Antimicrobials Flashcards
Infections that cannot switch from parenteral to PO abts
Osteomyelitis
Endocarditis
Admin of most PCNs
Parenteral as they are unstable in the acidic environment of the stomach
Distribution of PCNs
Distributed widely and penetrate CSF in presence of inflammation
Half life of PCN in adults with normal renal function
30-90 min
PCN mech of action
Inhibition of bacterial cell growth by interference with cell wall synthesis
Agents of choice for gram+ infections
PCNs
High dose PCNs in severe renal dysfunction
Associated with seizures and encephalopathy
PCN adverse rxn when tx spirochetes (especially syphilis)
Jarisch-Herxheimer reaction:
Fever, chills, sweating, flushing
PCN drug interactions
Probenecid will increase half life
Parenteral carboxypenecillins have increased Na content (take care with sodium/fluid restrictions)
How does PCN resistance develop
Drug is inactivated by bacteria-produced penecillinases or beta-lactamases
Development of beta-lactam inhibitor combos
Inhibitor prevents breakdown of beta-lactam by organisms that produce the enzyme
Beta-lactamase producing organisms
S. Aureus
Haemophilus influenza
Bacteroides fragilis
Distribution of beta-lactam inhibitor combos
Most body tissue except brain and CSF
Beta-lactam inhibitor combos (Drugs)
Amoxicillin-clavulanic acid (Augmentin) Ampicillin-sulbactam (Unasyn) Piperacillin-tazobactam (Zosyn) Ticarcillin-clavulanic acid (co-ticarclav) Ceftazidime-avibactam
Beta-lactam inhibitor combo half life
Approx 1h
Beta-lactam combo mech of action
Interfere with bacterial cell wall synthesis by binding to and in activating PBPs
Clinical uses of beta-lactam inhibitor combos
Polymicrobial infections
Extensively:
intra-abdominal and gynecologic infections
Skin/soft tissue infections (human/animal bites)
DM foot infections
Also used for aspiration pna, sinusitis, and lung abcess
Adverse events of beta-lactam inhibitor combos
Hypersensitivity rxns
GI SEs
Are cephalosporins a beta-lactam group
Yes
Beta-lactam groups
Cephalosporins
Monobactams
Carbapenems
How are cephalosporins divided
Into generations
1st-4th indicated increase in gram- coverage and decrease in gram+
Absorption of cephalosporins
Absorbed well through GI tract
2nd-4th penetrate CSF and play a role in tx of bacterial meningitis
Clinical uses for 1st generation cephalosporins
Gram+ skin infections, pneumococcal resp infections, UTI, surgical ppx
Clinical use of 2nd generation cephalosporins
Community acquired pna, other resp infections, skin infections
Only cephalosporin that covers MRSA
Ceftaroline fossil (Teflaro) IV
Cephalosporin tx of bacterial meningitis
Typically 3rd generation like ceftriaxone or cefotaxime
Cephalosporin tx of nosocomial infections
Commonly ceftazidime or cefepime because broad spectrum covers gram- organisms (P. aeruginosa)
Most common SE with cephalosporin
GI: N/V, diarrhea
Cephalosporin drug interactions
Rare
Probenecid can increase half life
Monobactams
Aztreonam (Azactam) is the only one commercially available
Primarily active against gram- organisms
Safer alternative to aminoglycosides
Distribution of monobactams (Aztreonam)
Well into most tissues
Penetration into CSF with inflamed meninges
Not extensively bound to proteins
Half life of Aztreonam
2 hours
Aztreonam mech of action
Interferes with cell wall synthesis by binding to/inactivation PBPs
Almost no action against gram+
Not active against anaerobic organisms
Clinical uses of aztreonam
Complicated and uncomplicated UTIs and resp tract infections (one, bronchitis) when needing aerobic gram-coverage
Cross allergy PCN, cephalosporin, Aztreonam
If all to PCN and cephalosporin should be able to take Aztreonam
Carbapenems
Bicyclal beta-lactams with a common carbapenem nucleus
Most broad spectrum agents available
Carbapenems
Administration of carbapenems
IV, not absorbed PO
Half life of carbapenems
Approx 1h
Distribution of carbapenems
Widely distributed
CSF penetration depends on degree of meningeal inflammation
Carbapenem mech of action
Interferes with cell wall synthesis by binding to PBPs
Drugs with the broadest spectrum of activity of all beta-lactam compounds
Imipenem, meropenem, doripenem
Carbapenem with no aignificant activity against P. aeruginosa
Ertapenem
Why use meropenum over imipenem in tx of CNS infections
Lower risk of causing seizures
Carbapenems adverse events
GI
Neurotoxicity (seizures)
Risk factors: impaired renal function
Improper dosing
Age
Previous CNS disorder
Meds that decrease seizure.
