Cefotaxim-MIP 1 g

Pharmacotherapeutic group: Third-generation cephalosporin, ATC code: J01DD01 Mechanism of action The bactericidal activity of cefotaxime results from the inhibition of bacterial cell wall synthesis (during the period of growth) caused by an inhibition of penicillinbinding proteins (PBPs) like transpeptidases. Mechanism of resistance A resistance to cefotaxime may be caused by following mechanisms: • Inactivation by beta-lactamases. Cefotaxime can be hydrolysed by certain betalactamases, especially by extended-spectrum beta-lactamases (ESBLs) which can be found in strains of Escherichia coli or Klebsiella pneumoniae , or by chromosomal encoded inducible or constitutive beta-lactamases of the AmpC type which can be detected in Enterobacter cloacae . Therefore infections caused by pathogens with inducible, chromosomal encoded AmpC- beta-lactamases should not be treated with cefotaxime even in case of proven in-vitro susceptibility because of the risk of the selection of mutants with constitutive, derepressed AmpC- beta-lactamases-expression. • Reduced affinity of PBPs to cefotaxime. The acquired resistance of Pneumococci and other Streptococci is caused by modifications of already existing PBPs as a consequence of a mutation process. In contrast to this concerning the methicillin- (oxacillin-) resistant Staphylococcus , the creation of an additional PBP with reduced affinity to cefotaxime is responsible for resistance. • Inadequate penetration of cefotaxime through the outer cell membrane of gramnegative bacteria so that the inhibition of the PBPs is insufficient. • The presence of transport mechanism (efflux pumps) being able to actively transport cefotaxime out of the cell. A complete cross resistance of cefotaxime occurs with ceftriaxone and partially with other penicillins and cephalosporins. Breakpoints: The following minimal inhibitory concentrations were defined for sensitive and resistant germs: EUCAST (European Committee on Antimicrobial Susceptibility Testing) break points (2019-01- 01):Pathogen Susceptible Resistant Enterobacteriaceae ≤ 1 mg/l > 2 mg/l Staphylococcus spp. Note1 Note1 Streptococcus (group A, B, C,G) Note2 Note2 Streptococcus pneumoniae ≤ 0.5 mg/l > 2 mg/l Viridans group streptococci ≤ 0.5 mg/l >0.5 mg/l Haemophilus influenzae ≤ 0.125 mg/l > 0.125 mg/l Moraxella catarrhalis ≤ 1 mg/l > 2 mg/l Neisseria gonorrhoeae ≤ 0.12 mg/l > 0.12 mg/l Neisseria meningitidis ≤ 0.12 mg/l*** > 0.12 mg/l Not species-specific breakpoints**** ≤ 1 mg/l > 2 mg/l Susceptible Resistant Enterobacteriaceae < 1 mg/L >2 mg/L Staphylococcus sppHE Note1 Note1 Streptococcus (group A, B, C, G Note2 Note2 Streptococcus pneumoniae ≤0.5 mg/L >2 mg/L Viridans group streptococci ≤0.5 mg/L >0.5 mg/L Haemophilus influenzae ≤0.125 mg/L >0.125 mg/L Moraxella Catarrhalis ≤1 mg/L >2mg/L Neisseria gonorrhoeae ≤0.125 mg/L >0.125 mg/L Neisseria Meningitidis3 ≤0.125 mg/L >0.125 mg/L Pasteurella multocida ≤0.03 mg/L >0.03 mg/L Kingella Kingae ≤0.125 mg/L >0.125 mg/L PK-PD (Non-species related) breakpoints ≤1mg/L >2mg/L HE = high exposition / high dose only for S. aureus (high dose of at least 3 x 2 g iv) 1 Susceptibility of staphylococci to cephalosporins is inferred from the cefoxitin susceptibility except for cefixime, ceftazidime, ceftazidime-avibactam, ceftibuten and ceftolozane-tazobactam which do not have breakpoints and should not be used for staphylococcal infections. 2 The susceptibility of streptococcus groups A, B, C and G to cephalosporins is inferred from the benzylpenicillin susceptibility. 3 Non-susceptible isolates are rare or not yet reported. The identification and antimicrobial susceptibility test result on any such isolate must be confirmed and the isolate sent to a reference laboratory. Susceptibility The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable particularly when treating severe infections. If the efficacy of cefotaxime is questionable due to the local prevalence of resistance, expert opinion should be sought regarding the choice of therapy. In particular in the case of severe infections or failure of therapy, a microbiological diagnosis including a verification of the germ and its susceptibility should be aspired. COMMONLY SUSCEPTIBLE SPECIES Gram-positive aerobe Staphylococcus aureus (Methicillin-susceptible) Streptococcus agalactiae Streptococcus pneumoniae(incl. penicillin-resistant strains) Streptococcus pyogenes Gram-negative aerobes Borrellia burgdorferi Haemophilus influenzae Moraxella catarrhalis Neisseria gonorrhoeae Neisseria meningitides Proteus mirabilis % SPECIES FOR WHICH ACQUIRED RESISTANCE MAY BE A PROBLEM Gram-positive aerobes Staphylococcus aureus Staphylococcus epidermidis + Staphylococcus haemolyticus + Staphylococcus hominis + Gram-negative aerobes Citrobacter freundii Enterobacter aerogenes Enterobacter cloacae Escherichia coli % Klebsiella oxytoca % Klebsiella pneumoniae J % Morganella morganii Proteus vulgaris Serratia marcescens Anaerobes Bacteroides fragilis INHERENTLY RESISTANT SPECIES Gram-positive aerobes Enterococcus spp. Listeria monocytogenes Staphylococcus aureus (methicillin-resistant) Gram-negative aerobes Acinetobacter spp. Pseudomonas aeruginosa Stenotrophomonas maltophilia Anaerobes Clostridium difficile Others Chlamydia spp Chlamydophila spp. Legionella pneumophila Mycoplasma spp. Treponema pallidum + In at least one region the resistance rate is > 50 %. # In Intensive Care Units the resistance rate is < 10 %. % Extended Spectrum Beta-Lactamase (ESBL) producing strains are always resistant