Antibiotics Flashcards
Which organism is always coagulase positive?
Staph aureus
Bacteriocidal vs Bacteriostatic
Cidal: kills bacteria
Static: stops the reproduction of the bacteria
Should you use bacteriocidal or static in immunocompromised patients?
CIDAL
Penicillins MOA
Bind to penicillin binding protein resulting in inhibition of peptidoglycan synthesis and activation of autolytic enzymes in cell wall
Bactericidal (kills)
Penicillins modes of resistance
- Production of B lactamase enzymes
- Lack of PBPs or altered PBPs
- Efflux of drug out of cell
- Failure to synthesize peptidoglycans such as mycoplasmas or metabolically inactive bacteria
Natural penicillin and coverage
Pen G
Acid labile: injection only
Treats gram positive infections like strepococci, pneumococci, meningcocci, spirochetes (syphillis), clostridia, enterococci, etc
Methicillin, cloxacillin
Isoxazolyl penicillins
Coverage: more designed for S. aureus. Less GP and no MRSA coverage
Aminopenicillins
Amoxicillin (PO), Ampicillin (IV) -> amp more acid labile than pen and poor F
Coverage: GP (strep, enterococci) and GN (neiserria, e coli, non beta lactamase h influenzae, P mirabilis, etc)
Not good for staph
Beta lactamase inhibitor
Clavulanic acid
Now good for staph
Beta-lactamases open the beta-lactam ring of penicillins and cephlaosporins; no longer active
ESBL (extended spectrum beta lactamases) found in E. Coli and Klebsiella pneumoniae
- beta lactamase inhibitors cannot stop ESBLs BTW!!!
Ureidopenicillins
Piperacillin
Coverage for Pseudomonas!!
Parenteral only because very acid labile
Available with tazobactam (B lactam inhibitor)
How are penicillins excreted?
By the kidney
- Cloxacillin can be excreted by liver if kidneys arent great
- Pen G will accumulate if kidneys suck
Penicillins are great at getting places like lungs, meningiitis, etc.`
Adverse effects of penicillins
N/V/D, skin rash, allergic reactions, fever/nephritis/esoinophilia as a triad, CNS symptoms
General penicillin facts
Concentration independent killing
All taken on empty stomach except for amoxi
Distributed in breastmilk but low risk and safe in pregnancy
Can use in immunocompromised
Cephalosporin MOA
Same as penicillins, PBP and peptidoglycan and cell wall n shit
Bacteriocidal
Cephalosporin resistance
- Lack of or altered PBP
- Beta lactamase production
- Resistance to beta lactams
- Efflux
- Inability of drug to penetrate
First gen cephs and coverage
Cefazolin, cephalexin, cefadroxil
Gram positive, not enterococci or MRSA
Gram negative, PEK (Proteus, E coli, Klebsiella)
Does not cross the BBB btw
Second gen cephs and coverage
Cefuroxime (IV/IM/PO), cefprozil (PO)
Cefoxitin = cephamycin, good for diabetic foot infections (mixed infection of ana and aerobic)
Coverage: gram positive (same as first), gram negative H PEK (add h influenzae), moraxella
3rd gen cephs and coverage
Cefotaxime (kidney), ceftriaxone (liver)
Cefixime (oral) used for gonorrhea
Ceftazidime (reserve for Pseudomonas as only one that covers it)
Less gram positive coverage (except strep) and way more gram negative bacilli coverage
HEN PEKS
Ability to penetrate CNS for brain infections
4th gen cephs and coverage
Cefepime - enhanced activity against enterbacter and citrobacter, simliar gram positive coverage and better gram negative. Not good for MRSA though
Ceftaroline and Ceftobiprole have activity against MRSA, E facaelis, and pen resisitant strep pneumoniae
Adverse effects of cephalosporins in general
Diarrhea, hypersensitivity, skin rash, fever
Low risk of cross sensitivity
Carbapenems
Meropenem, ertapenem, imipenem-cilastin (prevents breakdown by renal peptidases)
Structurally similar to penicillins
Gram positive, gram negative coverage, anaerobes, very broad spectrum
Ertapenem does not have Pseudomonas coverage but the other two do, and less enterococci than the other two as well (but the enterococci coverage sucks for all of them really)
Seizure risk imipenem>meropenem
Similar a/e to cephs
Macrolides and MOA
Erythromycin, clarithromycin, azithromycin
Attach to the 23S rRNA on the 50S subunit of bacterial ribosome resulting in inhibition of protein synthesis
Human cells do not have the 50S subunit, so very specific
Bacteriostatic
Macrolide mode of resistance
- Methylation of RNA receptor
- Inactivating enzymes encoded by mef genes
- Active efflux msr gene
Macrolide coverage
Large
Gram positive - streptococci, pneumococci, corneybacteria
And M pneumoniae, Chlamydia trachomatis, L pneumophilia, campylobacter jejuni
Also covers those that lack a typical cell wall
Why is erythromycin not used as IV?