threshold
Carbapenemen drug interactions
Probenecid causes decreased clearance and increased half life
Most commonly prescribed FQs
Ciprofloxacin
Levofloxacin
Moxifloxacin
Pharmacodynamics of FQs
Bacetericidal Excellent bioavailability (easy transition from IV to PO) Distributes well into most tissues except CNS
Half life of FQs
4-12h
Longest half lives: levofloxacin, gemifloxacin, moxifloxacin
FQ mech of action
Strong inhibitors of components of bacterial DNA, without which it cannot replicate
Only oral agents available to tx P. aeruginosa
Ciprofloxacin
Levofloxacin
Preferred agents for nosomial pna and other hospital acquired infections
Cipro or Levaquin
Recommended for meningococcal ppx
Cipro
Rare but serious SE of FQs
QT prolongation
Tendon rupture
Tendonitis
Peripheral neuropathy
FQs may increase effects of…
Theophylline
Warfarin
Tizanidine
Propranolol
What can decrease absorption of FQs
Antacids Sulcrafate Magnesium Calcium Iron salts
FQs with corticosteroids
Increased risk of tendonitis and tendon rupture
Only agent known as a ketolide
Telithromycin
Macrolides
Azithromycin
Clarithromycin
Erythromycin
Distributions of macrolides
Good tissue penetration
Achieve high intracellular concentrations
Exhibits minimal protein binding
Half life of erythromycin
2h
Half life of clarithromycin (Biaxin)
4-5h
Half life of azythromycin
50-60h
Clarithromycin and erythromycin with renal failure
Dosage adjustments are needed
Half life of telithromycin
Approx 10h
Macrolide mech of action
Inhibition of bacterial protein synthesis by binding to the 50s subunit of ribosome
FQ suffix
-Oxacin
Macrolides and atypical organisms
Chlamydia Mycoplasma Legionella Rickettsia Mycobacteria Spirochetes
Rare but serious SE of macrolides
Hepatotoxicity
Adverse rxn associated with telithromycin
Acute hepatic failure
Severe liver injury
Drug interactions of macrolides and ketolides
Inhibits CYP34A and interacts with an extensive list of meds including warfarin
Take care when Admin with meds that prolong QT interval
Major drawback of aminoglycosides
Potential for nephrotoxicity and cytotoxicity
Length of therapy is restricted
Absorption and distribution of aminoglycosides
Poorly absorbed through GI tract. Parenteral admin necessary for systemic infections
Distributes into ECF
Absorption and distribution of aminoglycosides
Poorly absorbed through GI. Parenteral Admin needed for systemic infections
Distributs into ECF (may be sig affected in ICU patients and in malnutrition, obesity, ascites)
Half life of aminoglycosides
Approx 1-3h
Increased with renal impairment
What is used to monitor therapy with aminoglycosides
Renal function and serum levels
Narrow range between therapeutic and toxicity
Macrolides (drugs)
Azithromycin
Clarithromycin
Erythromycin
Telithromycin (ketolide)
Aminoglycosides (drugs)
Gentamicin
Tobramicin
Streptomycin
Amikacin
Aminoglycoside mech of action
Binds to 30s ribosomal unit of bacteria inhibiting bacterial protein synthesis
Activity of aminoglycosides
Aerobic gram- bacilli
Gram+ cocci (with cell wall active agent like ampicillin, ampicillin, vancomycin)
Clinical uses of aminoglycosides
Empiric tx of neutrogenic fever and nosocomial infections
Routinely used in combo with other agents
Monotherapy not recommended except with UTIs
How does nephrotoxicity occur with aminoglycosides
Accumulation of drug in proximal tubule cells of the kidney
Labs monitored with aminoglycosides
BUN/creat and serum levels
Forms of aminoglycoside ototoxicity
Auditory (healing loss, tinnitus)
Vestibular (N/V, vertigo)
Increases when admin with high dose loop diuretics, macrolides, or vancomycin
