Antibiotics 1 Flashcards
Ciprofloxacin (otic)
Cipro HC, Cipro XR
Ciprofloxacin (oral)
Cipro, Cipro Xr
Gatifloxacin (ophthalmic)
Zymar, Zymaxid
Levofloxacin
Levaquin
Moxifloxacin (ophthlamic)
Vigamox
Moxifloxacin (oral)
Avelox
Nitrofurantoin
Macrodantin, Macrobid
Sulfamethoxazole/Trimethoprim (SMZ/TMP)
Bactrim, Septra
Mupirocin
Bactroban
Therapeutic Class - Ciprofloxacin (otic)
Fluoroquinolone antibiotic
Therapeutic Class - Ciprofloxacin (oral)
Fluoroquinolone antibiotic
Therapeutic Class - Gatifloxacin (ophthalmic)
Fluoroquinolone antibiotic
Therapeutic Class - Levofloxacin
Fluoroquinolone antibiotic
Therapeutic Class - Moxifloxacin (ophthalmic)
Fluoroquinolone antibiotic
Therapeutic Class - Moxifloxacin (oral)
Fluoroquinolone antibiotic
Therapeutic Class - Nitrofurantoin
Nitrofuran antibiotic
Therapeutic Class - SMZ/TMP
Sulfonamide antibiotic
Therapeutic Class - Mupirocin
Topical antibacterial
Dosage Forms - Ciprofloxacin
IR Tablet: 100, 250, 500, 750 mg
ER Tablet: 500, 1000 mg
Oral Suspension: 250 mg/5 mL, 500 mg/5 mL
Otic Solution: 0.2%
Otic Suspension: 6 %
Dosage Forms - Gatifloxacin
Ophthalmic Solution: 0.5%
Dosage Forms - Levofloxacin
IR Tablet: 250, 500, 750 mg
Oral Solution: 25 mg/mL
Dosage Forms - Moxifloxacin
IR Tablet: 400 mg
Ophthalmic Solution: 0.5%
Dosage Forms - Nitrofurantoin
IR Capsule: 25, 50, 100 mg
Oral Suspension: 25 mg/5 mL
Dosage Forms - SMZ/TMP
IR Tablet: 400 mg/80 mg (SS = Single Strength), 800 mg/160 mg (DS = Double Strength) Oral Suspension (per 5 mL): 200 mg/40 mg
Dosage Forms - Mupirocin
ALL 2%
Topical Ointment
Topical Cream
Nasal Ointment
MOA - Ciprofloxacin
Inhibits bacteria DNA gyrase, an enzyme responsible for the unwinding of DNA for transcription and subsequent supercoiling of DNA for packaging into chromosomal subunits
Activity - Ciprofloxacin
Broad-spectrum
Highly active against aerobic, Gram (-) bacilli
FDA-Approved Indications - Ciprofloxacin (otic)
- Otitis externa, acute (adults and children >1 year of age): 0.25 mL (entire single-use container) into affected ear(s) BID (approximately q12h) x 7 days
- Otitis media with effusion: 0.1 mL (6 mg) once intratympanically to each affected ear following suctioning of middle ear effusion during tympanostomy tube placement
FDA-Approved Indications - Ciprofloxacin (oral)
- Anthrax, post-exposure prophylaxis
Adults - 500 mg q12h x at least 60 days
Children - 15 mg/kg BID x at least 60 days, max 500 mg/dose - Bacterial prostatitis, chronic: 500 mg q12h x 28 days
- Bronchitis, lower respiratory tract infection, infection of bone, skin, or soft tissue, sinusitis: 500-750 mg q12h x 7-14 days
- UTI: 250-500 mg q12h x 3 days (IR); 500 mg q24h x 3 days (ER)
Off-Label Uses - Ciprofloxacin (oral)
- Traveler’s diarrhea: 750 mg as a single dose (mild); 500 mg BID x 3 days (sever)
- Diabetic foot infection: 500 mg q12h (750 mg q12h if P. aeruginosa is suspected), duration dependent
MOA - Gatifloxacin
Inhibits bacterial DNA gyrase and topoisomerase IV
Activity - Gatifloxacin
Broad-spectrum
Highly active against aerobic, gram-negative bacilli, especially Enterobacteriaceae
Has poor activity against streptococci and anaerobes
FDA-Approved Indications - Gatifloxacin (ophthalmic)
- Bacterial conjunctivitis (adults and children > 1 year): 0.5 % ophthalmic solution - 1 drop into affected eye(s) q2h while awake on day 1 (MAX 8 doses/day), then QID while awake for 6 more days
MOA - Levofloxacin
Inhibits bacterial DNA gyrase, an enzyme responsible for the unwinding of DNA for transcription and subsequent supercoiling of DNA for packing into chromosomal subunits
