section 15. infection disease and anti-infective drugs ( 感染性疾病与抗感染药 )

Section 15. Infection disease and Anti-infective drugs( 感染性疾病与抗感染药 )

Charpter 2. Anti-infective drugs

( 抗感染药物 )

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医学院科研 C422

mailto:[email protected]

ContentsContents

Part 1.Part 1. General considerations of anti-microbial General considerations of anti-microbial agentsagents

PartPart 2.2. -Lactam antibiotics-Lactam antibioticsPart 3. MacrolidesPart 3. Macrolides, , lincomycinslincomycins, , and vancomycinsand vancomycinsPart 4. Aminoglycosides & polymyxinsPart 4. Aminoglycosides & polymyxinsPart 5. Tetracyclines & chloramphenicolPart 5. Tetracyclines & chloramphenicolPart 6. Synthetic antimicrobial agentsPart 6. Synthetic antimicrobial agentsPart 7. Antifungal agentsPart 7. Antifungal agentsPart 8. Antiviral agentsPart 8. Antiviral agentsPart 9. Antituberculous drugsPart 9. Antituberculous drugsPart 10. Clinical uses of antimicrobial agentsPart 10. Clinical uses of antimicrobial agentsPart 11. The drugs treated parasitic infectionsPart 11. The drugs treated parasitic infections

According to bio-activityAccording to bio-activity

Anti GAnti G++ antibiotic antibiotic Anti GAnti G-- antibiotic antibiotic Broad-spectrum antibioticBroad-spectrum antibiotic Anti mycobacteriumAnti mycobacterium （（分支杆菌分支杆菌））

antibioticantibiotic Anti anaerobeAnti anaerobe （（厌氧菌厌氧菌）） antibioticantibiotic β- lactamase inhibitorβ- lactamase inhibitor

Antimicrobial drugs Antimicrobial drugs classificationclassification

According to the chemical structureAccording to the chemical structure ：：

11 、、 β-lactams: Penicillins; Cephalosporins;β-lactams: Penicillins; Cephalosporins;

22 、、 Aminoglycosides;Aminoglycosides;

33 、、 Macrolides; Lincosamides ;VancomycinsMacrolides; Lincosamides ;Vancomycins

44 、、 Tetracyclines; Chloramphenicol Tetracyclines; Chloramphenicol

55 、、 QuinolonesQuinolones

66 、、 SulphonamidesSulphonamides

77 、、 Nitrofurans Nitrofurans

88 、、 Antimycobacterial agents Antimycobacterial agents

99 、、 others: Oxazolidinones; Streptograminsothers: Oxazolidinones; Streptogramins

History of Antimicrobial TherapyHistory of Antimicrobial Therapy

1909 Ehrlich discovers Salvarsan （撒尔佛散，治疗梅毒特效剂）“ Magic bullet” for treatment of syphilis （梅毒）

1928 Fleming discovers penicillin( 青霉素 )1932 Domagk discovers sulfonamides （磺胺类药物）1940s Penicillin and streptomycin （链霉素） used widely,

cephalosporins （头孢菌素） discovered1947 Chloramphenicol （氯霉素） discovered, first broad spectrum

agent1950s Tetracycline （四环素） in use1952 Erythromycin （红霉素） discovered (macrolides 大环内酯类 )1956 Vancomycin （万古霉素） used for penicillin-resistant S.

aureus1957 Kanamycin （卡那霉素） discovered (aminoglycosides 氨基苷

类 )1962 Nalidixic acid （萘啶酸） discovered (quinolones 喹诺酮类 )1980s Fluoroquinolones （氟喹诺酮类） , broad spectrum

cephalosporins2000s Newer agents to combat resistant pathogens

Part 1.Part 1.

General General considerations of considerations of antimicrobial antimicrobial agentsagents(( 抗微生物药物概论抗微生物药物概论 ))

Contents

1. Overview2. Term and definition3. Classification and

mechanism of antibacterial action

4. Bacterial resistance

1. Overview:

(1)Chemotherapy( 化学治疗 , 简称化疗 )(2)Chemotherapeutic drugs: Antimicrobial drugs( 抗微生物药 ); Antiparasitic durgs( 抗寄生虫药 ); Antineoplastic drugs( 抗肿瘤药 ).

