Lecture 3: Antibiotics Part 2 Flashcards
What two amino acids connect bacterial cell walls together?
D-Ala to D-Ala
What drug class does vanco fall under?
Glycopeptide
What is the MOA of vanco and is it bactericidal or bacteriostatic?
Inhibits bacterial cell wall synthesis by binding to the D-ala D-ala chain and preventing the formation of peptidoglycan.
Results in a weakened cell wall and inability to replicate further.
It is a bactericidal drug.
How does VRE resist vanco?
Alters the binding site to D-ala-D-Lac.
What is the main hole in vanco coverage?
G-. Does not cover G-!
What are the main things vanco is good for?
MRSA!!!!!!! (IV)
C. Diff (oral)
Minor:
Listeria
Corynebacterium
Strep
Staph Pneumo
S. entercoccus
Is MRSA a G+ cocci or bacili?
G+ Cocci
Is C. Diff a G+ cocci or bacilli?
G+ Bacilli
What are the indications for vanco?
MRSA - IT IS THE INPATIENT DRUG OF CHOICE
C. diff - only for severe for refractory C. diff colitis.
How is vanco metabolized/excreted?
NO liver metabolism
Renal Excretion
Therefore adjust for renal impairment!
What pregnancy category is vanco?
Oral is B
IV is C
If someone has impaired renal function, how is dosing adjusted?
Less frequent dosing intervals.
What two things about a person determine their general vanco dosing?
CrCl
Total Body weight
How is vanco monitoring done?
Severe MRSA and other severe infections use AUC calculations.
All other normal infections are trough level.
When is a loading dose indicated for vanco?
Severe infections.
Why does vanco need monitoring?
It has a narrow therapeutic window.
When do I measure a trough level for vanco?
30 mins prior to next infusion AFTER SS is reached.
How many doses of vanco does it typically take to reach SS?
4 doses.
When do I get peak levels of vanco?
1-2 hours post dose.
What is the main adverse effect of vanco that is not life-threatening?
Hyperemia/red-man syndrome.
What is hyperemia caused by and how do I treat it?
It is pruritis with erythematous rash of the face, neck, and upper torso.
Caused by rapid infusions or high doses.
Treated by slowing the infusion and/or pretreating with an antihistamine.
What is a deadly adverse effect of vanco and what demographics are most susceptible?
Nephro and ototoxicity with high daily doses.
Occurs most frequently in renally impaired or elderly pts.
Occurs even more frequently when used with an aminoglycoside.
Requires monitoring of BUN/Cr and s/s of auditory dysfunction.
What are some alternatives to vanco?
For MRSA:
Telavancin, Dalbavancin, and Oritavancin are similar.
Daptomycin work EXCEPT if MRSA is in the lungs. (ALSO GOOD FOR VRE)
Linezolid: oral (uncommon)
Note:
All of these work vs VRE also except tela and dalba.
What are the 4 main aminoglycosides?
Gentamicin
Tobramycin
Amikacin
Streptomycin
Note:
micin
mycin
cin
Where do aminoglycosides work on the bacteria?
30S subunit, leading to inhibition of 50S subunit as well.
Are aminoglycosides bactericidal or bacteriostatic?
Bactericidal
What is the MOA of an aminoglycoside?
Binds to the 30S subunit, inhibiting protein synthesis.
What are the 4 ways a bacteria can build resistance to an aminoglycoside?
- Chromosomal mutation (AKA can’t bind to ribosome)
- Enzymatic destruction
- Lack of permeability through the cell wall.
- Efflux pumps
What are the primary indications for an aminoglycoside?
Gram -
MYCOBACTERIUM TUBERCULOSIS (TB!!!)
Note:
AmiNOGlycosides = no G+
What is one of the most common combinations an aminoglycoside is used with?
Ampicillin + gentamicin.
What are the BBW for an aminoglycoside?
Ototoxicity
Nephrotoxicity
Neuromuscular paralysis
Is an aminoglycoside OK to give in pregnancy?
No. Category D.
What is aminoglycoside dosing dependent on?
Weight and renal function
Note:
Pretty much the same as vanco.
How are aminoglycosides monitored?
Serum drug levels, aka peak and trough.
It has a narrow therapeutic window and therefore a high risk of toxicity, just like vanco.
Monitor BUN/Cr and audiometry.
What are the tetracyclines?
Tetracycline
Doxycycline
Minocycline
What is the MOA of a tetracycline?
Binds to 30S subunit.
Blocks tRNA.
Is tetracycline bacteriostatic or bactericidal?
Bacteriostatic
How do bacteria build resistance to tetracycline?
- Efflux pumps
- Enzymatic deactivation.
Note:
Resistance is increasing! Concerning because doxy is used a lot as first-line for many things.
What is the coverage of the tetracyclines?
G+ and G-
MRSA!!!
