Antibiotic Classes and Drugs Flashcards
Antibiotic Resistance Patterns
Staphylococcus - B-lactamases - affects all pcn
MRSA - Alter PBP - affects pcn cephalosporins, some fluoroquinolones
Streptococcus - Alter binding sites - pcn, macrolides
Enterococcus - alterations to target site - vancomycin
Pseudomonas - reduced permeability - pcn, cephalosporins, carbapenems, aminoglycosides, fluoroquinolones
Pseudomonas - B-Lactamase production - pcn
Enterobacteriaceae - b-lactamase production - pcn
Cell Wall Synthesis Inhibitors
Includes B-Lactams (pcn, cephalosporins, Carbapenems), Glypcopeptides (Vancomycin), Lipopeptides (Daptomycin)
All function similarly by interfering with or binding to the protein that synthesizes the cell wall.
Penicillins (Cell Wall Synthesis Inhibitors)
Natural Penicillins - pcn v (oral), pcn G (IV)
Aminopenicillins - Amoxicillin oral, ampicillin IV
Penicillinase-resistant - Oxacillin, nafcillin
Extended-spectrum/antipsuedomonal - Piperacillin
Natural PCN (Cell Wall Synthesis Inhibitors)
PCN VK and G
These cover gm + streptococcus (not pneumoniae) and enterococcus
gm - Neisseria, Treponema pallidum (syphilis)
Only covers mouth flora anaerobes.
Commonly used for pharyngitis, erysipelas, and syphilis (pcnG)
Does not cover Staphylococci due to penicillinase.
Amino-penicillins
Ampicillin and Amoxicillin
gm + streptococcus, Enterococcus, Listeria monocytogenes
gm - proteus mirabilis, salmonella, Shigella, some e coli, and some H. influenzae
Only mouth anaerobes.
Commonly used for
URI
H. pylori w/ clarithromycin and PPI
Enterococcal infections
Skin infections
UTIs
CAPs
Lymphadenitis
Penicillinase Resistant Penicillins
Dicloxacillin, Nafcillin IV, oxacillin IV
Only cover Gm + Staph (not MRSA), Strep spp
Commonly used against:
B-lactamase producing staph
Cellulitis
Diabetic foot infections
Septic arthritis
Endocarditis
Extended-spectrum PCNs
Good for B. Fragilis
Pipercillin/tazobactam
GM+ staph, strep, enterococci (not MRSA)
GM- Enterobacteriaceae (E. Coli, Proteus), PA, H. Influenzae
Good for B. Fragilis (anaerobe)
Commonly used for
Nosocomial Pnuemonia
Intra-abd. infections
gynecological infections
SSTI
Two major forms of PCN resistance
Antibiotic destroying enzymes - Penicillinase, B-lactamases, Extended-spectrum B-lactamase (ESBL)
Altered target site - PCN cannot bind to the PBP as seen in MRSA
B-Lactamase Inhibitors
Can defeat some beta-lactamase producing organisms
Amoxicillin + clavulanate, Piperacillin + tazobactam, Ampicillin+Sulbactam
ABX Toxic Rxns and immune mediated ADRs
Toxic rxns:
disruption of host microbiome may lead to nausea, vomiting, diarrhea
overgrowth of toxic organisms (C. diff)
Antibody mediated:
Type 1 immediate hypersensitivity (IgE-mediated) - leads to hives, angioedema, bronchospasm, CV collapse, anaphylaxis
Type II -hemolytic anemia, thrombocytopenia, leukocytopenia
Type III immune-complex Reaction (4-10 days to develop) - Vasculitis, serum sickness, Arthus Reaction
T-Cell Mediated:
DRESS (2-8wk s/p)
Liver injury, interstitial nephritis
SJS/TEN
PCN allergies
10% of Pt report a PNC allergy, but that doesnt preclude the use of the drugs, unless reaction was anaphylaxis.
Can do a skin or oral challenge
prescribe cephalosporins - not if it was an anaphylactic allergy!
