Intro to ABX (Clinical Pearls) - Block 1 Flashcards
Penicillin MOA
Inhibits the cross-linking of peptidoglycan in cell wall, causing autolysis & cell death
Types of penicillins?
- Natural
- ANti-staph
- AMinopenicillins
- Aminopenicillisn + BLI
- Extend spec + BLIs
Natural penicillins?
Penicillin G and V
Pen G benzathine
Natural penicillin indication?
- Pharyngitis
- Syphillis
BBW of penicillins?
Pen G benzathine should not be given IV -> fatal
What is Pen G benzathine specifically used for?
Bicillin LA -> drug ofchoice for syphillis
Types of anti-staph pens?
- Nafcillin
- Oxacillin
- Dicloxacillin
Indications for anti-staph pens?
MSSA: ABX are therapeutically interchangeable
Because of the short half-life and frequent dosing what do you need to consider about anti-staphs?
Increased risk for phlebitis -> consider using 1st gen cephs for better tolerability
CP of anti-staphs?
- Metabolized by liver -> no renal dose adj
- Consider sodium content in CHF on Na restriction
- ABXs are interchangeable for MSSA
Types of aminopenicillins?
- Amoxicillin
- Ampicillin
Indications for aminopenicillins?
- URTIs
- Otisi media
- Strep throat
- H. pylori
- enterococci
CP of aminopenicillins?
- Diarrheas as PO
- Amoxicillin»_space; ampicillin
- Alternative for UTIs in pregnant women
When would ampicillin be considered over amoxicillin?
Suspectible enterococci infections
* E. faecalis = S
* E. faecium = R
Types of Aminopenicillins + Beta-Lactamase Inhibitors?
Amoxicillin/clavulanate (PO)
Ampicillin/sulbactam (IV)
Indication for Aminopenicillins + Beta-Lactamase Inhibitors?
- URTIs
- LRTIs
- Animal and human bites
CP for Augmentin?
Causes diarrhea -> take with food
Do Beta-lactamase inhibitors cause complete inactivation of all BL enzymes?
No
CP of ampicillin/sulbactam?
active against Acinetobacter baumannii associated with nosocomial infections
Types of extended spec + BLI?
Zosyn
Indication for ZOsyn?
- Empiric coverage of nosocomial infections
- Susceptible P. aeruginosa infection
CP of Zosyn?
- Broad spec activity against G- and G+ anaerobes
- COnsider sodium content in BHF on Na restriction
ADRs of penicillins?
Hypersensitivity
C. diff colitis
Monitoring parametrs of penicillins?
Hypersensitivity reactions
Cephalosporins MOA?
Inhibits the cross-linking of peptidoglycan in cell wall, causing autolysis & cell death
Types of 1st gen cephalosporins?
- Cefazolin
- Cephalexin
- Cefadroxil
Indication of 1st gen cephs
- SSTI
- surigical prophylaxis
- MSSA bacteremia and endocarditis
CP of 1st gen cephs?
- Alt agent for anti-staph
- Cephalexin and cefadroxil -> high cross reactivity to beta-lactams
- Ceffazolin: low cross reactivity to beta-lactams
Types of 2nd gen cephs?
- Cefuroxime
- Ceprozil
- Cefoxitin
- Cefotetan
Indication for 2nd gen ceph?
- URTIs
- CAP
- Surgical prophylaxis (Cefoxitin and cefotetan)
How does 2nd gen compare to 1st gen?
Less strep and staph activity
2nds gen cephs that have anaerobic coverage?
Cefoxitin and cefotetan
ADR of cefotetan?
MTT side chain -> inhibits Vit K production and causes prolonged bleeding
Which 2nd gen has a high cross reactivity with beta lactams
Cefprozil
Types of 3rd gen cephs?
- Cefdinir
- Cefpodoxime
- Cefotaxime
- Ceftriaxone
- Seftazidime
Indication for 3rd gen?
- URTIs
- LRTIs
- gonorrhea
- SSTIs
- Bacteremia
- Osteomylitis
- Menigitis and Lyme (ceftriaxone)
- Nosocomial and febrile neuropenia (Ceftazidime)
ADR of 3rd gen?
