Antimicrobials Flashcards
Beta-Lactam Antibiotics:
Penicillins
contain a beta-lactam ring as part of their structure
bactericidal against susceptible MO by blocking bacterial transpeptidase, an enzyme that cross-links polymers of bacterial cell wall
typically used to treat susceptible strep and staph infections
bacteria have developed beta-lactamase enzymes, leading to the development of combo meds containing a beta-lactamase inhibitor
Penicillins: ADME
A: variable absorption; sometimes food affects absorption
D: wide distribution, inc. CSF
M: minimal liver metabolism (except nafcillin/oxacillin, which have hepatic metabolism)
E: rapid and extensive renal elimination
Penicillins: Patient Education
Women on BCP should use alternative method until next period, or at least for one week after abx course complete
GI side effects common, esp. diarrhea
Ideally taken on an empty stomach
Finish entire course of abx
Beta-Lactam Antibiotics:
Cephalosporins
Similar mechanism of action to PCNs, but more stable to many beta-lactamases, and therefore are broader spectrum
General rule of thumb: later generations have better gram negative coverage
Cephalosporins: ADME
A: variable absorption; rate but not total extent affected by food, so may be taken with or without
D: wide, inc. to CSF
M: minimal metabolism, except cefpodoxime is de-esterified in GI tract to active form
E: high percentage excreted in urine
Cephalosporins: Patient Education
Most common side effects are GI
Cross-sensitivity with PCN allergy ranges from 2-12% in studies (give if mild allergy to PCN like rash without urticaria; avoid if severe allergy to PCN)
Ceftriaxone should not be used in premature neonates (can compete with bilirubin for binding sites and result in kernicterus)
Types of Beta-Lactam Antibiotics
Penicillins, Cephalosporins, and Carbapenems (used in acute care setting only, broad spectrum, typically not first-line agents)
Examples of First Generation Cephalosporins & Common Uses
Cephalexin (Keflex), Cefadroxil (Duricef), IV Cefazolin (Ancef)
Often used for simple skin & soft tissue infections
Examples of Second Generation Cephalosporins & Common Uses
Cefuroxime (Ceftin), Cefaclor (Ceclor), Cefprozil (Cefzil)
Often used as an alternate choice for URI
Examples of Third Generation Cephalosporins & Common Uses
Cefpodoxime (Vantin), Cefixime (Suprax), IV Ceftriaxone (Rocephin), IV Ceftazidime (Fortaz or Tazicef), IV Cefotaxime (Claforan or Cefotan)
Part of most protocols for CAP
Examples of Fourth Generation Cephalosporins & Common Uses
IV Cefepime
Clinical role similar to that of third generation cacapabilities
Vancomycin
bactericidal for susceptible gram positive bacteria by inhibiting bacterial cell wall synthesis
po form used to treat C Diff if metronidazole is ineffective
very poor oral absorption, results in no detectable serum level
IV dosing requires monitoring levels and adjustment for patient size and renal function
Examples of Tetracyclines
Vibramycin, Tetracycline, Doxycycline, Minocycline, Demeclocycline
Tetracyclines
four ring chemical structure
bacteriostatic by entering MO (in part by active transport and in part by passive diffusion) and binding to 30s subunit of bacterial ribosome, interfering with protein synthesis
Tetracyclines: ADME
A: divalent cations (calcium, magnesium, iron) bind to drug and inhibit absorption
D: highly protein bound; widely distributed, EXCEPT for CSF
M: concentrated by liver in bile and feces
E: all (except doxycycline) extensively renally excreted as unchanged drug
Tetracyclines: Patient Education
Potential for increased photosensitivity
GI side effects common- take with food
Should not be given to children 8yr or younger (binds to calcium deposits in bone/teeth, causing deformity of bone, tooth enamel dysplasia); avoid in pregnancy for same reason
Examples of Macrolides and Common Uses
Erythromycin, Clarithromycin (Biaxin), Azithromycin (Zithromax)
Firstline in many CAP protocols (generally have good coverage versus atypical bacteria; staph/strep coverage based on local susceptibility patterns)
Treatment of STIs (chlamydia)
Macrolides