ATYPICALS (mycoplasma, rickettsiae, chlamydiae, spirochetes)
What 5 diseases/infections is Doxy first-line for?
Chylamydial infections
Rocky mountain spotted fever (Rickettsiae)
M. Pneumonia (Walking pneumonia)
Lyme disease (Spirochetes)
Cholera (Vibrio)
What are the 4 first-line treatment indications for doxy? (Diseases)
Lyme disease
Rocky mountain spotted fever
Cholera
Acne
Note:
Additional include Chylamydia, PID, and empiric therapy for CAPs.
What is a tetracycline CI in?
ABSOLUTE CI < 8 y/o due to tooth discoloration.
ABSOLUTE CI in pregnancy.
Relative CI < 13 y/o
What is the PK of tetracyclines?
Liver metabolism
Urine and Bile excretion.
What can you not take with tetracyclines?
Counseling:
No antacids (TUMS)
No dairy
What infections can be CAUSED by tetracycline?
Candida infections
C. Diff
What is a counseling point regarding tetracycline use and the sun?
Photosensitivity of skin.
Sunburns can happen very easily.
What is a counseling point regarding minocycline use?
Vestibular issues.
What are the macrolides?
Azithromycin
Erythromycin
Clarithromycin
Note:
-thromycin
What is the MOA of a macrolide?
Inhibition of protein synthesis and translocation via binding to the 50S subunit.
Is a macrolide bacteriostatic or bactericidal?
Bacteriostatic
How does a bacteria develop resistance to a macrolide?
- 50S subunit target modification
- Efflux pumps
- Degradation enzymes
What is significant to remember about macrolide spectrum?
DOES NOT CROSS BBB.
What is the spectrum of coverage of a macrolide?
G+:
S. aureus
S. pneumo
C. diph
G-:
M. cat
B. pertussis
H. flu
Legionella
Atypicals:
T. pallidum
M. pneumo
C. pneumo
C. trachomatis
What is the summarized version of macrolide coverage?
Chlamydial infections
M pneumo
Syphilis (for pts allergic to PCN)
Corynebacterium Diph
Legionnaire’s
What are the main first-line treatments involving macrolides?
CAPs: Atypicals including Myco and Chlamydia
Chlamydia
Legionella
Diphtheria
COPD acute exacerbations
What are macrolides second-line for?
OM
Pharyngitis
What should I never treat sinusitis with and why?
DO NOT USE AZITHROMYCIN.
Sinusitis requires a 10-day dosing but azithromycin cannot be dosed that long.
Preferred: Augmentin
What is the main diff between erythromycin and azithromycin?
Azithromycin has more dosing options + Broader spectrum of coverage.
What is the PK of a macrolide?
CYP450 inhibitor = liver metabolism (except zithro is less so.)
Bile excretion
Relative CI in liver impairment as a result.
What are the main adverse effects of macrolide use?
C. Diff
HEPATOTOXICITY
Prolonged QT interval
Transient ototoxicity.
Is macrolide use CI in pregnancy?
No.
Category B
What drugs can cause prolonged QT interval as an adverse effect?
Macrolides
Antihistamines
Antidepressants
Antifungals
What is the MOA of clindamycin?
Same as a macrolide. :)
50S subunit
Is clindamycin bacteriostatic or bactericidal?
Bacteriostatic
What is the main coverage of clindamycin?
G+, esp. some MRSA strains.
ORAL ANAEROBES
Note:
Vanco backup
What are the indications for clindamycin?
ORAL ABSCESSES
Endocarditis prophylaxis
Bacterial vaginosis (suppository and cream)
MRSA SSTIs
What is the BBW for clindamycin?
C. Diff Colitis
What are some counseling tips for clindamycin use?
Take with food or probiotic.
Women esp. should take with probiotic to prevent bacterial overgrowth.
Is clindamycin CI in pregnancy?
No.
Category B.
What are the main quinolones?
Ciprofloxacin
Moxifloxacin
Levofloxacin
Note:
-floxacin
What is the MOA of a quinolone?
Inhibition of DNA gyrase and topoisomerase IV.
Is a quinolone bactericidal or bacteriostatic?
Bactericidal
How do bacteria develop resistance to quinolones?
- Chromosomal mutation
- Efflux pump
- Decreased cell wall permeability.
What is the main coverage of quinolones?
G-:
H. flu
M. cat
Legionella
Salmonella
Shigella
C. jejuni
Vibrio
E. Coli
PSEUDOMONAS
What is the clinical rule of thumb regarding quinolone use?
Cipro for bellybutton down.
Levo and Moxi for bellybutton up.
What two bacteria are becoming more resistant to quinolones?
E. Coli
Pseudomonas
What is the main weakness/coverage hole of cipro?
G+.
Which quinolone has anaerobe coverage?
Moxifloxacin
What are quinolones first-line treatment for?
