Antibiotics Flashcards
Cell wall active
Pen, Ceph, Carbapenims, Vanc, dapto, poly
Beta lactam side effects
Seizures (imipenem, cefepime), anaphylaxis, biliary stasis (ceftriaxone), interstitial nephritis, hypersensitivity hepatitis (oxacillin), myelosuppression - leukopenia, hemolytic anemia
ESBL pattern
R to pen, aztreonam, cefazolin, ceftazidime, ceftriaxone (avoid pip/tazo)
KPC resistance pattern
All tested cephalosporins, carba, aztreonam
Chromosomal induced AMP C resistance
KEC: Klebsiella (previously Enterobacter) aerogenes, Enterobacter cloacae, Citrobacter freundii
Van A or Van B Enterococci - what is the species?
Enterococci faecium, Vanc MIC > or = to 32
Enterococci with vanc MIC 8-16
E. gallinarum, E. casseliflavus/flavescens. Not epidemiologically significant in hlthcare setting
UL97 mutation in CMV confers what resistance
ganciclovir, marabvavir
Mycoplasma hominis - what abx to use?
Can’t use cell wall active drugs. Use tetracycline, FQ, Clinda. Do NOT use AF, TMP, Erytho or azithromycin
UL54 mutation confers what resistance?
ganciclovir, cidofovir, foscarnet
UL56 mutation confers what resistance?
Letermovir
cephalosporins 1
cidal, time dependent, fewer side effects than pen, most renally excreted, CSF penetration with 3rd gen
cephalosporins 2 key points
- enterococci: none are active
- only cephamycins active against anaerobes: cefoxitin, cefotetans both have high level of resistance
Ceftaroline
- Gram +, including MRSA, MDR S. Pneumo
- limited anaerobes - Cutibacterium (formerly Prprionobacterim), Actinomyces spp
Ceftaroline 2
- active against gram neg: E. coli, Kleb spp, H. influ, M. catarrhalis
- NOT for Pseudomonas or ESBL GNB
Vanc resistance
- Not in Strep
- Rare in Staph
- Common in Enterococcus faecium (rare in E. faecalis
- change in vanc binding site
Vanc toxicity with other drugs
AG, NSAIDS, contrast, Cyclosporin, tacrolimus, loop diuretics, ACEI, pip/tazo (pseudo interaction)
Daptomycin
cidal, lipopeptide, Gram + activity (including MRSA & VRE), concentration dependent, cell membrane depolorization
Daptomycin indications
- cSSSI, S. aureus bactermia, rt sided endocarditis
- NOT for pneumonia - inactivated by surfactant
Daptomycin toxicity
- monitor CPK twice weekly - d/c if myopathy or CPK > 5x ULN
- eosinophilic pneumo
- falsely prolonged prothrombin time
- muscle inflammation - renal failure, obesity, statins
Long acting glycopeptides
- Oritavancin and Dalbavancin
- inhibit cell wall synthesis
Ortivancin & Dalbavancin dosing
- IV only
- Ortivancin - 1 dose over 3 hours
- Dalbavancin - 1000 mg x1, then 500 mg q 7 days or 1500 mg x1
Ortivancin & Dalbavancin indications
- skin & soft tissue
- Dalba - osteo & rt sided endocarditis
- Orti - FDA warning against use in osteomyelitis
lipo/glycopeptide toxicities
- vanc: nephro, histamine release
- Dapto: CPK increase, myopathy
- Telavancin: nephro
- Ortivancin: LFT increase, increase in PT & activated whole blood clotting time x 5 days, false increase aPTT,
-Dalba: LFT increase
FQ good for MRSA
Delafloxacin but not if invasive disease
ABX active intracellularly
FQ, Tetracyclines, Linezolid, TMP/SMZ, Pleuromutilins
FQ resistance
- drug permeability mutations
- occurs spontaneously on therapy
cipro spectrum
- poor Strep
- Some MSSA
- Best FQ for Pseudo & E. Coli (watch antibiogram - may have resistance)
Levo spectrum
- Good Strep
- Some MSSA
- Best FQ for Stenotrophomonas
Moxi spectrum
- Good Strep
- Good MSSA
- Best FQ for anaerobes - use in intra-abdominal
- Not effective against Gm neg - DO NOT use for UTI
FQ properties
-therapeutic concentration in CSF, but lower than in serum
- levo/cipro - renal excretion
- Moxi >60% hepatic/biliary unchanged
FQ side effects
- QT prolongation - watch for low K+, Mg++, bradycardia, cardiomyopathy
-aortic aneurysm/aortic dissection - dysglycemia - high and low
- AMS - dizzy, HA, insomnia
- C diff
- tendonopathy (older, poor renal fxn, steroids)
Delafloxacin
IV and oral BID
- MRSA actrivity
- broad spectrum including pseduomonas but not great
- approved skin and soft tissue
Tetracyclines activity
-Lyme
-Anaplasmosis
- Ehrlichiosis
- RMSF
- community acquired MRSA
- STIs
- Acne
Omadacycline (tetra)
- CABP
- ABSSSI
- IV & oral
- Gm pos including MRSA, VRE
- GM neg including ESBL, CRE (not all), anareobes
- side effects: GI, rash
Eravacycline (tetra)
- complicated intra-abdom IV only, not complicated UTI
- IV & oral
- dose adjust for hepatic failure
- Gm pos including MRSA, VRE
- GM neg including ESBL, CRE (not all), anareobes
- hihg MIC Pseudomonas, Burkholderia
- side effects: GI, rash
Oxazolidinone
Linezolid & Tedizolid
- bind 50s ribosome
-gram Pos cocci (MRSA & VRE)
- mycobacteria
Linezolid
- resistance S. aureus reported
- BID
- FDA approval - skin, soft tissue, Pneumonia, VRE
- NOT for bloodstream infection - black box warning
