Antibiotics Flashcards
Penicillins: drug interactions
Probenecid - increases levels of beta lactams by inhibiting their excretion. This is sometimes done intentionally.
Methotrexate - penicillins can increase the concentration of MTX
Warfarin - peniciilins EXCEPT nafcillin and dicloxacillin can enhance the anticoagulant effect of warfarin by inhibiting the production of clotting factors. Nafcillin and dicloxacillin can inhibit the anticoagulant effect of warfarin because they are CYP inducers.
Which penicillin is a vesicant?
Nafcillin; use cold packs and hyaluronidase injections
Penicillins: side effects (8)
- Seizures (with accumulation); must renally dose adjust
- GI upset, diarrhea
- Rash - including SJS/TEN and allergic reactions
- Anaphylaxis
- Hemolytic anemia; identified with positive Coombs test
- Myelosuppression with prolonged use
- Renal failure
- Increased LFTs
Penicillins: monitoring
Renal function
Symptoms of anaphylaxis
CBC and LFTs with prolonged courses
Penicillins: contraindications
All penicillins: type 1 hypersensitivity reaction to other penicillin or beta lactams
Amp/sulbactam and Amox/Clav: history of cholestatic jaundice or hepatic dysfunction with prior use
Extended-release forms of amoxicillin and amox/clav: severe renal impairment (CrCl < 30) - do not use extended-release forms (Augmentin XR) or the 875 mg dose of amox/clav
Which penicillin has a boxed warning and why?
Penicillin G benzathine: not for IV use, can cause cardiorespiratory arrest and death. IM use only.
Antistaphylococcal penicillins are preferred for…
MSSA soft tissue, bone and joint, endocarditis, and bloodstream infections
Cephalosporins: contraindications
Ceftriaxone: hyperbilirubinemic neonates; causes biliary sludging and kernicterus
Ceftriaxone: concurrent use with calcium-containing IV products in neonates
Cephalosporins: warnings
Cross-reactivity with penicillin allergy (< 10%)
Cefotetan has a side chain that can increase the risk of bleeding and cause a disulfiram-like reaction with alcohol ingestion
Cephalosporins: side effects (8)
- Seizures (with accumulation); must renally dose adjust
- GI upset, diarrhea
- Rash, allergic reactions, anaphylaxis
- Serious skin reactions (SJS/TEN)
- Hemolytic anemia; identified with positive Coombs
- Drug fever
- Myelosuppression with prolonged use
- Increased LFTs
Cephalosporins: monitoring
Renal function
Symptoms of anaphylaxis
CBC, LFTs
Which cephalosporin is available as a chewable tablet?
Cefixime
Which cephalosporine has activity against MRSA?
Ceftaroline
Ertapenem is the Exception because…
It has no activity against PEA: Pseudomonas, Enterococcus, or Acinetobacter
Carbapenems: contraindications
Anaphylactic reactions to other beta lactams
Carbapenems: warnings
Do not use with penicillin allergy
CNS adverse effects - states of confusion and seizures; highest risk with imipenem/cilastatin, large doses, and renal impairment
Doripenem: do not use for treatment of pneumonia, including HAP and VAP
Carbapenems: monitoring
Renal function
Symptoms of anaphylaxis
CBC, LFTs
Carbapenems: drug interactions
Valproic acid (divalproex, etc.): carbapenems decrease serum valproic acid concentrations, leading to loss of seizure control - avoid combination
Drugs that lower seizure threshold (clozapine, quinolones, bupropion, tramadol)
Ertapenem can only be diluted with…
normal saline
Cephalosporins: drug interactions
Ceftriaxone and calcium-containing IV products: precipitates form when used together. Concurrent use is contraindicated in neonates. In adults, avoid simultaneous administration and flush line between each product.
Drugs that decrease stomach acid and oral cephalosporins: decreased bioavailability of cephalosporin. Cefuroxime, cefpodoxime, and cefdinir should be separated by 2 hours from antacids. Avoid H2RAs and PPIs.
Aminoglycosides demonstrate … activity
Concentration-dependent
If a patient is underweight, how do you dose an aminoglycoside?
