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A pt has a sinus infx susceptible to both amoxicillin and ampicillin. Which agt would you choose and why?
Amoxicillin because it has better bioavailability, can be given with or without food, and has less frequent dosing (bid or tid vs. qid)
An MD wants to presribe Augmentin 500 mg TID for a pt with recurrent sinusitis. The pt can't swallow Augmentin 500 mg tablets. He writes for Augmentin 250 mg 2 tabs TID. Is this a good idea? Why?
No. The pt would receive more clavulanic acid than with the 500 mg tabs which could lead to diarrhea.
A pt has a severe PCN allergy. Can the patient receive aztreonam? A carbapenem?
Which FQs inhibit DNA gyrase? Topoisomerase IV? What is the advantage of inhibiting Topoisomerase IV?
- all FQs
- 3rd and 4th Generation
- Less resistance to G- and enhanced G+ activity
Why shouldn't pediatric pts generally receive FQs? Which pediatric pts sometimes receive FQs?
- cartilage malformations (note: this is not the same as the tendon problems in adults)
- CF pts
A pt develops a sternal wound infx following bypass surgery after an acute MI. He is placed on vancomycin. the pt is now complaining of severe itching on his face and neck. the nurse just hung the vanco bag on this pt about 10 min ago. He has been receiving vanco for about 7 days. What is the most plausible explanation for this event? How can you treat/prevent this reaction?
- Red Man Syndrome
- slow the rate of infusion, give diphenhydramine, give fluids, dilute, change antibiotics
What is the difference in indications for vanco PO and IV?
PO is for C. diff and IV is for G+ resistant infx (MRSA, MRSE)
Describe the ototoxicity and nephrotoxicity that can occur with AGs
- Oto - cochlear and vestibular
- may or may not be reversible
- related to prolonged duration of therapy, concurrent ototoxic drugs
- Nephro - acute tubular necrosis
- prolonged trough, concurrent nephrotoxic agents
Which macrolide would you not use for bacteremia because of its extensive tissue penetration?
Why should you drink a full glass of water with tetracyclines and not take any doses at bedtime?
to prevent esophogeal ulcerations
Which of the following antibiotics can be used to treat CAP in a pt on antiarrhythmics? Moxifloxacin? Azithromycin? Doxycycline?
You have a pt on clindamycin that developed severe diarrhea and is C. difficile (+) by toxin assay. How would you manage the diarrhea? List antibiotics that can be used to treat AAD.
Stop the clindamycin. Give flagyl 1st line. Vanco is 2nd line.
List 3 unique side effects of metronidazole. what drug intx would you caution a pt about?
- furry tongue feeling, abnormal taste, peripheral neuropathy
- Disulfiram-like reaction with alcohol
What are rifampin's indications for use? Why isn't rifampin ever used alone to treat an infx?
- TB (tx and prevention)
- Asymptomatic carriers of N. meningitides
- In combo with a penicillin or vanco for endocarditis or osteomyelitis
- for synergy in G+ infx
- Increased chance of resistance - develops rapidly
If a pt is allergic to bactrim what other non-antibiotic drugs may they also be allergic to?
Statins should be stopped for pts on which antibiotic because of the risk of increased CPK/myopathy?
Which antibiotic has an increased risk of serotonin syndrome if given concomitantly with SSRIs or MAOIs?
Which antibiotic is available PO for the treatment of hospital-acquired MRSA/MRSE?
Which antibiotics are assoc with dysglycemia?
Which antibiotics exhibit concentration-dependent killing?
AGs, FQs, metronidazole, daptomycin
What drug interaction should you warn young women about with all antibiotics?
- OCs - efficacy can be decreased (esp with rifampin)
- use a backup method for the duration of the course, and for an add'l 7 days after finishing
Name all antibiotics that interact with CYP 450 enzymes. Which antibiotics interact with warfarin most significantly?
- Macrilides but not azithromycin
- most signif intx with warfarin - bactrim and flagyl
A pt is on an antibiotic that discolored her urine. Which antibiotics can discolor urine?
Which antibiotics cause photosensitivity? How would you counsel a pt on this SE?