Activity - Levofloxacin
Broad-spectrum
Highly active against aerobic, gram-negative bacilli
FDA-Approved Indications - Levofloxacin
- Bacterial prostatitis, chronic: 500 mg QD x 28 days
- Bacterial sinusitis, acute: 750 mg QD x 5 days
- Bronchitis, chronic, acute bacterial exacerbation: 500 mg QD x 7 days
- Community-acquired pneumonia: 500 mg QD x 7-14 days, or 750 mg QD x 5 days
- Infection of skin and/or subcutaneous tissue (uncomplicated): 500 mg QD x 7-14 days
- Pyelonephritis, acute: 250 mg QD x 10 days
Off-Label Uses - Levofloxacin
- Chlamydial inflection: 500 mg QD x 7 days
2. Traveler’s diarrhea: 500 mg QD x 1-3 days
MOA - Moxifloxacin
Inhibits bacterial topoisomerase II and IV
Activity - Moxifloxacin
Broad-spectrum
Anaerobes
Effective for respiratory tract infections caused by S. pneumoniae, H. influenzae, and others
FDA-Approved Indications - Moxifloxacin (ophthalmic)
- Bacterial conjunctivitis (adults and children >4 months of age): 1 drop into affected eye(s) BID (Moxeza) or TID (Vigamox) x 7 days
FDA-Approved Indications - Moxifloxacin (oral)
- Acute bacterial exacerbation of chronic bronchitis: 400 mg QD x 5 days
- Bacterial sinusitis, acute: 400 mg QD x 10 days
- Community-acquired pneumonia: 400 mg QD x 7-14
- Infection of skin and/or subcutaneous tissue: 400 mg QD x 7-21 days
- Complicated intra-abdominal infections: 400 mg QD x 5-14 days
Off-Label Uses - Moxifloxacin (oral)
- Tuberculosis: 400 mg QD x 6 months
MOA - Nitrofurantoin
Synthetic nitrofuran inactivates bacterial ribosomes and is bactericidal in urine at therapeutic doses
Activity - Nitrofurantoin
Active against most bacteria that cause UTIs except nearly all strains of Pseudomonas are resistant
FDA-Approved Indications - Nitrofurantoin
- UTI treatment (adults and children >12 years of age): Macrobid 100 mg BID x 5-7 days; Furadantin, Macrodantin 50-100 mg q6h x 5-7 days
- UTI treatment (children >1 month of age): 5-7 mg/kg/day in divided doses q6h x 7 days (max 400 mg/day)
- UTI prophylaxis (adults): 50-100 mg QHS
- UTI prophylaxis (children > 1 month of age): 1 mg/kg/day in divided doses every 12-24 hours (max dose 100 mg/day)
Off-Label Uses - Nitrofurantoin
- Asymptomatic bacteriuria in pregnancy: 100 mg BID x 4-7
MOA - SMZ/TMP
SMZ competitively inhibits the synthesis of dihydropteroic acid (an inactive folic acid precursor) in microorganisms. TMP inhibits the enzymatic reduction of dihydrofolic acid to tetrahydrofolic acid. The combination is active against many bacteria and P. carinii. SMZ/TMP has in vitro activity against MRSA, but clinical success has been variable and unpredictable
FDA-Approved Indications - SMZ/TMP
- Acute infective exacerbation of COPD: 800 mg SMZ and 160 mg TMP q12h x 3-7 days
- HIV infection, Pneumocystis pneumonia: 1600 mg SMZ and 320 mg TMP BID x 21 days
- HIV infection, Pneumocystis pneumonia, prophylaxis (adults): 800 mg SMZ and 160 mg TMP QD
- HIV infection, Pneumocystis pneumonia, prophylaxis (children > 1 month of age): 750 mg/m^2/day SMZ and 150 mg/m^2/day TMP in 2 divided doses 3 times/week on consecutive days
- Traveler’s diarrhea: 800 mg SMZ/160 mg TMP BID x 5 days
- UTI (adult): 800/160 BID x 10-14 days
- UTI (children > 2 months of age): 8 mg/kg TMP component/day BID x 10 days
Off-Label Uses - SMZ/TMP
- Sinusitis: 800 mg/160 mg BID x 10-14 days
2. Prostatitis: 800 mg/160 mg BID x 4-6 weeks
MOA - Mupirocin
Inhibits bacterial protein synthesis by reversibly and specifically binding to bacterial isoleucyl transfer-RNA synthetase. Because of this unique mechanism, mupirocin demonstrates no in vitro cross-resistance with other classes of antimicrobial agents