PRescribe a non b-lactam; check allergies
Perform PCN desensitization - very labor intensive and req the ICU to monitor
Cephalosporins (cell wall inhibitors)
Different generations have different spectrums of activity and NONE COVER ENTEROCOCCUS
Cephalosporin Generations
5 Generations:
1st - cephalexin Oral, Ceazolin IV
2nd -Cefaclor oral, Cefotaxime IV
3rd - Cefpodoxime oral, Ceftriaxone IV
4th - Cefepime IV
5th - Ceftaroline IV
Cephalosporin Properties
Similar MOA to PCN -both bind PBP, destroy the cells wall. and are time-dependent killers
Similar Chemical structure - Ampicillin, amoxicillin, cefaclor, cephalexin, cefadroxil; may increase risk for cross-reactivity b/w these agents
Both are considered first-line for the majority of infections - effective and well-tolerated oral/IV, relatively inexpensive.
First Gen Cephalosporins
Cefadroxil oral, Cephalexin oral, Cefazolin IV
SPEcK Coverage
GM+ Staph and strep
GM- Proteus, E. coli, Klebsiella pneumoniae
Commonly used for:
UTI
Pharyngitis
Mild SSTI
URI/LRI
2nd Gen Cephalosporins
Cefuroxime - lyme dz
cefoxitin and cefotetan -B. fragilis
Cefaclor oral, Cefprozil oral, Cefuroxime oral, Cefotetan IV, Cefoxitin IV
HNMSPEcK coverage
GM+Staph and strep
GM- hemophilus influenzae, N. gonorrhea, Moraxella catarrhalis, Proteus mirabilis, E. Coli, Klebsiella pneumoniae
Commonly used for:
Sinusitis, pharyngitis, otitis media, LRIs
Cefuroxime - lyme dz
cefoxitin and cefotetan -B. fragilis
3rd Gen Cephalosporins
ceftazidime Covers PA
Cefidinir oral, cefditoren oral, cefixime oral. cefpodoxime oral, cefotaxime IV, ceftazidime IV, Ceftizoxime IV, Ceftriaxone IV
GM+ Strep. Pneumoniae,
Gram- Enterobacteriaceae, H. influenzae, Moraxella catarhalis
Commonly used for:
CAP, Otitis media, URIs,
Meningitis, febrile neutropenia
ceftazidime Covers PA
Fourth Generation Cephalosporins
Cefepime IV
GM+ Strep and Staph
GM- Enterobacteriaceae, H. Influenzae, moraxella, PA
Commonly used for:
Meningitis
febrile neutropenia, pneumonia, nosocomial infections, pyelonephritis.
5th Generation Cephalosporins
Ceftazidime+avibactam - for complicated intra-abd infections with metronidazole, complicated UTIs, good against carbapenems resistant Enterobacteriaceae with ESBL
Ceftolozane+tazobactam - Same indications as above, active against MDR PA; less affected by efflux pumps
Ceftaroline - CAP, SSTI, MRSA/VRSA; Coverage similar to ceftriaxone
Cephalosporins cross reactivity
2% risk, first generation has the most risk.
Cross sensitivity with penicillin is about 2%
Pt with a positive PCN seem to be at a higher risk.
Monobactams
Aztreonam
only one in the USA, Gram - coverage includes PA,
No gram +, atypical, or anaerobic coverage
resistant to many B-lactamases produced by gram - bacteria.
No cross sensitivity with PCN or Cephalosporins; but possible risk with ceftazidime due to similar R1 side Chain
IV or IM Administrations, not available PO
Dose must be adjusted for decreased renal function
Low incidence of adverse effects such as diarrhea.
Carbapenems - First line against ESBL!
(E. coli/K. pneumoniae)
All IV: Ertapenem, Imipenem/cilistatin, Meropenem, Doripenem
Reserved for srs infections due to ESBLs such as E. coli/K. pneumoniae
Covers Strep, MSSA, Enterococcus, Pseudomonas.
Ertapenem does not cover Pseudomonas or enterococci.
ADRs: GI intolerance, rash, seizures
Special considerations:
Imipenem/cilastatin may decrease seizure threshold.
Carbapenems may increase valproic acid clearance - sup-therapuetic levels.
Doripenem associated with worse survival than imipenem for pneumonia.