- C. diff infection
- Increased risk of GNR resistance
- Cefpodoxime -> MMT side chain inhibits Vit K production -> prolonged bleeding
How does ceftazidime coverage differ from other 3rd gens?
Only has Pseudomonas activity, poor strep and staph coverage
rd gens that are used for CNS infection?
- Ceftriaxone (meningitis and Lyme)
- Cefotaxime
- Ceftazidime (febrile neutropenia)
Ceftriaxone
Dosing, DDI, ADR, CI
Dosing: QD, menigitis BID
* No renal adjustment
DDI: intercts with calcium-containing meds (forms crystals in lungs and kidneys)
ADR: biliary sludging -> hyperbilirubemia
CI: Neonates (cefotaxime is safer)
Types of forth gen cephs?
Cefepime
Indication cefepime?
- Empiric therapy for nosocomial infection
- Febrile neutropenia
- Intra ab infction
- SSTIs
- UTI
Pseudomonas activity (permanent charge)
Caution with cefepim?
- Neurotoxicity
- Renal dose adjustment
Types of 5th gen cephs?
Ceftaroline
Indication of ceftaroline?
- CAP
- MRSA
- Complicating SSRI
ADR of ceftaroline?
Neutropenia
Types of sideophor ceph? MOA
Cefiderocol (Fetroja): contains a sideophore side chain that allows it to be taken up into the abcteria bypassing resistance mechanisms
Indication for Cefiderocol?
- Complicated UTI
- HAP
- P. aeruginosa, ESBL- and carbapenemase producing organisms)
- Only used in patients with resistance of common ABX for the inidcation
Types of Cephalosporin + Beta-Lactamase Inhibitors?
ceftazidime/avibactam (IV), ceftolozane/tazobactam (IV), cefepime/enmetazobactam (IV)
Indication for Cephs + BLI?
- MDR P. aeruginosa
- ESBL-producign organsims
- ONLY in patients with bacterial infections which are resistant to other commonly-used antibiotics for the indication
What ceph combo has activity against carbapenem resistant enterobacterales?
Ceftazidime/avibactam
What can be added to ceph +BLI therapies if resistance is observed?
Metronidazole
ADR of Cephs?
- Hypersensitivity rx
- C diff colitis
Monitoring parameters of cephs?
- Hypersensitivity rx
- Renal function
MOA of carbapenems?
Inhibits the cross-linking of peptidoglycan in cell wall, causing autolysis & cell death
Types of cabapenems?
- Imipenem/cilastatin
- Meropenem
- Ertapenem
Indications for carbapenems?
- Nosocomial
- Febrile neutropeia
- Intra ab infection
- ESBL infections
ABX with the broadest spec? Caution?
Imipenem/cilastatin and meropenum -> should not be used as empiric therapy for CA infections
ADRs of imipenem/cilastatin?
Seizures
* Renal adjustment to minimize sz
DDI with carbapenems?
Valproic acid
* carbapenems induce VPA -> sub therapeutic VA [C] and breakthrough sz
How does ertapenen differ from other carbapenems?
- QD (more convenient)
- Weaker spec
* Pooractivity against Pseudmonas, acinetobacter, enterococci
Types of Carbapenems + Beta-Lactamase Inhibitors?
imipenem/cilastatin/relebactam (IV)
meropenem/vaborbactam (IV)
Indication for carbapenems + BLI?
- Complicated UTI
- Intra ab infection
- HAP
- VAP
ADR of carbapenems?
- Hypersensitvity
- C diff colitis
CP of carbapenems + BLI?
- Activity against carbapenemase-producing Enterobacterales and ESBL
- Imipenem/cilastatin/relebactam has . carbapenem-resistant Pseudomonas coverage
- Vaborbactam has no CR-pseudomonas coverage
Monitoring paratmeters of carbapenems?
- Hypersensitivity rx
- Renal function
Cautions when using carbapenems?
SZ higher in elderly with hx of sz or renal dysfunction
MOA of monobactams?
