Abx and infections pt.1 Flashcards
Normal Flora of Mouth
Gram +
› Viridans Group Streptococci
› Other Strep spps.
› Lactobacillus
› Actinomyces spps.
Gram-
› Prevotella spps.
gram state of most oral bac
* morph?
* Oxygen tolerance?
* Cell wall?
Gram Positive organisms:
* Bulk of oral bacteria
* Primarily cocci or irregular shape (pleomorphic)
* Oxygen tolerance varies from facultative anaerobes to strict anaerobes
* Cell wall has thick peptidoglycan layer
Three important genera of gram +
- Lactobacillus
- Streptococcus
- Actinomyces
Actinomyces: O2, where?
Actinomyces - facultative anaerobe; periodontal pockets, dental plaques, on carious teeth
Lactobacillus -O2, where?
Lactobacillus - facultative anaerobe; produce lactic acid; role in dentine caries rather than enamel caries
Streptococcus - O2, where?
Streptococcus - facultative anaerobic cocci; produce lactic acid some implicated in caries
Streptococci Species in the Oral Cavity
Oral streptococci are referred to as viridans streptococci (Streptococcus viridans)
› Isolated from all sights of the mouth, each species has specific properties for
colonizing different oral sites
› Large proportion of resident microflora
bad streptococci of the mouth
- Acid?
- Highly associated with?
- Bacterial communities collected from dentin carious lesions contain?
Strep mutans:
* Acidogenic (acid producing) and aciduric (acid tolerant) species
* Highly associated with caries (+++)
* Bacterial communities collected from dentin carious lesions contain notorious
acidogenic and aciduric species, including S. mutans, Scardovia wiggsiae, Parascardovia
denticolens, and Lactobacillus salivarius
good strep spp?
- First oral organisms?
*relation with us? - portective?
- First oral organisms detected in newborn infants (primary colonizers)
- Commensals
- Peroxigenic (produce hydrogen peroxide) inhibits the growth of S. mutans and Porphyromonas gingivalis, and other oral pathogens
- often killed by abx
strep sinugiunas and viridans
Gram Negative organisms of the mouth
* Many Gram-negative bacteria found in the mouth, especially in?
* O2? most important ones are?
* E sources?
* Cell wall?
- Many Gram-negative bacteria found in the mouth, especially in
established/subgingival plaque ESTABLISHED INFECTIONS - Range of oxygen tolerance but most important strict or facultative anaerobes
- Some fermentative, produce acids which other organisms use acids as an
energy source, others produce enzymes which break down tissue - Cell wall different to Gram positive with a thin peptidoglycan layer, has B-
lactamase which breaks down penicillin, also has LPS/endotoxin
gram - spp of oral cavity
what can they found with?
- Porphyromonas: P. gingivalis major periodontal pathogen, produces collagenase
- Prevotella: P. intermedia a periodontal pathogen
- Fusobacterium: F. nucleatum periodontal pathogen
- Actinobacillus/Aggregatibacter: A.actinomycetemcomitans associated with aggressive periodontitis and prduces leukotoxin while also enhancing osteoclast activity
- Treponema: group important in acute periodontal conditions i.e ANUG
- Neisseria
- Veillonella
progression of oral infections
move from mainly gram+ aerobes to more gram - anerobes
what Abx works for all oral bac
augmentin
penicillin typical spectrum
mainly gram + (strep, actino, peptostrep) some gram - but possible resistance
what gram - can penicillin cover (possible R)
what gram - is not covered by penicillin
porphyromanas
bacterioides (anaerobes)
neiserria
aggregibacter
amoxicillin coverage
covers gram + (strep, lacto, actino, pepto)
good/SR with some gram -
what gram - can amox cover
neiserria
what gram - is not covered by amox
bacterioides (anaerobes)
aggregibacter
cephlexin coverage
viridans strep
strep spp
peptostrep
Lacto and actino are questionable
does cephlexin have any gram - cover
NO
questionable with prevotella and fuso
cefaclor spp coverage
viridans strep
peptostrep
strep spp
lacto
actino maybe
and gram - cover of fusobacterium and aggregibacter
clindamyacin coverage
what does clinda not cover
neiserria and aggregibacter
metro coverage
- mainly gram - except for neiserria and aggregibacter
- also covers peptostrep
- can be combined with penicillin for similar effect as augmentin
when should we use augmentin
when amox fails
doxy cover
covers gram + and - except for neiserria and veillonella
what can be used for prohylaxis with G+ suspected
penicillin
what spp do penicillins not work on
lactobacillus
porphyromanas
bacteriodes
neiserria
aggrebacter
metronidazole works on what spp?