(3)Antimicrobial drugs: Antibacterial drugs( 抗菌药 ); Antifungal drugs( 抗真菌药 ); Antiviral drugs( 抗病毒药 ).

Pharm

acokineti

Pharm

acokineti

cscs

Adverse

Adverse

effects

effects

pathogenicipathogenicityty

ImmunologicalImmunologicalresponsesresponses

Ther

apeu

tic

Ther

apeu

tic

Effec

ts

Effec

ts

Res

ista

nce

Res

ista

nce

The relationship of the host, microorganisms, antimicrobial

drugs.

1. Antibacterial drugs( 抗菌药 )2. Antibiotics( 抗生素 )3. Bacteriostatic drugs( 抑菌药 )4. Bactericidal drugs( 杀菌药 )5. Antibacterial spectrum( 抗菌谱 )6. Chemotherapetic index ( 化疗指数 ,CI)7. Minimum inhibitory concentration ( 最小抑菌浓度 ,

MIC)8. Minimum bactericidal concentration ( 最小杀菌浓

度 , MBC)9. Concentration Dependent killing10. Post antibiotic effect ( 抗生素后效应 ,PAE) 11. Time-dependent killing

TerminologyTerminology

2. Terms and definition:

(1)Antibacterial drugs( 抗菌药 ): Substances that can kill

bacteria and/or inhibit its growth.

including: ①Antibiotics( 抗生素 ); ②Synthetic antimicrobial agents,

such as sulfonamides( 磺胺类 ) and quinolones( 喹诺酮类 ), etc.

(2)Antibiotics( 抗生素 ):

Substances produced by various species of microorganisms(bacteria, fungi, actinomyces, etc.), which can kill other microorganisms or inhibit their growth.

Terms and definition

(3)Chemotherapetic index: LD50/ED50, or LD5/ED95

(4)Antibacterial spectrum( 抗菌谱 );

(5)Bacteriostatic drugs( 抑菌药 );

(6)Bactericidal drugs( 杀菌药 );


agentagentss


(7)Minimum inhibitory concent-ration(MIC);

(8)Minimum bactericidal concen-tration(MBC):

MBC ≥ MIC;

if MBC > 32 times MIC resistance.


Antimicrobial Susceptibility Testing

7. Minimum inhibitory 7. Minimum inhibitory concentration concentration (MIC)(MIC)

8. Minimum 8. Minimum bactericidal bactericidal concentration concentration (MBC): (MBC): 99.9% decrease in growth over 24 hours

Incubate 18 to 24 hr at 37℃

Measure Measure diameters ofdiameters ofnongrowthnongrowthzoneszones

Disk diffusion method for testing bacteria for susceptibility to specific antimicrobial drugs. Disk diffusion method for testing bacteria for susceptibility to specific antimicrobial drugs.

9. Concentration Dependent killing: situation in which the bactericidal activity of a drug depends by how much the drug concentration exceeds the Minimum inhibitory concentration of the organism in question. e.g. aminoglycosides and quinolones

10. Time-dependent killing: situation in which the bactericidal activity of a drug depends how long the drug concentration exceeds the Minimum inhibitory concentration of the organism in question. e.g. b-lactams and vancomycin

11. Post antibiotic affect (PAE) (PAE) : Persistence of suppression of bacterial growth after limited exposure to an antimicrobial agent. e.g. aminoglycosides


(1) inhibit synthesis of bacte-rial cell walls;

(2) act directly on the cell membrane of the microorganism and affect its permeability, and leading to leakage of intracellular compounds;

(3) inhibit protein synthesis;(4) affect bacterial nucleic acid

metabolism;(5) The antimetabolites of folic acid, that

can block essential enzymes of folic acid synthetic metabolism.

Classification and mechanism of antibacterial action:

①①

②②

③③

④④

⑤⑤

Classification and mechanism of action

(1)Inhibiting synthesis of bacterial cell walls:

UDP- 乙酰胞壁酸 -5 肽双糖十肽聚合物


transpeptidasetranspeptidase

vancomycivancomycinn

-Lactam -Lactam antibioticsantibiotics


(2)Affecting permeability of membrane: ①Ionic-adsorbed(streptomycin); ②binding to ergosterol(amphotercin B); ③Inhibiting the synthesis of ergosterol (imidazoles);

④Surface-active agent, that interact strongly with phospholipids(polymixins).


