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