Total body weight
If a patient is obese, how do you dose an aminoglycoside?
Adjusted body weight
Using traditional dosing, what is the dose (mg/kg) of gentamicin or tobramycin for gram-positive infections? Gram-negative infections?
1 mg/kg/dose for gram-positive
2.5 mg/kg/dose for gram-negative
Using extended-interval dosing, what is the dosing range (mg/kg) of gentamicin or tobramycin?
4-7 mg/kg/dose - usually 7 mg/kg
What is Plazomicin used for?
Complicated, MDR gram-negative UTI
Aminoglycosides: boxed warnings (4)
Nephrotoxicity
Ototoxicity - hearing loss, vertigo, ataxia
Neuromuscular blockade and respiratory paralysis - avoid with other neurotoxic/nephrotoxici drugs
Fetal harm if given during pregnancy
Aminoglycosides: warnings
Use caution in patients with impaired renal function, the elderly, and patients taking other nephrotoxic drugs.
Aminoglycosides: monitoring
Drug levels
Renal function, urine output
Hearing tests
When using extended-interval aminoglycoside dosing nomograms, if a level plots on a line, how do you choose the dosing interval?
Round up to the next dosing interval to avoid toxicity
When using traditional aminoglycoside dosing, what is the goal trough of gentamicin or tobramycin when treating a gram-negative infection?
< 2 mcg/mL
“Respiratory quinolones” are…
Why are they called that?
Levofloxacin and moxifloxacin
Because they have enhanced coverage of S. pneumo and atypical pathogens
Which quinolone is active against MRSA and is the preferred quinolone for SSTI caused by MRSA?
Delafloxacin
Can moxifloxacin be used for UTI?
No.
Which quinolone has enhanced gram-positive and anaerobic activity and can be used alone for polymicrobial infections?
Moxifloxacin
Which quinolones have enhanced gram-negative activity and activity against Pseudomonas?
Ciprofloxacin and levofloxacin
Quinolones: boxed warnings (5)
- Tendon inflammation and/or rupture - within hours/days after starting and up to several months after treatment. Increased risk with concurrent steroids, organ transplant patients, and age > 60 years. DC immediately if symptoms occur.
- Peripheral neuropathy - can last months to years after discontinuation, may be permanent. DC immediately if symptoms occur.
- CNS effects - seizures, tremor, restlessness, confusion, hallucinations, depression, paranoia, nightmares, insomnia, increased intracranial hemorrhage. Use caution in patients with CNS disorders or with drugs that cause seizures or lower seizure threshold.
- Avoid in patients with myasthenia gravis - exacerbates weakness
- Use last-line for bacterial sinusitis, acute exacerbation of chronic bronchitis, and uncomplicated UTI
Quinolones: contraindications
Ciprofloxacin: concurrent use with tizanidine
Quinolones: warnings (8)
QT prolongation (highest risk with moxifloxacin) > levofloxacin > ciprofloxacin
Hypo- or hyperglycemia
Psychiatric disturbances
Avoid systemic quinolones in children, pregnancy, and breastfeeding due to musculoskeletal toxicity
Aortic aneurism or dissection - increased risk with longer durations
Photosensitivity
Hepatotoxicity
Crystalluria
Which liquid antibiotic can not be put through an NG or other feeding tube?
Cipro oral suspension; ok to crush tablets and give via feeding tube.
Quinolones: drug interactions (7)
Antacids, polyvalent cations, multivitamins, sucralfate, and bile acid resins - chelation and inhibition of quinolone absorption.
Phosphate binders - lanthanum carbonate and sevelamer - can decrease concentration of PO quinolones; separate by at least 2 hours with lanthanum carbonate, or 6 hours after sevelamer.
