit doxycycline for ≤21 days in children of all ages
* Avoid during pregnancy, teratogenic
* GI upset: More common with hyclate salt but Monohydrate less acidic, better tolerated
* Erosive esophagitis – avoid taking at bedtime, drink full glass of water
* Peak plasma concentration may be reduced ~20% by high-fat meal or milk
* Phototoxicity (skin rashes) may occur
* Renal/hepatic disease patients can use doxycycline
dental use of tetrcyclines
periodontal only, no longer for odontogeinc infections due to resistance
perio use of tetracyclines
■Management of ?
■AA sensitive to?
■Additive Effects:
Concentrates?
collagen?
inflammation?
Inhibition of?
Promotes?
■Management of localized juvenile periodontitis (Aggressive Periodontitis) – Aggregatibacter
actinomycetemcomitans (AA) –make b-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 reattachmen
Low-dose systemic doxycycline for refractory agg. periodontitis
● dose
● Periostat™ (100 mg PO daily
Local application of tetracyclines in adjunctive tx for resistant periodontitis:
Atridox™ gel (doxycycline)
Arestin™ (minocycline microspheres)
macrolides
names, moa, dependent on?
do we fw ERTHYROMYCIN?
●spectrum?
■ Adverse effects:
■ Strong inhibitor of?
■ Highest risk of?
NOT USED
●Narrow spectrum: LOTS of resistance
■ Adverse effects: Prokinetic, GI disturbances, diarrhea (can be used with gastroparesis, cramping
■ Strong inhibitor of CYP3A –many drug interactions.
■ Highest QTc prolongation risk among antimicrobials
Clarithromycin (Biaxin) –used?
Liver metabolism?
metabolim?
Less drug-drug interactions than?
AVOID USE
Liver metabolism: Moderate CYP3A inhibitor.
Prodrug: metabolized to active compounds
Less drug-drug interactions than Erythromycin but more than azithromycin
where could claritholmyacin be used?
H.pylori – chronic dyspepsia, peptic ulcer
development, and gastric cancer
Triple Therapy (PPI, amox, clarith) or Quadruple (PPI,
amox, Flagyl, and bismuth)
clarithromyacin adr
metallic taste
Both Erythromycin and Clarithromycin slow what? implications of this?
Both Erythromycin and Clarithromycin slow CYP3A4
Accumulation of other drugs that are metabolized through 3A4
* Benzodiazepines
* Transplant Drugs (cyclosporine, tacrolimus)
* HIV Drugs
* CCBs (amlodipine, diltiazem)
does azithromyacin influence CY3A4
limited effect
Azithromycin (ZPack; Zithromax) – IV and PO
● Improved facotrs?
● Concentrates in?
● metabolism?
● Eliminated how? what does this mean?
● t1/2? dosing?
● Must use?
● 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
● Long half-life (60hrs) - qday dosing.
● Must use loading dose. (2x)
azithrhomyacin Side Effects:
- Possible reversible tinnitus with large doses
- Liver reports – jaundice, necrosis, failure
Macrolides
Dental uses:
Dental uses: Used in odontogenic and periodontal infections in early, non-abscess infections as 2nd alternative or in severe penicillin allergies
why are macrolides not top choice for odontogenic infections?
■ No activity againstwhich common pathogen?
■ Alternative?
■ Less effective than?
■ Overall limit use due to?
■ % of viridans group Streptococci resistant? implications?
■ No activity against Bacteroides, common in dental abscesses
■ Alternative antibiotic in odontogenic infections.
■ Less effective than b- Lactams (2nd choice)
■ Overall limit use due to already high resistance rates.
■ 50% of viridans group Streptococci resistant, not good for prophylaxis
macrolide dosages
Orofacial Infection:
Perio Infection:
Orofacial Infection: 500mg, then 250mg PO Daily x 4 days.
Perio Infection: 500mg PO Daily x 5 days
Drug Selection Factors
* Common pathogens =
* Site?
* Ability to?
* Patient hx of?
* metabolic factors?
* med hx?
* women?
Drug Selection Factors
* Common pathogens = Empiric Therapy Targets
* Site of Infection
* Ability to penetrate infection site
* Patient Allergies and Drug Adverse Reactions (Tolerance)
* Renal and Hepatic Function, Patient’s Age
* Clearance and Metabolism of Antibiotics
* Concomitant Medications (drug interactions) and Past Medical History
* Pregnancy or Breastfeeding
Teratogen –
Agent that can potentially cause a birth defect or negatively alter cognitive and behavioral outcomes
* Physical, cognitive, behavioral
determinants of tetrogenicity
Determinants –
* Dose of toxicant
* Half-life of toxicant
* Placental permeability
* Stage of development
Normal Fetal Development time frame and exposures
extreme effects in first 14wks, up to 20wks can also lead to organ functional changes
Pregnancy and Lactation
* Good Safety abx
- Cephalosporins, penicillins, clindamycin, azithromycin
Pregnancy and Lactation bad abx
- Doxycycline – Ca++ chelation
- Fluoroquinolones – kidneys/cartilage
- Sulfamethoxazole/trimethoprim – various/kernicterus
- Metronidazole in 1st Trimester – limited data
Approaches to abx tx
prophylactic, empiric, directed
When Are Antibiotics Indicated/ Recommended in dentistry?
* NUG ?
* Periodontitis?
* infection where?
* Endo/Perio?