Inhibits the cross-linking of peptidoglycan in cell wall, causing autolysis & cell death
Types of monobactams?
Aztreonam
Indication for manobactams?
- G- infections including Pseudomonas (especially hx of beta-lactam allergy)
ADR of monobactams?
C diff colitis
Anaphylactic penicillin allergy
Avoid if patient has a ceftazidime allergy
Monitoring parameters of aztreonam?
Renal function
Macrolides MOA?
Binds to 50S subuntis on bac ribosome -> inhibits it from adding new aa to elongate protein chain
Types of macrolides?
- Azithromycin
- Clarithromycin
- Erythromycin
Indication of macrolides?
- RIs
- Atypical infection
- Travelers diarrhea (Azitrhomycin)
- H pylori PUD (clarithromycin)
- CAP butnot as a monotherapy due to increasing resistance
DDI of Macrolides?
Not Azithromycin: potent CYP3A4 inhibits
ADRs of macrolides?
- GI intolerance
- Diarrhea (Erythromycin -> prokinetic and GI stimulating)
- QTc prolongation
MOA of fluroquinolones?
Inhibits DNA topoisomerase -> DNA breakage and cell death
Types of fluroquinolones?
- Ciprofloxacin
- Levofloxacin
- Moxifloxacin
- Delafloxacin
Quinolones indicated for MRSA?
Delafloxacin
Quinolone not for respiratory?
Ciprofloxacin: poor S. pneumoniae coverage)
What is not an indication for moxifloxacin?
UTI -> poor urinary concntration
All quinolones reque renal adjustment?
Except for moxifloxacin
CI of quinolones?
Pregnancy and children -> imparied bone and cartilage development
BBW of quinolones?
- Tendon rupture
- Peripheral neuropathy
- CNS effect
- Myasthenia gravis
Precaution of quinolones?
- Aortic aneurysm and dissection
- Hyperglycemia
- Hypoglycemia
Quinolones with P. aeruginosa coverage?
Levofloxacin and ciprofloxacine must be given in higher doses when treating infection
______ is necessary due to increasing resistance of P. aeruginosa?
Susceptibility testing
Compare bioavailabilties of quinolone formulations?
Levofloxacin and moxifloxacin: PO=IV
Cipro and delafloxacin: PO<IV
DDIs with qinolones?
Mulivalent cations -> separate by at least 2 hrs
ADRs of fluoroquinolones?
- GI intolerance
- Photosensitivity
- QTc prolongation
- Tendon rupture
- Peripheral neuropathy
- SZ
- C diff colitis
Monitoring parameters of fluoroquinolones?
Renal function
MOA of tetracyclines?
Binds to 30S subunit of bacterial ribosome -> preventing the docking of tRNA with new amino acids from adding to elongating protein chain
TYpes of tetracyclines?
- Doxycycline
- Minocycline
- Tetracycline
Indication of tetracyclines?
- URTIs
- LRTIs
- SSTIs
- Atypicals
What is a con for tetracyclines have a large Vd?
Good tissue penetration -> not good for bacteremia
Doing of doxycycline and minocycline?
PO andIV are equivalent
DDI of tetracycline?
Multivalent cations -> separate for at least 2 hrs
Types of modified tetracyclines?
- Tigecyclne
- Eravacycline
- Omadacycline
Why is tigecycle not used?
BBW -> increased risk of mortality
Tetracyclines that don’t require renal dosing?
Eravacycline and omadacycline
How should omadacycline be dosed?
- Empty stomach
- 2 hrs before or 4 hrs after meals
- DDI with multivalent cations
Modified tetras have better activity against ___ than normal tetras?
VRE and MRSA
ADR of tetras?
- Esophageal ulcerations
- Photosensitivity
- Pseudotumor cerebri
- C diff colitis
Counseling points fr Tetras?
- Takewith 8 oz of water and sit upright for 30 minutes
- Avoid in pregnancy
- Doxycycline can be used in pediatrics <21 days
MOA of pleuromutilins?
Inhibits protein synthesis through various interaction with A and P sites of PTC (peptidyl transferase center) in domain V of 23S rRNA of the 50S ribosomal subunity
Types of pleuromutilins?