Aminoglycoside drug interactions
Increased risk of neuromuscular blockade when Admin with neuromuscular blockers, general anesthetic, calcium channel blockers
Admin of calcium glucometer often reverses blockade
Tetracycline suffix
-cycline
Activity of tetracyclines
Gram+, gram-, atypical organisms
Adsorption of tetracyclines
GI tract
Empty stomach increases absorption except with long acting (doxycycline, minocycline)
Eliminated by glomerular filtration except for doxycycline
Tetracycline mech of action
Binds to 30s ribosomal unit to inhibit protein synthesis
Clinical uses for tetracyclines
When beta-lactams aren’t an option
Doxy for early Lyme disease and community acquired pna
Tx of SIADH
Demeclocycline (Declomycin)
Adverse events of tetracyclines
Anorexia, N/V, epigastric distress, gray-green discoloration of teeth (not for kids under 8)
Sensitivity to the sun
Drug interactions with tetracyclines
Absorption decreased by iron, cholestyramine, sulcrafate, antacids, dairy
Potentiate the effects of warfarin by impairing vitamin k synthesis by intestinal flora
Glycylcycline
Tigecycline
Available IV only
Tigecycline dosage adjustments
Not for renal insufficiency but for severe underlying liver disease
Tigecycline mech of action
Binds to 30s subunit to inhibit bacterial protein synthesis
Activity against MRSA and VRE
Clinical uses for Tigecycline
Complicated skin infections, intra-abdominal infections, community acquired pna
Adverse events Tigecycline
N/V, asymptomatic hyperbilirubinemia
Sulfonamides (drugs)
Sulfadiazine
Sulfisoxazole
Trimethoprim
Trimethoprim-sulfamethoxazole (bactrim)
Absorption/distribution of sulfonamides
Readily absorbed through GI
Distributed through all body tissues including CSF, plural fluid, synovial fluid
Half life of sulfonamides
Varies from hours to days
Sulfonamide mech of action
Inhibits the incorporation of para-aminbenzoic acid required for folic acid synthesis necessary for bacterial cell growth
Sulfonamide used to treat ulcerative colitis
Sulfasalazine
Lacks sig microbial activity
Why are sulfonamides typically used with other agents
Limited spectrum of activity and increasing resistance
Adverse events of sulfonamides
Rash (occurs within 1-2 wks), fever, GI
Hemolytic anemia with G6PD deficiency
Sulfonamide drug interactions
Potentiates effect of warfarin, phenytoin, hypoglycemic agents, methotrexate
Glycopeptides (drugs)
Vancomycin
Dalbavancin
Oritavancin
Telavancin
Monitoring glycopeptides
Monitor renal function
Serum monitoring with unpredictable kidney function, severe infection, when therapy exceeds 3-5 days
Clinical uses for vancomycin
Serious gram+ when allergic or unable to tolerate beta-lactams
Drug of choice for MRSA and other resistant organisms
Adverse events of glycopeptides
Fever, chills, “red man” syndrome (associated with rate of infusion of vanc)
Red man syndrome
Pruritus, flushing of head, neck, and face, hypotension
Glycopeptide contraindicated during pregnancy
Telavancin
Drug interactions of glycopeptides
Unlikely as it does not undergo sig hepatic metabolism
Oxazolidinones available
Linezolid (Zyvox)
Tedizolid (Sivextro)
Absorption and administration of oxazolidinones
GI tract absorption
Bioavailability greater than 90%
Admin without regard to food
Eliminated nonrenally
Oxazolidinone mech of action
Binds to 50s ribosomal subunit to disrupt bacterial protein synthesis
Particularly good action against resistant organisms
Oxazolidinones drug interactions
Sympathomemtic agents like pseudoepinephrine, SSRI antidepressants, herbal products, and foods rich in tyramine
Lipopeptide available