peptostreptococcus (only gram + one)
porphyromanas
prevotella
veillonella
fusobacterium
bacteriodies
Bacteriostatic
requires pt to have?
Bacteriostatic – Arrests growth of organism
* Must have active immune system
Bactericidal
Bactericidal – Kill the organism
* Neutropenic, Meningitis, Endocarditis
Bactericidal Abx’s
Cell Wall Inhibitors
*Beta Lactams
*Penicillins
*Cephalosporins
Inhibit DNA
*Fluoroquinolones
*Metronidazole
Bacteriostatic abx
* Protein Synthesis Inhibitors
– Macrolides
– Clindamycin
– Doxycycline
cidal or static w/ severe infection or supression
cidal
Concentration dependent
- Higher concentration, more
extensive/faster kill. Maximize peak
concentation
DOES HAVE PAE, may be due to increased WBC activity
Post-antibiotic effect
- Bacterial suppression after antibiotic
concentrations fall below MIC, usually in concentration dependent
Time dependent
- The more time above the MIC, more
inhibition. Maximize duration of
exposure above MIC
USUALLY NO PAE
Concentration versus Time Dependent affect?
how abx are dosed
Concentration dependent
* Higher concentration leads to?
* example abx’s?
- Higher concentration greater killing, higher doses with less frequent dosing (1 or 2 a day)
- fluoroquinolones, metronidazole
Time-dependent killing
* Concentrations need to be? lead to?
* More exposure leads to?
* No PAE:
* Some PAE:
Time-dependent killing
* Concentrations need to be reinforced, leading to more dosing (3 or more times a day)
* More exposure more killing
* No PAE: Beta-lactams
* Some PAE: clindamycin, azithromycin, tetracyclines
Optimizing Cephalexin Dosing
* Usual dosage range:
* dependent on?
* Half-life:
* Excretion:
* Cellulitis dose
* Cystitis dose
* Suggests minimum of hours of subtherapeutic blood concentrations with Q12hr dosing
- Usual dosage range: 250 to 1,000mg every 6 hours or 500mg every 12 hours
- Time Dependent Drug: works best the longer concentrations stay above MIC
- Half-life: approximately 1-hour for adults
- Excretion: Urine 80-100% as unchanged drug in 6-8 hours
- Cellulitis: 500mg 4 times daily
- Cystitis: 500mg twice daily
- Suggests minimum 4-6 hours of subtherapeutic blood concentrations with Q12hr dosing
Amoxicillin Pharmacokinetics
adult dosing immeadiate and extended release
all dosing based on which formula?
what timeframe for dosing is usually used?
8hrs usually used
amoxicillin dosage for periodontitis
Amoxicillin Pharmacokinetics
* absorbtion path
* rates of absorbtion based on formula
* distribution
* pro binding %
* t1/2 adults
* time to peak
* excretion
Penicillin Allergy Problem
* Results in significantly more what abx’s?
* Collateral damage associated with?
