-
4 MOA of antibiotics
- 1) inhibition of cell wall synthesis
- 2) inhibition of ribosomal protein synthesis
- 3) inhibition of folate (RNA purines)
- 4) inhibition of DNA synthesis
-
MOA beta lactams
inhibits cell wall synthesis by binding to PBPs
-
4 classifications of penicillins
- 1) natural penicillins
- 2) penicillinase-resistant penicillins
- 3) aminopenicillins
- 4) beta-lactam/beta-lactamase inhibitors
-
2 natural penicillin drugs and dosage forms
- 1) pen G - IV
- 2) pen VK - PO
-
3 clinical uses of natural penicillins
- 1) strep infections
- 2) syphilis
- 3) dental infections
-
natural penicillins - spectrum
- narrow
- gram + , some gram - (not that good), anaerobes, spirochetes
-
elimination of natural penicillins
renally
-
Penicillinase - resistant penicillins (antistaph)
3 agents + dosage form
- NOD
- nafcillin (Unipen) - IV
- oxacillin - IV
- dicloxacillin (Diclox) - PO
-
penicillinase-resistant penicillins (antistaph)
spectrum
- beta-lactamase staph a. - best for cellulitis
- NOT mrsa
- strep (but not as well as PCN)
-
aminopenicillins
2 agents + dosage form
- 1. ampicillin - po/iv
- 2. amoxicillin - po
-
aminopenicillins
spectrum
more gram NEGATIVE
-
aminopenicillins
clinical uses
- 1) acute OTITIS MEDIA
- 2) bacterial sinusitis
- 3) prophylaxis endocarditis before DENTAL procedures
-
beta lactam/lactamase inhibitors
4 agents + dosage form
- 1) amoxicillin/clavulanic acid (Augmentin) PO
- 2) ampicillin/sulbactam (Unasyn) IV
- 3) ticarcillin/clavulanic acid (Timentin) IV
- 4) pipercillin/tazobactam (Zosyn) IV
-
9 beta-lactamase producing organisms
- gram - = HNM PEK
- Haemoph, N. Gonnor, Morexalla, proteus, ecoli, klebsiella
- gram + = staph a
- anaerobes = bacteriodes
-
Sinusitis tx
- Augmentin - PO
- amoxicillin/clavulanic acid
-
IV equivalent of Augmentin
- Unasyn - IV
- ampicillin/sulbactam
-
beta-lactamase inhibitors
cover PSEUDO
- 1. ticarcillin/clavulanic (Timentin) - IV
- 2. pipercillin/tazobactam (Zosyn) - IV
also aspiration pneumonia (covers anaerobe bacteroides)
-
Adverse Drug reactions***
penicillins
- Hypersensitivity
- - rash,pruritis
penicillin --> degraded --> penicilloic acid, or forming antigens --> antibody formation
-
ADR
penicillin
hypersensitive - 3 options
- 1) alternative antibiotic
- 2) skin testing - major and minor antigenic determinants
- 3) desensitization - gradual increasing doses of penicillin
-
# generations of cephalosporins
5
-
cephalosporins
coverage
gram NEGATIVE coverage INCREASES , except ceftaroline
-
cephalosporins are INACTIVE against
- AtLE
- atypicals
- listeria
- enterococcus
-
listeria for, age group, and tx
- meningitis
- young and elderly
- ampicillin
-
MTT side chain
- 2nd gen
- cefotetan (TT)
- - bleeding and disulfiram (no alcohol)
-
1 st gen cephalosporins (3) + dosage form
- 1. cefazolin (Ancef/Kefzol) - IV
- 2. cephalexin (Keflex) - PO
- 3. cefadroxil (Duricef) - PO
-
2nd gen cephalosporins (6) + dosage forms
- 1. cefoxitin (Mefoxin) - IV
- 2. cefuroxime (Zinacef) - IV, (ceftin) - PO
- 3. cefotetan (Cefotan) - IV
- 4. cefaclor (Ceclor) - PO
- 5. cefprozil (Cefzil) - PO
- 6. loracarbef (Lorabid) - PO
-
3 rd gen cephalosporins (9) + dosage forms