Lefamulin
Indication for lefamulin?
CAP (G+, G-, MRSA, Atypicals)
How is lefamulin metabolized?
CYP3A4 -> avoid CYP3A4 inhibitors -> QTc prolongation
ADr of pleuromutilins?
- Gi intolerance
- QT prolongation
- C diff colitis
Monitoring parameters of pleuromutilins?
Pregnancy testing -> teratogenic
Counseling points for Lefamulin?
- Take 1 hr before or 2 hr after meals
- Swallow whole with 6-8oz of water
- Don’t crush or divide tablets
MOA of AGs?
Binds to 30S subunit of bacterial ribosome -> misreading of genetic code, incorrect protein
What are the types of AG?
- Gentamicin
- Tobramycin
- AMikacin
- Plazomicin
- Streptomycin
What is plazomicin used for?
Complicated UTIs from MDR enterobacterales (ESBL and cabapenem resistant strains)
How is AG dosed?
IBW or AdjBW, but not TBW
Can AG be used has a monotherapy?
No, due to poor concnetrations achieved in the lungs and CNS
What are types of dosing strategies for AG?
- Traditional
- Extended interval
What is traditional dosing?
Before 4th dose: draw trough level wihin 30 min before next dose
After 4th dose: draw a peak level 30 min after infusion
What is the difference between peak and trough?
Peak: measures efficacy
Trough: measures toxicity
How do we fix peak?
Adjust dose
How do we fix trough?
Adjust dosing intervals
Who should not get extendd interval dosing?
- Pregnancy
- Critcally ill
- Renal dysfunction
- Morbidly obese
Dosing for extended interval?
Draw a random level after 1st dose based on Hartford nomagram
ADR of AG?
- Tubular necrois (nephrotox)
- Renal failure (nephrotox)
- Vestibulr and cochlear toxicity (ototox)
Monitoring paramters for AG?
- Renal function
- Serum drug concentration
MOA of glycopeptides
Binds to terminal D-ala D-ala chains on PG in the cell wall preventing elongation of PG chains
Types of glycopeptides?
Vancomycin
What is the preferred option for MSSA infections starting out?
b-lactams
What is vanc for?
- MRSA
- C diff (PO only)
PK/PD of vanc?
Time dependent, bactericidal
Dosing of vancomycin?
SHould not exceed 5 mg/mL by IV infusion over >60minutes
* Infusion period of 30 minutes for every 500 mg administered
Goal range for vanc?
Normal: 10-20 mcg/mL
Severe infection: 15-20 mcg/mL
Monitoring of vanc levels should include?
Trough taken 30 minutes before next dose
* before 4th dose
Ho should we adjust vanc?
Trough > goal range: increasing the interval or decreasing the dose
Trough < goal range: decreasing the interval or increasing the dose
What is the the target AUC value?
400-600
ADR of glycopeptides?
Vanc flushing syndrome
* Prolonging vanc infusions -> premedicate antihistamines
Monitoring paraemters of vancs?
- Renal function
- Serum drug concentration
MOA of lipoglycopeptides?
- Binds to D-al D-ala chains on PG in the cell wall, preventing elongation of PG chains
- Interferes with cell membrane disrupting membrane function
Types of lipogycopeptides?
- Telavancin
- Dalbavancin
- Oritavancin
Indications of lipoglycopeptides?
- SSTIs
- HAP (telavancin)
Describe the efficacy of telavancin over vanc?
Bactericidal effects more rapidly than vanc
DOA for lipoglycopeptides?
Oritavancin and dalbavancin: >1 week t1/2
DDI of lipoglycopeptids?
Heparin and warfarin: Oritavancin alters PT and activated pTT
Scope of activity of lipoglycopeptides?
- MRSA
- VRE (oritavancin)
ADR of lipoglycopeptides?
- C. diff colitis
- Infusion related rx
- Nephrotox
- Metallic taste disturbances (telavancin)
- Foamy urine (telavancin)
Monitoring parameters of lipoglycopeptides?
