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Quinolones were first developed in the 1960s and can be classified into generations based on antimicrobial activity.
First Nalidixic acid in 1962.
Quinolones
First Generation
Gram-negative, but Pseudomonas spp.
Second GenerationGram-negative, some
gram-positive and mycobacteria.
Third and Fourth Generation
Have increased activity against gram-positive pathogens including S. pneumoniae. They are also active against many agents causing zoonotic infection and against mycobacteria.
First Generation Cinoxacin Nalidixic Acid Oxolinic acid
Second Generation Ciprofloxacin Enoxacin Fleroxacin Lomefloxacin Levofloxacin Norfloxacin Ofloxacin rulfloxacin
Third Generation Gatifloxacin Grepafloxacin Pazufloxacin Sparfloxacin Tosufloxacin
Fourth Generation Clinafloxacin Gemifloxacin Moxifloxacin Trovafloxacin
Quinolones
The fluoroquinolones act by inhibiting type 2 bacterial DNA topoisomerases, DNA gyrase and topoisomerase IV. They bind to and trap the enzyme-DNA complex. This blocks DNA synthesis and cell growth and ultimately has a lethal effect on the cell.
Quinolones
The fluoroquinolones are potent bactericidal agents against:
E. coli and various species of Salmonella, Shigella, Enterobacter, Campylobacter, and Neisseria
Ciprofloxacin is more active than norfioxacin against P. aeruginosa
Fluoroquinolones also have good activity against staphylococci, including methicillin resistant strains
Several intracellular bacteria are inhibited by fluoroquinolones these include species of Chlamydia, Mycoplasma, Legionella, Brucella, and Mycobacterium (including Mycobacterium tuberculosis)
Quinolones
Resistance to quinolones may develop during therapy via mutations in the bacterial chromosomal genes encoding DNA gyrase or topoisomerase IV, or by active transport of the drug out of the bacteria.
Quinolones
Agent Administration Absorption Half-Life (hrs) DispositionNorfloxacin Oral 50% 4 (8 in anuria) M (20%) R (27%)Ciprofloxacin Oral, IV 75% 4 (10 in anuria) R (50%) MLevofloxacin Oral, IV 98% 7 R (80%)Gatifloxacin Oral, IV 96% 7-8 R (70%)Moxifloxacin Oral, IV 89% 10-14 R (20%) M (25%) (in liver)Nitrofurantoin Oral Adequate 0.6-1.2 R, M (in tissue)Polymyxin B Topical, oral, IV Not absorbed in
adults; absorbed in children
6 by IV R
M, Metabolized; R, renal excretion as unchanged drug.
Quinolones
Disease RecommendationsRESPIRATORY TRACT INFECTIONSPharyngitis, otitis media Not appropriateNecrotizing otitis Ciprofloxacin for Pseudomonas
aeruginosaSinusitis Third-generation fluoroquinoloneCommunity-acquired pneumonia Third-generation fluoroquinoloneHospital-acquired pneumonia Ciprofloxacin, for susceptible gram-
negative pathogensURINARY TRACT INFECTIONSCystitis, uncomplicated All effective (second generation
most appropriate)Pyelonephritis All effective (second generation
most appropriate)Prostatitis All effectiveSKIN STRUCTURE INFECTIONSPrimary cellulitis Not appropriate as first line therapyAnaerobic soft-tissue infections Not appropriate
Disease RecommendationsOSTEOMYELITISGram-negative bacterial infections CiprofloxacinBACTERIAL DIARRHEAL DISEASES
Ciprofloxacin used most commonly; all considered likely to be effective
SEXUALLY TRANSMITTED DISEASESGonorrhea Resistance testing requiredChlamydia Ofloxacin, levofloxacinChancroid All likely to be effectiveMycoplasma Ofloxacin, levofloxacinSyphilis Not appropriateMYCOBACTERIAL DISEASESDisseminated M. avium complex Ciprofloxacin, ofloxacin as fourth
agent if neededM. tuberculosis Ofloxacin, levofloxacin for drug-
resistance or intolerance to first-line agents
Quinolones
Gastrointestinal effects
Central nervous system agitation (rarely seizures)
Damage to growing cartilage (not recommended for use in children)
Theophylline interaction (with ciprofloxacin)