Download - Rho Chis Clinical Pearls of Virology, Exam 1
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Go to class! Listen to lecture Make study guides
Read cases Quiz each other Go to review sessions Ask for help Follow bolded information; DIs; ADRs IDSA guidelines Review!
Easy points: brand/generic/generation
Remember case specific allergies!!
Tips for Success
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G+ aerobes: staph, strep, enterococci G- aerobes: Enterobacter, Pseudomonas,
Haemophilus, Moraxella
Anaerobeso Mouth: peptoo Gut: bacteroides, C. dif.
Atypical: mycoplasma, chlamydia,legionella Gram Stain
o
Positive - purpleo Ne ative - ink
Bacteria
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Class ClinicalPearls
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MOA: bind to PCN binding proteins needed to form cellwall
ADR: n/v, diarrhea, allergic reaction
Curve Chart Time-dependent Don't admin w/ aminoglycosides in same IV line Classes
o Natural Penicillinso Penicillinase resistanto Aminopenicillinso Extended-Spectrumo B-lactamase inhibitors
Clinical Pearls for Penicillins
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Penicillin G (IV/IM)o Aqueous crystalline: Acute severe infection b/c high
peako Benzathine PCN G: not for severe or acute infection
Penicillin V (po)o ~6 hour action, small peak
G+ strep, mouth anaerobes W/o food Watch Na/K b/c renal/heart Requires dose adjustment in renal disease Resistance: B-lactamase
Allergic rxn
Clinical Pearls for Natural PCNs
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Nafcillin/Oxacillin IV Dicloxacillin/Cloxacillin PO aka 'anti-staph' PCN staph, strep, no anaerobes, no MRSA hepatic metabolism warfarin and nifedipine interaction with nafcillin
Clinical Pearls for Penicillinase-Resistant PCNs
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Ampicillin (IV/po): no food Amoxicillin (po): with food staph, strep, enterococci, limited G- (PCN + G-)
o used primarily for respiratory tract infections dose adjustment renal disease allergy, diarrhea DIs w/ contraceptives, methotrexate, warfarin,
venlafaxine
Clinical Pearls for Aminopenicillins
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aka 'anti-pseudomonal' PCN Carboxypenicillin: Ticarcillin (disodium salt) Ureidopenicillin: Piperacillin Aminopenicillins + pseudo
o Pseudo: Piperacillin > Ticarcillin synergy w/ aminoglycoside watch Na/K, renal, cardiac Use: more severe broad G- infection/ pseudomonas Do NOT co-administer with AG in same IV line AE: Thrombophlebitis
Clinical Pearls for Extended-Spectrum PCNs
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Prevent B-lactamase degradation Augmentin (amoxicillin+clavulanic acid) Timentin (ticarcillin +clavulanic acid)
Unasyn (ampicillin+sulbactam) Zosyn (piperacillin+tazobactam) Increased efficacy NOTE: B-lactamase inhibitors have NO abx activity
Clinical Pearls for B-lactamaseinhibitors
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Aztreonam IV G-, pseudomonas no nephrotoxicity no PCN cross-reactivity
Clinical Pearls for Monobactams
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Staph, strep, G-, pseudo, anaerobes, ESBL 11-50% cross-reactivity with PCN IV ADR: mental status changes, seizures Imipenem-cilastatin: broadest spectrum, highest seizure
risko Cilastatin is not an antibiotic, it prevents hydrolysis
of imipenem to improve efficacy Meropenem: wider TI, low seizure incidence, meningitistreatment
Ertapenem: q daily (longest t 1/2), no pseudo Doripenem: no neurotoxicity
Clinical Pearls for Carbapenems
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MOA: Inhibit cell wall synthesis by binding to proteins needed tomake structure
Generations have increasing G- activityo 1: SPEcK;
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MOA: binds 30S, create membrane holes/fissures IV/IM Gentamicin, Tobramycin, Amikacin, Streptomycin G- including pseudo! Gent has staph/strep ADR: nephrotoxicity (reversible), ototoxicity (not) ,
neuromuscular blockade (rare) Synergy w/ penicillinase-resistant, cefaz, vanco, ampic Renal adjustment Once daily Dosing --> concentration v. time-dependent Post antibiotic effect
Clinical Pearls for Aminoglycosides
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Dosingo loading: based on BODY WT (standard dose of
2mg/kg)o maintenance: depends on severity and renal function
levels and monitoringo trough: 30 min before 4th dose
@ steady stateo peak: 30 min after 30 min infusion
Trough goalso Gent/Tobramycin:
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KNOW EVERYTHING ABOUT MOA: physically blocks cross-linking in G+ cell wall G+ coverage ONLY including MRSA and enterococci
IV; C. diff. PO
Renal adjustment if CrCl