- FQs, TCs, sulfonamides
- Don't need to avoid the sun completely, but do wear sunscreen
Which antibiotics require therapeutic drug level monitoring?
- Vancomycin IV
Which antibiotic is telithromycin related to? Which antibiotic is tigecycline related to? Whcih antibiotic is tinidazole related to?
Which antibiotics inhibit bacterial cell wall synthesis? Inhibit protein synthesis?
- Beta-lactams and vanco
- AGs, TCs, glycocyclines, chloramphenicol, lincosamide, macrolides, synercid . . .
Which antibiotics are pregnancy category B?
- macrolides (not clarityromycin)
- metronidazole (except in the 1st trimester)
- sulfonamides (except in the 3rd trimester)
What are some general counseling points for pts being started on an antibiotic?
- can cause diarrhea
- if rash or diarrhea, call Dr
- take until gone
- how to take in regard to meals and other meds
- when to expect sx improvement
What 4 categories of antibiotics are beta-lactams?
What is the MOA for all beta-lactams?
- Inhibit bacterial cell wall synthesis - bind to PBPs (catalyze cell wall synth) and interfere with production of mucopeptide layer resulting in weak cell wall which becomes leaky then the bacterial cell expands and bursts
Name 3 beta-lactamase inhibitors
What is the main SE of clavulanate?
GI - diarrhea
Penicillins demonstrate ________-dependent killing.
SEs of beta-lactams
- GI: N/V/D
- hematologic effects (anemia, decr platelets, incr INR)
- acute interstitial nephritis (methcillin, nafcillin)
- Excess sodium load (ticarcillin)
- CNS (seizures)
- Hepatitis (oxacillin)
Which type of hypersensitivity to antibiotics is IgE mediated? Which is not?
- Immediate is IgE mediated (type I)
- Late is not (type II, III, IV)
What pregnancy category are beta-lactams?
What is the main cephalosporin used?
Ceftriaxone (Rocephin) - 3rd Generation
Which generations of cephalosporins penetrate CSF? What is the purpose of this?
- 2nd and 3rd
- to treat meningitis
Side Effects of cephalosporins
- Hematologic effects (incr INR)
- Disulfiram-like reaction
- HA, dizziness
- Bilirubin encephalopathy (ceftriaxone - can displace bilirubin - avoid in neonates)
- Increased mortality with cefepine vs. other beta-lactam antibiotics
Which ceph should not be administered with calcium-containing IV fluids in neonates? Why?
ceftriaxone because of increased risk of precipitation
Which antibiotic is a monobactam?
What route of administration are all carbapenems?
What is the role of cilastatin in Primaxin (imipenem/cilastatin)?
It has no antibacterial activity. It inhibits the DHP-I enzyme in renal tubular cells that inactivates imipenem by hydrolyzing the beta-lactam ring. Cilastatin's role is to prevent renal tubular damage from imipenem and to increase its urinary recovery.
SEs of carbapenems
- HA, confusion, seizures (highest risk with imipenem)
- Nephrotoxicity (imipenem >/= meropenem)
- All preg Cat B except imipenem which is Cat C
DIs with carbapenems
Valproic acid - its levels are reduced by meropenem
Which meds are aminoglycosides?
- the ones that end in mycin/micin (and kacin)
- (gent, tobra, ami, strepto, neo, kana, netil, paromo)
MOA of aminoglycosides
- Inhibit bacterial protein synthesis by irreversibly binding to the 30s subunit of bacterial ribosomes - misreading of codons - wrong amino acids inserted - faulty bacterial proteins produced
- Long PAE vs. G- organisms
What other antibiotics does gentamicin have synergy with and against which microbes?
- vancomycin or a penicillin
- vs. G+ aerobes
Do aminoglycosides require monitoring of levels?
What are the black box warnings on AGs?
- nephrotoxicity (selectively toxic to proximal tubule - can cause acute tubular necrosis and glomerular nephrotoxiciy)
- ototoxicity - cochlear and vestibular damage
Can AGs be used concurrently with other nephrotoxic drugs?