FDA-Approved Indications - Mupirocin
- Impetigo: apply topically TID x 3-5 days, reevaluate if no response
- Secondary skin infections: apply topically TID x 10 days, reevaluate if no response in 3-5 days
- Eradication of nasal colonization of MRSA during institutional outbreaks: apply 1/2 of single use tube to each nostril BID x 5 days
Off-Label Uses - Mupirocin
- Surgical prophylaxis in MRSA carriers: apply 1/2 of single tube to each nostril BID x 5 days
Kinetics - Ciprofloxacin (oral)
Absorption: F = 50-80%, minor food effect
Distribution: widespread (bile, CSF, gyn tissue, liver, lung, prostate, peritoneum, synovial fluid, sputum, etc)
Metabolism: not metabolized; P-gp substrate, strong inhibitor of CYP1A2
Elimination: renal 30-57%; T1/2 = 3-6 hours
Hepatic Dose Adjustment: none
Renal Dose Adjustment: CrCl 30-50 mL/min = 250-500 mg q12; CrCl 5-29 mL/min = 250-500 mg q18h
Kinetics - Levofloxacin
Absorption: F = 99%, no food effect, take without regard to meals
Distribution: widespread (bile, blister, CSF, gyn tissues, lung, prostate, synovial fluid, sputum, tonsils)
Elimination: renal 87%; T1/2 = 6-8 hours
Hepatic Dose Adjustment: none
Renal Dose Adjustment: CrCl 20-50 mL/min = reduce dose by 50%; CrCl 5-19 mL/min = extend dosing interval to q48h
Kinetics - Moxifloxacin (oral)
Absorption: F = 90%, no food effect, take without regard to meal
Distribution: Vd = 1.7-2.7 L/kg; abdominal tissue, bronchial mucosa, CSF, sinus, sputum; 30-50% protein binding
Metabolism: 52% hepatic via glucuronide and sulfate conjugation
Elimination: renal 20%; T1/2 of 12 h
Hepatic and Renal Dose Adjustment: none
Kinetics - Nitrofurantoin
Absorption: F = 94%, food increases absorption
Distribution: 60-90% protein bound
Metabolism: in all tissues to inactive metabolite
Elimination: renal 20-25%; T1/2 = 1 hour
Hepatic Dose Adjustment: none
Renal Dose Adjustment: contraindicated if CrCl <60 mL/min
Kinetics - SMZ/TMP
Absorption: F = 90%, no effect of food on absorption
Distribution: CSF, middle ear fluid, sputum, and vaginal fluid
Metabolism: hepatic >90%, TMP is CYP2C9 and CYP3A4/5 substrate; TMP is moderate inhibitor of CYP2C8 and CYP2C9
Elimination:
SMZ - renal 10-30%; T1/2 = 8-11 hours
TMP - renal 50-75%; T1/2 = 6-17 hours
Hepatic Dose Adjustment: none
Renal Dost Adjustment: CrCl 15-30 mL/min = reduce dose by 50%; CrCl <15 mL/min = avoid, or reduce by 50% and increase interval to 24 hour
Drug Interactions - SMZ/TMP
- CYP3A4 and CYP3A5 inducers/inhibitors
- CYP2C8 and CYP2C9 substrates
- Agents that prolong QTc interval/antiarrhythmics - increased risk for arrhythmia (avoid use when possible)
- Methotrexate - synergistic antifolate effects (avoid use or monitor closely)
Drug Interactions - Nitrofurantoin
- Fluconazole - increased risk for hepatic and pulmonary toxicity, mechanism unknown (avoid use or monitor closely)
Drug Interactions - Oral Fluoroquinolones
- Di- and trivalent cations (Ca++, etc.), iron, sevelamer = decreased absorption by chelation (take 2 hour before or 6h after)
- Antidiabetic agents = hypo-and hyperglycemia, mechanism unknown (monitor closely)
- Corticosteroids = increased risk for tendon rupture (avoid concomitant use when possible)
- Warfarin - increased bleed risk (monitor INR closely)
- Agents that prolong QTc interval/antiarrhythmics - increased risk for arrhythmia (avoid use)
- Ciprofloxacin interacts with P-gp inducers/inhibitors
Ciprofloxacin in Pregnancy/Lactation
Pregnancy: category C
2.