Newer Carbapenems
Tx CRE
Meropenem+vaborbactam - works for UTIs, against KP carbanpenemase
Imipenem.cilistatin+relebactam - UTIS, IAbd; against KP and PA
Glycopeptides -Vancomycin
Inhibit the cell wall through a slightly different method to PCNs/etc
Commonly used for MRSA, Enterococcus, Streptococcus, C. Diff (enteral or rectal)
Well tolerated, but can be related to nephrotoxicity, ototoxicicty, neutropenia, thrombocytopenia.
Therapeutic drug monitoring required to ensure adequate dosing.
May need higher doses for pneumonia, meningitis, endocarditis.
VIR
Vancomycin-infusion reaction
Infusion related rxn w/ erythematous or urticarial rxn, flushing, tachycardia, and hypotension.
From the release of histamine and is not an allergic reactions.
Management:
Stop infusion and wait for SE to subside.
Restart are 1gm/hr and adjust rate as tolerated.
May administer diphenhydramine prior to infusion
Telavancin -
A lipoglycopeptide, similar to vanco, but only has a once daily dosing.
BBW for pregnancy.
Good for complicated SSTI, and nosocomial pneumonia
IV only; adjust for renal dysfuntion
More frequent ADR to Vanco; Nausea and taste changes.
Redman syndrome; infuse overs 60 min, can cause nephrotoxicity, GI upset, metallic taste.
Ortavancin and Dalbavancin
2nd gen lipoglycopeptides, IV only
Approved for Tx of SSTI
Oritavancin is a one time dose for SSTI
Dalbavancin - ones weekly dosing
Daptomycin - the Lipopeptide Antibiotic
Works by inserting itself into the Cytoplasmic membrane leading to ION leakage and cell death!
Coverage is similar to vancomycin, but covers VRE as well
Use for SSTI, Bacteremia, endocarditis.
Cannot be used in meningitis as it does not distribute into the CNS
Cannot be used in pneumonia as surfactant destroys it.
Adjust for Renal Dysfunction.
ADR:
Common injection site reaction, fever, chills, D/N/V
Srs rhabdomyolysis. D/C immediately if muscle pain/cramps + elevation of CPK >5 times upper limit of normal.
Protein Synthesis inhibitors
Includes Tetracyclines, Linezolid, Macrolides, and Aminoglycosides.
Tetracyclines (protein synthesis inhibitors) - General stuff
Prevents the binding of tRNA to MRNA-ribosome complex, thus inhibiting protein synthesis
Common ADRs include photosensitivity, sunburn, N/V
Can cause
tooth discoloration (enamel agenesis),
Abn bone growth (do not use in pregnancy or in children <8y/o)
Vestibular toxicity with minocycline - dizziness, ataxia, n/v which resolves 24-48 hours after d/c
Must monitor for hepatic toxicity with high doses or long-term use.
Tetracyclines (protein synthesis inhibitors) - Usage
Tetracycline PO, doxycycline IV/PO, minocycline PO
GM+ S. pneumoniae, S. Pyogenes, CA -MRSA
GM- E. Coli, Klebsiella, H. influenzae
Atypical - Chlaymidia pneumoniae, Mycopalsma pneumoniae, Legionella pneumoniae, chlamydia, trachomatis, Borrelia burgdorferi (lyme)
Commonly used for:
Respiratory infections
CA -MRSA, SSTI, acne
Doxycucline - anthrax, chlamydia, lyme, CA-MRSA
Want to separate from foods containing Al, Mg, Ca, Fe by 1-2 hours
Mino can be taken with or without food
Tertra should be taken on an empty stomach
Doxycycline - must be taken with food due to GI intolerance, but decreases absorption by 20%
Tigecycline
IV derivative of minocycline
good for MDR GNR (not PA), B fragilis, Strep/Staph (MRSA too!) Enterococcus (some VRE) and Aypicals
Commonly used in SSTI, I-ABd infections, CAPs
ADR n/v anemia
BBW risk of death; only use when all other therapies are unsuitable
Omadacycline
Approved for CAP, SSTI with no known cases of c diff associated diarrhea in clinical trials
No known CYP450 drug interactions
IV and PO
Eravacycline
Approved for complicated I-Abd infections
less incidence of n/v than tigecycline
Worse than levofloxacin for UTIs
