Synthetic organic antimicrobials
1. Quinolones
（1）Brief introduction of quinolones: Four generations
First generation :1962 nalidixic acid
Second generation: 1974 pipemidic acid
Third generation : 1980’s fluoroquinolones
Fourth generation: late 1990’s moxifloxacin and gatifloxacin
（2）Antibacterial activity of fluoroquinolones
 Excellent activity against gram-negative aerobic bacteria include enterobacteriacea,
neisseria, pseudomonas, haemophilus and campylobacter etc
 Good activity against gram-positive aerobic bacteria : eg pneumoniae and staphylococci
 Mycoplasmas, chlamydiae, mycobaterium tuberculosis and anaerobes
（3）Mechanism of action
To G-: DNA gyrase
A2B2/ To G+: Topo Ⅳ C2E2
（4）Resistance
Mutation of DNA gyrase/ Change in the permeability of membrane/ Active efflux pump
（5）Pharmacokinetics
Absorbed rapidly and completely/ Widely distributed/ Long T ½/ Low adverse reaction/
No cross-resistance with other drugs
（6）Clinical uses
 Urinary tract infections
 Bacterial diarrhea caused by shigella, salmonella or campylobacter
 Infections of soft-tissues, bones, joint and respiratory tract
(7) Adverse reactions
 The most common: nausea, vomiting and diarrhea
 CNS: headache, dizziness, insomnia and anxiety
 Allergic effect: skin rash, photosensitivity
 Damage growing cartilage and cause arthropathy
2. Drugs
（1）Nalidixic acid and pipemidic acid: Used only in urinary tract infection
（2）Norfloxin:
The least active in fluoroquinolones, F low
No effects on mycoplasma, chlamydiae, mycobacterium tuberculosis, legionella
Urinary tract and intestinal tract infections
（ 3 ） Ciprofloxacin: The most active agent in fluoroquinolones against gram-negatives,
particularly P. aeruginosa
（4）Ofloxacin
Improved quality in pharmacokinetics
F 89%
Effective on mycobateria, chlamydiae and some anaerobes
Effective on resistant bacteria
Second line agent for tuberculosis
（5）levo-ofloxacin: F
100%
 Superior activity against gram-positive organisms
 Effective on mycoplasma, legionella, chlamydia and anaerobes
 Lowest toxicity among fluoroquinolones
（6）Lomefloxacin:
（7）Sparfloxacin:
Photosensitivity
Long-acting
C8-F
t ½>16h/ Improved activity against G+ bacteria, anaerobes,
mycobateria, mycoplasma, chlamydiae / Second line agent for tuberculosis
（8） Moxifloxacin : fourth generation
F
90%,t ½
12~15h / High activity on most G+ ,G-, anaerobes, mycobateria,
mycoplasma, chlamydiae / Low toxicity
3. Sulfonamides
（1）Classification
①Used in systemic infections
Short-acting: SIZ/ Medium-acting: SD, SMZ/ Long-acting: SMD
②Used in intestinal infections: sulfasalazine
③Topical sulfonamides: SD-Ag, SA-Na, SML
（2）Antimicrobial activity: Broad-spectrum bacteriostatic agents
Both G+ and G- , nocardia, chlamydia, trachomatis and some protozoa
（3）Mechanism of action
Inhibit dihydropteroate synthesis and block bacteria folic acid synthesis
（4）Clinical uses
 Urinary tract infection: SIZ, SMZ
 Meningococcal meningitis: SD first choice
 Ulcerative colitis: sulfasalazine
 Topical use for trachoma and conjunctivitis
 Prevent infections of burn wounds
（5）Adverse effects
 Urinary tract disturbance: crystalluria, hematuria, obstruction
 Allergic reactions: fever, skin rashes, exfoliative dermatitis, photosensitivity
 Hematopoietic disturbances
Granulocytopenia, thrombocytopenia
Hemolytic reactions: lack of glucose-6-phosphate dehydrogenase
4. Trimethoprim （TMP）
（1）Inhibit bacterial dihydrofolic acid reductase
（2）Used in combination with sulfonamides: synergism
5. Metronidazole
（1）Clinical uses
Extraluminal amebiasis: drug of choice / Infections caused by anaerobes
Giardiasis/ Trichomoniasis
（2）Adverse reactions
 Gastrointestinal irritation: metallic taste in mouth, nausea, dry mouth and headache
 disulfiram-like effect
 CNS: vertigo, paranesthesia, ataxia and seizures
 Mutagenic and carcinogenic
6.Tinidazole