Mechanism of Action
The bactericidal action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV (both Type II topoisomerases), which are required for bacterial DNA replication, transcription, repair, and recombination.
Mechanism of Resistance
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. Resistance to fluoroquinolones occurs primarily by either mutations in the DNA gyrases, decreased outer membrane permeability, or drug efflux. In vitro resistance to ciprofloxacin develops slowly by multiple step mutations. Resistance to ciprofloxacin due to spontaneous mutations occurs at a general frequency of between < 10 -9 to 1×10 -6 .
There is no known cross-resistance between ciprofloxacin and other classes of antimicrobials.
Ciprofloxacin has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections [see Indications and Usage (1)].
Staphylococcus aureus (methicillin-susceptible isolates only)
Staphylococcus epidermidis (methicillin-susceptible isolates only)
The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for ciprofloxacin (≤1 mcg/mL). However, the efficacy of ciprofloxacin in treating clinical infections due to these bacteria has not been established in adequate and well-controlled clinical trials.
Staphylococcus haemolyticus (methicillin-susceptible isolates only)
Staphylococcus hominis (methicillin-susceptible isolates only)
Susceptibility Test Methods
When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drug products used in resident hospitals to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antibacterial drug product for treatment.
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 test method (broth and/or agar). 5,6,7 The MIC values should be interpreted according to criteria provided in Table 14.
Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method. 6,7,8 This procedure uses paper disks impregnated with 5 mcg ciprofloxacin to test the susceptibility of bacteria to ciprofloxacin. The disc diffusion interpretive criteria are provided in Table 14.
|1. The current absence of data on resistant isolates precludes defining any results other than “Susceptible.” If isolates yield MIC results other than susceptible, they should be submitted to a reference laboratory for further testing. 2. MIC is determined by the agar dilution method|
|MIC (mcg/mL)||Zone Diameter (mm)|
|Enterobacteriaceae||≤1||2||≥4||≥21||16 to 20||≤15|
|Enterococcus faecalis||≤1||2||≥4||≥21||16 to 20||≤15|
|Staphylococcus aureus||≤1||2||≥4||≥21||16 to 20||≤15|
|Staphylococcus epidermidis||≤1||2||≥4||≥21||16 to 20||≤15|
|Staphylococcus saprophyticus||≤1||2||≥4||≥21||16 to 20||≤15|
|Pseudomonas aeruginosa||≤1||2||≥4||≥21||16 to 20||≤15|
|Haemophilus influenzae 1||≤1||-||-||≥21||-||-|
|Haemophilus parainfluenzae 1||≤1||-||-||≥21||-||-|
|Salmonella typhi||≤0.06||0.12 to 0.5||≥1||≥31||21 to 30||≤20|
|Streptococcus pneumoniae||≤1||2||≥4||≥21||16 to 20||≤15|
|Streptococcus pyogenes||≤1||2||≥4||≥21||16 to 20||≤15|
|Neisseria gonorrhoeae 2||≤0.06||0.12 to 0.5||≥1||≥41||28 to 40||≤27|
|Bacillus anthracis 1||≤0.25||-||-||-||-||-|
|Yersinia pestis 1||≤0.25||-||-||-||-||-|
|S=Susceptible, I=Intermediate, and R=Resistant.|
A report of “Susceptible” indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations at the site of infection necessary to inhibit growth of the pathogen. 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 that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations usually achievable at the infection site; other therapy should be selected.
Standardized susceptibility test procedures require the use of laboratory controls to monitor the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individuals performing the test. 5,6,7,8 Standard ciprofloxacin powder should provide the following range of MIC values noted in Table 15. For the diffusion technique using the ciprofloxacin 5 mcg disk the criteria in Table 15 should be achieved.
|1 MIC is determined by the agar dilution method|
|Bacteria||MIC range (mcg/mL)||Zone Diameter (mm)|
|Enterococcus faecalis ATCC 29212||0.25 to 2||-|
|Escherichia coli ATCC 25922||0.004 to 0.015||30 to 40|
|Haemophilus influenzae ATCC 49247||0.004 to 0.03||34 to 42|
|Pseudomonas aeruginosa ATCC 27853||0.25 to 1||25 to 33|
|Staphylococcus aureus ATCC 29213||0.12 to 0.5||-|
|Staphylococcus aureus ATCC 25923||-||22 to 30|
|Neisseria gonorrhoeae ATCC 49226 1||0.001 to 0.008||48 to 58|
|Campylobacter jejuni ATCC 33560||0.06 to 0.25 and 0.03 to 0.12||-|
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