Gram-positive bacilli β－Lactam Antibiotics Penicillins 【 Antibacterial activity 】 Gram-positive coccus Gram-negative coccus Gram-positive bacilli Helicoids

Semisynthetic penicillin Penicillinase-resistant penicillin( Oxacillin ) (1) They kill penicillinase-producing staphylococci (2) They can’t kill Methicillin-resistant strains of Staphylococcus aureus (MRSA)

Extended spectrum penicillins (Ampicillin) Antipseudomonal penicillins They are more effective against gram-negative bacilli They can not kill pseudomonas aeruginosa Antipseudomonal penicillins Carbenicillin Piperacillin

Cephalosporins Feature First Second Third G＋ ＋＋＋ ＋＋ ＋ G－ Pseudomonas aeruginosa － anaerobes nephrotoxic ＋＋＋

Other β-lactams antibiotics Carbapenems Imipenem + cilastatin β-lactamase inhibitors Clavulanic acid + Amoxicillin

Chapter 37 Macrolides Lincomycins Polypeptide antibiotics

Macrolides Erythromycin Clarithromycin Azithromycin

一、Erythromycin 【Pharmacokinetics】 Erythromycin base is destroyed by gastric acid It distributes well to all body fluids including prostatic fluid ,but it does not enter the cerebrospinal fluid (CSF) Erythromycin is extensively metabolized and is excreted in the bile, and only 5% is excreted in the urine.

【Antibacterial activity 】 Erythromycin is bacteriostatic It is effective against gram-positive organisms It is active against some gram-negative organisms Mycoplasma, Chlamydozoan, Legionella and campylobacteria are susceptible.

Inhibit protein synthesis 【Mechanism of action】 P A Inhibit protein synthesis Erythromycin(50S) P A P A translocase

【Clinical uses】 Gram-positive coccus infection staphylococci: bouton (boil) streptococci: pharyngitis, febris rubra streptococcus pneumoniae: pneumonia genuina 2. Corynebacterium diphtheriae 3. Chlamydial infections urethral, endocervical, rectal, epididymal, urogenital 4. Mycoplasmal pneumonia 5. Legionella pneumonia

Contraindications: hepatic dysfunction 【Adverse effect】 1. Gastrointestinal effects Anorexia, nausea, vomiting, and diarrhea 2. Cholestatic jaundice estolate form of erythromycin 3. Ototoxicity Transient deafness Contraindications: hepatic dysfunction

methylation of an adenine of the 23S bacterial ribosomal RNA 【Drug resistance】 1. Reduced permeability of the cell membrane or active efflux 2. Modification of the ribosomal binding site 3. Production of esterases that hydrolyze macrolides methylation of an adenine of the 23S bacterial ribosomal RNA

二、Clarithromycin Its activity against Chlamydia, Legionella and Ureaplasma is higher than that of erythromycin. It has lower frequency of gastrointestinal intolerance

三、 Azithromycin Azithromycin is more active against Haemophilus influenzae and Chlamydia than erythromycin It is less active against streptococci and staphylococci It is now used for urethritis caused by Chlamydia trachomatis. It is rapidly absorbed and well tolerated orally.

Section 2 Lincomycins   Lincomycin Clindamycin

【 Antibacterial action and Clinical uses 】 1. Clindamycin is significantly effective against anaerobic bacteria 2. It is employed primarily in the treatment of infections caused by anaerobic bacteria 3. Enterococci and clostridium difficile are resistant 4. It distributes well into bone, so treats medullitis 5. It does not penetrate into cerebrospinal fluid , not use to treat Epidemic meningitis alone

vancomycin metronidazole 【Adverse effect 】 vancomycin metronidazole Fatal pseudomembranous colitis Impaired liver function

Section 3 Polypeptide antibiotics Vancomycins polymyxins

一、Vancomycin 【Antibacterial activity 】 It is bactericidal agent It is primarily active against gram-positive bacteria (MRSA and MRSE),but enterococci are resistant 3. All species of gram-negative bacilli and mycobacteria are resistant to vancomycin

【Mechanism of action】 Vancomycin

【Clinical use and Adverse effect 】 1. Gram-positive bacteria infections: pneumonia, empyema, endocarditis, osteomyelitis, and soft-tissue abscesses, MRSA infection 2. Fatal pseudomembranous colitis due to Clostridium difficile or staphylococci 3. Adverse effects: ototoxicity, nephrotoxicity , "red man syndrome

二、Polymyxins They are bactericidal agent, active against gram-negative bacilli 2. They increased permeability of the bacterial membrane resulting bacterial cell death 3. They are available for external otitis, corneal ulcers caused by Pseudomonas 4. Adverse effects: nephrotoxicity, neurotoxicity, hypersensitive reaction

