Ariana Hurtado Garcia Medico Interno

 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 Generation Gram-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 trapp 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 methicillin­resistant 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

AgentAdministrationAbsorptionHalf-Life (hrs)Disposition NorfloxacinOral50%4 (8 in anuria)M (20%) R (27%) CiprofloxacinOral, IV75%4 (10 in anuria)R (50%) M LevofloxacinOral, IV98%7R (80%) GatifloxacinOral, IV96%7-8R (70%) MoxifloxacinOral, IV89%10-14R (20%) M (25%) (in liver) NitrofurantoinOralAdequate R, M (in tissue) Polymyxin BTopical, oral, IVNot absorbed in adults; absorbed in children 6 by IVR M, Metabolized; R, renal excretion as unchanged drug.

Quinolones

DiseaseRecommendations RESPIRATORY TRACT INFECTIONS Pharyngitis, otitis mediaNot appropriate Necrotizing otitis Ciprofloxacin for Pseudomonas aeruginosa SinusitisThird-generation fluoroquinolone Community-acquired pneumoniaThird-generation fluoroquinolone Hospital-acquired pneumonia Ciprofloxacin, for susceptible gram- negative pathogens URINARY TRACT INFECTIONS Cystitis, uncomplicated All effective (second generation most appropriate) Pyelonephritis All effective (second generation most appropriate) ProstatitisAll effective SKIN STRUCTURE INFECTIONS Primary cellulitisNot appropriate as first line therapy Anaerobic soft-tissue infectionsNot appropriate

DiseaseRecommendations OSTEOMYELITIS Gram-negative bacterial infectionsCiprofloxacin BACTERIAL DIARRHEAL DISEASES Ciprofloxacin used most commonly; all considered likely to be effective SEXUALLY TRANSMITTED DISEASES GonorrheaResistance testing required ChlamydiaOfloxacin, levofloxacin ChancroidAll likely to be effective MycoplasmaOfloxacin, levofloxacin SyphilisNot appropriate MYCOBACTERIAL DISEASES Disseminated M. avium complex Ciprofloxacin, ofloxacin as fourth agent if needed M. tuberculosisOfloxacin, 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)

Quinolones

Quinolonas disponibles en nuestro medio: -Acido nalidíxico: tabletas de 500 mg y susp. 250mg/5ml. 1gr c/6h VO (Acido Nalidixico y Wintomylon) -Acido pipemídico: comprimidos de 200 y 400 mg -Ciprofloxacino: comprimidos de 250, 500, 750 mg. ampollas de uso i.v de 100, 200 y 400 mg mg c/12h VO mg c/12h IV (Cilaxon, Cigram,Cifloxin, Cipro, Cipro XR, Ciprofloxacina, Quinoprón)

-Levofloxacino: comprimidos de 250, 500 mg y frasco- ampollas de uso i.v de 500 mg. 500mg VO o IV c/24h (Levaquin, Levovax, Respilox, Tavanic) -Norfloxacino: comprimidos de 400 mg. 400mg c/12h VO (Ambigram, Nefrixine, Noprose, Norfloxacino, Senro, Urigen, Zoronix) -Pefloxacino: comprimidos y ampollas de uso IV 400 mg. -Moxifloxacino: comprimidos de 400 mg

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