Tedizolid dosing
- once daily dosing
linezolid adverse events
- mitochondrial toxicity
- cytopenias - monitor CBC
- peripheral & optic neuropathy
- rare lactic acidosis, serotonin syndrome with SSRIs
- increase mortality with IV catheter associated bacterimia
TMP/SMX spectrum
- gram Positive
– staph great
– Strep - controversial
– Enterococcus - not effective - gram Negative
– increasing resistance E. Coli
– relatively effective enterobacterales
– not effective pseudomonas, acinetobacter
– often drug of choice for Stenotrophomonas
Lefamulin
- pleuromutilin
- IV & PO
- static
- FDA approved CABP
–5 days po lefamulin
Macrolides
- 50s ribosome
- Spectrum
– Strep pneumo (increasing resistance- fo not use if local R is >25%)
– H. influ
– Moraxella catarrhalis
– Legionella spp
– Strep Aa, C, G
VRE (E. Faecium) drugs if vanc and amp resistant
- Linezolid (FDA approved)
- Dapto plus amp or ceftaroline or ceftriaxone
- Amp if MIC < 32
- Unasyn if resistance due to beta lactamase
- NOT Quinupristin/dalfopristin as FDA approval withdrawn
- Cystitis - nitrofurantoin or fosfamycin
Antipseudomonal cephalosporins
- cefepime
- ceftazidime
- ceftolozone/tazo
Protein synthesis inhibitors
tetracyclines, linezolid, AG, Macrolides, clindamycin
Concentration dependent (post antibiotic effect)
AG, dapto, metronidazole, FQ
Time dependent
Pen, Ceph, aztreonam, carbapenems
time and post antibiotic effect
vanc, macrolides, tetra, linezolid, clindamycin
CAP and Doripenem
Do not use! Failed against CAP.
pip/tazo and nephrotoxicity
pip competes with creatinine for secretion in the proximal tubules - pseudotoxicity
Non fermenters
Acinetobacter, Burkholderia, Pseudomonas aeruginosa, Stenotrophomonas maltophilia
GN rod resistant to aztreonam
think ESBL
ESBL preferred txt
Meropenem or alternate is ceftolozane/tazo or cefepime (if low MIC)
- others - FQ, plazomicin
- avoid pip/tazo
ESBL uncomplicated UTI
-fosfomycin
-amox/clav
-nitrofurantoin
AMP C enzymes hydrolyze all cephalosporins except
- ceftolozone/tazo
-ceftaz/avibactem - cefideracol
- emperic txt of KEC meropenen or ceftolozane/tazo
2 mechanisms for AMP C
1) on plasmid gene - constitutive synthesis (found in E coli and Klebsiella spp)
2) xsome of KEC
KEC organisms
1) Klebsiella aerogenes (previously Enterobacter)
2) Enterobacter cloacae
3) Citrobacter freundii
AMP C often repressed, activated on exposure to cephalosporin
- emperic txt of KEC meropenen or ceftolozane/tazo
define difficult to treat P. aeruginosa
R to pip/tazo, ceftaz, cefepime, aztreonam, meropenem, imipenem, levo, cipro
- drug to treat - ceftolozane-tazobactam
cephalosporin crossreactivity
- ceftazidime
- cefiderocol
- aztreonam
have identical side chains
cephalosporin that crsytalizes in biliary tree
ceftriaxone
pseudo-cholelithiasis
cephalosporin with non-convulsive status epilepticus side effect
cefepime
carbapenem with no Pseudomonas nor non-fermenter activity
Ertapenem
avoid which carbapenem in meningitis
Imipenem-cilastatin
due to seizures
relebactam in imipenem - cilastatin - relebactam not protective against which organisms
Morganellacea gp
- providencia
- morganella
- proteus
Carbapenem not active against
- MRSA
- Steno maltophilia
- Acinetobacter (variable)
- E. faecium
FQ that doesn’t get into the urine
Moxifloxacin
which FQ inhibits cytochrome P450
cipro
what FQ drug interaction lowers seizure threshold
NSAIDs and FQ
-displaces GABA from receptors
what drugs lower serum level of Moxifloxacin
rifampin and rifapentine
- important for combined txt of mycobacteria
what factors increase risk of tendinopathy with FQ
- age over 60
- oral steroids
FQ adverse events
- aortic aneurysm/dissection
- tendinopathy
- arthropathy
AG have no activity against
- gram pos cocci
- anaerobes
- non-fermentors
only monotherapy for AG
- tularemia
- plague - Yesinia pestis
Bacteroides txt
- gold standard metronidazole
- pip/tazo
- amp/sulb
-carbapemems
-moxi - erava/omadacycline
indications for metronidazole
- Bacteroides
- bacterial vaginosis
- amebiasis
- giardiasis
- trichomonas vaginitis
- combo therapy for H pylori
Anaerobes resistant to metronidazole
- P. (Cutibacterium acnes
- Peptostreptococci
-Eikenella - Actinomyces
amphotericin B resistant
- Scedosporium apiospermum (previously Pseudallescheria boydii)
- Aspergillus terreus
- variable with Candida lusitaniae, C. aureus
fluconazole resistant
- all moulds
- C. krusei
- C. aureis
- C. haemulonii
- some C. glabrata
Voriconazole resistant
- mucormycosis
- uncommon cryptic Aspergillus spp (lentulus, ustus, calidoustus)
posaconazole resistant
- mucormycosis (more activity than vori)
- uncommon cryptic Aspergillus spp (lentulus, ustus, calidoustus)
Echinocandin resistant
- cryptococcus
-trichosporon - histoplasma
- blastomyces
- coccidioides
- molds other than aspergillus