- 1. cefotaxime (Claforan) - IV
- 2. ceftizoxime (Cefizox) - IV
- 3. ceftazidime (FORTAZ) - IV PSEUDO
- 4. cefibuten (Cedax) - PO
- 5. cefdinir (Omnicef) - PO
- 6. cefpodoxime (Vantin) - PO
- 7. Ceftriaxone (Rocephin) - IV
- 8. cefixime (Suprax) - PO
- 9. cefditoren (Spectracef) - PO
-
cephalosporin
PSEUDO coverage
ceftazidime - Fortaz - IV
-
4th gen cephalosporin (1) + dosage form
cefepime (Maxipime) - IV
-
4th gen cephalosporin
spectrum
- improved +, - and PSEUDO
- cefepime (Maxipime) - IV
-
4th gen PSEUDO
cefepime (Maxipime) - IV
-
5th gen cephalosporin (1) + dosage form
ceftaroline (Teflaro) - IV
-
5th gen cephalosporin
spectrum + indication
- MRSA
- gram positive, negative
- indication: skin structure infections
- CAP - Mssa only and others
-
Carbapenems (4) + dosage forms
- DIME (DIM/E) - GORILLA-cillins
- 1) imipenem/cilastatin (Primaxin) - IV
- 2) meropenem (Merrem) - IV
- 3) ertapenem (Invanz) - IV
- 4) doripenem (Doribax) - IV
-
Carbapenems
spectrum
- PAN coverage
- positive
- negative
- anaerobes
-
Carbapenems
PSEUDO
- DIM
- 1) doripenem (Doribax) - IV
- 2) imipenem/cilastatin (Primaxin) - IV
- 3) meropenem (Merrem) - IV
-
ertapenem (Invanz) - IV
LACKS coverage
NO PEA
- pseudomonas
- enterococcus
- acinetobacter
-
CAN'T USE CARBAPENEMS
- Seizures - imipenem
- 3-5% cross reactivity with beta-lactams (ALLERGY)
-
Monitor in carbapenems??
RENAL impairment
-
Monobactams
agent (1) + dosage form
aztreonam (Azactam) - IV
-
Monobactam
spectrum
- aztreonam (Azactam) - IV
- gram NEGATIVE ONLY
- PSEUDO
no cross reactivity with other beta-lactams!!!
-
4 ways for beta-lactam resistance
IMPORANT
- 1) altered PBP
- - MRSA
- -Strep pneumo and enterococci (pen resist)
- 2) altered outer membrane permeability (gram NEG)
- 3) production of beta-lactamases or other deactivating enzymes
- -pens, cephs, carbapenems
- 4) efflux pump (gram NEG)
-
Otitis media - in kids
- avoid resistance
HIGH dose AMOX 80-90 mg/kg/day
-
Aminoglycosides
2 toxicities
- 1) ototoxicity
- 2) nephrotoxicity
-
aminoglycosides
spectrum
- gram NEGATIVE ... synergy with beta-lactams = positive
- PSEUDO
-
aminoglycosides
spectrum with beta-lactams
- SYNERGY for ENDOCARDITIS (gram + cocci)
- 1) enterococcus faecalis
- 2) staph a
-
aminoglycosides
MOA
30 s RIBOSOMAL to inhibit protein synthesis
-
aminoglycosides
resistance
transferase enzyme inactivate aminoglycosides
-
aminoglycosides
PK info
- concentration DEpendent killing (dose-dependent killing)
- Post antibiotic effect (PAE)
- PEAK/MIC ratio
- -traditional vs once daily dosing
-
aminoglycoside agents (4)
TAGS
- 1) tobramycin (Nebcin)- IV - better PSEUDO
- 2) amikacin (Amikin) - IV - RESISTANT bacteria use3) gentamicin (Garmycin) - IV - most widely used4) Streptomycin - IV- 2nd line TB in combo
-
Macrolides agents (3) + dosage form
- ACE
- 1. azithromycin (Zithromax, Zmax) - PO/IV
- 2. clarithromycin (Biaxin) - PO
- 3. erythromycin - PO/IV
-
atypicals (3)
- mycoplasma
- legionalla
- chlamydia
-
Macrolides: potent 3A4 inhibitors/drug interactions (2)
IMPORTANT
- 1. erythromycin - PO/IV
- 2. clarithromycin (Biaxin) - PO
- avoid STATINS, benzos, carbamazepine, cyclosporin, theophylline
-
not to use Macrolides??