OE, opthalmic infections (topical cipro/levo)
Pyelo (cipro)
Prostatitis (cipro)
Traveller’s diarrhea/infectious diarrhea (cipro)
Anthrax (cipro)
URI’s/pneumonia WITH comorbidities (Levo/Moxi)
What is the PK of a quinolone?
Strong CYP450 inhibitor.
Liver metabolism
Urine and feces excretion.
What are the main CIs of a quinolone?
Prolonged QT/arrhythmias
Myasthenia Gravis
Is a quinolone CI in pregnancy?
Relatively.
Pregnancy Category C.
What is the BBW of quinolone use?
Tendinitis/tendon rupture.
What are the adverse effects of quinolone use?
Nephrotoxicity
LOWERS SEIZURE THRESHOLD
C. Diff
HA/dizziness
Hepatotoxicity
Glucose level alterations
Photosensitivity
What abx affects folate synthesis?
TMP-SMZ
Trimethoprim-sulfamethoxazole (Bactrim)
What is the MOA for TMP-SMZ?
TMP is a folate reductase inhibitor
SMZ is a folate synthesis inhibitor
Is TMP-SMZ bacteriostatic or bactericidal?
Bacteriostatic
What are the main infections TMP-SMZ can cover?
Pneumo jiroveci pneumonia
Listeriosis
H. flu
GI (shigella and salmonella non-typhoid)
Prostate and UTIs
What is another name TMP-SMZ is known as besides bactrim?
Cotrimoxazole
What is TMP-SMZ first-line for?
Outpatient MRSA
Uncomplicated UTIs/cystitis
Prophylaxis and prevention of P. jiroveci
Additional is legionella and certain pneumonias.
What treats inpatient MRSA?
Vanco IV.
What demographic gets P. jiroveci infections most commonly?
HIV and AIDs. It is an opportunistic infection.
What is the PK of TMP-SMZ?
Liver metabolism.
CYP450 inhibitor
Partial kidney excretion.
What kind of patients should I be cautious of giving TMP-SMZ?
Sulfa allergy is an absolute CI.
Hepatic/renal impairment.
Pregnancy (Folate)
What are the main adverse reactions of TMP-SMZ?
Megaloblastic anemia (due to folic acid def. Therefore be cautious in alcoholics as well.)
Photosensitivity
Hepatotoxicity
What pregnancy category is TMP-SMZ?
Category C.
What is the MOA of macrobid/nitrofurantoin?
Urinary antiseptic that inhibits bacterial enzymes and damages DNA.
What is the main indication for macrobid?
E. Coli
E. faecalis
UTIs
Who should macrobid be avoided in?
Severe renal impairment (it only works in urine so…)
Avoid in pregnancy
If a pregnant lady has a UTI, what is the preferred treatment since macrobid can’t be used?
Keflex for cystitis
What is the MOA of metronidazole/Tinidazole?
Disruption of microbial DNA
What is the main coverage of metro and tinidazole?
PROTOZOANS: Trich, Giardia, Entamoeba histolytica
G-/+ ANAEROBES: Clostridium, bacteroides, fusobacterium, gardnerella.
What is metro/flagyl first-line for?
Trichomonas
Bacterial vaginosis
C. Diff colitis
Amebiasis
Giardiasis
What is the PK of metro/flagyl?
Minor CYP450 inhibitor
Liver metabolism
Kidney excretion
What are the main adverse reactions to metro/flagyl?
Metallic taste
DISULFRAM-LIKE REACTION.
Note:
If you take metro/flagyl with alcohol, this reaction will cause hypotension and make a person feel very ill.
Metallic metros
What is the BBW of metro/flagyl?
Carcinogenic in mice and rats
What demographics should we be cautionary in giving metro/flagyl to?
Severe liver disease
Anemia
What is silver sulfadiazine used for and what is the concern?
Topical cream for burns.
Sulfa allergy!
What is sulfacetamide used for and what is the concern?
Opthlamic infections
Sulfa allergy!
What is pyrimethamine used for and what is it similar to?
Antiparasite/antimalarial
Adjunct for toxoplasmosis (parasite)
Malarial prevention
Similar to bactrim.
What is bacitracin used for and why?
Staph and Strep G+ only.
Cream only due to nephrotoxicity.
What is polymixin B used for and why?
Pseudomonas in the eye.
Mainly used only as opthlamic due to its toxicity.
It can be given parenterally, but only for MDR bacteria that are literally only sensitive to polymixin B.
Note:
Polymixin B is a cell membrane agent that is very general, so it is very potent, hence the toxicity.
Why is chloramphenicol rarely used anymore?
SE profile.
High risk of hematologic toxicity even if only used topically.
What is mupirocin/bactroban’s main indication?
IMPETIGO.
It is also used with chlorhexidine to decolonize MRSA carriers (pre-surgery prep)
