Infectious disease I Flashcards
What is collateral damage?
unintended consequences of antibiotic use
common resistant pathogens
- Kill Each And Every Strong Pathogen
- Klebsiella (ESBL, CRE)
- E.coli (ESBL, CRE)
- Acinetobacter
- Enterococcus (VRE)
- S.aureus (MRSA)
- Pseudomonas
hydrophilic drugs
- beta-lactams
- aminoglycosides
- glycopeptides
- daptomycin
- polymyxins
lipophilic drugs
- quinolones
- macrolides
- rifampin
- linezolid
- tetracyclines
hydrophilic drugs PK parameter
- small Vd -> poor tissue penetration
- renal elimination -> nephrotoxicity possibility
- low intracellular concentration -> not effective against atypical infections which is mostly intracellular
- increased Cl and/or distribution in sepsis
- poor/moderate bioavailability -> either no PO or IV:PO not 1:1
lipophilic drugs PK parameter
- large Vd -> good issue penetration
- hepatic metabolism -> hepatotoxicity possibility
- good intracellular concentrations -> yes for atyipicals
- Cl/distribution not changes in sepsis
- good bioavailability -> IV:PO 1:1
beta-lactam MOA
bind to PCN-binding proteins (PBPs) -> inhibit bacterial wall synthesis
PCN coverage
- gram positive cocci
- Streptococci, Enterococci
aminopenicillins coverage
PCN coverage + HNPEK
HNPEK
- Haemophilus
- Neisseria
- Proteus
- E.coli
- Klebsiella
aminopenicillins + beta lactamase inhibitors coverage
same as aminopenicillins plus:
- MSSA
- more resistant HNPEK
- anaerobe (B.fragilis)
Zosyn coverage
same as aminopenicillins + beta lactamase inhibitors plus:
- CAPES
- Pseudomonas
CAPES
- Citrobacter
- Acinetobacter
- Providencia
- Enterpbacter
- Serratia
antistaph PCN
- strep
- staph (MSSA)
PCN pearls
- PCN G benzathine IM only; NOT for IV (can cause cardioresp arrest and death)
- do not use extended forms of amox or augmentin or augmentin 875 in patients w/ CrCl < 30
- ADE: seizure with accumulation, GI upset, diarrhea, rash
- amox has chewable forms available
- IV amp diluted in NS only
- zosyn can be given via extended infusion (4h)
- sodium in zosyn
- no renal dose adjustments in antistaph pcn
- nafcillin is vesicant; risk of extravasation; if happens, use cold packs and hyaluronidase
PCN drug interactions
- probenecid can increase beta-lactams (interfere with renal excretion)
- beta-lactams (except naf and dicloxacillin) enhance warfarin
- PCNs increase methotrexate
- PCNs decrease mycophenolate
Key: PCN VK
1st line for strep throat and mild nonpurulent
Key: amoxicillin
- first line treatment for acute otitis media (80-90mg/kg/day)
- 1st choice for infective endocarditis prophylaxis before dental procedure (2g 30-60 min before procedure)
- used in H.pylori treatment
Key: augmentin
- 1st line for acute otitis media (90mg/kg/day) and sinus infection if indicated
- use lowest dose of clav to decrease diarrhea
Key: PCN G benzathine
- 1st line for syphilis (2.4 millions units IM once)
- not for IV use; can cause death
Key: zosyn
- active against psuedomonas
- can be used with extended infusion (4h)
Key: antistaph PCN
- cover MSSA only
- no renal dose adjustments needed
T/F: cephalosporin not active against Enterococcus
True
first generation cephalosporins
- *cefazolin (Ancef)
- *cephalexin (Keflex)
- cefadroxil
second generation cephalosporins
- *cefuroxime (Ceftin)
- *cefotetan (Cefotan)
- cefaclor
- cefoxitin
- cefprozil
third generation cephalosporins
- *cefdinir (Omnicef)
- *ceftriaxone (Rocephin)
- *cefotaxime
- cefditoren (Spectracef)
- cefixime (Suprax)
- cefpodoxime
- ceftibuten