IV only
Macrolide - protein synthesis inhibitor - general stuff
Important to be aware of QTc prolongation CYP450 drug interactions
inhibits translocation of step of protein synthesis
CYP450 interactions: inhibits cyp3A4: erythromycin> clarithromycin>azithromycin
Some GI intolerance w/ n/v/d abd pain (25% with erythromycin)
CV: QT prolongation risk (same order as above)
Food interactions:
Clarithromycin with or w/o food
Azithromycin ER suspension and erythromycin: 1 hour before or 2 hours after a meal
Fidaxomicin: with or w/o food
Macrolide - protein synthesis inhibitor - general stuff
Important to be aware of QTc prolongation CYP450 drug interactions
inhibits translocation of step of protein synthesis
CYP450 interactions: inhibits cyp3A4: erythromycin> clarithromycin>azithromycin
Some GI intolerance w/ n/v/d abd pain (25% with erythromycin)
CV: QT prolongation risk (same order as above)
Food interactions:
Clarithromycin with or w/o food
Azithromycin ER suspension and erythromycin: 1 hour before or 2 hours after a meal
Fidaxomicin: with or w/o food
Macrolides - protein synthesis inhibitors - Uses
erythromycin IV/PO, Clarithromycin PO, Azithromycin IV/PO
Gm+ Strep
Gm_ H. influenzae, N. gonorrhea
Atypical - Chlaymidia pneumoniae, Mycopalsma pneumoniae, Legionella pneumoniae, chlamydia, trachomatis
Common uses:
Alternative for PCN allergic Pts
CAPs
Pharyngitis
SSTI
Otitis media
Azithromycin - urethritis, MAC, COPD exacerbation prevention (anti inflammatory)
Erythromycin Tx post op ileus and improves GI Motility.
Fidaxomicin PO is for C. Diff
Clindamycin - Protein Synthesis Inhibitor - general stuff
Lincosamide - associated with C. Diff colitis
ADRs:
N/D, dyspepsia
less commonly -hepatotoxicity, skin rashes
Higher incidence of C. Diff associated D vs other ABX
Food Considerations:
Take with food due to GI Upset.
Full glass of water to decrease Esophageal ulceration.
Clindamycin - Protein Synthesis Inhibitor - Usages
Clindamycin IV/PO
Gm+ SA (MSSA/CA-MRASA) Strep, Peptostreptococcus.
Anaerobes Clostridium (not diff), bacteroides, Prevotella, Fusobacterium.
Common uses:
SSTI (CA-MRSA), Strept, Anaerobic infections, aspiration pneumonia.
Alternative Pcn allergic Patients with otitis media, dental prophylaxis
Can be used for CA-MRSA, but resistances can develop rapidly.
Oxazolidinediones Protein Synthesis Inhibitor - General Stuff
Linezolid and tedizolid; good for MRSA IV or PO
ADRs with prolonged Tx >2 weeks:
myelosuppression –> thrombocytopenia
peripheral or optic neuropathy (which can be partially reversible)
less risk with tedizolid v linezolid
Increased risk of serotonin syndrome:
hyper-reflexia, hallucinations, myoclonus, tachycardia, shivering
use with caution with Pts on SSRIs, TCAs, or MAOIs
avoid tyramine-rich foods such as wine, cheese, processed meat
less risk with tedizolid v linezolid
Increased risk of hypertension
Oral formulation shows 100% bioavailability
Oxazolidinediones Protein Synthesis Inhibitor - Linezolid
IV or PO
Gm +: SA (all) Strep, enterococcus faecium
Used for resistant infections such as MRSA or Vancomycin resistant E. Faecium
Used for SSTI, Bone and joint infections, bacteremia, Pneumonia
BID dosing.
Oxazolidinediones Protein Synthesis Inhibitor - Tedizolid
Approved For Acute bacterial skin and skin structure infections only. Once daily dosing.
IV or PO
Gm +: SA (all) Strep, enterococcus faecium
Used for resistant infections such as MRSA or Vancomycin resistant E. Faecium
Aminoglycosides Protein Synthesis Inhibitor - General stuff
Use high-dose extended interval dosing if the Pt has good renal function.
Have risk of ototoxicity and nephrotoxicity -
usually when >5 day durations.
More common in the elderly or in patients with impaired renal function.