(3)Inhibiting protein synthesis: affecting the function of 30S, or

50S ribosomal subunits to cause a reversible inhibition of protein synthesis (strepto-mycin, erythromycin, etc.).

binding to the 30S ribosomal subunit and altering protein synthesis, which eventually leads to cell death (strepto-mycin, etc.).


(4)Affecting bacterial nucleic acid metabolism: quinolones, etc.


Pteridine(Pteridine( 蝶啶蝶啶 )) ++ PABA(PABA( 对氨苯甲对氨苯甲酸酸 ))Blocked by sulfonamidessulfonamides

Dihydropteroic acid(Dihydropteroic acid( 二氢蝶酸二氢蝶酸 ))

Dihydrofolic acid(Dihydrofolic acid( 二氢叶酸二氢叶酸 ))

Glutaminic Glutaminic acidacid

Tetrahydrofolic acid(Tetrahydrofolic acid( 四氢叶四氢叶酸酸 ))

Blocked by trimethoprimtrimethoprim

NADPHNADPH

NADNADPP

Dihydropteroate

synthase

Dihydrofolate

reductasease

(5)(5)Blocking enzymesBlocking enzymesof folate metabolism:of folate metabolism:


Bacterial ResistanceBacterial Resistance

4. Bacterial resistance:

(1)(1)Category of resistance:Category of resistance: ①① Intrinsic resistance:Intrinsic resistance:

Inherent features Inherent features ，， usually expressed by usually expressed by chromosomal geneschromosomal genes

②② Acquired resistance:Acquired resistance: emerge from previously sensitive bacterial emerge from previously sensitive bacterial

populationspopulations Caused by mutations in chromosomal genesCaused by mutations in chromosomal genes Or by acquisition of plasmids or Or by acquisition of plasmids or

transposonstransposons

Bacterial Resistance (2)Mechanism of bacterial resistance:

①to produce inactivated enzyme;

②to inhance active efflux system:

③the drug does not reach its target;

④ the target is altered;

Resistance: mechanisms, pathways

IM

OM

Penicillin

-lactamPenicillinase

Inactive

Kanamycin

Acetylation

Phosphorylation

Adenylyation

1A. Enzymatic inactivatione.g. b-lactamase

1B. Enzymatic modification e.g. Aminoglycoside modification

2. Active effluxe.g. Tetracycline resistance

3. Decreased permeabilitye.g. Porin mutations -cephalosporin

4. Target alterationStreptomycin resistancepenicillin binding proteins

①To produce inactivated enzyme: 1)Production of aminoglycoside

modify-ing enzymes, such as deactivated enzyme to streptomycin;

2)Production of -lactamase, such as penicillinase;

3)Production of inactivated enzymes to other antibiotics, etc.

Bacterial Resistance Mechanism of bacterial resistance

② To enhance active efflux system:


③The drug does not reach its target: Absence of, mutation in, or loss of the appropriate porins( 膜孔蛋白 ) channel can slow the rate of drug entry into the cell, or prevent entry altogether, reducing the effective

drug concentration at the target site.


Porin channel( 膜孔蛋白通道 )


④ The target is altered: Mutation of the natural target(such as resistance to fluoroquinolone). Target modification(ribosomal protec-tion type of resistance to macrolides and tetracyclines). Substitution with a resistant alternat-ive to the natural, susceptible target (such as methicillin

resistance in staphy-lococci).


The transfer of resistance genes:

Bacterial Resistance

①Mutations;

②Transduction;

③Transformation;

④Conjugation.

Bacterial Resistance The transfer of resistance genes

①Mutations( 突变 ): which may occur in the gene encoding. 1)The target protein; 2)The protein involved in drug

transport; 3)Act on regulatory gene or promoter

( 启动子 ) affecting expression of the target, a transport protein, or an inactivating enzyme.

such as aminoglycosides, quinolones, etc.