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Lipoglycopeptides Improved vanco: does everything vanco does IV
Clinical Pearls for Televancin &Dalbavancin
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Quinupristin/Dalfopristin MOA: Inhibition of early/late protein synthesis via
synergy
G+, including MRSA (3rd line) IV, incompatible w/ NS, use D5W or Sterile Water Hepatic metabolism ADR: site reaction, myalgias (STATINS) inhibits cyp 3A4
o STATINS, cyclosporin, Ca2+ channel blockers,antihistamines
Clinical Pearls for Synercid
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Cubicin MOA: depolarization of bacterial cells = interferes w/
protein/RNA/DNA synthesis
G+, including MRSA IV High protein binding = Interactions (warfarin,
phenytoin, ibuprofen)
Doesn't penetrate into lung/CSF (not for pneumonia) Renal elimination Myopathy = increased CPK levels
Clinical Pearls for Daptomycin
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Flagyl MOA: nitro reduction into free radicals GUT ANAEROBES, C. diff., H. pylori
IV/po Excellent oral bioavailability Hepatic elimination via cyp3A4
o DIs: coumadin, carbamazepine, cyclosporine
Renal excretion (no adjustment mild/mod) ADRs: GI, dry mouth, metallic taste, neuropathy,seizures, DISULFIRAM reaction
Clinical Pearls for Metronidazole
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MOA: bind to 30S and inhibit binding of tRNA toacceptor site
Tetra, Mino, Doxy (IV/po)
Respiratory, strep, staph, atypicals Bacteriostatic Tetracycline renal, doxy hepatic ADRs: photosensitivity, tooth discoloration in
children, nausea, GI, teratogenic, Fanconi Syndome DIs w/ cations, bile acid sequestrants,anticonvulsants
Clinical Pearls for Tetracyclines
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MOA: inhibit trNA translocation by binding 50S BACTERIOSTATIC Erythromycin, Azithromycin, Clarithromycin
G+, Respiratory tract + HIV + H. pylorio Azithromycin has some G- coverage FOOD ADRs: n/v, diarrhea, dizziness
o Azith least , Eryth most ADR (check LFTS)o All equal QT prolongation risk (new study)o Cyp 3A4 inhibition (except Azith!)
DIs: antacids, warfarin, benzos, cyclosporine,carbamazepine
Clinical Pearls for Macrolides
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Cleocin BACTERIOSTATIC G+ (no MRSA), mouth anaerobes
IV, po Excellent oral bioavailability Use if can't use B-lactam May cause C. diff Hepatic elimination
Clinical Pearls for Clindamycin
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MOA: DNA gyrase/topo inhibitor Coverage:o Cipro- pure G-, resp, pseudomonaso Levo- G+/G-, resp, pseudomonaso Moxi-G+/G-, resp, NO pseudo, anaerobes Bioavailability: Levo/moxi 1:1; Cipro 80% Elimination: Levo/cipro renal; moxi hepatic FOOD DOESNT MATTER (except cations ex. calcium in milk)
Cations 2/2, 2/6, 4/8 (hour spacing before/after) ADRs: C. diff., GI, taste perversion, HA, dizziness, seizures, photo,tendon, QT prolongation, allergies, hyper/hypoglycemia
DIs: theophylline, coffee increases CNS effect, anticoag drugs,arrhythmia, NSAIDs, cyclosporine
Clinical Pearls for Quinolones
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Avoid use in 1st trimester anduse older agent w/ more data Weigh risks/benefits B- may be acceptableo Azithromycin (likely ok
breastfeeding)o Cephalosporins
(breastfeeding ok)o Clavulanic Acido Erythromycin (breastfeeding
ok)o Nitrofurantoin (3rd
contraindicated)o Penicillinso Sulbactam (breastfeeding ok)
Pregnancy
C- use with cautiono Bactrim (1st/3rdcontraindicated)
o Clarithromycino Fluoroquinolones (safer
alternatives, no breastfeeding) D- positive evidence of risk (nobreastfeeding)
o Aminoglycosideso Tetracyclines
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Helpful Lists
Pseudomonal Coverage
Extended Spect PCNCeftazadime (G-3)
Cefepime (G-4) Aminoglycosides AztreonamCipro/LevoCarbapenam (Except Ertapenam)
MRSA Coverage
VancoTelevancin
LinezolidCeftaroline (G-5)DaptomycinTigecyclineSynercidMinocycline, Bactrim,
Clindamycin (CA-MRSA)
C. Diff Coverage
MetronidazoleVanco PO
Photosensitivity
TetracyclinesBactrimQuinolones
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How can you differentiate the members of the PCN class? How can you differentiate the cephalosporins? How do you dose & monitor aminoglycoside & vanco therapy? Name all antibiotics with G+ activity; rank according to use. Name all antibiotics with G- activity. Which have pseudomonas activity? Which have MRSA activity? Which are bacteriostatic vs. bactericidal? Which can cause photosensitivity? Which need therapeutic drug monitoring? Which can cause seizures? Which are nephrotoxic? Ototoxic? Which are primarily hepatically eliminated? Which are "safe" in pregnancy? What are the brand/generics? Define MBC, MIC and PAE.
Study questions
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Med Chem!
