Lecture 16: Antibiotics Part 2 Flashcards
Are all DNA synthesis agents bactericidal or bacteriostatic?
Bactericidal
What do all fluoroquinolones end in?
Floxacin
What are the main 3 FQs used in clinical practice?
Ciprofloxacin
Levofloxacin
Moxifloxacin
What is the MOA of a FQ?
Inhibits bacterial DNA topoisomerase and gyrase, promoting DNA breakage
What is unique about the spectrum of an FQ?
Atypical coverage
If I want anaerobic coverage in an FQ, which one would I choose?
Moxifloxacin
When I see respiratory FQs, what am I referring to?
Levofloxacin, Moxifloxacin, and Gemifloxacin.
When I see antipseudomonal FQs, what am I referring to?
Levofloxacin, Ciprofloxacin, delafloxacin
What do FQs generally lack coverage of?
Staph A, except for Delafloxacin!
What is the novel FQ that can cover MRSA?
Delafloxacin
What is the major concern when prescribing an FQ to the elderly?
CNS effects.
Which FQ does not have QT prolongation concerns?
Delafloxacin
What bacterial GI effect is heavy FQ use associated with?
C. Diff diarrhea
What is the BBW of an FQ?
Tendonitis/Tendon rupture
What is the MOA of metronidazole?
Cause loss of DNA helical structure and strand breakage
What drug class is metronidazole?
Nitroimidazole
What is the coverage of metronidazole?
Anaerobes only (good for b fragilis)
What is metronidazole often combined with?
Levofloxacin, since levofloxacin has poor anaerobic coverage.
What is the BBW of metronidazole?
Carcinogen!!
DO NOT DRINK WITH ALCOHOL
How many weeks of metronidazole therapy do I start to see CNS toxicity?
4 weeks
What kind of drug-drug interactions does metronidazole have?
Metronidazole increases effects of warfarin and lithium
Metronidazole effects are Decreased by phenobarbital and phenytoin, and increased by cimetidine
What is the MOA of rifampin?
Inhibits beta-subunit of DNA-dependent RNA polymerase
What is rifampin’s main clinical use regarding staphylococcus?
Used as synergistic therapy. It prevents staph A from sticking to prosthetics like heart valves or limbs.
What are the 3 bacteria rifampin is mainly used for?
Staphylococcus
Mycobacterium
Neisseria
What is the main side effect that I need to counsel patients about regarding rifampin?
Red-orange staining for body fluids!
What are the side effects of extended rifampin usage > 4 weeks?
Myelinolysis?
What should I always do when attempting to order rifampin?
Drug interaction check!!!!!
What medications does rifampin have proven interference with?
Oral contraceptives.
What are the two folate antagonists?
Sulfamethoxazole
Trimethoprim
What bacteria are the folate antagonists the drug of choice for?
Stenotrophomonas maltophilia
What is the common side effect of folate antagonists?
SJS/TEN
Steven johnson syndrome
Toxic epidermis necrolysis
AKA RASH
What hypersensitivity reaction should I be wary about regarding folate antagonists?
Sulfa allergies.
What kind of drugs should I be wary about when adding a folate antagonist?
Any drug that can cause hyperkalemia as well.
What kind of patients must avoid folate antagonists?
G6PD deficiency
What are the protein inhibitors?
30S:
Tetracyclines
Glycylcyclines
30S & 50S:
Aminoglycosides
50S:
Macrolides
Lincosamides
Streptogrammins
Oxazolidinones
Are protein inhibitors bacteriostatic or bactericidal?
Bacteriostatic, aka inhibition of growth but does not kill bacteria.
What are the 3 tetracycline drugs?
Tetracycline
Doxycycline
Minocycline
What can tetracyclines cover that is significant?
Atypicals!
What drug can treat MDR acinetobacter?
Minocycline
What are tetracyclines absolutely contraindicated in?
Pregnant women and children < 8 yo because of teeth discoloration (permanent)
Which of the tetracyclines is the most well-tolerated?
Doxycycline
What causes impaired absorption of tetracyclines?
Vitamins, such as products with Ca, Fe, Mg, Al, or Zinc.