Mutations Mutations

May occur in the gene encodingMay occur in the gene encoding

i) The target proteini) The target protein

ii) A protein involved in drug transportii) A protein involved in drug transport

iii) A protein important for drug activation iii) A protein important for drug activation

iv) A regulatory gene or promoter iv) A regulatory gene or promoter

affecting expression of the target, a affecting expression of the target, a

transport protein, or an inactivating transport protein, or an inactivating

enzyme. enzyme.

②Transduction( 转导 ): acquisition of bacterial DNA from bac-teriophage( 噬菌体 ) that has incorporated DNA from a previous host

bacterium with-in its outer protein coat. Some phages can carry plasmids that code for penicillinase, or genes encod-ing resistance to erythromycin, tetracy-cline, or chioramphenicol.


Transduction Transduction


③Transformation( 转化 ): Uptake and incorporation of

DNA that is free in the environment into the host genome by homologous recombination.


④Conjugation( 接合 ): The passage of genes from cell

to cell by direct contact through a sex pilus( 性菌毛 ) or bridge( 桥接 ).

Transformation Transformation Conjugation Conjugation

Bacterial Resistance

Multi-drug resistance MDR Multi-drug resistance MDR (( 了解了解 ))

11 、、 Methicillin-resistant coagulase negative Methicillin-resistant coagulase negative staphylococci, MRCNS staphylococci, MRCNS

PBP-2aPBP-2a22 、、 Penicillin-resistant streptococcus Penicillin-resistant streptococcus

pneumoniae, PRSPpneumoniae, PRSP PBP-1a, PBP-2a, PBP-2x, PBP-2bPBP-1a, PBP-2a, PBP-2x, PBP-2b Active efflux systemActive efflux system33 、、 Vancomycin-resistant Enterococcus, VREVancomycin-resistant Enterococcus, VRE PBP avidityPBP avidity （亲合力）（亲合力） ↓ ↓ van-A, van-B, van C-1, van C-2, van D, van Evan-A, van-B, van C-1, van C-2, van D, van E

4. The 34. The 3rdrd generation-cephalosporins - generation-cephalosporins -resistant resistant

• Extended spectrumβ-lactamases, ESBLExtended spectrumβ-lactamases, ESBL

• Class I chromosone mediated β-Class I chromosone mediated β-lactamaseslactamases

5.5. Carbapenem -resistantCarbapenem -resistant

• OprD porinOprD porin

6. Quinolone-resistant escherichia coli, 6. Quinolone-resistant escherichia coli, ARECAREC

• Active efflux systemActive efflux system

Multi-drug resistance MDR Multi-drug resistance MDR (( 略略 ))

Let’s take a rest !

PartPart 2.2.

--Lactam Antibiotics

Classification of -Lactam Antibiotics

Ⅰ. Penicillins( 青霉素类 ) Ⅱ. Cepharosporins( 头孢菌素类 ) Ⅲ. Other -lactam antibiotics: 1. Cephamycins( 头霉素类 ) 2. Carbapenems( 碳青霉烯类 ) 3. Monobectams( 单环类 ) 4. Oxacephalosporins( 氧头孢烯类 ) Ⅳ. -lactamase inhibitors( 内酰

胺酶抑制剂 )

(( 青霉素青霉素类类 ))

(( 头孢菌素类头孢菌素类 ))

Core Core structures of structures of beta-lactam beta-lactam antibiotic antibiotic familiesfamilies

Beta-Lactam antibioticsBeta-Lactam antibiotics

(( 单环类单环类 ))

(( 碳青霉烯碳青霉烯类类 ))

(( 亚胺培南亚胺培南——碳青霉烯类——碳青霉烯类 ))

ChemicalChemical structurestructure of penicillinsof penicillins

ⅠⅠ. . PenicillinsPenicillins( 青霉素类 )

( 酰基侧链 ) ( 噻唑烷环 )

((-- 内酰胺环内酰胺环 ))

(( 青霉素类青霉素类 ))