- *ceftazidime (Fortax, Tazicef) / avibactam (Avycaz)
- ceftolozane/taxobactam (Zerbaxa)
fourth generation cephalosporins
*cefepime (Maxipime)
fifth generation cephalosporins
*ceftaroline fosamil (Teflaro)
first generation cephalosporins coverage
- gram + cocci (strep, staph esp MSSA)
- a little gram -: PEK
second generation cephalosporins coverage
- Staph
- more resistant S.pneumoniae
- HNPEK
- cefotetan and cefoxitin: same plus anaerobes (B.fragilis)
third generation cephalosporins coverage
+ Group 1:
- more resistant Strep, HNPEK, and also gram + anaerobes and MSSA
+ Group 2:
- no gram + but covers psuedomonas; with beta lactamase inhibitor, can also cover MDR gram -‘s
fourth generation cephalosporins coverage
- HNPEK
- CAPES
- pseudomonas
- staph, strep
fifth generation cephalosporins coverage
- MRSA
- HNPEK
- broad gram +
cephalexin dosing
250-500mg Q6-12h
cephalosporin pearls
- ceftriaxone CI in neonates due to biliary sludging and kernicterus and in neonates 28 days or younger who are also receiving Ca products
- 10% cross sensitivity with PCN allergy
- cefotetan has side chain which can increase risk of bleeding and disulfiram-like reaction with etoh
- ADE: seizure with accumulation, GI upset, diarrhea, rash
- cefixime has chewable tablet
- ceftaz/avibactam covers some CRE
cephalosporin pearls
- ceftriaxone CI in neonates due to biliary sludging and kernicterus and in neonates 28 days or younger who are also receiving Ca products
- 10% cross sensitivity with PCN allergy
- cefotetan has side chain which can increase risk of bleeding and disulfiram-like reaction with etoh
- ADE: seizure with accumulation, GI upset, diarrhea, rash
- cefixime has chewable tablet
- ceftaz/avibactam covers some CRE
cephalosporin drug interactions
- decrease stomach acid can decrease bioavailability of some cephalosporins -> avoid H2RA and PPI
- cefuroxime and cefpodoxime separated from short-acting antacids
Key: outpatient cephalosporins
- cephalexin: common for MSSA skin infections or strep throat
- cefuroxime: common for acute otitis media, CAP, sinus infection
- cefdinir: common for CAP, sinus infection
Key: inpatient cephalosporins
ceftriaxone and cefotaxime used in CAP, meningitis, spontaneous bacterial peritonitis, pyelonephritis
carbepenem coverage
- gram + and - (including ESBL)
- anaerobes
- DO NOT COVER: atypical, MRSA, VRE, C.diff, Stenotrophomonas
- ertapenem DOES NOT COVER: pseudo, acinetobacter, enterococcus
carbepenem pearls
- warning: in pts with seizures
- do not use in pts with PCN allergy
- ertapenem DOES NOT COVER: pseudo, acinetobacter, enterococcus
carbepenem drug interactions
decrease valproic acid
Key: carbepenems
commonly used for:
- polymicrobial infections (like diabetic foot infection)
- empiric when resistant organisms are suspected (pseudo and acinetobacter)
monobactam MOA
bind to PCN-binding proteins (PBPs) -> inhibit bacterial wall synthesis
monobactam coverage
- gram - including pseudomonas
- NO gram positive
aminoglycoside MOA
bind to ribosome -> interferes with protein synthesis -> defective bacterial cell membrane
aminoglycoside coverage
gram - including pseudomonas
aminoglycoside pearls
- if actual body weight < IBW, use actual body weight for dosing
- if obese, use adjusted body weight for dosing
- traditional: gentamicin and tobramycin: 1-2.5 mg/kg/dose
- extended: gentamicin and tobramycin: 4-7 mg/kg/dose
- traditional renal dose adjustments: CrCl >= 60 -> Q8h
- extended interval frequency determined by nomogram
- teratogenic