Strep pneumo infections (watch for resistance!)
-
Lincosamides agent (1) + dosage form
clindamycin (Cleocin) - PO/IV
D- TEST!!!!
-
Lincosamides
spectrum
- gram +/- ANaerobes
- gram + aerobes - CA-MRSA
vs metronidazole - anaerobes, parasites
-
lincosamides
Side effect (1)
C. DIFF
-
chloramphenicol (Chloromycetin)
spectrum
- BROAD
- positive, negative, anaerobes
-
chloramphenicol (Chloromycetin)
Adverse effects
- bone marrow suppression
- gray baby syndrome (preggo category C)
- - not used much
-
tetracyclines agents (4) + dosage form
- 1) doxycycline (Vibramycin) - IV/PO
- 2) tetracycline (Sumycin) - PO
- 3) minocycline (Minocin) - PO
- 4) demclocycline (Declomycin) - PO
-
tetracyclines
spectrum
- fair positive, negative, mycoplasma
- TICKS! - rickettsia
- chlamydia, plasmodium
-
tetracyclines
MOA
ribosome 30 s - inhibit protein synthesis
-
Tetracyclines
clinical uses
- TICKS
- CA-MRSA - but BACTRIM IS FIRST CHOICE
-
SIADH tetracycline
demeclocycline (Declomycin) - PO
-
Tetracyclines
Drug interactions
- di-tri- valent cations
- = decrease absorption! (bind up so space use)
-
tetracyclines
Adverse effects
- teeth discoloration < 8 yo AVOID
- photosensitivity
-
glycylcline agent (1) + dosage form
tigecycline (Tygacil) - IV
-
Glycylcycline
Spectrum
- positive - MRSA, VRE!!!
- negative - NO PSEUDO
- anaerobes
-
glycylcycline
moa
- inhibit binding to 30 s ribosome
- all similar to tetracycline!!!
-
trimethoprim/sulfamethoxazole (Bactrim)
spectrum
- DOC: UTI, PCP, Upper resp infections (URI)
- -gram negative URINARY pathogens, positive, CA-MRSA
-
trimethoprim/sulfamethoxazole (Bactrim)
drug interactions
warfarin, phenytoin
-
trimethoprim/sulfamethoxazole (Bactrim)
dosing?
important
- SS tab = 80 mg TMP/ 400 SMX PO
- DS tab = 160 mg TMP/800 SMX PO
-
2nd gen FQ agents (2) + indication
- 1. ciprofloxacin (Cipro) - PSEUDO
- 2. ofloxacin (Floxin)
- use: UTI
-
3rd gen FQ agents (3) + indication
- 1. levofloxacin (Levaquin) - PSEUDO
- 2. gemifloxacin (Factive)
- 3. moxifloxacin (Avelox)
- use: RESPIRATORY FQ (Strep PNEUMO)
-
FQ MOA
inhibit TOPO 2 (gyrase), and 4 - inhibit DNA synthesis
-
FQ - PSEUDO
- 1. ciprofloxacin (Cipro) - 2nd gen
- 2. levofloxacin (Levaquin) - 3rd gen
-
FQ
spectrum
- gram -
- not really for staph
- strep pneumo is 3rd gen respiratory quinolones
- atypicals: chlamydia, mycoplasma, legionella, brucella
- anaerobic = MOXIFLOXACIN (Avelox)
-
FQ
pk/absorption
EXCELLENT BA (80-95%) - iv:po
-
FQ
clinical use
NOT for UTIs (1)
moxifloxacin (Avelox)
-
FQ
Adverse effects (5)
- 1. CNS - seizures
- 2. QT prolongation
- 3. tendonitis, tendon rupture - elderly
- 4. joint cartilage damage/arthropathy <18 yo immature beagle puppies!!!