A. NatureA. Nature PenicillinsPenicillins:

1. Classification of Penicillins: (1)Nature penicillins: Penicillin G( 苄青霉素 , 简称青霉素 ) (2)Penicillinase-resistant penicillins: Oxacillin( 苯唑西林 ) (3)Broad-spectrum penicillins: Amoxicillin( 阿莫西林 ) (4)Anti-pseudomonas penicillins: Ticarcillin( 替卡西林 ) (5)Anti-G- bacilli penicillins: Mecillinam( 美西林 )

PenicilliPenicillinsns

2. Antimicrobial activity: The penicillin-susceptible bacteria:(1)G+ bacilli( 革兰阳性杆菌 ); (2)Non-penicillinase-producing

strains of most G- cocci( 大多数不产青霉素酶的球菌 ) and Nisseria( 奈瑟菌属 ), etc.

such as: Meningococcus( 脑膜炎球菌 ), Gonococcus( 淋球菌 ), etc.

(3)Spirochetes( 螺旋体 ), etc.


3. Mechanism of action:

(1)Inhibiting transpeptidase( 转肽酶 , PBP, 青霉素结合蛋白 ), and inhibiting the synthesis of bacterial cell walls.

(2)Activation of cell-wall autolytic enzy-me( 自溶酶 ).


Comparison of the structure and composition of G+/ G- cell walls.


Penicillins & cephalosporins can inhibit the transpeptidase reaction in sen-sitive organism ( 敏感菌 ).


PenicillinPenicillins s

4. Mechanism of resistance:


(( 酰胺酶酰胺酶 ))(( 青霉素青霉素酶酶 ))

(6-(6- 氨基青霉烷酸氨基青霉烷酸 )) (( 青霉素裂解酸青霉素裂解酸 ))

(1)to produce penicillinase(-lactamase) by bacteria;

Penicillin Penicillin --Mechanism of resistanceMechanism of resistance

Penicillin -Penicillin -Mechanism of resistanceMechanism of resistance

(2)to alter PBP, decreased affinity for the antibiotic;

(3)to make deficiency of porins, or enhance active efflux system,

let penicillins does not reach its target, and inability to be effective.

(4) Lack of the autolysins


Antibiotic efflux pumps of G- bacteria.


5. Clinical Uses: (1)Streptococcal( 链球菌 ) infections: such as: Pharyngitis( 咽炎 ), Scarlet fever( 猩红热 ); Rheumatic fever( 风湿热 ), Pneumonia( 肺炎 ), Endocarditis( 心内膜炎 ), etc.

(2)Nisseria ( 奈瑟菌 ) infections: Meningitis( 脑膜炎 ); Gonorrhea( 淋病 ), etc.


(3)Leptospira( 螺旋体 ) infection: such as: Liptospirosis( 钩端螺旋体病 ), Syphilis( 梅毒 ), Recurrent fever( 回归热 ).

(4)G+ bacilli(G+ 杆菌 ) infection: such as: Diphtheria( 白喉 ), Tetanus( 破伤风 ), Anthrax( 炭疽病 ), etc.

(5)Staphylococcal( 葡萄球菌 ) infection (generally resistant to penicillin G).


6. Adverse effects: Penicillins are among the safest of antibiotics, produce few direct toxic reactions,

the most of the serious side effects are hypersensitivity reactions.


(1)Hypersensitivity reactions: Itching( 痒 ), rashes, fever, serum sick-ness, angioneurotic oedema( 血管神经性水肿 ).

Anaphylactic shock (5/10 000).(2)Other adverse reactions: Phlebitis( 静脉炎 ), when i.v.; Local inflammatory reactions, in injection site when i.m.; Jarisch-Herxheimer reaction( 赫氏反应 ) when treatment of syphilis, liptospirosis.


7. ADME of Penicillin G: Be destroyed easily by p.o. Administration by i.m. or i.v. gtt. widely distributed (even in CSF,

when menings is infective);

Eliminated in the urine.


8. Preparation of long-acting penicillin G:

Benzathine penicillin G( 苄星青霉素 )

Procain penicillin( 普鲁卡因青霉素 )


1. Penicillins by oral administration （耐酸青霉素） :

Phenoxymethylpenicillin( 苯氧甲基青霉素 , Penicillin V)

It is resistant to gastric acid, and be well absorbed(60%) when it is given on an empty stomach. Its half-life(t½) is longer than that of penicillin G. A satisfactory substitute for Penicillin G to treat tonsilitis( 扁桃体炎 ), or Pharyn-gitis( 咽炎 ), etc.