- neuromuscular blockade
- levels: for traditional, draw trough 30 min before 4th dose and peak 30 min after infusion of 4th dose; for extended, draw random level per timing on nomogram
- goal trough for gent gram - infection and tobramycin: <2 mcg/mL
quinolone MOA
- inhibit bacterial DNA topisomerase IV and DNA gyrase (topisomerase II)
- concentration dependent antibacterial activity
quinolone coverage
- gemi, levo, moxi are resp quinolones: enhanced coverage of S.pneumoniae
- cipro and levo: enhanced gram - including pseudomonas; commonly used in combo with beta lactams when treating psuedomonas empirically
- moxi: enhanced gram + and anaerobic
- dela: MRSA
quinolone pearls
- warning: peipheral neuropathy, hypo- and hyperglycemia, psychiatric disturbances, avoid in children and pregnant/breastfeeding due to musculoskeletal toxicity, photosensitivity
- caution: seizures
- QT prolongation (highest risk with moxi)
- cipro oral suspension: shake vigorously 15 min, NO NG tube
- moxi: no urine concnetration, no UTI, no renal dose adjustments
quinolone drug interactions
- antacids and polyvalent cations chelate and inhibit quinolone absorption
- lanthanum carbonate (Fosrenol) and sevelamer decrease concentration of oral quinolone; separate administration
- quinolone increase effect of sylfonylureas, insulin, and hypoglycemic drugs
- probenicid and NSAIDS can increase quinolone
- levo and moxi: IV:PO 1:1
What are the atypicals?
- Legionella
- Chlamydia
- Mycoplasma
- Mycobacterium
macrolide MOA
bind to 50S ribosomal subunit -> inhibit RNA-dependent protein synthesis
macrolide coverage
atypicals
macrolide uses
- CAP, LRTI
- STD (chlamydia, gonorrhea)
macrolide pearls
- Tri Pak: 500mg daily for 3 days
- do not use clarithro or erythro with lovastatin or simvastatin
- warning: QT prolongation, hepatotoxicity
- clarithro: caution in pts with CAD (increased mortality)
- ADE: GI upset
macrolide drug interactions
- erythro and clarithro are CYP3A4 inhibitors; close monitoring with colchicine, apixaban, dabigatran, rivaroxaban, theophylline, WARFARIN
- azithro: fewer drug interactions
Key: macrolides
- used as alternative to beta-lactam for strep throat
- azithro: monotherapy for chlamydia, combo therapy for gonorrhea, prophylaxis for MAC, choice for travelers’ diarrhea
- clarithro: tx of H.pylori
- erythro causes most GI upset
tetracyclines MOA
bind to 30S ribosomal -> inhibit protein synthesis
tetracyclines coverage
- Gram positive: staph, strep, enterococci, nocardia, bacillus, propionibacterium
- Gram negative: haemophilus, moraxella
- Other: atypicals, rickettsiae, bacillus anthracis, treponema
doxycycline
- has broader coverage compared to other tetracyclines
- used for: CAP, tick/rickettesial diseases, STD (chlamydia and gonorrhea), CA-MRSA skin infections, VRE UTIs
tetracycline pearls
- no renal dose adjustments for doxycyline
- minocycline: drug-induced lupus erythematosus (DILE)
- mino and docy IV:PO 1:1
tetracycline drug interactions
- antacids, polyvalent cations, multivitamins, sucralfate, bismuth subsalicylate, bile acid resins can chelate and inhibit tetracycline absorption; separate administration
- docy and mino taken with food to decrease GI upset
- lanthanum carbonate (Fosrenol) decrease tetracyclines; separate administration
- tetracyclines enhance effect of warfarin and neuromuscular blocking drugs
Key: tetracyclines
- doxy and mino used for CA-MRSA skin infections
- doxy first line for lyme disease, rock mountain spotted fever, CAP, COPD exacerbations, sinusitis, VRE UTI
