Moxifloxacin microbiology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Abdurahman Khalil, M.D. [2]
Microbiology
Mechanism of Action
The bactericidal action of moxifloxacin results from inhibition of the topoisomerase II (DNA gyrase) and topoisomerase IV required for bacterial DNA replication, transcription, repair, and recombination. It appears that the C8-methoxy moiety contributes to enhanced activity and lower selection of resistant mutants of Gram-positive bacteria compared to the C8-H moiety. The presence of the bulky bicycloamine substituent at the C-7 position prevents active efflux, associated with the NorA or pmrA genes seen in certain Gram-positive bacteria.
Mechanism of Resistance
The mechanism of action for fluoroquinolones, including moxifloxacin, is different from that of macrolides, beta-lactams, aminoglycosides, or tetracyclines; therefore, microorganisms resistant to these classes of drugs may be susceptible to moxifloxacin. Resistance to fluoroquinolones occurs primarily by a mutation in topoisomerase II (DNA gyrase) or topoisomerase IV genes, decreased outer membrane permeability or drug efflux. In vitro resistance to moxifloxacin develops slowly via multiple-step mutations. Resistance to moxifloxacin occurs in vitro at a general frequency of between 1.8 x 10–9 to < 1 x 10–11 for Gram-positive bacteria.
Cross Resistance
Cross-resistance has been observed between moxifloxacin and other fluoroquinolones against Gram-negative bacteria. Gram-positive bacteria resistant to other fluoroquinolones may, however, still be susceptible to moxifloxacin. There is no known cross-resistance between moxifloxacin and other classes of antimicrobials.
Moxifloxacin 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)].
Gram-positive bacteria
• Enterococcus faecalis • Staphylococcus aureus • Streptococcus anginosus • Streptococcus constellatus • Streptococcus pneumoniae (including multi-drug resistant isolates [MDRSP]**) • Streptococcus pyogenes
- MDRSP, Multi-drug resistant Streptococcus pneumoniae includes isolates previously known as PRSP (Penicillin-resistant S. pneumoniae), and are isolates resistant to two or more of the following antibiotics: penicillin (MIC) ≥2 mcg/mL), 2nd generation cephalosporins (for example, cefuroxime), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole.
Gram-negative bacteria
• Enterobacter cloacae • Escherichia coli • Haemophilus influenzae • Haemophilus parainfluenzae • Klebsiella pneumoniae • Moraxella catarrhalis • Proteus mirabilis
Anaerobic bacteria
• Bacteroides fragilis • Bacteroides thetaiotaomicron • Clostridium perfringens • Peptostreptococcus species
Other microorganisms
• Chlamydophila pneumoniae • Mycoplasma pneumoniae
The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitrominimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for moxifloxacin. However, the efficacy of AVELOX in treating clinical infections due to these bacteria has not been established in adequate and well controlled clinical trials.
Gram-positive bacteria
• Staphylococcus epidermidis • Streptococcus agalactiae • Streptococcus viridans group
Gram-negative bacteria
• Citrobacter freundii • Klebsiellao xytoca • Legionella pneumophila
Anaerobic bacteria
• Fusobacterium species • Prevotella species
Susceptibility Tests 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.
• 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 method (broth and/or agar). 1 The MIC values should be interpreted according to the criteria in Table 8.
• Diffusion Techniques
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 prove should be determined using a standardized test method.2,3 This procedure uses paper disks impregnated with 5 mcg moxifloxacin to test the susceptibility of bacteria to moxifloxacin. The disc diffusion interpretive criteria are provided in Table 8.
• Anaerobic Techniques
For anaerobic bacteria, the susceptibility to moxifloxacin can be determined by a standardized test method.4 The MIC values obtained should be interpreted according to the criteria provided in Table 8.
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 infection site 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 a high dosage of the drug product 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.
• Quality Control
Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay and the techniques of the individuals performing the test.1,2,3,4 Standard moxifloxacin powder should provide the following range of MIC values noted in Table 9. For the diffusion technique using the 5 mcg moxifloxacin disk, the criteria in Table 9 should be achieved.
References
http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21277slr018,21085slr023_avelox_lbl.pdf