* % higher cost of antibiotics
* length of hospitalization
drug-resistant organisms:
* % increased risk of MRSA infections
* % more VRE infections
* % increased risk of C. difficile infectio
- Results in significantly more vancomycin, clindamycin, & fluoroquinolones
- Collateral damage associated with reported penicillin allergy
- 63-158% higher cost of antibiotics
- Increase length of hospitalization, average 0.59 more total hospital days
- Increased drug-resistant organisms
- 69% increased risk of MRSA infections
- 30.1% more VRE infections
- 26% increased risk of C. difficile infectio
Penicillin Allergy Statistics
~% of US outpatients & % inpatients self-report penicillin allergy
* Studies have found % of penicillin allergic patients tolerate penicillins
* % test positive for penicillin allergy using skin testing
~10% of US outpatients & 15% inpatients self-report penicillin allergy
* Studies have found 80-90% of penicillin allergic patients tolerate penicillins
* 10% test positive for penicillin allergy using skin testing
study results of penicllin allergy (rate of anaphylaxis)
0.00044%; 1 in 225,706 exposures
Adverse Drug Reaction Versus Allergy
Type A [Side Effect] - common?
* Predictable?
* Overdose
* Side Effect -
Type B [Allergy] - common?
* predictable?
* mechanisms
Type A [Side Effect] - common
* Predictable (pharmacologic action), Dose Related, Can Affect Anyone
* Overdose - Hepatic failure (acetaminophen)
* Side Effect - Nephrotoxicity (with aminoglycosides); diarrhea (amoxicillin)
Type B [Allergy] - uncommon
* Unpredictable (hypersensitivity reaction), Not dose related, Cannot affect anyone
* Anaphylaxis; photoallergy
* Antibody or T-cell Stimulatio
Allergic-like” or “Pseudo-allergic” Reactions
- Resemble allergic reactions; NOT Immune-mediated
- Vancomycin ‘Redman Syndrome’; Morphine rash (due to alkaline state causing histamine release)
rxns 1-4 and idiopathic
allergy Classification – Modified Gell and Coombs System
Most Reported Reactions Inconsistent With Immunologically Mediated Hypersensitivity
Low-Risk factors of Penicillin Allergy Assessment
utacaria may be a reuslt of viral infection and misinterpreted aas an allergy.
Low-risk allergy symptoms – most commonly rash and itching – likely do not represent true IgE allergy
high risk factors of penicillin allergy
Urticaria | Hives
Affects % of population at some point in their lives
* Viral infections cause % of all cases of acute hives in children
Affects 20% of population at some point in their lives
* Viral infections cause >80% of all cases of acute hives in children
Low-risk allergy symptoms of penicillins
– most commonly rash and itching –
likely do not represent?
Low-risk allergy symptoms
– most commonly rash and itching –
likely do not represent true IgE allerg
IgE mediated drug cutaneous rxns
* onset?
* itch?
* raised?
* lasts for?
* scar?
benign t cell mediated cutaneous drug rxn
* onset
* itch
* lasts for
* resolution
*
severe t cell mediated drug skin rxn
* onset
* tissues involved
* skin
* requires?
low risk hx and action for penicillin allergies
Questions to ask when assessing an allergy
Describe reaction
route?
How long ago?
Timing of reaction?
tx?
Use of what before reaction?
Use of what since reaction?
Describe reaction
Administered PO or IV?
How long ago did the reaction occur?
Timing of reaction?
Immediate (< 4hrs)
Delayed (>24 hrs)
Any treatment required?
Use of penicillins or cephalosporins before reaction?
Use of penicillins or cephalosporins since reaction?
Time Elapse Since Adverse Response
Patients positive (skin test) for penicillin allergy
* 1-year later % have a negative response
* 5-years later % have a negative response
* 10-years later % have a negative response
- 1-year later 10-20% have a negative response
- 5-years later 50% have a negative response
- 10-years later 80% have a negative response
- decreased repsonse with increased time
Penicillin-Cephalosporin Cross-Sensitivity
Classic Teaching, % Penicillin-Cephalosporin cross-reactivity
* Based on studies in?
* 1980’
* Early cephalosporins contaminated with?
Classic Teaching, 10% Penicillin-Cephalosporin cross-reactivity
* Based on studies in 1960s and 1970s
* 1980’s cephalosporin purification techniques developed
* Early cephalosporins contaminated with penicillins: derived from Acremonium mold
ADRs of non-Beta lactams compared to beta lactams, significance of this?