- tetracycline used in H.pylori treatment
sulfonamide MOA
inhibit bacterial folic acid production
sulfonamide coverage
- Staph (MRSA and CA-MRSA)
- broad gram -: haemophilus, proteus, E.coli, klebsiella, enterobacter, shigella, salmonella, stenotrophomonas
- opportunistic pathogens: nocardia, pneumocystis, toxoplasmosis
- does NOT cover pseudo, entercocci, atypicals, anaerobes
sulfonamide pearls
- dose based on TMP component
- DS: 800/160
- uncomplicated UTI: 1 DS tab PO BID x 3d
- warnings: SJS/TEN, thrombotic purpura (TTP), do not use if pt has G6PD deficiency
- ADE: photosensitivity, increased K, hemolytic anemia (positive coombs test), crystalluria
sulfonamide drug interactions
- Bactrim is CYP2C9 inhibitor -> can increase INR
- do not use with CYP2C9 inducers; levels can decrease
- Bactrim therapeutic effects can decrease with use of leucovorin
vancomycin MOA
bind to D-alanyl-D-alanine cell wall precursor -> inhibit bacterial wall synthesis
vancomycin pearls
- systemic infections: 15-20 mg/kg Q8-12h
- dose based on actual body weight
- CrCl 20-49: Q24H
- C.Diff: 125-500mg QID x 10d
- ototoxicity and nephrotoxicity
- goal trough 15-20 mcg/mL for pneumonia, endocarditis, osteo, mening, bacteremia
lipoglycopeptide MOA
- bind to D-alanyl-D-alanine cell wall precursor -> inhibit bacterial wall synthesis
- disrupt bacterial membrane potential
lipoglycopeptide pearls
- concentration dependent antibacterial activity
- televancin approved for use of SSTI; boxed warning: fetal risk, nephrotoxicity
- oritavancin & dalbavancin: do not use IV UFH 5 days after administration due to falsely elevated aPTT; long half life -> single dose regimen
- can falsely increase caogulation tests; red man syndrome
lipoglycopeptide drug interactions
- televancin: use caution in QT prolongation or HF
- oritavancin: has effect on CYP2C9, CYP2C19, CYP3A4, CYP2D6
daptomycin MOA
bind to cell membrane -> depolarization
daptomycin pearls
- concentration dependent antibacterial activity
- falsely elevated PT/INR
- check CPK weekly
- use NS
oxazolidinones MOA
bind to 50s subunit -> inhibit protein synthesis
oxazolidinones pearls
- no renal dose adjustments
- Iv to PO 1:1
- do not use within 2 weeks of MAOi
- longer duration = higher risk for myelosuppression (common thrombocytopenia)
- other warnings: peripheral and optic neuropathy, serotonin syndrome, hypoglycemia
- ADE: low platelets
- don’t shake suspension
oxazolidinones coverage
like vanc + VRE
quinupristin/dalfopristin MOA
bind to 50s subunit -> inhibit protein synthesis
quinupristin/dalfopristin coverage
- gram +
- MRSA
- VRE.faecium
quinupristin/dalfopristin pearls
- ADE: arthralgias/myalgias, infusion reactions, hyperbilirubinemia
- D5W only
- central line
tigecycline MOA
bind to 30s subunit -> inhibit protein synthesis
tigecycline coverage
- gram +
- MRSA
- VRE
- gram -
- anaerobes
- atypical
tigecycline pearls
- related to tetracyclines
- increase risk of death
- do not use for bloodstream infections
- reconstituted solution should be yellow-orange
polymyxin coverage
- Enterobacter
- E.coli
- Klebsiella pneumoniae
- Pseudomonas
polymyxin pearls
- MDR gram - pathogens
- colistimethate prodrug converted to colistin
- inhalations: mixed right before administration
- nephro and neurotoxicity
- resp paralysis from neuromuscular blockade
chloramphenicol MOA
bind to 50s subunit -> inhibit protein synthesis
chloramphenicol pearls
warning: Gray syndrome
lincosamide MOA
