Other Antibiotics Flashcards
List of Quinolones
4 listed
- Ciprofloxacin
- Levofloxacin
- Moxifloxacin
- Norfloxacin
Quinolones MOA
Inhibit bacterial topoisomerase enzymes for bacterial DNA synthesis
- DNA gyrase
- induces double-stranded break
- Repairs break
- Topoisomerase IV
- separated daughter chromosomes
- “Decantenation”
Inhibition of these -> DNA damage -> Cell death
Quinolones AKA
Fluoroquinolones if they have a Fluorine attached
Mechanisms of resistance to Quinolones
3 listed
- Alterations of DNA gyrase and/or Topoisomerase IV
- Alterations in cell permeability
- Efflux of drug
Coverage of Quinolones
- Many
- Gpos
- Gneg
- Atypicals
Clinical uses of Quinolones
Adults only
- UTIs (E. coli, other enteric gram negatives)
- Pneumonia (S. pneumo, H. flu, atypicals)
- Abdominal infections (enteric gram negatives)
What is Nalidixic acid and Norfloxacin?
- Not a fluoroquinolones but just a Quinolones because they didn’t have fluorine
- Had mostly Gneg coverage and limited/no Gpos coverage
Ciprofloxacin coverage
- some Gpos coverage
- rarely used for Gpos (resistance)
- very good Gneg coverage
- Most reliable Pseudomonas coverage
Ciprofloxacin Clinical uses
Used in
- UTIs
- GI infections
- Ciprofloxacin ear drops for otitis externa (swimmer’s ear caused by Pseudomonas)
Otitis externa
Swimmer’s ear caused by Pseudomonas
Swimmer’s ear
Otitis externa caused by Pseudomonas
Levofloxacin coverage
More than ciprofloxacin
- Gpos
- Atypicals
- better strep penumo
- covers most Methicillin-susceptible Staph aureus
- Less effective against Pseudomonas than ciprofloxacin
Levofloxacin Clinical uses
Commonly used in Pneumonia (Strep, Atypicals)
Modern quinolones
3 listed
- Gatifloxacin
- Sparfloxacin
- Moxifloxacin
Modern Quinolones coverage
- Better Gpos/Atypical coverage than Levofloxacin
- Less effective for Pseudomonas than Levofloxacin
Modern Quinolones clinical uses
Also used in Pneumonia
Quinolones adverse effects
- GI upset
- Anorexia, NV and abdominal discomfort
- 17% of patients
- Neurologic side effects
- Headache, dizziness
- 2 to 6% of patients
- Very rare but feared: QT prolongation of EKG
- caused by blockade of K+ channels
- can lead to Torsade de pointes
- Tendon rupture/tendonitis
- most commonly achilles
- More common older patients (>60), people on steroids
- Mechanism not well understood
- Cannot use in pregnancy or children
- toxic to developing cartilage in animal studies
Antacids and Quinolones
- Disrupt the absorption of many drugs
- Aluminum and Magnesium hydroxide
- Sucralfate (contains aluminum)
- key drugs
- Tetracycline
- Fluoroquinolones
- Isoniazid
- Iron supplements
Vancomycin MOA
Inhibits peptidoglycan formation (cell wall)
binds D-alanyl-D-alanine peptides and prevents cross linking causing cell wall breakdown > formation -> cell death
Basically same effect as beta-lactams but via a different mechanism
Beta-lactams inhibit transpeptidases (PBPs)
Vancomycin blocks transpeptidase binding
Vancomycin bacterial effect
Bacteriocidal
Mechanisms of resistance to Vancomycin
- Terminal amino acids change
- D-alanyl-D-alanine changed to D-alanyl-D-lactate
- VRSA emerges
VRSA resistance mechanism
- Terminal amino acids change on peptidoglycan D-alanyl-D-alanine changed to D-alanyl-D-lactate
- VRSA emerges
Vancomycin coverage
Gpos only because it is an enormous molecule so it is too large to pass Gneg outer membranes
Vancomycin clinical uses
generally 2 common uses
- Methicillin Resistant Staph Aureus (MRSA)
- Oral therapy for C. diff Pseudomembraneous colitis
Also, often given empirically when MRSA is a concern
- Endocarditis
- Severe pneumonia/sepsis
Vancomycin adverse effects
Generally well tolerated but
- nephrotoxicity
- less common with modern preparations
- increased risk if concomitant aminoglycoside therapy
- Ototoxicity
- Tinnitus
- vertigo
- hearing loss (rare)
- Red man syndrome
- flushing, erythema, itching
- usually affects the upper body, neck, face more than the lower body
- 10-20 minutes post-infusion
- Direct activation of Mast cells -> histamine release (Pseudoallergic drug reaction)
- may develop with first administration
- often infusion related -> slow infusion = no symptoms
Metronidazole MOA
- Prodrug: must be reduced to activate it
- reduced metronidazole results in increased drug uptake by the cells
- the activated form (reduced) generated free radicals causing DNA damage leading to cell death
Metronidazole coverage
- Only anaerobic bacteria are capable of reducing metronidazole
- Good coverage of anaerobes below the diaphragm
- B. fragilis
- C. diff
Metronidazole clinical uses
- anaerobes below the diaphragm
- B. fragilis
- C. difficile
- Peritonitis
- Abdominal abscesses
- Diverticulitis
- often given with quinolone for anaerobic/GI Gneg
- Ciprofloxacin/metronidazole often used for diverticulitis as well
- H. pylori and Gardnerella vaginalis
- Facultative anaerobic bacteria that are susceptible to Metronidazole
- part of the triple therapy for H. pylori
- Treatment of bacterial vaginitis
- Anaerobic Protozoa (lack mitochondria)
- Trichomonas vaginalis
- Entamoeba histolytica
- Giardia lamblia
Metronidazole AKA
Flagyl
Metronidazole adverse effects
- Unpleasant metallic taste
- GI: abdominal discomfort, nausea
- Neuro: Neuropathy, headache
- Disulfiram-like reaction (when drinking alcohol)
Metronidazole bacterial effect
Bactericidal
Nitrofurantoin MOA
Exact mechanism is incompletely understood
Nitrofurantoin bacterial effect
Bactericidal
Nitrofurantoin coverage
Rarely used
Only used in UTIs because the drug concentrates in the urine
Nitrofurantoin clinical uses
- Only used in UTIs because the drug concentrates in the urine
- especially for pregnancy because (TMP-SMX and Quinolones are contraindicated)
- Can trigger hemolysis in G6PD patients
Nitrofurantoin adverse effects
can trigger hemolysis in G6PD patients
