Ceftaroline microbiology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Abdurahman Khalil, M.D. [2]
Mode of Action
Ceftaroline is a cephalosporin within vitroactivity against Gram-positive and -negative bacteria. The bactericidal action of ceftaroline is mediated through binding to essential penicillin-binding proteins (PBPs). Ceftaroline is bactericidal againstS. aureusdue to its affinity for PBP2a and againstStreptococcus pneumoniaedue to its affinity for PBP2x.
Mechanisms of Resistance
Ceftaroline is not active against Gram-negative bacteria producing extended spectrum beta-lactamases (ESBLs) from the TEM, SHV or CTX-M families, serine carbapenemases (such as KPC), class B metallo-beta-lactamases, or class C (AmpC cephalosporinases).
Cross-Resistance
Although cross-resistance may occur, some isolates resistant to other cephalosporins may be susceptible to ceftaroline.
Interaction with Other Antimicrobials
In vitrostudies have not demonstrated any antagonism between ceftaroline or other commonly used antibacterial agents (e.g., vancomycin, linezolid, daptomycin, levofloxacin, azithromycin, amikacin, aztreonam, tigecycline, and meropenem).
Ceftaroline has been shown to be active against most of the following bacteria, bothin vitroand in clinical infections[see Indications and Usage ].
Skin Infections
Gram-positive bacteria
Staphylococcus aureus(including methicillin-susceptible and -resistant isolates)
Streptococcus pyogenes
Streptococcus agalactiae
Gram-negative bacteria
Escherichia coli
Klebsiella pneumoniae
Klebsiella oxytoca
Community-Acquired Bacterial Pneumonia (CABP)
Gram-positive bacteria
Streptococcus pneumoniae
Staphylococcus aureus(methicillin-susceptible isolates only)
Gram-negative bacteria
Haemophilus influenzae
Klebsiella pneumoniae
Klebsiella oxytoca
Escherichia coli
The followingin vitrodata are available, but their clinical significance is unknown. Ceftaroline exhibitsin vitroMICs of 1 mcg/mL or less against most (≥ 90%) isolates of the following bacteria; however, the safety and effectiveness of Teflaro in treating clinical infections due to these bacteria have not been established in adequate and well-controlled clinical trials.
Gram-positive bacteria
Streptococcus dysgalactiae
Gram-negative bacteria Citrobacter koseri
Citrobacter freundii
Enterobacter cloacae
Enterobacter aerogenes
Moraxella catarrhalis
Morganella morganii
Proteus mirabilis
Haemophilus parainfluenzae
Susceptibility Test Methods
When available, the clinical microbiology laboratory should provide the results ofin vitrosusceptibility test results for antimicrobial drugs used in local hospitals and practice areas 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 test method1,3, (broth, and/or agar). Broth dilution MICs need to be read within 18 hours due to degradation of ceftaroline activity by 24 hours. The MIC values should be interpreted according to the criteria inTable 6.
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 should be determined using a standardized method. This procedure uses paper disks impregnated with 30 mcg of ceftaroline to test the susceptibility of bacteria to ceftaroline. The disk diffusion interpretive criteria are provided inTable 6.
A report of “Susceptible” indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentration 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. 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, 3Standard ceftaroline powder should provide the following range of MIC values provided inTable 7. For the diffusion technique using the 30-mcg ceftaroline disk the criteria provided inTable 7should be achieved.
References
http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/200327s001lbl.pdf