TARIVID Solution for infusion Ref.[7844] Active ingredients: Ofloxacin

Pharmacotherapeutic group: Quinolone antibacterials, Fluoroquinolones
ATC code: J01MA01

Mechanism of action

Ofloxacin is a quinolone-carboxylic acid derivative with a wide range of antibacterial activity against both Gram-negative and Gram-positive organisms.

The primary mode of action of the quinolones is the specific inhibition of bacterial DNA gyrase. This enzyme is required for DNA replication, transcription, repair and recombination. Its inhibition leads to expansion and destabilisation of the bacterial DNA and hence to cell death.

It appears that certain quinolones, including ofloxacin, have a second non RNA dependent action on bacterial cells, which enhances bactericidal effectiveness. The nature of this second action has not yet been clarified.

PK/PD relationship

Fluoroquinolones have a concentration-dependent bactericidal activity, with a moderate post antibiotic effect. For this class of antimicrobials, the ratio between AUC and MIC or C_max and MIC is predictive of clinical success.

Mechanisms of resistance

Resistance to ofloxacin is acquired through a stepwise process by target site mutations in both type II topoisomerases, DNA gyrase and topoisomerase IV. Other resistance mechanisms such as permeation barriers (common in Pseudomonas aeruginosa) and efflux mechanisms may also affect susceptibility to ofloxacin.

Susceptibility testing breakpoints

Breakpoints separate susceptible strains from strains with intermediate susceptibility and the latter from resistant strains.

Breakpoints set by EUCAST:

^a Breakpoints relate to high dose therapy
^b Wild type S. pneumonia are not considered susceptible to ofloxacin and are therefore categorized as intermediate

Susceptibility

The prevalence of resistance may vary geographically and over time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

Commonly susceptible species, including microorganisms with intermediate susceptibility:

Aerobic Gram-positive micro-organisms:

Bacillus anthracis
Bordetella pertussis
Corynebacteria
Streptococci

Aerobic Gram-negative micro-organisms:

Campylobacter
Enterobacter
Haemophilus influenzae
Legionella pneumophila
Moraxella catarrhalis
Morganella morganii
Proteus vulgaris
Salmonella
Shigella Yersinia

Other micro-organisms:

Chlamydia
Chlamydophila pneumonia
Mycoplasma hominis
Mycoplasma pneumoniae
Ureaplasma urealyticum

Species for which acquired resistance may be a problem:

Aerobic Gram-positive micro-organisms:

Staphylococci coagulase negative
Staphylococcus aureus (methicillin-sensitive)
Streptococcus pneumoniae

Aerobic Gram-negative micro-organisms:

Acinetobacter baumannii
Citrobacter freundii
Escherichia coli
Klebsiella oxytoca
Klebsiella pneumoniae
Neisseria gonorrhoeae
Proteus mirabilis
Pseudomonas aeruginosa
Serratia

Inherently resistant organisms:

Aerobic Gram-positive micro-organisms:

Enterococci
Listeria monocytogenes
Nocardia
Staphylococci methi-R

Anaerobic micro-organisms:

Bacteroides spp.
Clostridium difficile

Therapeutic doses of ofloxacin are devoid of pharmacological effects on the voluntary or autonomic nervous systems.