Yes, they are not CI'd, but use with caution
Name 2 factors contributing to nephrotoxicity of AGs
- prolonged high trough level
- increased duration of therapy
SEs of AGs
- neuromuscular blockade
- teratogenic - pregnancy category D
DIs with AGs
- Loop diuretics (incr risk of ototox)
- NM blockers (incr effect)
- Other nephrotoxic drugs (cisplatin, amphotericin B, vancomycin, cyclosporine) (incr risk of nephrotox - use with caution)
MOA of fluoroquinolones
- Inhibit DNA gyrase (topoisomerase II), an enzyme responsible for replication, transcription, and repair of bacterial DNA
- Newer FQs inhibit topo IV in addition to topo II - this decreases resistance and increases G+ activity
- Have PAE for all bacteria
What suffix do FQs have?
BBW with FQs
- tendonitis and tendon rupture
- risk factors: > 60 y.o.a., organ transplantation, concomitant corticosteroid use
SEs of FQs
- dizziness, HA, somnolence, confusion, seizures
- rash (limit gemifloxacin use to NMT 7 days - more common in young women)
- cartilage malformations
- Pregnancy category C
- BBW: tendonitis, possible tendon rupture
- QT prolongation
- Dysglycemia (hyper or hypo)
DIs with FQs
- ciprofloxacin, ofloxacin and norfloxacin inhibit CYP1A2 (warfarin)
- decreased absorption with multivalent cations (Mg, Al, Zn, Fe, sucralfate) - separate doses by at least 4 h
- All except moxifloxacin and gatifloxacin have decr absorption from calcium and dairy products - separate doses by 2 h
- Antiarrhythmics - incr QT interval, so avoid using FQs
MOA of vancomycin
- Bactericidal or bacteriostatic depending on the organism
- Tricyclic glycopeptide which binds to and inhibits bacterial cell wall synthesis (diff stage and target than beta-lactams)
- Molecule is too large to penetrate outer cell membrane of G- bacteria
What is PO vanco used for?
C. diff only
Does vanco exhibit time or concentration dependent killing?
Monitoring levels for vanco
- Peak: 20-40 mcg/ml (30-60 min after infusion)
- Trough: 10-20 mcg/ml
Is routine monitoring of vanco recommended?
SEs of vanco
- infusion-related rxn (redman syndrome)
- Pregnancy category C
What is the cause of Redman Syndrome, the characteristics and the treatment?
- Related to rate of infusion of vancomycin
- Characterized by flushing/itching of face/neck/chest/upper extremities. May also cause tachycardia and hypotension.
- d/t non-immunological release of histamine
- give 1 g no faster than over 1 hour
- Treatment: give infusion over longer period of time, dilute vanco in larger fluid volume, lower vanco dose, treat with antihistamines and IV fluids, consider alternative abx
DIs with vancomycin
other nephrotoxic or ototoxic drugs
Name 3 macrolides/azalides
- azithromycin (PO/IV)
- clarithromycin (PO)
- erythromycin (PO/IV)
MOA of macrolides/azalides
- Bind to the 50s ribosomal subunit of bacteria to inhibit protein synthesis (by inhibiting translocation)
- Bacteriostatic (but azithromycin is BS vs. S. pyogenes and H. influenzae)
SEs of macrolides/azalides
- N/V/D (take with meals to minimize) - High dose IV erythro can cause abdominal cramps, QTc prolongation or transient hearing loss - PO erythro can incr GI motility - clarithro can cause abnormal taste
- QT prolongation
- Cholestatic hepatitis
- incr liver enzymes
- pregnancy category B (except clarithromycin is C)
DIs with macrolides/azalides
- Erythromycin and clarithromycin inhibit CYP 1A2 and 3A4
Which antibiotic is a ketolide?
MOA of ketolides
Bind to 50s ribosomal subunit of bacterial to inhibit protein synthesis (inhibits translocation) (same as macrolides)
SEs of ketolides (telithromycin)
diarrhea, hepatotoxicity, potential for QTc prolongation, Pregnancy category C, BBW: resp failure in pts with myasthenia gravis
CIs of ketolides
BBW for ketolides
respiratory failure can occur in pts with myasthenia gravis - must give medication guide
What is telithromycin's advantage over erythromycin?
- useful for macrolide-resistant S. pneumoniae
- QD dosing
MOA of tetracyclines
- Inhibit 30s ribosomal subunit of bacteria, inhibiting protein synthesis
tetracyclines are the DOC for which infections?
