Some things to remember about ABx Flashcards
Macrolide drugs and MOA. Which enzyme?
Azithromycin, Clarithromycin, Erythromycin
MOA: Bind to the 50S ribosome – STATIC
Time Dependent Killing Effect
Inhibit CYP 3A4 system (ERY, Clarithromycin»_space;> Azithromycin)
What bacteria does Macrolide cover the best? Worst?
Cover: Atypicals, H. flu, M. cat, H. pylori, MAC, Strep. spps
Poor: Staph, enteric Gram (-), anaerobes
Erythromycin - what to know?
Narrow spectrum: Aerobic gram positives and “Atypicals”:
LOTS of resistance but retains atypical and Spirochetes
Adverse effects: Prokinetic, GI disturbances, diarrhea (maybe used for gastroparesis), cramping
Strong inhibitor of CYP3A –many drug interactions.
Highest QTc prolongation risk among antimicrobials
Clathromycin - what to know?
(Biaxin) – PO (IR and XR)
Spectrum – improved vs. erythromycin w/ more reliable gram + activity
More gram neg activity – But less gram negative activity than azithromycin
Liver metabolism: Moderate CYP3A inhibitor.
Prodrug: metabolized to active compounds
Taste Disturbances: Metallic taste
Azithromycin - what to know?
Improved gram negative activity
Improved tissue penetration and half life
No phase I metabolism.
Eliminated unmetabolized – no drug interactions - no cytochrome inhibition
Long half-life (60hrs) - qd dosing. Must use loading dose. (2x)
Side Effects: Possible reversible tinnitus with large doses
H. Pylori tx:
PPI po BID
Amox 1g po BID
Clarith 500mg po BID
Duration x14days
Use quadruple Tx if:
area resistance to clarithromycin is ≥15%
patients with repeated or recent clarithromycin
second-line tx who fail initial triple therapy
Fluoroquinolones MOA
MOA: Inhibit DNA gyrase and topoisomerases
Blocks transcription/replication
Bactericidal
Concentration-dependent killing
Fluoroquinolones drugs
2nd gen:
ciprofloxacin (Cipro),
ofloxacin (Floxin)
3rd gen:
levofloxacin (Levaquin)
norfloxacin (Noroxin),
4th gen:
gemifloxacin (Factive),
moxifloxacin (Avelox),
FQ cautions and ADR
Ca+/ Mg + Drug Interactions
Can’t take w/ divalent cations(metals) like Ca, Mg, Fe, Zn. Etc.
Tendinopathy
Not indicated in children - joint injury
Cipro is only one associated with ↓ Sz threshold
QTc prolongation is possible
False + drug screens
Tendinopathy with FQ
Cipro most common
Dose/duration dependent
Risk Factors:
>60yo; steroid therapy; renal failure; diabetes; hx of rupture
Athletes, marathon runner are larger risks due to excessive leg movement
Achilles tendon (90%)
Tendonitis to tendon rupture
Median onset 6-days
Coverage for 2nd gen FQ
2nd Gen: Good Gram neg activity (including Pseudomonas)
Uses: Urinary tract infections, GI infections, prostatitis, sexually-transmitted diseases
only quinolone that lowers Sz thresh
Ciprofloxacin (Cipro) - best Gram neg activity
Think: OLDER more GN … NEWER more GP
Coverage for 3rd gen FQ
3rd Gen: Same Gram neg with Strep activity + improved Gram +
Strep & more Staph activity.
Uses: Lung infections
Little hepatic metabolism – few drug:drug interactions.
Cipro & Levo- Least effect on QT interval.
Levofloxacin (Levaquin)
Coverage for 4th gen FQ
4th Gen: Very broad-spectrum: Gram – (NO Pseudomonas), Gram + (pneumococcal), and anti-anaerobe
More liver metabolism than early generations – drug interactions, liver toxicity,
prolong QT more than other FQ.
Moxifloxacin (Avelox)–anaerobes –Highest risk for QT, neuropathy
Think: OLDER more GN … NEWER more GP
Cephalosporins MOA and things to know
Beta-Lactams = SAME bacterial properties (bactericidal) & MOA as penicillins
Several “Generations”
Each successive generation includes more Gram Negatives
Not inhibited by Beta-lactamases.
Resistance through altered PBPs = MRSA and ESB-Lactamase = GNRs
Short half-lives ~ 3- 4 hours.
High therapeutic to toxicity ratio
Cephalosporins has no coverage on
Poor against anaerobes.
Cephs No Activity Against: “LAME”
Listeria, Atypicals*, MRSA, Enterococci
1st gen Cephalosporins drugs
Orals
cephalexin (Keflex™)
cephradine (Velosef™)
cefadroxil (Duricef™)
IV:
Cefazolin
2nd gen Cephalosporins drugs
Orals cefaclor (Ceclor™) cefuroxime (Ceftin™) cefprozil (Cefzil™) loracarbef (Lorabid™)
3rd gen Cephalosporins drugs
Orals: cefpodoxime (Vantin™) cefixime (Suprax™) cefdinir (Omnicef™) ceftibuten (Cedax™)
IV:
Ceftriaxone (IM/IV)
CeftaZidime
Cefotaxime
1st gen Cephalosporins cover
Excellent GRAM POSITIVE Coverage – Strep. spps. & Staph aureus
some gram negative activity:
Proteus, E. coli, and Klebsiella (PEcK)
Mostly skin
Cefazolin used for
IV bSSSIs and Pre-op prophylaxis
Cephalexin
PO bSSSIs; Cefadroxil alternative PO option; BID longer t1/2
2nd gen Cephalosporins cover
Mostly respiratory
Additional gram negatives from 1st gen:
Haemophilus, Enterobacter, Neisseria. (HENPEcK)
Morexella
3rd gen Cephalosporins cover
Aerobic, Gram negatives mainly
Primarily: Gastrointestinal and genitourinary infections
Less gram positive activity than 1st or 2nd generation
No anaerobic activity.