B. Semi-syntheticB. Semi-synthetic PenicillinsPenicillins:

SemisyntheticSemisynthetic PenicillinsPenicillins

2. The penicillinase-resistant penicillins( 耐酶青霉素 ):

Oxacillin( 苯唑西林 ), Cloxacillin( 氯唑西林 ),

Dicloxacillin( 双氯西林 ) It is stable in an acidic medium, can be administrated by po, or im, iv ; and it is resistant to cleavage by penicillinase.

It is used for treatment of penicillin G-resistance staphylococcal infection.

3. Broad spectrum penicillins（广谱青霉素） :

Amipicillin( 氨苄西林 ), Carbenicillin( 羧苄西林 ),

Piperacillin( 哌拉西林 ), etc.

They have similar antibacterial activity and a broader spectrum.

All can be destroyed by -lactamase.


Broad spectrum Broad spectrum penicillinspenicillins


(1)Ampicillin( 氨苄西林 ), Amoxicillin( 阿莫西林 ) Pseudomonas aeruginosa( 铜绿假单孢菌 ——绿脓杆菌 )-resistance. Clinical Uses: Upper respiratory infections;

Urinary tract infections; Meningitis; Salmonella infections.

(2)Carbenicillin( 羧苄西林 ),Ticarcillin( 替卡西林 )

With activity against Pseudomonas aeruginosa and some Proteus( 变形杆菌 ).

Broad spectrum Broad spectrum PenicillinsPenicillins


(3)Piperacillin( 哌拉西林 ),Mezlocillin( 美洛西林 )

They have the broadest antibacterial spectrum, and the most activity of the penicillins, with activity against Pseudo-monas aeruginosa, etc.

Clinical Uses: For the treatment of the patients

with severe infection caused by G-

bacteria, us-ually in combination with

aminoglycoside ( 氨基苷类 ).

4. Anti-G- bacilli penicillins:


Mecillinam( 美西林 ), Temocillin( 替莫西林 )

They are bacteriostatic drugs, and have narrow

antibacterial spectrum, with activity against some G- bacilli.

Ⅱ. CepharosporinsCepharosporins( 头孢菌素类 )

A. Classification:

CepharosporiCepharosporinsns

The well-accepted system of classification by “generations” is based on general features of anti-microbial activity.

B. Classification and Features:


1. First generation:1. First generation: Cefazolin(Cefazolin( 头孢唑林头孢唑林 ), ), Cefradine(Cefradine( 头孢拉定头孢拉定 ), ),

Cefalexin(Cefalexin( 头孢氨苄头孢氨苄 ), ), etc.etc. (1)more active than second and third genera-tion (1)more active than second and third genera-tion

against certain G+ microoganisms;against certain G+ microoganisms; (2)more impervious than second and third(2)more impervious than second and third ge-ge-

neration to attack by staphyloccal neration to attack by staphyloccal -lactamase;-lactamase; (3)less active than second and third(3)less active than second and third genera-tion genera-tion

against certain G- microoganisms;against certain G- microoganisms; (4)non-stable to G- bacilli (4)non-stable to G- bacilli -lactamase;-lactamase; (5)more activity against certain (5)more activity against certain PseudomonasPseudomonas

(( 铜绿假单孢菌铜绿假单孢菌 ), ), anaerobes(anaerobes( 厌氧菌厌氧菌 ), ), etcetc; ; (6)certain kinds have kidney toxicity.(6)certain kinds have kidney toxicity.


2. Second generation:2. Second generation: Cefuroxime(Cefuroxime( 头孢呋辛头孢呋辛 ), ), Cefamandole(Cefamandole( 头孢孟多头孢孟多 ), Cefaclor(), Cefaclor( 头头孢克洛孢克洛 ), ), etc.etc. (1)more active than first generation (1)more active than first generation against certain Gagainst certain G-- bacilli and more bacilli and more impervious than first generation Gimpervious than first generation G-- bacilli bacilli -lactamase;-lactamase; (2)somewhat less active than first (2)somewhat less active than first generation against Ggeneration against G++ coccicocci butbut moremore than thirdthan third generation;generation; (3)active(3)active againstagainst anaerobes(anaerobes( 厌氧菌厌氧菌 ));; (4)lack activity against (4)lack activity against PseudomonasPseudomonas; ; (5)less toxic than first generation to (5)less toxic than first generation to kidney.kidney.

