Quinolones and fluoroquinolones

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)