[항생제 각론] 항생제의 분류와 각각의 기능 (1)

세균의 분류

Gram (+)

  1. cocci (GPC): staphylococci, streptococci, enterococci

  2. bacilli (GPB): Listeria

Gram (-)

  1. cocci/coccobacilli (GNC): Haemophilus, Neisseria

  2. bacilli (GNB): Enterobacteriaceae (E. coli, Klebsiella)

                      Non-enteric (Pseudomonas, Acinetobacter)

Anaerobe

  1. G (+): peptostreptococci / Clostridium

  2. G (-): Bacteroides, Prevotella

Miscellaneous: Intracellular, Spirochetes, Mycoplasma

 

 

1. 세포벽에 작용하는 항생제

(β-lactams: penicillins, cephalosporins, carbapenem, monobactam)

 

Peptidoglycan의 cross-linking을 억제

  : Beta-lactam

Dissacharide pentapeptide의 유리 억제

  : Glycopeptide

Lipid carrier의 활성화 억제

  : Bacitracin, fosfomycin

D-alanyl-D-alanyl synthetase의 억제

  : Cycloserine

 

1) Penicillins

① 페니실린 : Penicillin G

Ix: Group A sterptococcus의한 Rhematic fever, syphillis. S.pyogenes, N.gonorrhoeae.

② 항포도구균성 페니실린 : Methicillin, Nafcillin, Oxacillin, Cloxacillin

Ix: β-lactamase 생산하는 MSSA가 유일한 Ix (DOC)

③ 광범위 페니실린 : Ampicillin, amoxicillin, piperacillin

Ampicillin Ix: Enterococcus, Listeria (DOC)

Amoxicillin Ix: S. pneumoniae (DOC)

Piperacillin Ix : P. aeruginosa

 

•Natural Penicillins :  Penicillin G, Penicillin V

•Penicillinase-resistant Penicillins

  : Methicillin, Oxacillin, Nafcillin, dicloxacillin

•Aminopenicillins :  Ampicillin,  Amoxicillin

•Anti-Pseudomonal Penicillins

   - Carboxypenicillin : Ticarcillin

   - Ureidopenicillin : Piperacillin

 

2) Cephalosporins

①1세대.: cefadroxil, cefazolin(IV), cephalexin, cephalothin, cephaprin, cepharadine

1st. Cephalosporins의 임상적응증

MSSA, Streptococci (except for S. pneumoniae)

  1. Skin & soft tissue infection

  2. Surgical prophylaxis

    : cardiac & vascular surgery, orthopedic surgery,

       head & neck surgery that crosses oropharynx

  3.  Osteomeylitis, septic arthritits

  4.  S. aureus infective endocarditis

 

②2세대: cefoxitin, cefaclor, cefamandole, cefonicid, cefuroxime, cefproxil

2nd. Cephalosporins의 임상적응증

S. pneumoniae, H. influenzae, M. catarrhalis

Community-acquired respiratory tract infection

  : Pneumonia, acute sinusitis, acute otitis media

Cephamycin의 임상적응증

GNB  +  Anaerobes

   1. Mixed infections, mild to moderate severity

    :  Intra-abdominal infection

        Pelvic infection

   Diabetic foot infection

   2. Surgical prophylaxis for colorectal surgery

 

③3세대: cefoperazone, cefotaxime, ceftazidime, ceftizoxim, ceftriaxone, cefixime

3rd. Cephalosprin의 임상적응증:

Ceftriaxone/Cefotaxime

   : Streptococci (S. pneumoniae 포함), GNB, GNC

   1. Empirical therapy of Community-acquired sepsis

     : meningitis, pneumonia, UTI

   2. viridans streptococci infective endocarditis

   3. Salmononella infection

Ceftazidime : P. aeruginosa infection

 

④ 4th gen: cefepime

4rd. Cephalosporin의 임상 적응증:

  Streptococci, GNB, P. aeruginosa

  1. 3rd. Cephalosporin의 적응증과 비슷

  2. Febrile neutropenia

 

Cephalosporins의 분류

1st

•Cephalothin, cefazolin, cephapirin, ceftezole, cefazedone / cephalexin, cefatrizine, cephradine, cefadroxil

2nd

•Cefamandole, cefuroxime, ceftezole, cefotiam / cefaclor, cefprozil, cefuroxime acetil,

•Cephamycin: cefoxitin, cefotetan, ceftmetazole

3rd

•Cefotaxime, ceftriaxone, ceftizoxime / cefixime, cefpodoxime

•Ceftazidime, cefoperazone

4th

•Cefepime, cefpirome

 

항생제	MSSA	Strept	PSSP	GNC	GNB-En	Pseudo	An-GPC	An-GNB
1st	3+	2+	1+	0	1+	0	1+	0
2nd	2+	2+	2+	3+	2+	0	1+	0
Cephamycin	1+	1+	0	2+	2+	0	2+	2+
3rd	1+	3+	3+	3+	3+	0	2+	1+
Ceftazidime	1+	1+	0	3+	3+	3+	0	0
4rd	2+	3+	3+	3+	3+	3+	1+	0

0: 효과 없음,  1+: 미약,   2+: 보통,  3+: 우수

 

Cephalosporins에 내성 균주

 

•MRSA/MRSE

•Penicillin high-level resistant S. pneumoniae

•Enterococcus

•Stenotrophomonas maltophila, B. cepacia

•Clostridium difficile

•Intracellular organisms/absence of cell wall

    : Listeria monocytogenes, Legionella,

      Mycoplasma, Rickettsia, Brucella,

      Salmonella (3rd generation cephems-effective))

 

 

3) Vancomycin

•대부분의 그람양성균에 효과적.