- 5. C. DIFF
-
FQ
drug interactions
- di-, tri- valent cations
- (antacids)
like tetracyclines!
-
ciprofloxacin (Cipro)
spectrum
- FQ 2nd gen
- UTI, pyelonephritis , etc.
- PO/IV,etc
-
Vancomycin
MOA
- inhibits cell wall synthesis
- d-ala, d-ala
-
Vancomycin
spectrum
- DOC: MRSA
- MSSA - staph/strep - slow - use NOD first!!!
- synergy with aminoglycosides - entero faecium and faecalis
- resistance VISA/GISA, VRSA
-
Vancomycin
clinical use
- PO - C DIFF
- IV - everything else, alternative to PCN
-
Vancomycin
adverse effects
- nephrotoxicity
- ototoxicity
"RED MAN syndrome" - not an allergy = slow infusion rate or increase infusion time
-
telavancin (Vibativ)
spectrum + efficacy
- similar to Vancomycin
- MSSA, MRSA
- -GISA
- HAP
-
telavancin (Vibativ)
Adverse effects
- taste disturbance, n/v, foamy urine
- cyp 3A4
- QTc, red man syndrome
-
metronidazole (Flagyl)
spectrum + pk/Absorption
- anaerobes vs CLINDAmycin (gram + aerobes too)
- parasites
BA 100%
-
metronidazole (Flagyl)
Adverse effects + Drug interactions
- GI, peripheral neuropathy
- big: disulfiram-like reaction (avoid alcohol), warfarin (INC INR)
-
metronidazole (Flagyl)
clinical use
- anaerobic infections
- C. DIFF - mild to moderate
-
tinidazole (Tindamax)
spectrum and dosing
- antiprotozoal (antiparasitic?)
- ONCE DAILY DOSING
-
linezolid (Zyvox)
MOA
ribosome RNA of 50s subunit
-
linezolid (Zyvox)
spectrum
MRSA, VRE (faecium), entero faecalis, MSSA
-
linezolid (Zyvox)
indication + pk/absorption
- VRE
- pneumonia (HAP), MRSA, MSSA
- CAP
- complicated, uncomplicated skin structures (DIABETIC FOOT infections)
- pk/absorption: BA 100% (hepatic adjust not renal adjust!!!!)
-
linezolid (Zyvox)
Adverse effect (2)
-
linezolid (Zyvox)
Drug Interactions
IMPORTANT
- weak, monoamine oxidase inhibitor
- AVOID SSRIs, decongestant (HTN)
-
quinupristin/dalfopristin (Synercid)
MOA
ribosomal 50 S
-
quinupristin/dalfopristin (Synercid)
spectrum
- MSSA, MRSA, VRE, atypicals
- no faecalis!!!!!
-
quinuprisint/dalfopristin (Synercid)
Adverse effect
- PAIN (local)
- give CENTRAL LINE
-
quinupristin/dalfopristin (Synercid)
Drug interaction
CYP3A4 inhibitor!!!
-
daptomycin (Cubicin)
MOA
cell membrane, insert tail and let potassium out (efflux)
-
daptomycin (Cubicin)
spectum
- like linezolid in terms of gram positive coverage
- MSSA, MRSA, faecalis, faecium (VRE)
-
daptomycin (Cubicin)
NOT to use in?
Adverse monitoring?
Drug interaction (1)?
- NOT for respiratory tract infections = bad with surfactant - strep pneumo)
- CPK elevation weekly
- HMG-CoA reductase inhibitors - STATINS avoid!!!
-
colistimethate sodium
spectrum
Adverse effects
- gram-negative
- nephrotoxicity (worse than aminoglycosides)
-
rifampin (Rifadin)
clinical use
Adverse event
- classic CYP450 enzyme INDUCER
- TB, N. men, H.influ, S. aureus (MRSA)
- ADR: orange discoloration
-
nitrofurantoin (Macrodantin, Macrobid)
Avoid?
renal dysfunction CrCl < 60 ml/min
-
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