macrocyclic lactone ring
bacteriostatic at low concentrations, but bactericidal at higher concentrations
inhibit protein synthesis via binding to 50s ribosomal subunit
*caution in patients with baseline prolonged QT or on other meds that prolong QT (erythromycin and clarithromycin worse than azithromycin)
azithromycin has long half-life (48-96hrs) allowing for shorter abx course (stays in system) due to extensive tissue penetration (exceeds serum concentration; slowly releases from tissues)
Macrolides: ADME
A: clarithromycin and azithromycin more readily absorbed than erythromycin
D: wide, EXCEPT for CSF
M: CYP450 inhibitors; extensive hepatic metabolism
E: < 10% excreted unchanged
Telithromycin (Ketolide class)
structurally related to macrolides
binds to ribosomal subunit 50s to inhibit protein synthesis
second or third line against CAP
hepatoxicity, loss of consciousness, and visual disturbances are serious side effects
Examples of Fluoroquinolones and Common Uses
ciprofloxacin (Cipro), moxifloxacin (Avelox), levofloxacin (Levaquin)
CAP (levofloxacin & moxifloxacin)
UTIs (NOT moxifloxacin; use cipro or leva)
Skin/soft tissue infections
Osteomyelitis (cipro- better bone penetration)
Fluoroquinolones
bactericidal by blocking bacterial topoisomerases which prevents relaxation of coiled DNA that is required for normal bacterial transcription
newer quinolones have better gram positive coverage=respiratory FQs (levaquin, avelox)
older quinolones were developed for gram negative activity (cipro)
mechanism of quinolone resistance developed- point mutations in quinolone binding region, also change in permeability of organism
- may cause significant QT prolongation (avelox more than levaquin)
- may cause altered glycemic control
Fluoroquinolones: ADME
A: excellent po absorption (80-95%); divalent cations (Mag, Ca+, iron) inhibit absorption
D: wide
M: minimal hepatic metabolism except moxifloxacin, which has extensive hepatic metabolism
E: other than moxifloxacin, extensive renal excretion (must dose adjust for CrCl <50)
Fluoroquinolones: Patient Education
Caution for CNS ADRs such as dizziness, confusion, somnolence
Potential for phototoxicity
Not used in pediatric patients, other than in those with cystic fibrosis (due to arthralgias/joint swelling risk)
Examples of Aminoglycosides and Common Uses
Garamycin, Gentamicin, Neomycin, Tobramycin
mostly used in acute care setting
Aminoglycosides
dosing and therapeutic drug monitoring necessary; adjust for patient size/renal function
nephrotoxicity- highest risk with prolonged use/concomitant nephrotoxin administration
ototoxicity (8th cranial nerve)
Types of Sulfonamides and Common Uses
Zonisamide (Zonegran), Sulfamethoxazole/Trimethoprim (Bactrim or Septra or TMP)
UTI, otitis media, traveler’s diarrhea, sinusitis
Sulfonamides
bacteriostatic
mimics PABA which is required in order to form dihydrofolic acid; prevents nucleic acid formation
Sulfonamides: ADME
A: agent specific
D: wide, inc. CSF
M: all have some element of hepatic metabolism
E: parent drug and inactive metabolites excreted (reduce dose in renal dysfunction or choose a different agent)
Sulfonamides: Patient Education
photosensitivity
GI side effects; ideally taken on an empty stomach, but okay to take with food for GI upset
adquate hydration to prevent crystaluria
severe but rare: blood dyscrasias (contraindicated in patients with G6PD deficiency- may present with jaundice, purpura, or sore throat)
Linezolid (Oxalodinone class)
treatment of MRSA/VRE
binds to 23s ribosomal RNA of the 50s subunit and interferes with protein synthesis
Linezolid: ADME
A: complete po absorption
D: approx 30% protein bound, distributes into well-perfused tissues
M: liver oxidation
E: 30% unchanged in urine
Linezolid: Patient Education
ADRs include: GI side effects, headache
Serious ADRs include: myelosuppression, neuropathy (with long courses may give vitamin B6/pyridoxine supplement to help prevent)
this drug is an MAO inhibitor, and may react with SSRIs and other agents that depend on MAO for metabolism (consider DC other MAOIs or SSRIs during treatment)