Causes phlebitis
Erythromycin A/E
GI, cholestatic hepatitis, QT prolongation
Clarithromycin and azithromycin specifics
Same coverage as erythromycin (staph and strep) but enhanced activity against organisms such as L. Pneumophilia, Chlamydia trachomatis, Moraexlla catarrhalis, H. Influenzae (azithro), Mycobacterium avium complex and other mycobacteria
Useful for some MRSA
If resistant to erythromycin, then resistant to all
Lower rate of GI s/e but still main ones
Azithromycin has least amount of DI
Clindamycin
MOA same as macrolides
Spectrum: anaerobes, Staph aureus, Strep, some MRSA
Used in those with pen allergies
High risk of C diff
Tetracyclines and MOA
Tetracycline, minocycline, doxycycline
Inhibit binding of aminoacyl-tRNA to the 30 S unit of ribosome thereby inhibiting protein synthesis
Bacteriostatic
Tetracycline mechanism of resistance
- Active against many gram positive and negative organisms but high rates of resistance (e.g. E.coli, S. Pneumoniae)
- Creating enzymes, efflux pump
Tetracycline coverage
DOC for rickettsiae, bartonella, chlamydiae and M pneumoniae
Nocardia, P acnes (mino usually), active against MRSA
Tetracycline A/Es
GI upset (N/V/D) most common Skin rashes, photosensitivity, yeast overgrowth, deposits in bone, hepatitis
DIs: calcium, dairy, di-valent cations, antacids
Glycylcyclines
Tigecycline (synthetic analogue)
Active against many things: MRSA, strep pneumoniae, enterococci, samonella, shigella, acinetobacter, anaerobes
Glycopeptides and MOA
Vanco!
Inhibits cell wall peptidoglycan synthesis
Bacteriocidal
Resistance of vancomycin
VRE, staph aureus, VISA (vanco intermediate staph aureus)
Spectrum of vanco
Gram positive
- Enterococci –> really hard to kill. If resistant to penicillin then use this
- PRSP
- MRSA
- Clostridia
When to use PO vanco
For C diff only
A/E of Vanco
Nephrotoxicity, ototoxicity, red man syndrome (drop in BP, increase in HR, itch, fever, erythema), granulocytopenia
Aminoglycosides and MOA
Streptomycin, gentamycin, tobramycin, amikacin
Inhibit protein synthesis by inhibiting 30S subunit of bacterial ribosome
Concentration dependent
Similar drugs to vanco
Teicoplanin
Daptomycin
Means similar spectrum to vanco –> gram positive cocci
AMG Resistance
Mutation or methylation of 16S rRNA binding site
Enzymatic destruction of the drug
Lack of permeability to the drug molecule
Active efflux (or lack of active transport)
AMG Spectrum
Aerobic gram negative bacilli
- Can be added to a penicillin and penetrate gram positive membrane
- Synergistic with penicillins for enterococci and streptococci
- Penetrates tissues poorly, no CNS
A/E of AMGs
Nephrotoxicity (dose dependent, may be reversible) , ototoxicity (irreversible)
Which ABX require TDM
AMGs, Vanco
Quinolones and MOA
Cipro, levo, and moxifloxacin
Inhibit DNA gyrase or topoisomerase IV
Bacteriocidal
Spectrum of FQs
Generally very broad spectrum
Gram negative bacilli, haemophilus sp, Neiserriae, Chlamyida
Cipro - most activity against P aeruingosa
Moxi - anaerobes
Levo - S pneumoniae
FQs Resistance
Alteration of the A or B subunit of DNA gyrase (binding site)
Mutation in ParC or ParE of topoisomerase IV (where antibiotic binds)
Change in outer membrane permeability
Efflux pumps
FQs uses
Lots of RT infections (not cipro, reduced gram -ve activity) UTIs (not moxi) STIs Travellers diarrhea Drug resistant mycobacterial infections
Excellent oral bioF and should only be used for complex cases
FQs A/E
Nausea, insomnia, headache, dizziness, seizures, skin rashes, impaired liver function, tendonitis, QT prolongation, dysglycemia, C diff
FQs DI
Binding to di/tri valent cations which makes drug inactive, so no antacids, multivitamins, etc.
“Administer oral quinolones at least several hours before (4 h for moxifloxacin and 2 h for others) or after (8 h for moxifloxacin, 6 h for ciprofloxacin, 2 h for, levofloxacin) oral iron preparations. Monitor for diminished effects of the quinolone if this duration of dose separation cannot be achieved.”
QT prolonging drugs too
Sulfa/Trim MOA!
SMX MOA – structural analogue of PABA (para-aminonezoic acid); competitively inhibits dihydrofolic acid synthesis
- Necessary for conversion of PABA to folic acid
TMP MOA- binds to dihydrofolate reductase therefore inhibiting the reduction of dihydrofolic acid to tetrahydrofolic acid
- Bacteria need to make their own folic acid to survive and in combo, these drugs block both mechanisms bacteria use to make folate
Synthetic! And bacteriostatic
Resistance of Sulfa/Trim
ability of cells to use preformed folic acid
Spectrum and Uses of Sulfa/Trim
Spectrum: Broad, Gram p, gram n, chlaymdiae, norcardiae, protozoa
Uses: UTI (trim alone!), SSTI (MRSA), PCP
Sulfa/trim A/Es
Skin rashes (SJS), hypersensitivity, GI, bone marrow suppression, hyperkalemia Avoid in 1st trimester and in 3rd semester, sulfonamides can cause kernicterus in nerborns
Metronidazole MOA and resistance
Unknown but possible inhibition of nucleic acid synthesis and disruption of DNA
Resistance is difficult to identify and unknown how much exists
Metronidazole spectrum
Anaerobes including c diff
Protozoa, trichomonas (vaginal), giardia
Older drug that isn’t used much apparently, excellent bioF
Metronidazole A/E
GI - common
Metallic taste - common
Headache - common
Dark urine
Peripheral neuropathy (long term, repeated courses of therapy)
Disulfram like reaction with alcohol which makes you feel sick af, counsel to avoid alcohol from 24 hours after last dose
Insomnia, stomatitis, mouth sores all rare