What drug is a glycylcycline?
Tigecycline (tiger!)
What is the common clinical use of tigecycline?
Second-line.
Note:
Very broad spectrum agent.
What is unique about the PK of tigecycline?
Rapid tissue periphery distribution.
This means it is also useless for bacteremia.
What is the main adverse effect that took tigecycline off primary use?
GI effects (30%!!!)
What is unique about the new tetracyclines’ coverage?
Cover atypicals!
What are the two new tetracyclines?
Omadacycline
Eravacycline
What are the 3 aminoglycosides?
Gentamicin
Tobramycin
Amikacin
Why are aminoglycosides commonly used in combination?
Monotherapy can cause resistance to build up very fast. They also don’t have great G+ coverage.
What toxicity should I be wary about in aminoglycosides? why?
Nephrotoxicity, because they build up in the urine.
What is the new aminoglycoside?
Plazomicin
What is the spectrum of plazomicin?
S. Aureus + MRSA
CRE
What are the 3 macrolides?
Erythromycin
Azithromycin
Clarithromycin
ACE mycins
What is unique about the coverage of macrolides?
Atypical coverage!
Why is erythromycin generally not used as an ABX anymore?
GI side effects and CYP 3A4 inhbition
Why do we prefer azithromycin among the macrolides?
No interaction with CYP 3A4.
What drugs should I avoid when using macrolides?
QT prolonging drugs
warfarin
What are the two treatments for C. Diff?
Vancomycin + Fidaxomicin
What is the MOA of fidaxomicin?
Inhibits RNA synthesis via RNA polymerase inhibition
What drug is a lincosamide?
Clindamycin
What is the boxed warning for clindamycin?
Pseudomembranous colitis
What drug is a streptogrammin?
Quinupristin-dalfopristin
Why do we not use streptogrammin anymore?
Myalgia/arthralgias
also causes hyperbilirubinemia
What drugs are oxazolidinones?
Linezolid
Tedizolid
What is significant about oxazolidinones?
G+ only, includes MRSA and VRE.
One of only 2 drugs? that is reliable for VRE treatment.
What is the most common adverse reaction with linezolid usage > 2 weeks?
Thrombocytopenia
Myelosuppression
What adverse reaction can occur with linezolid usage > 4 weeks?
IRREVERSIBLE peripheral neuropathy! and optic neuropathy.
Why is unique about the PK of linezolid?
PO bioavailability is the same as IV.
What is an interaction that we should still counsel pts about regarding linezolid?
Serotonin syndrome (which is proven to be not be the case anymore)
What drug is a pleuromutilin?
Lefamulin
What is significant about the spectrum of lefamulin?
Atypical coverage
What drugs are lefamulin CId with?
QT prolonging drugs
What is the MOA of nitrofurantoin?
Reduced by flavoproteins to active intermediates that may inactivate or damage ribosomal proteins, DNA and RNA
What is unique about the MOA of nitrofurantoin?
ONLY active in urine! Needs CrCl > 30
What is the main use of nitrofurantoin? Why?
E. Coli causing UTIs in elderly because it is well-tolerated and works only in urine.
What disease is caused by long-term use of nitrofurantoin?
Pulmonary fibrosis
What is the MOA of fosfomycin?
Interferes with bacterial cell wall synthesis by inhibiting enolpyruvyl transferase.
Active in urine only.
Why is fosfomycin not used frequently even though it has a broad spectrum?
G- bacteria can produce products that inactivate fosfomycin.
Describe the treatment modality for pseudomonas aeruginosa.
Empiric double-coverage.
Choose one of the beta lactams:
ES penicllin: Pip-tazo
3rd gen cephalosporin: Ceftazidime 4th gen cephalosporin: Cefepime Carbapenems: Doripenem, Imipenem-cilastatin, meropenem
Monobactam: aztreonam (Doripenem no longer used clinically.
Then
Choose one of the FQs or aminoglycosides:
Antipseudomonal FQs: Ciprofloxacin, Levofloxacin
Aminoglycosides: Amikacin, Tobramycin, Gentamicin
Note:
FQs are preferred over aminoglycosides due to nephrotoxicity.