avoid foods high in tyramine (cheese, wine, beer)
Clindamycin
binds to 50s ribosomal subunit of susceptible organisms inhibiting protein synthesis (similar to macrolides)
highly protein bound with wide Vd, but does not penetrate CSF well enough to use to treat CNS infections
Clindamycin: Common Uses
used for strong anaerobic coverage, but covers mixed infections as well
used in aspiration PNA protocols
penetrates well into abcesses (staph)
Clindamycin: Patient Education
common GI side effects
may cause antibiotic-associated colitis
Metronidazole
mechanism of action not well understood, but interferes with bacterial DNA synthesis
adjust in severe hepatic disease
good tissue penetration
Metronidazole: Patient Education
Disulfuram reaction (vs ETOH)- avoid all alcohol, even from cold medications
may cause darkening of urine (no concern unless volume of urine decreases)
Metronidazole: Common Uses
used for anaerobic coverage
covers certain gram negative and gram positive organisms
used for bacterial vaginosis, trichomonal vaginitis (treat both partners), C Diff infecctions, and other GI infections
Nitrofurantoin
used exclusively for UTIs, as therapeutic concentrations achieved ONLY in urine
inactivates bacterial ribosomal proteins
excreted through kidneys and not recommended for CrCl < 50-60 (drug loses effectiveness- less gets to site- and toxic effects are increased- lower excretion rate)
Examples of Azole Antifungals and Common Uses
ketoconazole, itraconazole, fluconazole, voriconazole, posaconazole
vaginal or cutaneous candidiasis, tinea infections, onychomycosis, systemic fungal infections (step-down from heavy IV antifungal therapy- use ID specialist)
Azole Antifungals
increased use has led to more resistant strains, esp in people with heavy usage of azole antifungals
work by reducing ergosterol synthesis by inhibiting fungal CYP450 enzymes (also cause human CYP450 interactions)
Azole Antifungals: Patient Education
look up drug interactions!
LFTs must be assessed prior to, starting, and throughout course (unless short course in otherwise healthy person)
avoid in pregnant women and nursing mothers
elderly patients more susceptible to hepatic effects, and may require lower doses for renal function as well
Examples of Adamantanes and Common Uses
Amantadine & Rimantidine
specifically inhibit replication of influenza A viruses, but not B; currently not being used for flu treatment due to recent CDC recommendation on resistant virus strains
now used for Parkinsons/movement disorders
Antivirals: Adamantanes
interfere with influenza A virus M2 protein, leading to virus uncoating and therefore inhibition of viral replication and decreased viral shedding
work for movement disorders due to CNS effects
Adamantanes: Patient Education
GI and CNS (anticholinergic) effects
caution in elderly, consider dose adjusting
teratogenic
psychological- can cause worsening of mental illness
Antivirals: Neuraminidase Inhibitors
block the active site of influenza viral enzyme neuraminidase, which reduces number of viruses released from infected cell
works on influenza types A and B
Examples of Neuraminidase Inhibitors & Common Uses
Zanamivir (Relenza)- inhaled powdered drug approved for age 7 and older for flu treatment and age 5 and older for flu prophylaxis
Oseltamivir (Tamiflu)- capsule or oral suspension for treatment or prophylaxis of flu in ages one and up
Neuraminidase Inhibitors: Patient Education
Be careful with Tamiflu in children- post marketing research shows increased incidence of self-injury and delirium in children; teach parents to watch for unusual behavior
must use within 48 hours of symptom onset
decreases s/sx by one day, but more importantly decreases viral shedding, so less risk of spreading
ADRs include GI effects, and in zanamivir, bronchospasm precipitation
NOT a substitute for vaccination
Herpes Antivirals
Acyclovir, Valacyclovir (prodrug of acyclovir), famciclovir (prodrug of penciclovir)
suppressive, not curative
phosphorylated by viral thymidine kinase (resistant strains often lack) and inhibit DNA polymerase and thus formation of viral DNA