- NUG – systemic symptoms or immunocompromised
- Aggressive Periodontitis non responsive to debridement
- Fascial space infection
- Endo/Perio with systemic symptoms
when are abx not needed in dentistry
* Endo?
* Periodontitis or Gingivitis?
* Perio?
* NUG>?
- Endodontic conditions
- Chronic Periodontitis or Gingivitis
- Periodontal Abscess
- NUG – no systemic symptoms
when should we consider systemic abx
* symptoms?
* onset?
* pt status
* spaces invovled?
* presence of?
Antibiotics in Odontogenic Infections
Antimicrobial agents are indicated if what has is present? Or infection has spread beyond?
Antimicrobial agents are indicated if fever and regional lymphadenopathy are present, or when infection has perforated the bony cortex and spread into surrounding soft tissue.
Early odontogenic Infection (< 3 days) abx
whatif there are allergies (mild/severe)?
what if there is no improvement?
late odontogenic infection (>3 days) abx
continue for 2 days after resolution of systemic symptoms
Bacterial Infective Endocarditis (BIE)
85% spp are?
~5% caused by?
- Infection of endocardium or valves from blood born bacteria.
- 85% are Staphylococci spps & Streptococci spps
- ~5% caused by HACEK group Gram-Negatives
- (Haemophilus spps, A. actinomycetemcomitans, Cardiobacterium
hominis, Eikenella corrodens, Kingella kingae) - HACEK are oral flora with potential for infection.
Rationale for Prophylaxis of BIE
Pathogenesis sequence?
requires thrombus and bacteremia
Antibiotic Prophylaxis & Infective Endocarditis
only for certain conditions, depends mostly on bactermia
what procedures requires BIE prophylaxis?
what conditions as well?
Benefit of prophylaxis for BIE in High-risk Patients
high risk BIE conditions
when to Avoid Antibiotic Prophylaxis
› injections?
› radio?
› Placement of?
› Placement or?
› Placement of ?
› Shedding of?
› Bleeding from?
› Routine anesthetic injections through noninfected tissue
› Dental radiographs
› Placement of removable prosthodontic appliances
› Placement or adjustment of orthodontic appliances
› Placement of orthodontic brackets
› Shedding of deciduous teeth
› Bleeding from trauma to the lips or oral mucosa
Notable Changes in
2021 AHA Statement for prophylaxis
- Consideration of adverse drug reactions – clindamycin
- Specific statement about penicillin allergies
- Consideration of drug resistance –resistance rates for macrolides higher
than for penicillin
Give dose 30-60 min before appt
Allergies: Amoxicillin Versus Cephalexin Versus Azithromycin
when is each used?
Antibiotic Considerations for prophylaxis
* Antibiotic should be prescribed and administered when?
* how many doses?
* If patient forgets to take antibiotic before procedure, what do you do?
* If procedure spans multiple days, what is done?
- Antibiotic should be prescribed and administered before procedure
- Single dose only
- If patient forgets to take antibiotic before procedure, instruct to take within 2- hours following procedure
- If procedure spans multiple days, a separate preventative dose is recommended for each procedure
Summary of prophylaxis
* Invasive dental procedures cause what? which can lead to?
* who is at highest risk of IE?
* Patients undergoing what procedures are at highest risk for bacteremia?
* Antibiotic prophylaxis reduces the incidence of? BUT?
* Warn high risk patients undergoing high risk dental interventions of the risk of?
- Invasive dental procedures cause bacteremia, which can be complicated by IE in those at increased risk of the disease
- Patients with prosthetic heart valves, previous infective endocarditis, and some types of congenital heart disease are at highest risk of IE
- Patients undergoing procedures that involve manipulation of gingival tissue, manipulation of the periapical region of teeth, or perforation of the oral mucosa are at highest risk for bacteremia
- Antibiotic prophylaxis reduces the incidence of bacteremia, but no high level studies exist to confirm that this reduces the incidence of IE
- Warn high risk patients undergoing high risk dental interventions of the risk of infective endocarditis. Offer these patients antibiotic prophylaxis, and discuss with them the risks and benefits of this option
preffered prophylaxis dose
Amoxicillin 2gm X1 dose 30-60mins prior to dental procedure preferred
is there a high risk for prosthetic joint infection and from dental procedures
No increased risk of PJI following high- or low-risk dental procedure not
administered antibiotic prophylaxis
no association btwn IDP and PJI
AAOS AUC decison tree for when to prescribe abx prohylaxis in joint pts
- Immunocompromised?
- Poor glycemic control?
- History of PJI that required operation?
- Time since joint replacement procedure?
AAOS Recommended Prophylaxis number one choice adult/child doses
Oral Amoxicillin
adult: 2g
child: 50 mg/kg
30-60 min before
what if pt cannot take oral abx but no allergies?.
PJI prophylaxis
Ampicillin 2g IM or IV 50mg/kg IM or IV
OR
Ceftriaxone 1g IM or IV 50mg/kg IM or IV
what if pt has a hx of penicillin allergies but can take oral abx (joint prophylaxis)
Cephalexin 2 g 50 mg/kg
OR
Azithromycin or clarithromycin 500 mg 15 mg/kg
Allergic to penicillins and unable to take oral
medication for pji prophy
Ceftriaxone 1 g IM or IV 50 mg/kg IM or IV
OR
Azithromycin or clarithromycin 500 mg 15 mg/kg
1st gen cephs names
2nd gen cephs names