Warfarin: quinolones can increase anticoagulant effects of warfarin
Sulfonylureas, insulin, and other hypoglycemic drugs: quinolones can increase effects
QT prolonging drugs, potassium, and magnesium - QT prolongation
Probenecid and NSAIDs - increased quinolone levels
Ciprofloxacin (strong CYP1A2 inhibitor) increased levels of caffeine, theophylline, and tizanidine
Macrolides are commonly used for…
Upper and lower respiratory tract infections, and some STIs chlamydia
Azithromycin “Tri-Pak” dosing
500 mg daily x 3 days
Macrolides: contraindications (3)
- History of cholestatic jaundice or hepatic dysfunction with prior use
- Clarithromycin and erythromycin: do not use with simvastatin and lovastatin pimozide, ergotamine, or dihyrdroergotamine
- Clarithromycin concurrent use with colchicine in patients with renal or hepatic impairment
Macrolides: warnings (4)
QT prolongation (erythromycin > azithromycin > clarithromycin)
Hepatotoxicity
Exacerbation of myasthenia gravis
Clarithromycin - caution in patients with CAD (increased mortality)
Macrolides: side effects (4)
- GI upset (diarrhea, abdominal pain, cramping)
- Taste perversion
- Ototoxicity
- Severe skin reactions (SJS/TEN/DRESS)
Macrolides: drug interactions
Erythromycin and clarithromycin - major substrates of CYP3A4 and are CYP3A4 inhibitors; Contraindicated with simvastatin and lovastatin. Caution with other substrates, including apixaban, colchicine, dabigatran, rivaroxaban, theophylline, and warfarin.
Azithromycin - minor substrate of CYP3A4 and weak CYP1A2 and Pgp inhibitor; fewer clinically significant drug interactions.
All macrolides - caution with CVD, low potassium or magnesium, and with other QT prolonging drugs.
Common uses of doxycycline
CAP, tickborne illnesses, community-acquired MRSA (CA-MRSA) skin infections, chlamydia, COPD exacerbations, bacterial sinusitis, VRE UTI, acne
Tetracyclines: warnings
Children age < 8 years, pregnancy, and breastfeeding: suppresses bone growth and discolors teeth do not use
Photosensitivity
Severe skin reactions (SJS/TEN/DRESS)
GI inflammation/ulceration
Minocycline - drug-induced lupus erythematosus (DILE)
Tetracyclines: side effects
N/V/D, rash
Tetracyclines: monitoring
LFTs, renal function, CBC
Doxycycline/minocycline IV:PO ratio
1:1
Doxycycline oral administration counseling
Take with at least 8oz of water, sit upright for at least 30 minutes to avoid esophageal irritation
Tetracycline drug interactions
Antacids, polyvalent cations, multivitamins, sucralfate, bismuth subsalicylate, and bile acid resins - chelation of tetracycline and inhibited absorption. Separate tetracycline by 1-2 hours before or 4 hours after chelating drug.
Lanthanum carbonate can decrease concentration of tetracyclines; take at least 2 hours before or after lanthanum.
Sulfonamides: general MOA
inhibition of the folic acid pathway
Bactrim dosing is based on which component (SMX or TMP)?
TMP
Bactrim SS dose
400 mg SMX/80 mg TMP
Bactrim DS dose
800 mg SMX/160 mg TMP
Bactrim dosing for uncomplicated UTI
1 DS tablet PO BID x 3 days
Bactrim dosing for PCP prophylaxis
1 DS or SS tablet daily
Sulfonamides: contraindications
Sulfa allergy
Anemia due to folate deficiency
Renal or hepatic disease
Infants < 2 months
Sulfonamides: warnings
- Blood dyscrasias - including agranulocytosis and aplastic anemia
- Skin reactions (SJS/TEN, thrombocytopenic purpura (TTP))
- Hemolytic anemia - can be immune related (positive Coombs test) or due to G6PD deficiency - do not use with known G6PD deficiency
- Thrombocytopenia
- Hypoglycemia
- Pregnancy - use only if benefit > risk; blocks folic acid metabolism, causes congenital deficits
Sulfonamides: side effects (9)
- Photosensitivity
- Hyperkalemia
- Crystalluria
- N/V/D
- Anorexia
- Rash
- Decreased folate
- False elevations in SCr
- Renal failure
Sulfonamides: monitoring
Renal function, electrolytes, CBC, folate
