Miscellaneous ABX Flashcards
What is the antimetabolite ABX?
TMP-SMX
Sulfa MOA
Inhibit dihydrofolic acid synthesis (structural analogue of PABA) -> interferes with bacterial folate synthesis
Trimethoprim MOA
Inhibits dihydrofolic acid reduction to tetrahydrofolate
TMP-SMX MOR
- Altered enzyme targets
- ↓ sulfa accumulation
- ↑ production of PABA
TMP & SMX are substrates of and moderate inhibitors of CYP___
CYP2C9
Drug interactions for TMP-SMX
Drugs that cause hyperkalemia (ACEI/ARB/spironolactone)
TMP-SMX pharmacology
- Renal excretion
- Bacteriostatic
TMP-SMX ADRs
- Hypersensitivity, esp. reversible myelosupression (w/ larger dose)
- Hemolytic anemia in G6PD pts. (AA male)
- hyperkalemia
Microbial coverage of TMP-SMX
- P. jiroveci
- Most E. coli, Klebsiella, Proteus, MRSA
Clinical indications for TMP-SMX
- Lower UTIs (2nd line)
- PCP/PJP
- MRSA treatment/suppression (not serious infections)
Nitrofurantoin MOA
Inhibits bacterial enzyme systems, including acetyl CoA, interfering with metabolism & possibly cell wall synthesis
Nitrofurantoin pharmacology
Renal excretion (does NOT penetrate renal tissue)
Nitrofurantoin contraindication
CrCl <60
- BUT new data suggests short term use is safe & effective if CrCl >30
Nitrofurantoin ADRs
Acute -> chronic pulmonary toxicity/fibrosis
Microbial coverage of nitrofurantoin
GNB & enterococci
Microbial resistance to nitrofurantoin
- E. coli <2%
- Klebsiella 1/3
Clinical indications for nitrofurantoin
- Lower UTI (cystitis)
- Prophylaxis of recurrent UTI
Fosfomycin MOA
Irreversibly binds pyuvyl transferase (enzyme in early step of bacterial cell wall synthesis)
Fosfomycin pharmacology
- Excreted unchanged in the urine
- Bacteriocidal
- May ↓ bacterial adhesion to urothelial cells
Microbial coverage of fosfomycin
GNB & enterococci / staph
- Includes MDR/EBSL CRE (GNBs) & VRE/MRSA; +/- for pseudomonas
Most E. coli is resistant OR susceptible to fosfomycin
Susceptible!
Clinical indications for fosfomycin
Uncomplicated cystitis (3g powder dissolved in water)
Two ABX derived from rifampin
- Rifaximin
- Rifamycin
Route of rifaximin, rifamycin
PO (non-absorbed)
Rifaximin, rifamycin MOA
Inhibit bacterial RNA synthesis
Clinical indications for rifaximin, rifamycin
- Noninvasive E. coli causing traveler’s diarrhea (NOT effective if bloody stool or fever)
- Prevention of hepatic encephalopathy in pts. w/ CLD
- IBS-D
Microbial coverage of chloramphenicol
- H. flu
- S. pneumo
- N. meningitides
- Some anaerobes
Chloramphenicol pearl
Reaches therapeutic levels in the CNS (used as last resort in CNS infections)
Why is chloramphenicol rarely used?
Toxicities: bone marrow suppression and possibly fatal aplastic anemia
1st gen anti-mycobacterial agents
- Rifampin (RIF)
- Isoniazid (INH)
- Pyrazinamide (PZA)
- Ethambutol (ETH)
2nd gen anti-mycobacterial agents
- Streptomycin
- Kanamycin
- Amikacin
- Levofloxacin
- Moxifloxacin
- Capreomycin
- Cycloserine
- Ethionamide
- Aminosalicyclic acid
Rifampin MOA
Inhibits RNA polymerase (protein synthesis)
Rifampin is an INDUCER of
MOST CYP enzymes (remember: 2C9, 3A4)
Clinical indications of rifampin
- Active Tb
- Latent Tb (alternative option)
- Meningococcal meningitis prophylaxis
Rifampin ADRs
- Red lobster syndrome
- Hepatitis
- Flu-like illness
Isoniazid MOA
Inhibits synthesis of mycolic acids
Isoniazid is an INHIBITOR of
MOST CYP enzymes (remember: 2D6, 3A4)
Acetylation determines blood concentration of isoniazid and is controlled by
Genetics
Rapid acetylators of isoniazid are more likely to get…
Hepatitis (↑ w/ ETOH)
Slow acetylators of isoniazid are more likely to get…
Peripheral neuropathy (↓ risk w/ vitamin B6)
Clinical indications of isoniazid
- Latent Tb (drug of choice)
- Component of active Tb tx
Clinical indication of pyrazinamide
Component of active Tb tx
Pyrazinamide ADRs
- Non-gouty polyarthralgias (tx w/ NSAIDs)
- Asymptomatic hyperuricemia
- Dose-related hepatitis
Ethambutol MOA
Inhibits cell wall synthesis
Clinical indications of ethambutol
Component of active Tb tx
Ethambutol ADR
Dose-related optic neuritis
Pathogenesis of ethambutol-induced optic neuritis
ETH is a metal chelator
- Chelation of copper or zinc though to play a role
- Supplementation does not help
Sx of ethambutol-induced optic neuritis
- ↓ visual acuity/color discrimination (red, green)
- Constricted fields
- Scotoma
- can lead to irreversible blindness
Management of pt. on ethambutol
Monthly f/u with ophthal for monthly visual acuity & color perception checks
