Zinforo

Pharmacotherapeutic group: Antibacterials for systemic use, other cephalosporins and penems, ATC code: J01DI02 The active moiety after Zinforo administration is ceftaroline. Mechanism of action Ceftaroline is a cephalosporin antibacterial with in vitro activity against Gram-positive and -negative bacteria.​‍​​​​​‍​‍‍‍‍​‍‍ The bactericidal action of ceftaroline is mediated through binding to essential penicillin-binding proteins (PBPs). Biochemical studies have shown that ceftaroline has high affinity for PBP2a of methicillin-resistant Staphylococcus aureus (MRSA) and PBP2x of penicillin non-susceptible Streptococcus pneumoniae (PNSP). As a result, minimum inhibitory concentrations (MICs) of ceftaroline against a proportion of these organisms tested fall into the susceptible range (see Resistance section below). Resistance Ceftaroline is not active against strains of Enterobacterales 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. Organisms that express these enzymes and which are therefore resistant to ceftaroline occur at very variable rates between countries and between healthcare facilities within countries. If ceftaroline is commenced before susceptibility test results are available then local information on the risk of encountering organisms that express these enzymes should be taken into consideration. Resistance may also be mediated by bacterial impermeability or drug efflux pump mechanisms. One or more of these mechanisms may co-exist in a single bacterial isolate. Interaction with other antibacterial agents In vitro studies have not demonstrated any antagonism between ceftaroline in combination with other commonly used antibacterial agents (e.g. amikacin, azithromycin, aztreonam, daptomycin, levofloxacin, linezolid, meropenem, tigecycline, and vancomycin). Susceptibility testing breakpoints MIC (minimum inhibitory concentration) interpretive criteria for susceptibility testing have been established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for ceftaroline fosamil and are listed here: https://www.ema.europa.eu/documents/other/minimum-inhibitory-concentration-mic-breakpoints_en.xlsx Pharmacokinetic/pharmacodynamic relationship As with other beta-lactam antimicrobial agents, the percent time above the minimum inhibitory concentration (MIC) of the infecting organism over the dosing interval (%T > MIC) has been shown to be the parameter that best correlates with the efficacy of ceftaroline. Clinical efficacy against specific pathogens Efficacy has been demonstrated in clinical studies against the pathogens listed under each indication that were susceptible to ceftaroline in vitro . Complicated skin and soft tissue infections Gram-positive micro-organisms • Staphylococcus aureus (including methicillin-resistant strains) • Streptococcus pyogenes • Streptococcus agalactiae • Streptococcus anginosus group (includes S. anginosus , S. intermedius , and S. constellatus ) • Streptococcus dysgalactiae Gram-negative micro-organisms • Escherichia coli • Klebsiella pneumoniae • Klebsiella oxytoca • Morganella morganii Community-acquired pneumonia No cases of CAP due to MRSA were enrolled into the studies. The available clinical data cannot substantiate efficacy against penicillin non-susceptible strains of S. pneumoniae . Gram-positive micro-organisms • Streptococcus pneumoniae • Staphylococcus aureus (methicillin-susceptible strains only) Gram-negative micro-organisms • Escherichia coli • Haemophilus influenzae • Haemophilus parainfluenzae • Klebsiella pneumoniae Antibacterial activity against other relevant pathogens Clinical efficacy has not been established against the following pathogens although in vitro studies suggest that they would be susceptible to ceftaroline in the absence of acquired mechanisms of resistance: Anaerobic micro-organisms Gram-positive micro-organisms • Peptostreptococcus spp. Gram-negative micro-organisms • Fusobacterium spp. In vitro data indicate that the following species are not susceptible to ceftaroline: • Chlamydophila spp. • Legionella spp. • Mycoplasma spp. • Proteus spp. • Pseudomonas aeruginosa