Lactation: weigh risks and benefits
Gatifloxacin in Pregnancy/Lactation
Pregnancy: category C
Lactation: weigh risks and benefits
Levofloxacin in Pregnancy/Lactation
Pregnancy: category C
Lactation: avoid
Moxifloxacin in Pregnancy/Lactation
Pregnancy: category C
Lactation: avoid
Nitrofurantoin in Pregnancy/Lactation
Pregnancy: category B
Lactation: usually safe
SMZ/TMP in Pregnancy/Lactation
Pregnancy: avoid in pregnancy due to risk for malformations
Lactation: weigh risks vs. benefits
Mupirocin in Pregnancy/Lactation
Pregnancy: category B
Lactation: weigh risks vs. benefits
Black Box Warning - Ciprofloxacin
May exacerbate muscle weakness in patients with myasthenia gravis, tendon inflammation and rupture, peripheral neuropathy, CNS effects, cardiac dermatologic and hypersensitivity reactions, aortic dissection and rupture, hypoglycemia, mental health adverse effects
Black Box Warning - Levofloxacin
May exacerbate muscle weakness in patients with myasthenia gravis, tendon inflammation and rupture, peripheral neuropathy, CNS effects, cardiac, dermatologic and hypersensitivity reactions, aortic dissection and rupture
Black Box Warning - Moxifloxacin
May exacerbate muscle weakness in patients with myasthenia gravis, tendon inflammation and rupture, peripheral neuropathy, aortic dissection and rupture, hypoglycemia, delirium (oral only)
Contraindications - Ciprofloxacin
Concomitant tizanidine with oral ciprofloxacin, hypersensitivity to any fluoroquinolone
Contraindications - Gatifloxacin
Hypersensitivity to any fluoroquinolone
Contraindications - Levofloxacin
Hypersensitivity to any fluoroquinolone
Contraindications - Moxifloxacin
Hypersensitivity to any fluoroquinolone
Contraindications - Nitrofurantoin
Hypersensitivity to nitrofurantoin, use in neonates or pregnant patients at term (38-42 wk) due to risk of hemolytic anemia, anuria or oliguria
Contraindications - SMZ/TMP
Hypersensitivity to sulfonamides, children <2 mo, pregnant patients at term, megaloblastic anemia due to folate deficiency, history of drug-induced thrombocytopenia with use of sulfonamides or trimethoprim, marked hepatic damage or severe renal disease, concomitant administration with dofetilide
Contraindications - Mupirocin
Hypersensitivity
Beers Criteria - Nitrofurantoin
Avoid in renal dysfunction, avoid long-term use
Adverse Effects - Ciprofloxacin (oral)
Common: tooth discoloration in infants, musculoskeletal signs and symptoms
Less common: N/V/D, rash, myalgia, arthralgia, tendonitis, headache, dizziness
Rare but serious: SJS, renal failure, anemia, neutropenia, thrombocytopenia, seizure, cardiac effects, liver failure, myasthenia gravis, tendon rupture, renal failure psychosis, QTc prolongation, peripheral neuropathy, CNS effects, severe cardiac, dermatologic, and hypersensitivity reactions
Adverse Effects - Ciprofloxacin (otic)
Common: application site pain/itching
Less common: fungal ear superinfection
Rare but serious: hypersensitivity reaction
Adverse Effects - Gatifloxacin
Common: none
Less common: Conjunctivitis, dry eyes, eye pain, subconjunctival hemorrhage, tearing and burning of the eyes, decreased visual acuity
Rare but serious: conjunctival hemorrhage
Adverse Effects - Levofloxacin
Common: photosensitivity
Less common: N/V, rash, myalgia, arthralgia, tendonitis, headache