Penetrates CSF w/ long-half lives.
(Meningitis & Gonorrhea involving brain)
Ceftriaxone
IV or IM
Once-daily, No renal adjustments, BBB; Meningitis 2gm Q12h
ADR: crystal formation – NO in NEONATES
Gonorrhea dose = 250mg IM add azithromycin for empiric chlamydia
CeftaZidime
IV only
Active anti-Psa, little GPC activity
May increase C.dif and VRE rates w/ excessive use
Oxazolidinones MOA
Inhibits initiation of protein synthesis at 50S ribosome AND 70S
Gram Positive activity ONLY – MRSA, VRE, Strep. spps
No gram negative
Linezolid
Zyvox® – IV and PO – 600mg BID
100% oral bioavailability, good pulmonary penetration
Cautions:
Thrombocytopenia, anemia and neutropenia (Myelosuppression)
Use >28 days associated with peripheral and optic neuropathy; rare lactic acidosis
D/t mitochondria toxicity
Weak, reversible inhibitor of monoamine oxidase
SEROTONIN SYNDROME
Tedizolid
Sivextro® 200mg daily x6d noninferior to linezolid 600mg BID x10d Poor Urine concentrations No for UTIs Advantages: Once-daily Shorter therapy Less myelosupression Less concern for serotonin syndrome
Trimethoprim/Sulfamethoxazole MOA
Bactericidal. Inhibits folic acid synthesis.
Bacteria must make folic acid. PABA (para-aminobenzoic acid) is a req’d. precursor for folic acid synthesis.
Sulfa drugs are structurally similar to PABA - Act as false substrates.
Combined with another folic acid inhibitor, Trimethoprim, increased effective. Binds the reductase enzymes in same pathway- blocks synthesis of tetrahydrofolic acid.
Antibiotic Synergy: (Combined effect on two sequential steps) - PIC IN PPT
Better efficacy than either drug alone.
Less chance for resistance to develop
TMP/SMX –IV and PO cover which bacteria or disease
Gram Negative and Gram Positive Pathogens: Chlamydia E.coli Proteus Salmonella, Shigella Haemophilus Pneumocystis & Toxoplasma (protozoal infections in HIV patients). Staphylococcus aureus*
Therapeutic uses:
Urinary & GI infections (E.coli, Proteus, Salmonella, Shigellosis)
Respiratory infections (Strep. pneumoniae, Haemophilus)
MRSA * infections.
ADRs TMP/SMX
ADR/Cautions:
Crystalluria and stone formation
DI: Warfarin->↑ INR
TMP competes for K & Cr excretion, ↑SCr and ↑K
7-day risk of sudden death (AOR =1.38)
Photosensitivity
CI 3rd trimester and infants <2mos
Allergic Reactions [Rash (common), SJS & TEN(rare)]
Normal dose for TMP/SMX
Dose is 1 DS Tab PO BID
160 mg TMP* to 800 mg SMX (1:5)
Normal dose for TMP/SMX
Dose is 1 DS Tab PO BID
160 mg TMP* to 800 mg SMX (1:5)
Clindamycin
MOA: Binds to 50S Ribosome (Static)
Broad spectrum: All classes of bacteria
Aerobic & anaerobic gram positives (Strep. & Staph. aureus, including CA-MRSA)
Anaerobic gram negatives: Bacillis, Bacteroides (increasing resistance)
Can penetrate staphylococcal biofilm
Use in foreign body associated infections OR chronic non-healing ulcers
GAS – may be added to PCN in nec fasc infections
RARE allergic reactions in pts who have aspirin hypersensitivity
Alters GI flora rapidly- 25% incidence of diarrhea, cramps, etc.
Assoc w/ severe diarrhea or Clostridium difficile infection development
Skin Infection Considerations:
PVL Toxin inhibition
D-test for inducible
Tetracycline
MOA: Bind to 30S subunit of Ribosome
Bacteriostatic
Broad spectrum activity but mostly for gram positives
Requires active transport to get into cells- source of resistance.
Chelate/Bind divalent cations. Binds with Ca++, Mg++, antacids, iron or multivitamins.
No renal or hepatic adjustment
Extended Spectrum: Gram Positives, Respiratory Gram Negatives & Atypicals
Chlamydial infections Rocky mountain spotted fever (Rickettsia) Lyme Disease (Spirochetes) Mycoplasma pneumoniae H. influenzae and M. catarrhalis Staph. spps (incl MRSA) Strep. spps Corynebacterium - ACNE
COPD exacerbations CAP Tick-borne diseases Skin infections Malaria Bioterrorism
Tetracycline drugs
Doxycycline
Minocycline
Tigecycline
Tetracycline ADR and kinetic
Adverse Effects:
Teratogenic. Bind to calcifying tissues – teeth and bones. Use in children <8 yo, nursing mothers, and during pregnancy is contraindicated. Pregnancy Category D.
Erosive esophagitis – avoid taking at bedtime, drink LOTS of water
Phototoxicity (skin rashes) can occur with tetracyclines.
Minocycline can produce ototoxicity, blue discoloration of gums, drug-induced Lupus, fever, serum sickness-like reaction; CNS effects: disorientation, vertigo, drowsiness
Characteristics:
Not metabolized: excreted unchanged EXCEPT minocycline.
Renal/hepatic disease patients can use doxycycline.
Minocycline: More lipid soluble, crosses BBB (CNS effects), more adverse side-effects, usually dosed bid instead of qd.