- Rickettsiae (rocky mountain spotted fever)
- Borrelia burgdorferi (Lyme disease)
SEs of TCs
- discoloration of teeth/depression of bone and teeth development
- pregnancy category D
- N/V/D/epigastric discomfort
- esophageal ulcerations (take with lots of water and not before bedtime)
- renal toxicity
- nephrogenic diabetes insipidus (from demeclocycline)
- vertigo (minocycline)
Which tetracycline comes IV in addition to PO?
DIs with TCs
Food, Antacids, Ca, Mg, Al, Fe decrease absorption of TCs (except minocycline and doxycycline)
Which medication is a glycylcycline and what class is it structurally related to?
- related to TCs - derivative of minocycline
MOA of tigecycline
inhibits 30s ribosomal subunit of bacteria, inhibiting protein synthesis
SEs of tigecycline
- inj site rxn
- Preg Category D
- discoloration of teeth in peds
- hypersensitivity in pts allergic to TCs
MOA of sulfonamides
- Competitively antagonize para-amino benzoic acid (PABA) synthesis which is essential for bacteria to make folic acid
SEs of sulfonamides
- HA, peripheral neuropathy, drowsiness, fever
- hypersensitivity - potential XR with celecoxib, sulfonylureas, and most diuretics
- Bone marrow suppression (neutropenia, thrombocytopenia)
- cholestatic hepatitis
- Preg Cat B (except is Category C in 3rd trimester)
- Kernicterus - yellow staining of certain parts of the brain - displaces bilirubin from protein leading to free bilirubin that can cross BBB
DIs with sulfonamides
- significant interaction - can increase INR with warfarin because they inhibit 2C9 - monitor INR carefully - recheck in 2-3 days
- effect of sulfonylureas increased
MOA of trimethoprim
- inhibits DHFR (dihydrofolate reductase)
Only indication for trimethoprim
SEs of trimethoprim
- fever, rash
- increased K+
- Pregnancy category C
Route of admin of TMP/SMX
PO or IV
SE of TMP/SMX
- bone marrow suppression (monitor CBC)
- hypersensitivity (potential XR with celecoxib, sulfonylureas, diuretics)
- pregnancy category C (but Category D in 3rd trimester)
DIs with TMP/SMX
can significantly increase effect of warfarin (because it inhibits 2C9) - monitor INR carefully
Which 2 drugs are lincosamides?
- clindamycin (po, iv)
- lincomycin (iv)
SEs of lincosamides
- clindamycin BBW: colitis
- C. diff diarrhea in up to 10% of pts on clindamycin - tx with flagyl 1st line, vanco 2nd line
- medicinal taste during infusion
- pregnancy category B
MOA of diarrhea for all antibiotics
- disturbance of composition and function of normal intestinal flora
- overgrowth of pathogenic organisms
- allergic and toxic effects of abx on intestinal ucosa
- pharmacologic effect on motility (erythromycin)
How does C. difficile cause diarrhea?
by producing toxins that cause mucosal damage and inflammation of colon
S/S of C. diff diarrhea
- > 3 loose stools a day
- abdominal cramping
- severe - bloody stool, fever, colitis
How does culture of C. diff Toxin A or B from stool or tissue guide treatment?
- lots of false negatives
- if + treat and d/c offending antibiotic
- if - don't treat unless highly suspicious; then repeat test or treat empirically
Treatment of C. diff diarrhea
- isolate pt
- d/c offending abx
- metronidazole 250 mg PO QID or 500 mg BID x 10 days
- vancomycin 125-250 mg PO QID x 10 days
- can add/use other agts, use higher doses, or longer course if recurrent
- avoid antiperistaltic agents
- prevent with probiotics
MOA of metronidazole
- Bactericidal to anaerobes
- Nitroimidazole: toxic to bacterial DNA and RNA
Is metronidazole IV or PO?
can be either
Does metronidazole exhibit time- or concentration- dependent killing?
What is the DOC for trichomoniasis, amebiasis, giardiasis?