（头孢西（头孢西丁丁））

（头孢孟（头孢孟多多））


3. Third generation:3. Third generation: Ceftazidime(Ceftazidime( 头孢他啶头孢他啶 ), Ceftriaxone(), Ceftriaxone( 头孢头孢曲松曲松 ), ), etc.etc. (1)far more active than first and (1)far more active than first and second gene-ration against Gsecond gene-ration against G-- bacilli; bacilli; (2)be highly resistant to (2)be highly resistant to -lactamase -lactamase produced by Gproduced by G-- bacilli; bacilli; (3)with the extended spectrum against (3)with the extended spectrum against anae-robes and anae-robes and PseudomonasPseudomonas;; (4)well absorbed, penetration into (4)well absorbed, penetration into tissue, blo-od and body cavity as well in tissue, blo-od and body cavity as well in sufficient concen-tration;sufficient concen-tration; (5)less active than first and second(5)less active than first and second generation against Ggeneration against G++ cocci; cocci; (6)less toxic to kidney.(6)less toxic to kidney.

（头孢哌（头孢哌酮酮））

（头孢噻（头孢噻肟肟））


4. Fourth generation:4. Fourth generation: Cefepime(Cefepime( 头孢匹肟头孢匹肟 ), ), Cefpirome(Cefpirome( 头头孢匹罗孢匹罗 ), ), etc.etc. (1)resistant to type 1 (1)resistant to type 1 -lactamase;-lactamase;

(2)more active than third generation (2)more active than third generation against Enterbacter(against Enterbacter( 耐肠杆菌耐肠杆菌 );); (3)less active than third generation (3)less active than third generation against against PseudomonasPseudomonas..

fourth


1st 2st 3st 4st1st 2st 3st 4st

抗菌谱抗菌谱 G+ G+ 强强 G-G-

酶稳定性好酶稳定性好肾毒性大肾毒性大半衰期长半衰期长血脑屏障通透性好血脑屏障通透性好

Ⅲ. OtherOther -lactamlactam antibioticsantibiotics

1. Cephamycins( 头霉素类 ):Cefoxitin ( 头孢西丁 )

It has the similar antibacterial activity and spectrum to the second generation cepharosporins,

also can be used for the treatment of anaerobic infections.

OtherOther -lactam-lactam antibioticsantibiotics

2. Carbapenems( 碳青霉烯类 ): Imipenem( 亚胺培南 )

Imipenem is markered in combination with cilastatin( 西司他丁 )——Tienam( 泰能 ), a drug that inhibits the degradation of imipenem by a renal tubular dipeptidase.

It has the broadest antibacterial spec-trum and the most activity of all the anti-biotic.

OtherOther --lactamlactam antibioticsantibiotics

3. Monobectams( 单环类 ): Aztreonam( 氨曲南 )

Carumonam( 卡芦莫南 ) For the treatment of aerobic G+ bacilli infections. Narrow-spectrum antibiotic.

Other Other -lactam -lactam antibioticsantibiotics

4. Oxacephalosporins( 氧头孢烯类 )Latamoxef( 拉氧头孢 ) Flomoxef( 氟氧头孢 )

Broad-spectrum antibiotic(anaerobic infections).

ⅣⅣ. . --lactamase inhibitorslactamase inhibitors((-- 内酰胺酶抑制剂内酰胺酶抑制剂 ))

Clavulanic acid( 克拉维酸 )Sulbactam( 舒巴坦 )

Tazobactam( 三唑巴坦 ) Binding to -lactamases and

inactivate them, thus preventing the destruction of -lactam antibiotics which are substrates for -lactamases.

END OF CLASSEND OF CLASS

section 15. infection disease and anti-infective drugs ( 感染性疾病与抗感染药 )

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