Rare but serious: Stevens-Johnson syndrome, renal failure, severe hypersensitivity, anemia, neutropenia, thrombocytopenia, seizure, cardiac arrest, cardiac arrhythmias, liver failure, tendon rupture, psychosis, glucose abnormalities,C. difficilecolitis, peripheral neuropathy, CNS effects, severe cardiac, dermatologic and hypersensitivity reactions
Adverse Effects - Moxifloxacin (oral)
Common: none known
Less common: N/D, dizziness, headache
Rare but serious: Stevens-Johnson syndrome, renal failure, severe hypersensitivity, anemia, neutropenia, thrombocytopenia, seizure, cardiac arrhythmias, liver failure, tendon rupture, psychosis, exacerbation of myasthenia gravis, peripheral neuropathy, CNS effects, severe cardiac, dermatologic and hypersensitivity reactions
Adverse Effects - Moxifloxacin (ophthalmic)
Common: none known
Less common: Conjunctivitis, dry eyes, eye pain, subconjunctival hemorrhage, tearing and burning of the eyes, decreased visual acuity
Rare but serious: fungal or bacterial ocular superinfection
Adverse Effects - Nitrofurantoin
Common: discoloration of urine
Less common: D/N, headache, superinfection
Rare but serious: Severe hypersensitivity, hepatic failure, hemolytic anemia, interstitial lung disease
Adverse Effects - SMZ/TMP
Common: D/N
Less common: skin rash, urticaria
Rare but serious: Severe hypersensitivity, renal failure, hepatic failure, pancytopenia, arrhythmias, Stevens-Johnson syndrome, hyperkalemia, hypoglycemia, hemolytic anemia
Adverse Effects - Mupirocin
Common: none known
Less common: headache, pruritis, burning at site of application, stinging sensation, rhinitis
Rare but serious: C. difficile diarrhea
Drug Monitoring - Ciprofloxacin
Efficacy: resolution of signs and symptoms of infection
Toxicity (systemic): renal function, baseline SCr
Toxicity (otic): secondary fungal infection, topical reactions
Drug Monitoring - Gatifloxacin
Efficacy: resolution of signs and symptoms of infection
Toxicity: topical reactions
Drug Monitoring - Levofloxacin
Efficacy: resolution of signs and symptoms of infection
Toxicity: renal function, baseline SCr
Drug Monitoring - Moxifloxacin
Efficacy: resultion of signs and symptoms of infection
Toxicity (systemic): renal function, baseline SCr
Toxicity (otic): topical reactions
Drug Monitoring - Nitrofurantoin
Efficacy: resolution of clinical signs and symptoms within 2-3 days
Toxicity: Severe diarrhea, yellowing of skin or eye, unusual bruising or bleeding, blistering skin rash, or shortness of breath. Signs of pulmonary reaction, numbness or tingling of extremities. With long-term use, CBC, LFTs, SCr.
Drug Monitoring - SMZ/TMP
Efficacy: resolution and improvement of clinical signs of infection within 2-3 days
Toxicity: monitor renal function (SCr), potassium in those with concurrent ACEIs. Monitor FBG with concurrent sulfonylureas, insulin. CBC monthly if using for PCP prophylaxis.
Drug Monitoring - Mupirocin
Efficacy: resolution of clinical signs of infection within 3-5 days, eradication of nasal colonization
Toxicity: seek medical attention if local adverse effects are severe
Counseling and Pearls - General Fluoroquinolones (oral)
Counseling:
- Seek medical attention immediately for any s/s of serious adverse effects, such as blistering skin rash or extreme fatigue, unusual bruising or bleeding, shortness of breath or chest pain, tendon pain, muscle weakness, a “pins and needles” tingling or pricking sensation, numbness in the arms or legs, confusion or hallucinations.