SEs of metronidazole
- N/V/A, furry tongue, metallic taste
- dysuria, cystitis, urine discoloration (red-brown)
- seizures, peripheral neuropathy
- BBW: carcinogenicity
- Preg Cat B (D in first trimester)
DIs with metronidazole
- Disulfiram-like reaction with alcohol (avoid for 2d after also)
- Inhibits CYP2C9 so effect of warfarin increases (monitor INR carefully)
MOA of tinidazole
- Nitroimidazole - toxic to bacterial DNA and RNA
- Bactericidal to anaerobes
SEs of tinidazole
- N/V/A/bitter taste
- Preg Cat C
- BBW: carcinogenicity
DIs with tinidazole
- disulfiram-like reaction with alcohol
- CYP3A4 substrate
MOA of rifampin
- Rifamycin: inhibits DNA-dependent RNA polymerase
- Never used alone - will develop resistance rapidly
- Used for synergy vs. G+
SEs of rifampin
- "flu-like" syndrome (esp with high-dose intermittent use)
- reddish-orange discoloration of urine, stool, saliva, tears, sweat, sputum
- increase in liver enzymes
- preg Cat C
DIs with rifampin
- Inducer of CYP 1A2, 2C9&10, and 3A4
- decreases effect of warfarin, OCs, phenytoin, theophylline, verapamil, etc.
- Clarithromycin, erythromycin, telithromycin are partially metabolized by 3A4
What is rifaximin and how does it work?
- non-systemic antibiotic
- semisynthetic deriv of rifamycin
- MOA: inhibits DNA-dependent RNA polymerase
MOA of nitrofurantoin
- Inhibits acetylcoenzyme A, interfering with bacterial carbohydrate metabolism
- Also inhibits cell wall synthesis
- BS at low doses; BC at high doses
What is nitrofurantoin used for?
treatment or prevention of UTIs
What do food and milk do to the absorption of nitrofurantoin?
SEs of nitrofurantoin
- discolors urine brown
- pulmonary toxicity
- G6P deficiency hemolytic anemia (don't give to nursing mothers of Mediterranean, Asian, or African descent)
- HA, peripheral neuropathy
- Preg Cat B until 38-42 weeks, then it's CI'd
DIs with nitrofurantoin
antacids decr its absorption
MOA of chloramphenicol
- Inhibits 50s ribosomal subunit of bacteria - inhibiting protein synthesis
BBW for chloramphenicol and other SEs
- BBW: bone marrow suppression
- Gray baby syndrome
- hemolytic anemia if G6PD deficient
- Preg category C
DIs with chloramphenicol
increases effect of phenytoin
What must we monitor with chloramphenicol
- peak and trough levels
- CBC (to monitor bone marrow suppression)
Which 2 drugs are streptogramins (Synercid)
MOA of streptogramins
- Inhibits 50s ribosomal subunit of bacteria to inhibit protein synth
- Individually the 2 drugs (quinupristin/dalfopristin) are BS, but they work synergistically, so together they are BC
- Have PAE for 10 h vs. G+ organisms
DIs with streptogramins
- Inhibit CYP 3A4
- incompatible with most diluents except D5W
Which med is an oxazolidinone?
MOA of linezolid
- inhibits 50s ribosomal subunit of bacteria, inhibiting protein synthesis
- time-dependent killing
What bugs does linezolid work against?
- Serious G+ aerobes like MRSA/E, VISA, VRE, pen/ceph resistant S. pneumoniae
- some anaerobes
- Indicated for VRE infx, G+ nosocomial pneumonia, complicated skin and skin structure infx
SEs of linezolid
- tongue discoloration (brown)
- Peripheral neuropathy
- Preg Cat C
What is the only oral treatment for hospital-acquired MRSA?
DIs with linezolid
- inhibits MAO enzymes - don't take oral product with tyramine-containing foods
- careful with serotonin-agonist drugs (SSRIs, meperidine, buspirone, TCAs, MAOIs) d/t risk of serotonin syndrome
What drug is a cyclic lipopeptide?
MOA of daptomycin
- inhibits DNA/RNA by depolarizing the bacterial cell membrane
- concentration-dependent killing
Which med can increase CPK at high doses?
DIs with daptomycin
consider d/c statins to decrease risk of myopathy