bind to 50s subunit -> inhibit protein synthesis
lincosamide coverage
- anaerobes
- Gram + (ex. CA-MRSA)
lincosamide pearls
- no renal dose adjustments
- warning: c.diff
- induction test (D-test) on S.aureus -> flattened zone = resistance
metronidazole MOA
loss of helical DNA structure and strand breakage -> inhibit protein synthesis
metronidazole coverage
- anaerobes
- protozoal infections
metronidazole uses
- bacterial vagionosis
- trichomoniasis
- IAI
metronidazole pearls
- IV:PO 1:1
- CI in: 1st trimester, use of alcohol within 3 days after tx course
- secnidazole can be taken as 2g single dose and can treat vulvovaginal candidiasis
metronidazole drug interactions
- disulfiram rxn: abd cramping, N/V, headaches, flushing
- can increase INR
fidaxomicin MOA
inhibit RNA polymerase -> inhibit protein synthesis
rifaximin MOA
inhibit RNA polymerase -> inhibit protein synthesis
rifaximin uses
- traveler’s diarrhea
- reduce hepatic enceph. occurrence
- IBS
- not for systemic infections
fosfomycin coverage
- E.coli (+ ESBL)
- E.faecalis (+VRE)
nitrofurantoin MOA
bacterial cell wall inhibitor
nitrofurantoin coverage
uncomplicated UTI only
- E.coli
- Klebsiella
- Enterobacter
- S.aureus
- Entreococcus (VRE)
nitrofurantoin pearls
- Macrobid: 100mg BID x 5 days
- do NOT use if CrCl < 60
- warning: hemolytic anemia, caution in pts with G6PD deficiency
- ADE: GI upset (take with food to help with GI upset), brown urine discoloration
Key: nitrofurantoin
- drug of choice for uncomplicated UTI
- Macrodantin is QID
- take with food to avoid GI side effects
drug of choice for CA-MRSA SSTI
- Bactrim
- doxy / mino
- clindamycin
- linezolid
drug of choice for severe MRSA SSTI
- vanc
- dapto
- linezolid
- ceftaroline
drug of choice for nosocomial MRSA
- vanc
- linezolid
- dapto
drug of choice for VRE.faecalis
- PenG or ampicillin
- linezolid
- dapto
- cystitis: nitroduran, fosfo, doxy
drug of choice for VRE.faecium
- dapto
- linezolid
- cystitis: nitroduran, fosfo, doxy
drug of choice for pseudomonas
- Zosyn
- cefepime
- ceftazidime +/- avibactam
- ceftolozane/tazobactam
- carbapenem (but not ertapenem)
- cipro, levo
- aztreonam
- aminoglycosides
- polymyxins
drug of choice for acinetobacter baumannii
carbapenem (but not ertapenem)
drug of choice for ESBL
- carbapenems
- ceftazidime/avibactam
- ceftolozane/tazobactam
drug of choice for CRE
- ceftazidime/avibactam
- polymyxins
drug of choice for bacteroides fragillis
- metronidazole
- beta-lactam +/- beta-lactamase inhibitor
- cefotetan, cefoxitin
- carbapenems
drug of choice for atypical organisms
- azithromycin
- doxycyline
- quinolones
drug of choice for HNPEK
beta-lactam +/- beta-lactamase inhibitor
Which oral suspensions require refrigeration after reconstitution?
- PCN VK
- ampicillin
- Augmentin
- recommend for amoxicillin to improve taste but not required
Which oral suspensions does not require refrigeration after reconstitution?
- cefdinir
- cipro
- azithromycin, clarithromycin
- doxycycline
- Bactrim
- clinda
Which medications make you more sensitive to the sun?
- quinolones
- tetracycline
- bactrim
Which medications should you take with food?
- Biaxin XL
- Augmentin
- nitorfuran
Which medications should you take with a full glass of water?
- quinolones (crystal formation)
- tetracycline (GI irritation)
- bactrim (crystal formation)
- clinda (GI irritation)
Which key drugs do not have renal dose adjustments?
- antistaph beta-lactam
- clinda
- doxy
- macrolides (azithro and erythro)
- metronidazole
- moxifloxacin
- linezolid