- May take with or without food, but do not take with dairy products no any other food containing high calcium
- Separate from antacids, vitamins/minerals, sucralfate, or other chelating agents by 2hrs before or 6hrs after
- If tendon pain occurs, stop use and seek medical attention
- Shake ciprofloxacin oral suspension well before use
- Ciprofloxacin oral suspension may be stored at room temperature
Pearl
- Not approved for use in children <18 yrs (except cipro for anthrax or complicated UTI)
- Increased risk of tendon rupture in patients >60 y of age
- Due to risk of adverse reactions and availability of alternatives, patients with common infections (acute bacterial sinusitis, acute uncomplicated cystitis, etc) should not receive quinolone therapy
- Medication guide required at dispensing
Counseling and Pearls - General Fluoroquinolones (otic, ophthalmic)
Counseling
- May warm solution in hands for 1 minute prior to administration
- Complete full course of therapy even if symptoms improve
- Otic: administer with affected ear upward, maintain position for at least 1 minute after instillation
- Ophthalmic: Wash hands with soap and water before/after use. Lie down or tilt head back. With index finger, pull down the lower lid of eye to form a pocket. Hold the dropper close to eye, but not touching, with the other hand. Drop the correct number of drops into the pocket between lower lid and eyeball. Gently close eyes. Place index finger over inner corner of eye for 1 min. Do not rinse or wipe the dropper or allow it to touch anything, including eye
Pearls
- Ciprofloxacin otic is not approved in children <1 y of age, not for ophthalmologic use, otic use only
- Intratympanic cipro product for use only during tympanostomy tube placement
- Available in otic formulation in combination with hydrocortisone (Cipro HC)
- Bacterial conjunctivitis is very contagious and spread by direct contact
Counseling and Pearls - General Fluoroquinolones (otic, ophthalmic)
Counseling
- May warm solution in hands for 1 minute prior to administration
- Complete full course of therapy even if symptoms improve
- Otic: administer with affected ear upward, maintain position for at least 1 minute after instillation
- Ophthalmic: Wash hands with soap and water before/after use. Lie down or tilt head back. With index finger, pull down the lower lid of eye to form a pocket. Hold the dropper close to eye, but not touching, with the other hand. Drop the correct number of drops into the pocket between lower lid and eyeball. Gently close eyes. Place index finger over inner corner of eye for 1 min. Do not rinse or wipe the dropper or allow it to touch anything, including eye
Pearls
- Ciprofloxacin otic is not approved in children <1 y of age, not for ophthalmologic use, otic use only
- Intratympanic cipro product for use only during tympanostomy tube placement
- Available in otic formulation in combination with hydrocortisone (Cipro HC)
- Bacterial conjunctivitis is very contagious and spread by direct contact
Counseling and Pearls - Nitrofurantoin
Counseling
- May make urine brown or red-tinged; this is not harmful and is a breakdown product of the drug
- Complete full course of therapy.
- For the suspension, shake well and store at room temperature, use within 30 days
- Avoid mixing suspension with food or beverages, but food can be taken afterward
- Symptoms should improve within 2-3 days; if they worsen, seek follow-up care
Pearls
- Nitrofurantoin does not reach effective levels in tissue and is only indicated for UTIs (not pyelonephritis)
- May resume normal activities after 24 h of antibiotics if afebrile
- Used to prevent recurrent UTIs but is also effective in the treatment of uncomplicated UTIs
Counseling and Pearls - SMZ/TMP
Counseling
- Complete full course of therapy
- Symptoms should improve in 2-3 days; if they worsen, seek follow-up with health-care practitioner
- For suspension, shake well and store at room temperature and protect from light
- May cause photosensitivity; use sunscreen
- Maintain adequate hydration during therapy to prevent kidney complications
- Seek medical attention for severe diarrhea, dark urine, yellowing of skin or eye, unusual bruising or bleeding, blistering skin rash, or shortness of breath
Pearls
- Avoid use in patients with G6PD deficiency (increased risk of hemolytic anemia)
- Preferred agent forPneumocystispneumonia prevention in HIV-infected patients when CD4 count is <200
Counseling and Pearls - Mupirocin
Counseling: instruct patient on proper application technique. Avoid drug exposure to open wounds, burns, or eyes
Pearls: the area treated may be covered with gauze dressing if desired