- Renal function
- Pregnancy test -> telavancin is teratogenic
MOA of cyclic lipopeptides?
Binds to cell membrane of G+ -> causing leakage of intracellular cations that maintain membrane polarization -> rapid depolarization and cell death
Types of cyclic lipopeptides?
Daptomycin
Indication of daptomycin?
MRSA, VRE
CI of cyclic lipopetides?
Pneumonia -> inacitivation by lung surfactant
ADR of daptomycin?
- Elevated cr phosphokinase (CPK)
- Rhabdomyolysis
Monitoring parameters of cyclic lipopetides?
- Renal function
- CPK (patients with prior or concomitant statin therapy)
Dosing of daptomycin?
- Elevated CPK >5 times ULN in patients with sx of rabdomyolysis
- Elevated CPK > 10 times ULN in asymptomatic patients
MOA of oxazolidinones?
Binds to 50S subunit -> blocks the formation of the 70S initiation complex resulting in the inhibition of protein synthesis
Types of oxazolidinones?
- Linezolid
- Tedizolid
Indication for Oxazolidinones?
MRSA, VRE
Dosing of oxazolidinones?
Linezolid and tedizolid: IV-PO (1:1)
Linezolid: No dose adjustment, not eliminated kidneys and liver
DDI of oxazolidones?
Linezolid -> serotonergic agents due to MOAI activity -> Serotonin syndrome
ADR of oxazolidinones?
- Myelosuppression (thrombocytopenia, leukopenia, anemia) - >2 weeks
- Peripheral neuropathy
- Serotonin syndrome
Monitoring parameters of oxazolidinones?
- CBC with differential
- Serotnin syndrome in patients on concomitant therapy with other serotonergic agents
MOA of folate antagonists?
Inhibits folate biosynthesis causing the depletion of the nucleotde pool -> inhibition of DNA synthesis in susceptible organisms
Types of folate antagonists?
- Bactrim
- Dapsone
- Pyrimethamine
- Sulfadiazine
Fixed ratio of Bactrim?
5:1
Indication of Bactrim?
- First line for uncomplicated UTIs
- ALt: nitrofurantoin if local E. coli >15-20%
- Avoid for empiric tx of complicated UTIs
CI of Bactrim?
- DDI wit warfarin -> increased bleeding risk -> monitor INR
- Infants <2 months old
- Pregnancy (inhibits folate)
ADR of folate antagonists?
- GI intolerance
- Rash
- Hyperkalemia
- Photosensitivity
- Crystalluria with azotemia
- SJS/TEN
- Sulfa allergy
- Methemoglobinemia in patients with G6PD def
MOA of streptogramins?
Bnds to different sites on the 5S subunit of the bacterial ribosome -> preventing of bacterial protein synthesis
Types of streptogramins?
Quinupristin - dalfopristin (Synercid)
Synercid scope of activity?
- No activity against E. faecalis
- Definitive therapy
- Only used for MRSA, VRE (E. faecium)
Bacteriostatic alone, bactericidal together
ADR of streptogramins?
- Myalgia
- Arthralgia
Dosing of Synercid?
- Mixed and administered with D5W
- 100% F
MOA of lincosamides?
Binds to 50S subunit inhibitng them from adding new aa to elongate protein chain (similar to macrolides)
Types of lincosamids?
Clindamycin
How do we test for lincosamide resistance?
D-test for erythromycin-resistant, clindamycin-susceptible strains:
* Positive D-test: inducible clindamycin resistance -> avoid clindamycin
ADR of lincosamides?
Diarrhea, C. diff colitis
MOA of nitromidazoles?
Forms free radicals can damage DNA and result in cell death of anaerobic bacteria and protozoa
Types of nitromidazoles?
- Metronidazole
- Tinidazole
DDI of nitromidazoles?
- Metronidazole inhibits aldehyde dehydrogenase -> concomitant use of alcohol -> disulfurim like rx
- CYP3A4 inhibition -> warfarin increased risk for bleeding
Bioavailability of metronidazole?
PO:IV -> 1:1
ADR of nitromidazole?