Vestibular and auditory toxicity is irreversible
Traditional Dosing:
Gentamicin/Tobramycin (2mg/kg q8): Goal is to peak at 6-10mg/dl, trough <2mg/dl
Amikacin(5mg/kg q8): goal is to peak at 25-30mg/dl, trough undetectable
High Dosing, extended interval (5-7mg/kg q24)
Considered more effective and less likely to induce resistance and has a lower risk of nephrotoxicity.
-
Aminoglycosides Protein Synthesis Inhibitor - Uses
Genamicin IV, Tobramycin IV, Amikacin IV
Gm+ synergy against SA, Strep, Enterococcus.
Gm- Enteric GNR, Pseudomonas
Rarely used alon, even for Gram (-) infections
Synergy with cell-wall active agents against gram + organisms as in endocarditis.
UTI, Pneumonia, Meningitis
NA synthesis Inhibitors
Include Sulfonamides, Fluoroquinolones, Metronidazole
Sulfonamides -NA synthesis Inhibitors - General Stuff
Bactrim has retained excellent activity against most pathogens, including CA-MRSA
Considered bacteriostatic; analogues of PABA
Sulfa allergy to non-sulfonamide drugs has minimal cross reactivity
Increases serum creatine when initiating; thus nephrotoxicity can occur
Dosed on trimethoprim component, and adjusted for renal function
N/V/D, photosensitivity, rash
SJS/TENS
Blood dyscrasias, aplastic Anemia, Granulocytopenia, thrombocytopenia, hemolytic anemia (in Pt with g6pd deficiency)
Sulfonamides -NA synthesis Inhibitors - Uses
Bacrtim IV/PO, Sulfisoxazole, Sulfadiazine, Sulfasalazine
Gm+ Staph, S. pneumoniae, Anthrax, Clostridium tetani
Gm- E. colio, Proteus, H. influenzae
Atypicals - Chlamydia trachomatis
Common uses:
UTI
toxoplasmosis (combo with pyrimethamine.
Considered 1st line for CA-MRSA, PJP Tx and prophylaxis, and URI
Fluoroquinolones - DNA synthesis inhibitors - general
Increased use of these has been associated with MRSA
Inhibit DNA gyrase and topoisomerase, preventing the uncoiling and De-catenation of copied DNA from its parent
Absortion is reduced when administered concomitantly with divalent or trivalent cations (Mg, Ca, Al, Fe, Zinc)
Avoid use with medications that prolong QT interval (cipro is least likely to cause issues, moxifloaxacin is the most likely)
GI intolerance, h/a, rash, photosensitivity, hypo/hyperglycemia
BBW = tendonitis or tendon rupture
Fluoroquinolones - DNA synthesis inhibitors - Cirprofloxacin, ofloxacin, norfloxacin
Cirprofloxacin, ofloxacin, norfloxacin - 2nd gen
Gm- Enterobacteriaceae, H. influenzae, M. catarrhalis, Neisseria, Pseudomonas (cipro only)
Cipro and ofloxacin cover atypicals
Common Uses:
Norfloxacin is for uncomplicated UTIs
Cipro and ofloxacin - Complicated and uncomplicated UTIs, Gastroenteritis, prostatitis, STDs, skin infections
Cirpo - anthrax
Overall Gm- activity Cipro> levo=gati=moxi>sparfloxacin
Fluoroquinolones - DNA synthesis inhibitors - Levo, Moxi, Gatifloxacin
Levo, Moxi, Gatifloxacin(ophthalmic only) - 3rd and 4th gen
Gm+ S. pnuemoniae
Gm- Enterobacteriaceae, H. influenzae, M. catarrhalis, Neisseria, Pseudomonas (levo)
Atypicals
Similar indications to 2nd gen plus CAP and URIs
Fluoroquinolones - DNA synthesis inhibitors - Delafloxacin
Delafloxacin - 5th gen
Similar to levo but also covers MRSA
SSTI infections only
Metronidazole - the basics
Anaerobic workhorse - Steals Ions to become a toxic free radical that destroys DNA
ADR - Peripheral neuropathy, GI intolerance, Dry mouth, metallic taste.
DO NOT drink alcohol during and 48 hrs s/p d/c - gives hangover reactions, with flushing, tachycardia, n/v, sob
