Drug Information for Ciprofloxacin Injection, USP (In 5% Dextrose) For Intravenous InfusionPremix in INTRAVIA Plastic Container (Baxter Healthcare Corporation): MICROBIOLOGY

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  • Ciprofloxacin has in vitro activity against a wide range of gram-negative and gram-positive microorganisms. The bactericidal action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination. The mechanism of action of fluoroquinolones, including ciprofloxacin, is different from that of penicillins, cephalosporins, aminoglycosides, macrolides, and tetracyclines; therefore, microorganisms resistant to these classes of drugs may be susceptible to ciprofloxacin and other quinolones. There is no known cross-resistance between ciprofloxacin and other classes of antimicrobials. In vitro resistance to ciprofloxacin develops slowly by multiple step mutations.

    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 of the package insert for Ciprofloxacin Injection, USP, (ciprofloxacin for intravenous infusion).

    Aerobic gram-positive microorganisms

    Enterococcus faecalis (Many strains are only moderately susceptible.)
    Staphylococcus aureus (methicillin-susceptible strains only)
    Staphylococcus epidermidis (methicillin-susceptible strains only)
    Staphylococcus saprophyticus
    Streptococcus pneumoniae (penicillin-susceptible strains)
    Streptococcus pyogenes

    Aerobic gram-negative microorganisms

    Citrobacter diversus
    Citrobacter freundii
    Enterobacter cloacae
    Escherichia coli
    Haemophilus influenzae
    Haemophilus parainfluenzae
    Klebsiella pneumoniae
    Moraxella catarrhalis
    Morganella morganii
    Proteus mirabilis
    Proteus vulgaris
    Providencia rettgeri
    Providencia stuartii
    Pseudomonas aeruginosa
    Serratia marcescens

    Ciprofloxacin has been shown to be active against Bacillus anthracis both in vitro and by use of serum levels as a surrogate marker (see INDICATIONS AND USAGE and INHALATIONAL ANTHRAX - ADDITIONAL INFORMATION).

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

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

    Aerobic gram-positive microorganisms

    Staphylococcus haemolyticus
    Staphylococcus hominis
    Streptococcus pneumoniae (penicillin-resistant strains)

    Aerobic gram-negative microorganisms

    Acinetobacter lwoffii Salmonella typhi
    Aeromonas hydrophila Shigella boydii
    Campylobacter jejuni Shigella dysenteriae
    Edwardsiella tarda Shigella flexneri
    Enterobacter aerogenes Shigella sonnei
    Klebsiella oxytoca Vibrio cholerae
    Legionella pneumophila Vibrio parahaemolyticus
    Neisseria gonorrhoeae Vibrio vulnificus
    Pasteurella multocida Yersinia enterocolitica
    Salmonella enteritidis

    Most strains of Burkholderia cepacia and some strains of Stenotrophomonas maltophilia are resistant to ciprofloxacin as are most anaerobic bacteria, including Bacteroides fragilis and Clostridium difficile.

  • Dilution Techniques:

  • Quantitative methods are used to determine antimicrobial minimum 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 powder. The MIC values should be interpreted according to the following criteria:

    For testing Enterobacteriaceae, Enterococcus faecalis, methicillin-susceptible Staphylococcus species, penicillin-susceptible Streptococcus pneumoniae, Streptococcus pyogenes, and Pseudomonas aeruginosaa:

    MIC (mcg/mL)Interpretation
    = 1 Susceptible (S)
    2 Intermediate (I)
    = 4 Resistant (R)

    aThese interpretive standards are applicable only to broth microdilution susceptibility tests with streptococci using cation-adjusted Mueller-Hinton broth with 2-5% lysed horse blood.

    For testing Haemophilus influenzae and Haemophilus parainfluenzaeb:

    MIC (mcg/mL)Interpretation
    = 1 Susceptible (S)

    bThis interpretive standard is applicable only to broth microdilution susceptibility tests with Haemophilus influenzae and Haemophilus parainfluenzae using Haemophilus Test Medium1.

    The current absence of data on resistant strains precludes defining any results other than "Susceptible". Strains yielding MIC results suggestive of a "nonsusceptible" category should be submitted to a reference laboratory for further testing.

    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:

    Organism MIC (mcg/mL)
    E. faecalis ATCC 29212 0.25 - 2.0
    E. coli ATCC 25922 0.004 - 0.015
    H. influenzaeThis quality control range is applicable to only H. influenzae ATCC 49247 tested by a broth microdilution procedure using Haemophilus Test Medium (HTM)1. ATCC 49247 0.004 - 0.03
    P. aeruginosa ATCC 27853 0.25 - 1.0
    S. aureus ATCC 29213 0.12 - 0.5
  • 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-mcg 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-mcg ciprofloxacin disk should be interpreted according to the following criteria:

    For testing Enterobacteriaceae, Enterococcus faecalis, methicillin-susceptible Staphylococcus species, penicillin-susceptible Streptococcus pneumoniae, Streptococcus pyogenes, and Pseudomonas aeruginosaa:

    Zone Diameter (mm)Interpretation
    = 21 Susceptible (S)
    16 - 20 Intermediate (I)
    = 15 Resistant (R)

    aThese zone diameter standards are applicable only to tests performed for streptococci using Mueller-Hinton agar supplemented with 5% sheep blood incubated in 5% CO2.

    For testing Haemophilus influenzae and Haemophilus parainfluenzaeb:

    Zone Diameter (mm)Interpretation
    = 21 Susceptible (S)

    bThis zone diameter standard is applicable only to tests with Haemophilus influenzae and Haemophilus parainfluenzae using Haemophilus Test Medium (HTM)2.

    The current absence of data on resistant strains precludes defining any results other than "Susceptible". Strains yielding zone diameter results suggestive of a "nonsusceptible" category should be submitted to a reference laboratory for further testing.

    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-mcg ciprofloxacin disk should provide the following zone diameters in these laboratory test quality control strains:

    Organism Zone Diameter (mm)
    E. coli ATCC 25922 30-40
    H. influenzaeThese quality control limits are applicable only to H. influenzae ATCC 49247 Testing using Haemophilus Test Medium (HTM)2. ATCC 49247 34-42
    P. aeruginosa ATCC 27853 25-33
    S. aureus ATCC 25923 22-30
  • Drug Information Provided by National Library of Medicine (NLM).
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