Daptomycin
Daptomycin txs what
MDR Gram+ pathogens
Daptomycin dosing
6mg/kg x 7 days
Half life of daptomycin
Approx 8h
Daptomycin mech of action
Bonds to bacterial membranes and causes a rapid depolarization of membrane potential. Low membrane potential leads to cell death
Daptomycin activity
MRSA, VRE
Clinical uses of daptomycin
Complicated skin infections
S. Aureus bacteremia
R sided endocarditis caused by methicillin susceptible and methicillin resistive isolates
Daptomycin drug interactions
CPK levels weekly for concomitant use of stations and/or renal insufficiency
Streptogramins
Only available is quinupristin/dalfopristin (Synercid)
Administration of Synercid
IV, not absorbed through GI tract
Synercid mech of action/activity
Binds to 50s ribosomal subunit inhibiting bacterial protein synthesis
Active against gram+ aerobic organisms
Clinical uses of Synercid
Skin infections, VRE
Administration of Synercid
Through a central line
Clindamycin
Anti anaerobic agent
Gram+ anaerobic bacterial infections
Distribution of clindamycin
Reaches most tissues and bone but distribution into CSF is limited
Clindamycin dosage adjustments
With liver impairment
Clindamycin mech of action
Binds to 50s subunit inhibiting protein synthesis
Clinical uses for clindamycin
Gram-/+ infections, toxoplasmosis, toxic shock
SE of clindamycin
Diarrhea assoc with c. Diff
Drug interactions with clindamycin
Skeletal muscle relaxants can potentiate neuromuscular blockade
Meteonidazole (flagyl) absorption and penetration
Completely absorbed through GI
Penetrates most tissues
Half life of flagyl
6-9h
Clinical uses for flagyl
Bacterial vaginosis
Trichomoniasis
C. Diff
Adverse events with flagyl
GI SE and metallic taste
Seizures with high doses
Peripheral neuropathy with prolonged therapy
Flagyl drug interactions
Enhances effect of warfarin
With alcohol disulfiram-like rxn (flushing, palpitations, nausea, vomiting)
What increases metabolism of flagyl leading to tx failure
Phenobarbital, phenytoin, and rifampin
Chloramphenicol
Wide spectrum of activity against gram+/-, and anaerobic organisms
Chloramphenicol limitation
Limited due to toxicity profile which includes gray baby syndrome, optic neuritis, and fatal aplastic anemia
Availability and penetrance of chloramphenicol
IV
Penetrates into most tissues and body fluids including CSF
Crosses the placenta
Chloramphenicol mech of action
Binds to 50s ribosomal subunit inhibiting protein synthesis
Half life of chloramphenicol
3-4h
Clinical usage of chloramphenicol
Alternative to tx meningitis when life threatening PCN allergy
Rocky mountain spotted fever and typhoid fever in patients allergic to tetracyclines or in pregnant women
Adverse events of chloramphenicol
Gray baby syndrome
Blood dyscrasias
Aplastic anemia,
Optic neuritis (assoc with long term use)
Chloramphenicol drug interactions
Prolongs half life of warfarin, phenytoin, and cyclosporine
Clinical usage of rifampin
1st line tx for TB
Post exposure ppx for n. Meningitidis and h. Influenza type b
Rifampin mech of action
Suppresses initiation of chain formation for RNA synthesis in susceptible bacteria by inhibiting DNA-dependent RNA polymerase
Absorption and distribution of rifampin
Completely absorbs
Distributes into most tissues and fluids including CSF
Half life of rifampin
Approx 3h
Adverse events of rifampin
Changes body fluids red-orange
Hepatotoxicity
Rifampin drug interactions
Increases clearance of antiarrhythmics, azole antifungals, clarithromycin, estrogens, most statins, warfarin, and many HIV meds
Macrobid
Only for uncomplicated UTIs
Half life of macrobid
Less than 30 min