‘Non-beta-lactam antibiotics were associated with more adverse drug
reactions than penicillins or cephalosporins, independently of the penicillin skin test result.
Cephalosporins can be used as safely or more safely than non-beta-lactam antibiotics in penicillin skin test positive and negative individuals.
does ceph cause allergic rxns in those with a hx cillin rxns
very unlikley (0,002%)
Penicillin-Cephalosporin Side Chain Comparison and cross reactivity
amox and ceph are similar
Penicillin-Cephalosporin Similar R-side Chain
Cephalosporins without similar side chains to penicillin considered?
* A reaction may occur by?
* Risk similar to?
Cephalosporins without similar side chains to penicillin considered low risk and safe in patients with reported history or positive skin test
* A reaction may occur to a cephalosporin by coincidence
* Risk similar to developing a reaction to sulfonamide antibiotic
» Cephalexin (Keflex) has a similar side chain to?
» Cephalosporins that DO NOT have similar side chains to penicillins:
» Cephalexin (Keflex) has a similar side chain to amoxicillin
» Cephalosporins that DO NOT have similar side chains to penicillins: IV Cefazolin, Cefuroxime, Cefdinir
Penicillin Allergy Summary
* True allergy?
* Review?
* Family history of penicillin allergy, GI symptoms, headache, yeast infection?
* Hive and non-hive rash reports [not SJS-like]?
* Severe/high-risk reactions [e.g. SJS, Anaphylaxis-like, DRESS, Serum sickness?
ñ True allergy (IgE) is rare; Penicillin-Cephalosporin cross-reactivity NOT 10%
ñ Review the documented allergy or Interview the patient
- Family history of penicillin allergy, GI symptoms, headache, yeast infection
►Not Allergy - Comfortable giving any penicillin or cephalosporin
- Hive and non-hive rash reports [not SJS-like]
►Likely not Type-1 Allergy - May give amoxicillin, especially with distant history and penicillin benign skin reaction
- Can use a cephalosporin without concern
- Severe/high-risk reactions [e.g. SJS, Anaphylaxis-like, DRESS, Serum sickness]
►Type-1 or CTC Allergy - Use an alternative antibiotic [reasonable to consider later generation cephalosporin]
2021 AHA Statement for those with cillin allergies
More cautious approach- not to use cepph in those with hx to pencillin allergies (anaphylaxis, utacaria, angioedema)
when would ceph not be used in those with a hx of rxns to cillins? what is used instead
use macrolides or doxy
best anti-infectives?
B-lactams
Beta-Lactams classes
- Penicillins
- Cephalosporins
- Carbapenems
penicillins names
- Penicillin
- Amoxicillin/Ampicillin
- Dicloxacillin
- Piperacillin
ceph names
Cephalexin (Keflex)
* Cefuroxime (Ceftin)
* Cefaclor (Ceclor)
* Cefprozil (Cefzil)
* Cefdinir (Omnicef)
carabpenems names
Ertapenem | Imipenem | Doripenem | Meropenem
B-lactam Mechanism of Action
Beta-Lactams
* MOA:
* ALL BETA LACTAMS ARE?
* common?
* Side-chains account for?
* placenta/breast
* excretion
- MOA: Binds to Penicillin Binding Proteins (PBPs); block cell wall
synthesis causing the walls to leak; lower cell death threshold - ALL BETA LACTAMS ARE BACTERICIDAL
- Most used & effective antibiotics with least toxicity.