- Metallic taste
- Peripheral neuropathy -> reversible
- Disulfirm rx with alcohol
MOA of Nitrofurans & Fosfomycin
Nitrofurantoin: redued by bacterial flavoproteins into reactive species that alters ribosomal proteins inhibitngprotein synthesis
Fosfomycin: inhibits bacterial cell wall synthesis by preventing the production of building blocks of PG
Indication of nitrofurantoin? Fosfomycin?
Uncomplicated UTIs
Both: acute cystitis from VRE
CI of nitrofurantoin?
CrCl < 60 mL/min
Short term use: >30 mL/min
ADR of nitrofurans and fosfomycin?
Nitrofurantoin:
1. Peripheral neuropathy
2. Hemolytic anemia
3. Urine discoloration
4. C. diff colitis
Fosfomycin:
1. GI intolerance
2. C. diff colitis
Monitoring parameters of nitrofurans and fosfomycin?
G6PD activity
Formulations of nitrofurans and fosfomycin?
Nitrofurantoin: Macrobid and Macrofantin
Fosfomycin: PO powder mixed with waters prior to admin as one-dase regimen
MOA of polymyxins?
Binds to outer membrane of G- causing disruption of membrane stability and leakage of cellular contents
Types of polymyxins?
- Colistin
- Polymyxin B
Indication for polymixins?
Last line by MDR G- (A. baumannii, P. aeruginosa, and carbapenem-resistant Enterobacterales (K. pneumoniae))
Dosing of colistin?
400 mg colistimethate = 150 mg colistin base activity
ADR of polymyxins?
- Nephrotox -> dose-dependent effect
- Neurotox
- Neuromuscular blockade
MOA of anti-c diff?
Inhibits RNA polymerase resulting in the inhibition of protein synthesis and cell death
Types of anti-c diff agents?
Fidaxomicin
Indication of fidaxomicin?
- Non-absorbble in narrow spec activity specifically C. diff
- First line agent for C diff treatment and prophylaxis
ADR of anti-c. diff agents?
- GI tolerance
- Hypersensitivyt reactions
Cons of fidaxomicin?
- Very expensive
- Avoid: PO vanc or metronidazole
Types of tubercular agents?
- Rifamycins
- Isoniazid
- Pyrazinamide
- Ethambutol
MOA of rifamycins?
Inhibits RNA polymerase, which prevents transcription by blocking mRNA production & protein synthesis
Spectrum of activity of rifamycns?
MRSA
ADR of rifamycins?
- Red orange discoloration of bodily fluids
- Hepatotox
Monitoring paramters of rifampin?
Hepatic function (LFTs)
CP of rifampin?
Poten CYP450 enzyme inducers
* Rifabutin is less potent
MOA of isoniazid?
Inhibits enzymes that catalyze the synthesis of mycolic acids in the cell wall
Spectrum of activity of isoniazid?
Mycobacterium tuberculosis & Mycobacterium kansasii ONLY
ADR of isoniazid?
- GI effects
- Hepatotox
- Peripheral neuropathy
Monitoring parameters?
Hepativ function (LFTs)
CP of isoniazid
Administer pyridoxine (B2) to prevent peripheral neuropathy
* Avoid use of alcohol or APA -> hepatotox
* Avoid serotonergic agents -> MAOI activity
MOA of pyrazinamide?
Inhibits fatty acid synthetase I, which prevents the production of mycolic acids in the cell wall
Soectrum of activity for pyrazinamide?
Mycobacterium tuberculosis ONLY
ADR of pyrazinamide?
Hepatotx (dose dependent)
Hyperuricemia
Pyrazinamide is only used in combo
Monitoring parameters of pyrazinamide?
- Hepatic function (LFTs)
- Serum urate
MOA of ethambutol?
Inhibits arabinosyl transferase III, which prevents the production of arabinogalactan, a key component of the mycobacterial cell wall
Spectrum of activity of ethambutol?
Mycobacterium
ADR of ethambutol?
Optic neuritis
Monitoring parameters of ethambutol?
eye exam
What is the only med that is not associated with hepatotox?
Ethambutol
* first line agent for MAC infections