Chapter 38 Aminoglycosides Streptomycin Neomycin Kanamycin Amikacin Gentamicin Tobramycin

Antibacterial spectrum : 【Antibacterial activity】 Antibacterial spectrum : All aminoglycosides are bactericidal They are effective against aerobic gram-negative bacilli They are ineffective against anaerobic organisms

【Mechanism of action】 interfere with the initiation complex Decoding P A interfere with the initiation complex nonfunctional or toxic protein synthesis aminoglycosides(30S,A) breakup of polysomes into nonfunctional monosomes P A P A

【Pharmacokinetics 】 Aminoglycosides must be given parenterally High concentrations accumulate in the renal cortex and in the endolymph and perilymph of the inner ear All may accumulate in fetal plasma and amniotic fluid. All are rapidly excreted into the urine

【Clinical uses】 Aminoglycosides are mostly used to treat infection caused by gram-negative bacteria Penicillin combination with aminoglycoside is used for treatment of enterococcal endocarditis , streptococcal and staphylococcal endocarditis

dizziness, visual extinction, ocular tremor, nausea, vomiting, ataxia. 【Adverse effect】 dizziness, visual extinction, ocular tremor, nausea, vomiting, ataxia. Ototoxicity ： vestibular dysfunction Injury of cochlear auditory nerve Nephrotoxicity: 3. Neuromuscular paralysis: 4. Allergic reactions: ear noises hearing diminution permanent deafness

【Drug resistance】 Synthesis of enzymes that modify and inactivate aminoglycoside antibiotics. Altered target site Decreased uptake of drug

Chapter 39 Tetracyclines and Chloramphenicol Section 1 Tetracyclines Tetracycline Doxycycline Demeclocycline Minocycline

【Antibacterial activity】 Tetracyclines are broad spectrum bacteriostatic antibiotics 2. They are active against many gram-positive and gram-negative bacteria 3. They are also active against Rickett's organism, helicoid, mycoplasma and Chlamydia

【Mechanism of action】 P A Tetracyclines (30S,A) tetracyclines enter microorganism by passive diffusion and an energy-dependent process of active transport. tetracyclines bind reversibly to the 30S subunit of the bacterial ribosome

【Pharmacokinetics】 Tetracyclines are adequately but incompletely absorbed after oral ingestion 2. Tetracyclines cross the placental barrier and concentrate in fetal bones and dentition 3. Tetracyclines are metabolized in liver and then are excreted from kidney, except doxycycline

【Clinical uses】 Rickettsial infection: fever, chill, ache in bones and joints Chlamydiae infection: pneumonia , urethritis, trachelitis, ophthalmia and trachoma Mycoplasma infection: mycoplasmal pneumonia Spirochetal infection: lyme disease Bacterial infection: cholera

【Adverse effect 】 Gastric discomfort: Nausea, vomiting, and diarrhea Bony structures and Teeth :discoloration and hypoplasia of the teeth and a temporary stunting of growth Fatal hepatotoxicity: in pregnant women Phototoxicity: severe sunburn

4. Vestibular problems: dizziness, nausea, vomiting 5. Pseudotumor cerebri: Benign intracranial hypertension , headache , blurred vision 6. Superinfections: pseudomembranous enterocolitis caused by Clostridium difficile. 7. Contraindications: renally-impaired patients , pregnant or breast-feeding women, or in children \under 8 years of age.

【Drug resistance】 Decreased intracellular accumulation production of protected proteins that interfere with tetracycline binding to the ribosome Enzymatic inactivation of tetracyclines

Section 2 Chloramphenicol 【 Antibacterial action】 Chloramphenicol is either bacteriostatic or bactericidal It is active against both aerobic and anaerobic gram-positive and gram-negative organisms It has effective against rickettsiae, helicoids, Chlamydia and mycoplasma.

【Mechanism of action】 Chloramphenicol(50S,A) Peptidyl transferase P A

【pharmacokinetics】 Chloramphenicol may be administered either intravenously or orally It penetrate blood-brain barrier, placental barrier, blood-ocular barrier It is inactivated by conjugation with glucuronic acid in liver, secreted by the renal tubule

【Clinical uses】 Bacterial meningitis: meningococcal meningitis Rickettsial infections: typhus or Rocky Mountain spotted fever Eye infection: outer eye infection, intraocular infection, eyeball infection Anaerobic infection: peritoneal abscess, pelvic inflammation and peritonitis

【Adverse effect】 Bone marrow depression Aplastic anemia Gray baby syndrome: poor feeding, depressed breathing, cardiovascular collapse, cyanosis

【Drug resistance 】 Produce inactivator： acetyl coenzyme A transferase Membrane permeability is decreased, chloramphenicol penetrate the organism less