- Side-chains account for differences: acid stability, absorption, spectrum,
susceptibility to beta-lactamases - Cross placenta and distributed into breast milk
- High renal excretion
penicillin are sensitive to?
beta lacatamase
natural penicillins
penicillin G and VK
natty penicillins work on:
Primarily - gram-positive Strep. species: Strep. viridans, Group A Strep, and anaerobic (Peptostreptococcus, Peptococcus sp.); activity against Actinomyces spps.
extended spectrum aminopenicillins
ampicillin and amxoicillin
extended spectrum aminopenicillins work on?
same as natty but Improved Oral absorption and gram negative coverage
Resistance Mechanisms
– decrease abx uptake
– enzymatic modification/degradation
– target modification
– bacterial overproduction
decreased abx uptake
- efflux pumps
- membrane permea
– enzymatic modification/degradation
- beta-lactamases
- transferases
- redox processesbility changes
– target modification
- altered PBP
- RNA modification
- DNA gyrase mutation
efflux pumps may affect
b lacs and marcolides
RNA mod may affect
macrolides and clindamyacin
Beta-Lactamase
hydrolyzes beat lactam ring of penicillins= degradative
how much abx do dentist rx
3rd most
An Evaluation of Dental Antibiotic Prescribing
Practices in the United States: what abx are commonly prescribed
Respiratory Infections (acute otitis media; pneumonia) resistance
* S. pneumoniae resistance to azithromycin >% in U.S.
* S. pneumoniae resistance to amoxicillin ~% in U.S.
* S. pneumoniae resistance to smx-tmp ~% in U.S
- S. pneumoniae resistance to azithromycin >40% in U.S.
- S. pneumoniae resistance to amoxicillin ~20% in U.S.
- S. pneumoniae resistance to smx-tmp ~30% in U.S
Urinary Tract Infections resistance stats
* E. coli resistance to amoxicillin ~% in U.S.
* E. coli resistance to smx-tmp ~% in U.S.
* E. coli resistance to fluoroquinolones ~% in U.S.
- E. coli resistance to amoxicillin ~50% in U.S.
- E. coli resistance to smx-tmp ~30% in U.S.
- E. coli resistance to fluoroquinolones ~30% in U.S.
Beta-Lactamase Inhibitors names
- Clavulanate (Paired with Amoxicillin)
- Sulbactam (Paired with Ampicillin)
- Tazobactam (Paired with Piperacillin)
Beta-Lactamase Inhibitors moa
● Mechanism of action:
■ Irreversibly bonds with beta-lactamase, more attractive ring
■ “Ties up” all beta- lactamase.
■ Allows the antibiotic to persist and extends
activity to B-lactamase producing pathogens
what abx can be used with b lactamase
ceph and augmentin
can we use b lactams with mutated PBP (S. aureus)
no
beta lactamase inhibiotrs extended coverage,what oral infections often need this? what spp is present?
Extends coverage, more Gram Negatives, anaerobes, & Staph.
Bacteroides spps. (common to oral abscesses) produce B-Lactamases
Augmentin™-
Augmentin™- amoxicillin+clavulanate = more gram negatives, anaerobes, & Staph.:
●Dental infections with abscess or failed amoxicillin
B-lactamase Resistance (MSSA) Versus MRSA
augmentin and amoxicillin dosage
therapeutic Spectrums
- Narrow - act on single organism or type of organisms
ex. Penicillin - Extended Spectrum - works on gram positives and also some gram negatives
ex. Amoxicillin-clavulanic acid - Broad Spectrum - affect a wide variety of organisms.
ex. Clindamycin › May cause “superinfections” of unaffected microbes or fung
Amoxicillin/Clavulanate
Pediatric Antibiotic Associated Diarrhea
- 35 articles reporting on 42 studies were included for analysis
- 33 trials reported on amoxicillin/clavulanate
- 6 trials on amoxicillin
- 3 trials on penicillin V
- In total, the 42 trials included 7729 children treated with an oral penicillin
about 19.8% incidence
Amoxicillin/Clavulanate
Antibiotic Associated Diarrhea
seen in 25% with 250: Amoxicillin 250 mg /clavulanate 62.5mg per 5mL
reducing augmentin shits
Goal 14:1 ratio of amoxicillin to clavulanate to lessen this side effect
ideal: 600: Amoxicillin 600 mg /clavulanate 42.9mg per 5mL *
cephlasporins allergies with time
decreased as purfication techniques enhanced
amoxicillin dosing
augmentin dosing
