Some things to remember about ABx

Question 1

Macrolide drugs and MOA. Which enzyme?

Answer 1

Azithromycin, Clarithromycin, Erythromycin

MOA: Bind to the 50S ribosome – STATIC
Time Dependent Killing Effect

Inhibit CYP 3A4 system (ERY, Clarithromycin&raquo_space;> Azithromycin)

Question 2

What bacteria does Macrolide cover the best? Worst?

Answer 2

Cover: Atypicals, H. flu, M. cat, H. pylori, MAC, Strep. spps

Poor: Staph, enteric Gram (-), anaerobes

Question 3

Erythromycin - what to know?

Answer 3

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

Question 4

Clathromycin - what to know?

Answer 4

(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

Question 5

Azithromycin - what to know?

Answer 5

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

Question 6

H. Pylori tx:

Answer 6

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

Question 7

Fluoroquinolones MOA

Answer 7

MOA: Inhibit DNA gyrase and topoisomerases
Blocks transcription/replication
Bactericidal
Concentration-dependent killing

Question 8

Fluoroquinolones drugs

Answer 8

2nd gen:
ciprofloxacin (Cipro),
ofloxacin (Floxin)

3rd gen:
levofloxacin (Levaquin)
norfloxacin (Noroxin),

4th gen:
gemifloxacin (Factive),
moxifloxacin (Avelox),

Question 9

FQ cautions and ADR

Answer 9

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

Question 10

Tendinopathy with FQ

Answer 10

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

Question 11

Coverage for 2nd gen FQ

Answer 11

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

Question 12

Coverage for 3rd gen FQ

Answer 12

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)

Question 13

Coverage for 4th gen FQ

Answer 13

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

Question 14

Cephalosporins MOA and things to know

Answer 14

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

Question 15

Cephalosporins has no coverage on

Answer 15

Poor against anaerobes.
Cephs No Activity Against: “LAME”

Listeria, Atypicals*, MRSA, Enterococci

Question 16

1st gen Cephalosporins drugs

Answer 16

Orals
cephalexin (Keflex™)
cephradine (Velosef™)
cefadroxil (Duricef™)

IV:
Cefazolin

Question 17

2nd gen Cephalosporins drugs

Answer 17

Orals
cefaclor (Ceclor™)
cefuroxime (Ceftin™)
cefprozil (Cefzil™)
loracarbef (Lorabid™)

Question 18

3rd gen Cephalosporins drugs

Answer 18

Orals:
cefpodoxime (Vantin™)
cefixime (Suprax™)
cefdinir (Omnicef™)
ceftibuten (Cedax™)

IV:
Ceftriaxone (IM/IV)
CeftaZidime
Cefotaxime

Question 19

1st gen Cephalosporins cover

Answer 19

Excellent GRAM POSITIVE Coverage – Strep. spps. & Staph aureus
some gram negative activity:
Proteus, E. coli, and Klebsiella (PEcK)

Mostly skin

Question 20

Cefazolin used for

Answer 20

IV bSSSIs and Pre-op prophylaxis

Question 21

Cephalexin

Answer 21

PO bSSSIs; Cefadroxil alternative PO option; BID longer t1/2

Question 22

2nd gen Cephalosporins cover

Answer 22

Mostly respiratory
Additional gram negatives from 1st gen:
Haemophilus, Enterobacter, Neisseria. (HENPEcK)
Morexella

Question 23

3rd gen Cephalosporins cover

Answer 23

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)

Question 24

Ceftriaxone

Answer 24

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

Question 25

CeftaZidime

Answer 25

IV only
Active anti-Psa, little GPC activity
May increase C.dif and VRE rates w/ excessive use

Question 26

Oxazolidinones MOA

Answer 26

Inhibits initiation of protein synthesis at 50S ribosome AND 70S
Gram Positive activity ONLY – MRSA, VRE, Strep. spps
No gram negative

Question 27

Linezolid

Answer 27

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

Question 28

Tedizolid

Answer 28

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

Question 29

Trimethoprim/Sulfamethoxazole MOA

Answer 29

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

Question 30

TMP/SMX –IV and PO cover which bacteria or disease

Answer 30

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.

Question 31

ADRs TMP/SMX

Answer 31

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)]

Question 32

Normal dose for TMP/SMX

Answer 32

Dose is 1 DS Tab PO BID

160 mg TMP* to 800 mg SMX (1:5)

Question 33

Normal dose for TMP/SMX

Answer 33

Dose is 1 DS Tab PO BID

160 mg TMP* to 800 mg SMX (1:5)

Question 34

Clindamycin

Answer 34

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

Question 35

Tetracycline

Answer 35

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

Question 36

Tetracycline drugs

Answer 36

Doxycycline
Minocycline
Tigecycline

Question 37

Tetracycline ADR and kinetic

Answer 37

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.