Drug Information for CIPRO XR (ciprofloxacin* extended-release tablets) (Bayer HealthCare Pharmaceuticals Inc.): MICROBIOLOGY

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  • Ciprofloxacin has in vitro activity against a wide range of gram-negative and gram-positive organisms. The bactericidal action of ciprofloxacin results from inhibition of topoisomerase II (DNA gyrase) and topoisomerase IV (both Type II topoisomerases), which are required for bacterial DNA replication, transcription, repair, and recombination. The mechanism of action of quinolones, including ciprofloxacin, is different from that of other antimicrobial agents such as beta-lactams, macrolides, tetracyclines, or aminoglycosides; therefore, organisms resistant to these drugs may be susceptible to ciprofloxacin. There is no known cross-resistance between ciprofloxacin and other classes of antimicrobials. Resistance to ciprofloxacin in vitro develops slowly (multiple-step mutation). Resistance to ciprofloxacin due to spontaneous mutations occurs at a general frequency of between < 10-9 to 1x10-6.

    Ciprofloxacin is slightly less active when tested at acidic pH. The inoculum size has little effect when tested in vitro. The minimal bactericidal concentration (MBC) generally does not exceed the minimal inhibitory concentration (MIC) by more than a factor of 2.

    Ciprofloxacin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

  • Aerobic gram-positive microorganisms

    Enterococcus faecalis (Many strains are only moderately susceptible.)

    Staphylococcus saprophyticus

  • Aerobic gram-negative microorganisms

    Escherichia coli

    Klebsiella pneumoniae

    Proteus mirabilisPseudomonas aeruginosa

  • The following in vitro data are available, but their clinical significance is unknown.

    Ciprofloxacin exhibits in vitro minimum inhibitory concentrations (MICs) of 1 μg/mL or less against most (≥ 90%) strains of the following microorganisms; however, the safety and effectiveness of CIPRO XR in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.

    Aerobic gram-negative microorganisms
    Citrobacter koseriMorganella morganii
    Citrobacter freundiiProteus vulgaris
    Edwardsiella tardaProvidencia rettgeri
    Enterobacter aerogenesProvidencia stuartii
    Enterobacter cloacaeSerratia marcescens
    Klebsiella oxytoca
  • Dilution Techniques:

  • Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method1 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of ciprofloxacin. The MIC values should be interpreted according to the following criteria:

    For testing Enterobacteriaceae, Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus saprophyticus:

    MIC (μg/mL)Interpretation
    ≤ 1Susceptible (S)
    2Intermediate (I)
    ≥ 4Resistant (R)

    A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

    Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard ciprofloxacin powder should provide the following MIC values:

    Microorganism MIC Range (μg/mL)
    Enterococcus faecalis ATCC 29212 0.25 -2.0
    Escherichia coli ATCC 25922 0.004 -0.015
    Staphylococcus aureus ATCC 29213 0.12 -0.5
    Pseudomonas aeruginosa ATCC 27853 0.25 -1
  • Diffusion Techniques:

  • Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 5-μg ciprofloxacin to test the susceptibility of microorganisms to ciprofloxacin. Reports from the laboratory providing results of the standard single-disk susceptibility test with a 5-μg ciprofloxacin disk should be interpreted according to the following criteria:

    For testing Enterobacteriaceae, Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus saprophyticus:

    Zone Diameter (mm) Interpretation
    ≥ 21 Susceptible (S)
    16 – 20 Intermediate (I)
    ≤ 15 Resistant (R)

    Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for ciprofloxacin.

    As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 5-μg ciprofloxacin disk should provide the following zone diameters in these laboratory test quality control strains:

    Microorganism Zone Diameter (mm)
    Escherichia coli ATCC 25922 30– 40
    Staphylococcus aureus ATCC 25923 22– 30
    Pseudomonas aeruginosa ATCC 27853 25– 33
  • Drug Information Provided by National Library of Medicine (NLM).
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