   G (+) cocci: staphylococci, streptococci, enterococci

   G (+) bacilli: Bacillus, Corynebacterium, Listeria

   Anaerobes: Actinomyces, Clostridium, Peptostrepto- coccus

   G (-) rod:  Elizabethkingia meningoseptica

•Vancomycin에 내성인 그람양성균

 : Leuconostoc, Erysipelothrix rhusipathiae, Nocardia

임상적 적응증

•MRSA, MRCNS 감염증의 1차 치료제

•PRSP (PCN MIC ≥ 2 mg/L) meningitis

•Penicillin-resistant enterococci/streptococci 감염

•C. difficile 장염의 2차 치료제

• Penicillin 또는 cephalosporin 제제 치료가 필요한 환자 중에서 β-lactam 항균제에 알레르기로 대체약제가 필요한 경우

 

Vancomycin 부작용

•Nephrotoxicity ( ~9%)

•Ototoxicity (rare)

•Infusion-related reactions

   : Red man syndrome, Phlebitis

•Neutropenia (1~2%)

•Skin rash (3%)

•Drug fever (2%)

Pregnancy category C

 

*Teicoplainin

Teicoplanin의 항균범위, 적응증

•항균범위

  - Vancomycin과 항균제의 작용기전이 같고, 항균 범위도 거의 유사하다.

  - Active against Van B-VRE

•임상적응증

  - Vancomycin의 임상적응증과 거의 비슷함

  - Van B, C- VRE infection

 

Vancomycin vs. Teicoplanin

 

	Vancomycin	Teicoplanin
Terminal  Half-life	5~6 hr	150 hr
투여 간격	12 hr	24 hr
Renal excretion	80~90%	80%
BBB penetration	7~21%	very poor
투여 방법	IV, PO	IV/IM, PO

 

4) Carbapenem : imipenem, meropenem, ertapenem

Active against nearly all clinical bacteria

   But, Inactive against

•MRSA,  MRCoNS

•VRE, Enterococcus faecium

•Stenotrophomonas maltophilia, Burkholderia cepacia

•Clostridium difficile

•Intracellular organisms/absence of cell wall

•Carbapenem-R strains : Acinetobacter, Pseudomonas

Carbapenem의 임상적응증

ESBL(+) E. coli에서 TOC

ESBL (+) or AmpC b-lactamase (+) GNB

Empirical use

 1. Neutropenic sepsis;

    patients with immunosupression or organ transplant

 2. Severe nosocomial intra-abdominal infection

 3. Late-onset nosocomial pneumonia

 4. Severe nosocomial infection in critically ill patients

 5. Failure of previous therapy with other antibiotics

 

			Antimicrobial coverage
	Dosage / interval	Half-life	G(+)	G(-)	Nonfermenters*	Anaerobes
Imipenem	500m g q 6-8hr	1hr	3+	3+	2~3+	3+
Meropenem	1 g q 8hr	1hr	3+	3+	3+	3+
Ertapenem	1g q 24hr	4hr	3+	3+	1+	3+

Imipenem:

경련유발가능하여 뇌병변이 있는 환자에서는 사용시 주의 요함

Ertapenem

 1g q 24hr

 IV/IM

 ESBL (+) E. coli & K. pn.

 Outpatient Tx.

 Low antipseudomonal effect

 

5) Monobactam :

•Aztreonam

•Activity: Only against Gram-negative bacilli

•No synergism with cephalosporin

–Do not use in stead of aminoglycoside

•Lesser adverse drug reaction

•No nephrotoxicity

•No cross reaction with other b-lactams

Ix: anaerobe G(-). 다른 β-lactam allergy

 

6) β-lactam / β-lactamase inhibitor

Ampicillin-sulbactam / Cefoperazone-sulbactam

   Amoxicillin-clavulanate / Ticarcillin-calvulanate

   Piperacillin-tazobactam

Spectrum of activity

  : b-lactamase produicing organism

–Staphylococcus, Streptococcus, Enterococcus

–E. coli, Proteus, other gram-negative bacilli

–Gram-negative coccobacilli

Anaerobes : B. fragilis

 

① amoxicillin/Clavulanic acid(Augmentin), Ampicillin/Sulbactam(Unasyn)

Spectrum of Activity

    - MSSA, Streptococci, enterococci

    - GNC, GNB (except for ESBL (+) or fermentor)

    -  Anaerobes

Ix: amoxicillin⋅ampicillin의 임상 적응증

- Otitis media / Sinusitis

    - Community-acquired pneumonia

    - Skin & soft tissue infections

    - Bite wound

 

② ticarcillin/clavulanic acid, piperacillin/tazobactam(Tazocin)

•Broad spectrum of activity

  :  active against GPC, GNB, Pseudomonas & anaerobes

     Little active against ESBL (+)

     No active against MR-Staph, PRSP, E. faecium, S. maltophilia

•Indications

  1. Polymicrobial infections :Intra-abdominal or pelvic infections

  2. Nosocomial pneumonia

  3. Skin & soft tissue infections (DM foot)