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Beta Lactams
Includes penicillins, cephalosporins andmonobactams
Basic structure is a cyclic amide in a 4membered ringBinds to cell wall proteins and prevents
bacteria from forming cell walls
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Bacterial resistance in the form of beta lactamase We can overcome beta lactamases by adding bulky R groups in
an alpha-carbon di-substituted system . We can also use beta lactamase inhibitor (clavulanic acid,
sulbactam, tazobactam) which also contain a beta lactam ringBacterial resistance in the form of beta lactamase
We can overcome beta lactamases by adding bulky R groups inan alpha-carbon di-substituted system .
We can also use beta lactamase inhibitor (clavulanic acid,sulbactam, tazobactam) which also contain a beta lactam ring
Penicillins Cont.
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A bioisostere of penicillin. The sulfur of thethiazolidine ring of penicillins is replacedwith a carbon
Not orally stable because they dont haveEWG
Imipenem: easily degraded by renalpeptidases, therefore requires cilastatinMeropenem, Doripenem and Ertapenem havemethyl groups to prevent degradation
Carbapenems
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Contains a single beta lactam ring with Rgroups.
Lactamase resistant due to alpha carbondi substitution system
Only beta-lactam with no history of allergies
Monobactams (Aztreonam)
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Contain 6 membered thiazine rings bound to a beta lactam ring They are more hydrophillic less likely than penicillins to cause
allergic reactions
Contains 2 R groupso One R group determines spectrum of activityo The second R group determines potency and oral stability
The better the leaving group, the more potent the drug Alpha-di-carbon substitution applies to cephalosporins as welland predicts beta lactamase resistance
In general, cephalosporins are not orally stable because their leavinggroups are esters.o We can improve oral stability by making ester pro-drugso Amino groups can contribute to oral stability
Be able to identify which cephalosporin is which generation and their general spectrum of activity based on the structure
Cephalosporins
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MOA: Binds to 30S unit of bacterial ribosome toinhibit translation of RNA
Potent G - agents due to hydrophilicity
Cannot be used orally and have poor bioavailability because they are polar
Streptomycin is no longer used due to
resistanceCannot be used with beta -lactams because
AG will break open the beta-lactam ring
and inactivate it
Aminoglycosides (AG)
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Structure: Macrocyclic lactones MOA: Binds to 50S ribosomal subunit, inhibiting peptide
formation
Unstable to acid due to the C9 ketone right next to theC6 alcohol ketalization and inactivationMost contain a cladinose sugar at C3
May cause gastric cramping, which can be solved by a
water insoluble formation or enteric coating
Macrolides
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These are sytemic polypeptides Vancomycin
MOA: Binds to peptidoglycan to prevent cross linking. However,it does not inactive PBP like penicillins.
Their structure contains amino acids on aromatic rings VISA: vancomycin intermediate sensitive S. aureus. Resistance
is due to thickened cell walls VRSA: vancomycin resistant S. aureus. Terminal D alanine has
mutated into a D-lactate, preventing vancomycin from binding
Synercid Protein synthesis inhibitor that inhibit initiation of translation Dalfopristin enhances binding of quinupristin
Vanco and Synercid
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Structure: Saturated Naphthacene nucleus MOA: Binds to 30S ribosome to inhibit peptide formation
Contains 3 ionizable groupsVinyl Alcohol pKa=3 Conjugated phenol pKa=7.5 Dimethylamino pKa 9.4
Problems with tetracycline structure that creates inactive drug Dimethylamino at position 4 must be in alpha position. Tautomerization can
occur and create beta formation Chelation can occur at C11 and C12Avoid dairy and antacids
Can undergo dehydration at C6If we have dehydration at C6 and an epimer at C4, we get epianhydrotetracycline, which is
highly toxic to the kidney This is not an issue in minocycline or doxycycline
Tetracyclines
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Structure: Contains a nitrophenyl, chloracetic acid and2 alcohols
Has 2 forms: palmitate and hemisuccinate
MOA: Inhibits protein synthesis by preventing thebinding of t-RNA to the A site. May inhibitmitochondrial protein synthesis in humans
Chloremphenicol
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Structure: Large cyclic lipopeptide MOA: Causes depolarization in bacterial
cells to interfere with protein andnucleic acid synthesis
Daptomycin
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Structure: NitroimidazoleMechanism of action unknownMay be reduced by an intracellular electron transport
proteinThis creates a concentration gradient which promotesintracellular transport
Free radicals are formed which are toxic to bacteria
Flagyl
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Structure: Polar glycosides containing athiomethyl amino octodie moiety
MOA: Protein synthesis inhibit bypreventing translation of t-RNA
Lincosamides
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Classification of resistance:o Intrinsic resistance Resistance due to inherent characteristics of bacteriao Acquired resistance - Initially the bacteria was susceptible but further
antibiotic exposure resulted in resistance
Types of resistanceo The bacteria can alter the target the antibiotic was acting ono Decreased influx/increased effluxo Degradation of the antibiotico Alternative pathways
Example: If antibiotics target a protein in cell wall creation, the bacteriawill use an alternative method of creating the cell wall while bypassingthat protein
How do bacteria acquire resistance?o Random mutationo Plasmidso Transposonso Integrons
Antibacterial Resistance
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