신현우 교수님 - Chap 20. 기타 항생제

Front 1

Quinolones

Back 1

Mech: quinolones inhibit gyrase, and Topoisomerase IV (@ higher conc)

-Broad spectrum, wide indications

-excellent absorption & F

-most are available in IV & PO form

-all quinolone have poor CNS penetration

-excretion in kidney

Front 2

Quinolones Use/Adverse Effects

Back 2

Use: UTI, bacterial diarrhea, gonococcal infection, legionellosis, respiratory infection, anthrax

Adverse effect: drug interaction, damage growing cartilage (<18 세 미만에서 사용 x)

Front 3

Spectrum of activity of quinolones

Back 3

2nd = ciprofloxacin ( aerobe), 3rd = levofloxacin (aerobe), 4th = moxifloxacin (anaeroe에도 효과적이다; spectrum넓어진 대신 pseudomonas에는 사용할 수 없다). 셋다 atypical에 어느정도 효과가 있다.

-Ciprofloxacin, levofloxacin: aerobic G(-) including P. aeruginosa

-Moxifloxacin & gatifloxacin: broader antibac. spectrum, weak activity against pseudomonas

-Gemifloxacin: most active against S. pneumoniae. MRSA에 대해 효과 있을수도, 없을수도.

-Fluoroquinolones: active against certain atypical organisms; UTI & prostatis 에 사용 (except for moxifloxacin)

-Ofloxacin & levofloxacin: pelvic inflammatory disease

-Levofloxacin & moxifloxacin: community-acquired pneumonia

Front 4

Tetracyclines 예

Back 4

-Terramycin = oxytetracycline (코피났을 때 윤활/항균 효과)

-Doxycycline

-Minocycline

Front 5

Tetracycline PK

Back 5

-PO: possible but various bioavailability; not with metal ions, less with food, better in fasting state

-IV, IM: possible

-half life: doxycycline + minocycline - 16 h.

-Distribution: poor BBB penetration/secretion to placenta, milk (toxic to fetus), accumulation in liver, spleen, BM, bone, teeth

*Doxycycline, minocycline: liver metabolism to feces

Front 6

Tetracycline side effects

Back 6

1. GI irritaiton**

-not with milk || antacids

2. Binding to Ca2+ tissues **

-yellow discoloration of teeth

-not for <5 years old

3. superinfection (pseudomembranous colitis)

4. phototoxicity

5. Liver toxicity** (tetracycline, oxytetracycline - less toxic)

6. IICP

Front 7

Tetracycline Indicators

Back 7

1. Broad spectrum

2. Rickettsia

3. Mycoplasma

4. Chlamydia

5. STD

(SBMCR 시발미친롬)

Front 8

Chloramphenicol

Back 8

-targets 50 S (vs. 30S targeting: tetracycline)

-blocks initation of translation/premature termination (이건 tetracycline과 유사) + chloramphenicol also inhibits mitochondrial ribosome

-VERY BROAD. aerobic G+, G-; anaerobic G+, G-.

Front 9

Indications of chloramphenicol

Back 9

-now obsolete; some rickettsial infection

-distribution: CNS, CSF (good BBB penetration)

-adverse reaction: GI & BM depression

**Gray baby syndrome (premature/new born with low hepatic function)

-antagonize b-lactam or AG.

Front 10

Chloramphenicol indication

Back 10

first consider others (due to high toxicity)

Typhoid fever, meningitis, anaerobic infection, rickettsia & brucellosis

(B-A-R-T: 토해서 머리가 아프다 (meningitis)) 그리고 앞글자가 B로 시작하니깐 BM suppression이 부작용.

Front 11

Macrolide

(erythromycin, clarithromycin, azithromycin

-외울 때: clathrin, zenith 연상하면 됨. zenith-꼭대기니깐 제일 반감기 김.

--뒤로 갈수록 반감기 길어짐)

Back 11

-narrow: aerobic G+ alone

-PO: destruction by gastric acid, so use acid stable enteric coated tablet.

-well distributed but BBB 통과 잘 못함;

-eliminated mainly in liver to bile, partly to kidney.

Front 12

Macrolide indication

Back 12

1. Mycoplasma

2. Legionellosis

3. Peptic ulcer due to H. pylori (clarithromycin-amoxicillin-omeprazole)

4. STD

5. Diphtheria, pertussis, tetanus

6. G+ infection

7. prophylaxis of rheumatic fever

(시팔로마 빨리뒤져 SPLMPDG)

Front 13

Clindamycin/Lincomycin

Back 13

-50S binding, bacteriostatic

-chloramphenicol, erythromycin, clindamycin: binds to the same site in 50S

-lipid soluble structure; metabolized in liver. 하지만 BBB 통과 못한다.

Side Effect:

1. Pseudomembranous colitis (C. difficile)

2. Hypersensitivity

3. Neuromuscular blockade

Indication = anaerobic infection; in case of mixed infection (abscess) --with AG.

(클린다와 링컨은 애를 안 낳음 (an-))

Front 14

Clindamycin, metronidazole

Back 14

-considered as agents of choice for anaerobic infections

-Most clostridium and bacteroides (anaerobe) are susceptible to clindamycin

-Metronidazole is the preferred agent for the treatment of bacterial vaginosis and infections caused by Entamoeba spp. and T. vaginalis.

Front 15

Polymyxin

Back 15

-membrane destruction as PP detergent

-topical use due to renal toxicity --> for superbug.

-pseudomonas infection to ext. ear

Front 16

Vancomycin

Back 16

-big molecule, not permeable to membrane

-bind to cell wall precursor

-effective to G+ only.

-used for GI infection by drug-resistance strain = PO / systemic infection by drug resistance strain = IV

-inner ear/kidney toxicities

Front 17

Vancomycin 내성 출현

Back 17

D-ala has been replaced by D-lactate, so vancomycin cannot bind.

Front 18

Bacitracin

Back 18

-big molecule, not permeable to membrane

-inhibit wall synthesis

-effective to G + only.

-topical application

Front 19

ESKAPE

Back 19

new drugs most urgently needed against ESKAPE pathogens

Front 20

Superbug #1 = Enterobacteriaceae

Back 20

only collistin (오래된 polymyxin) is effective

Front 21

serious g+ infection

Back 21

staphylococcus = nafcillin

strep = penicillin G\ ceftriaxone

entrrococcus, listeria = ampicillin

Front 22

Highly resistant

Back 22

G+ = VRE, MRSA

G- = pseudomonas, ESBL

Front 23

Double coverage for pseudomonas

Back 23

b -lactam (pip/tazo, cefepime, carbapenem) + anti-pseudomonal quinolones or AG.

Front 24

antibiotics for anaerobic bacteria

Back 24

metronidazole, carbapene,. b lactam + b lacatmase inhibitor, clindamycin.

Front 25

vs. Clostridium difficle

Back 25

-just two effective antibiotics

=metronidazole, vancomycin

Front 26

for atypical bacteria

Back 26

macrolide, tetracycline, quinolones, chloramphenicol.