Misc Antibiotics Flashcards
Fluoroquinolones
Ciprofloxacin (Cipro) - MC Levofloxacin (Levaquin) - MC Moxifloxacin (Avelox) - MC Gemifloxacin (Factive) Norfloxacin (Noroxin) Ofloxacin (Floxin) - otitis externa
PK of Fluoroquinolones
Distribution: tissue and fluids except CNS
Elimination: renal except moxifloxacin
Half-life: 4-12 hours
Fluoroquinolone MOA and Resistance
Inhibit ability of DNA gyrase and/or topoisomerase IV - inhibit ability of the bacterial DNA to replicate
Resistance: spontaneous mutations in genes of DNA gyrase or topoisomerase IV to reduce FQ affinity
Plasmid mediated
Fluoroquinolones SOA
Aerobic Gm neg. = all FQs
Pseudomonas aeruginosa = cipro and levo
Gm pos. streptococcus sp (respiratory) = levo, moxi, gemi
Anaerobic = moxifloxacin
Fluoroquinolone Clinical uses
UTI - cipro pneumonia - levo, moxi, gemi STI skin and soft tissue infx GI infections - good gm. neg coverage traveler's diarrhea - cipro osteomyelitis
Fluoroquinolones BBW
spontaneous tendon rupture
Esp. if >60 years, on corticosteroids, or kidney, heart, or lung transplants
Fluoroquinolones SE
nausea, diarrhea, dizziness, confusion, tendonitis, myopathy, peripheral neuropathy, aortic dissection/aneurysm, tendon rupture, QT prolongation
Fluoroquinolones drug interactions
Cipro = potent 1A2 inhibitor –> theopyhlline, warfarin, tizanidine, propranolol
Antacids, sucralfate, magnesium, calcium, iron = decreased absorptions of FQs
Fluoroquinolones Pseudomonas and special populations
Only oral agent against pseudomonas
Pregnancy and Lactation: exposure to infant
Peds: arthropathy and osteochondrosis
Caution in hepatic dysfunction
Sulfonamides
Sulfamethoxazole/Trimethoprim (SMX-TMP, Bactrim DS, Septra)
Good distribution to body tissues, CSF, pleural fluid, synovial fluid
Eliminated through liver and kidneys
Sulfonamide MOA and Resistance
Folic acid synthesis inhibitors to inhibit DNA synth
Mutations result in additional production of PABA, changes in enzyme binding sites for sulfonamids
Plasmid mediated
Sulfonamide SOA and Clinical Uses
SOA: no anaerobic coverage, wide Gm + and - coverage
Uses: UTI, toxoplasmosis, MRSA, PCP or PJP in AIDS, sinusitis and otitis media but not recommended
Sulfonamide SE
SE: rash, fever, NVD, SJS, vasculitis, thrombocytopenia
W/ G6PD deficiency = hemolytic anemia
SJS
cell death causes the dermis and epidermis to separate
Hypersensitivity reaction of skin and mucous membranes
Sulfonamide DI
up to 70% protein bout = displaces other drugs
Potentiates the effects of warfarin, phenytoin, hypoglycemic agents, methotrexate
Sulfonamide Excretion and special populations
Metabolized in liver Renally excreted - reduce dose by 50% if CrCl = 15-30 mL/min Don not use if CrCl < 15 mL/min Not for children < 2 mo Oral only Pregnancy Category C - CI at term due to kernicterus in infants Good for MRSA Do not use if sulfa allergy
Nitrofurantoin (Macrobid) Indications and PK
treatment and prevention of uncomplicated UTIs
PO = oral only
Rapidly absorbed = only in serum for 30 min then to urine
Cleared renally - only give if GFR normal
Macrobid MOA and indications
Disrupts bacterial cell wall synthesis through inhibition of bacterial enzymes
Effective against: E. coli, citrobacter, Staph saprophyticus, Enterococcus
Some eneterobacter and klebsiella resistance
Good for uncomplicated cystitis and lower UTI
Macrobid SE
MC: nausea and vomiting
Pulmonary reactions: pulmonary infiltrates, pneumonitis, pulmonary fibrosis
Hepatic effects: hepatitis, hepatic necrosis
Peripheral neuropathy
Macrobid Special Populations
No significant DI
Pregnancy Cat B - CI at term due to hemolytic anemia in neonate
Not for lactation
Safety and efficacy not established in <12 years & CI < 1 mo
Pulmonary toxicity = avoid in older adults and long term use
Metronidazole (Flagyl) PK/PD and MOA
Metabolized in liver - adjust for liver failure
Absorbed well PO
Good tissue penetration
Half-life 6-9 hrs
MOA: inhibits bacterial protein synthesis by causing DNA strand breakage
Flagyl SOA and Indications
SOA: Gm + and - anaerobes
C. diff, Giardia, H. pylori, trichomoniasis, BV
DOC for anaerobic infections, BV, trichomoniasis, C. diff
Flagyl Formulations
Oral
IV
Topical (roseacea)
Intravaginal
Flagyl Warning and SE
Warning: carcinogenic in mice and rats
SE: NV, abdominal pain, metallic taste, seizure w/ high doses, peripheral neuropathy w/ prolonged courses, pancreatitis
Flagyl DI
Enhances anticoag effect of warfarin
Alcohol: flushing, palpitations, nausea, vomiting
Inhibitor of 3A4 - DI with phenobarbital, phenytoin, rifampin = increased flagyl metabolism
Vancomycin type, MOA, resistance, ROA,
glycopeptide
inhibits cell-wall biosynthesis, alters cell membrane permeability, and RNA synthesis
Inhibits biosynthesis of peptidoglycan - complexes with D-ala-D-ala sequence to inhibit transpeptidation/cross-linking
Resistance occurs by substituting d-lactate for d-alanine decreasing affinity x 1000
ROA: IV, oral for C. diff only
Vancomycin SOA and Indications
SOA: Gram + with aminoglycoside Indications: MRSA, PCN allergy patients, failure to respond to other abx, endocarditis, septicemia, bone infections, lower resp. infx DOC for MRSA when IV therapy needed PO 2nd line for C. diff
Vancomycin SE
Rapid administration = red man syndrome - histamine and hypotension
Ototoxicity: transient or permanent
Nephrotoxicity: adjust in renal dysfunction
Vancomycin DI
Aminoglycosides: nephrotoxic effects of aminoglycosides enhanced
Neuromuscular blocking agents: enhance NM blockade
NSAIDs: increase serum concentration of vancomycin
Piperacillin: enhance nephrotoxicity of vanco
Vancomycin Special Populations
Pregnancy: B for oral, C for IV
Lactation: excreted in breast milk IV, less so in oral
Vanco PK/PD
Time-dependent antimicrobial killing - slowly bactericidal = AUC/MIC correlates with efficacy
Target range: use troughs to ensure efficacy
Absorption: bowel inflammation increases systemic oral absorption
Distributes widely except CSF, only crosses BBB with inflammation
50% protein binding
Eliminated 80-90% in urine unchanged
Half-life = 5-11 hours
