Description

CEFTECT SB CEFTECT SB is an Antibiotic Adjuvant Entity (AAE) comprising of cefepime hydrochloride, a fourth generation cephalosporin, sulbactam sodium, a betalactamase inhibitor and a non-antibiotic adjuvant L-arginine. It is available as sterile, dry powder for reconstitution before use. Cefepime hydrochloride, is a semi-synthetic, broad spectrum antibiotic for parenteral administration. Cefepime hydrochloride is a white to pale yellow powder and a molecular weight of 571.5 g/mol. It is highly soluble in water. Sulbactam sodium is a derivative of basic penicillin nucleus. It is an irreversible ß-lactamase inhibitor. The molecular weight is 255.22 g/mol. It contains 92 mg sodium per gram. L-arginine, at an approximate concentration of 72.5% of TM cefepime is added as excipient. CEFTECT SB is supplied for intramuscular and intravenous administration in strengths of 750 mg, 1.5 g and 3.0 g. It is packaged in tubular glass vials. Indications Mainly for the treatment of lower respiratory tract infections (LRTI; Nosocomial and community acquired pneumonia), uncomplicated and complicated urinary tract infections (UTI; including pyelonephritis) and mild to moderate bacterial septicemia. Additional indications: Skin and skin structure infections and severe/complicated intra-abdominal infections (including peritonitis and gallbladder infection). MICROBIOLOGY Cefepime and sulbactam act synergistically and have a broad spectrum of in vitro activity that encompasses a wide range of ESBL gram positive and gram negative bacteria. Cefepime exhibits rapid penetration into gram-negative bacterial cells. Cefepime and sulbactam combination has been shown to be active against ESBL strains of the following bacteria (including beta-lactamase producing isolates). Cefepime and Sulbactam have been shown to be active against most strains of the following microorganisms both in vitro and in clinical infection. Aerobes (Gram-negative bacteria): Enterobacter, Escherichia coli, Klebsiella pneumoniae, Proteus sp. (including indolepositive and indole-negative, Proteus mirabilis), Pseudomonas aeruginosa, Acinetobacter calcoaceticus subsp. Woffii, Citrobacter diversus, Citrobacter freundii, Enterobacter agglomerans, Haemophilus influenzae, Hafnia alvei, Klebsiella oxytoca, Moraxella catarrhalis,Morganella morganii, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia marcescens, Neisseria meningitidis. Aerobes (Gram-positive bacteria): Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pneumoniae, Streptococcus pyogenes(Lancefield's Group Astreptococci), Staphylococcus epidermidis(methicillinsusceptible isolates only), Staphylococcuss aprophyticus, Streptococcus agalactiae (Lancefield's Group B streptococci). Anaerobes (Gram-negative bacteria): Bacteroides fragilis, Citrobacter diversus, Citrobacter freundil, Providencia species, Salmonella species (including S. typhi), Shigella species. Anaerobes (Gram-positive bacteria): Peptostreptococcus species, Clostridium species, Peptostreptococcus species. The combination agent is useful in the treatment of moderate to severe infections particularly when a ESBLmicrobial etiology is suspected or documented. The combination of cefepime and sulbactam is active against all the organisms sensitive to cefepime. In addition, sulbactam itself has the highest intrinsic activity of the betalactamase inhibition against the opportunistic pathogen, Acinetobacter baumannii. In addition Sulbactam, has several advantages over Tazobactam. Sulbactam binds with plasmid mediated and chromosomal mediated beta-lactamases produced by Enterobacteriaceae, whereas Tazobactam binds with only plasmid mediated betalactamases produced by Enterobacteriaceae. Sulbactam displayed highest interaction energy in docking study against CTM-X class of beta-lactamases, whereas Tazobactam displayed less interaction energy in Docking study against CTM-X class of betalactamases. Sulbactam has higher intrinsic bacteriostatic property against Bacteroidesspp., Acinetobacterspp., and N. gonorrhoeae than Tazobactam. Mechanism Of Action CEFTECT SB containing cefepime is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Sulbactam is an irreversible ß-lactamase inhibitor which binds the ß-lactamase enzyme and does not allow it to interact with the antibiotic, thus extending their spectrum of activity. It has maximum activity against CTXM (Cefotaxime resistant β-lactamases gene) type of class A ß-lactamases, and moderate activity against TEM-β- lactamases gene & SHV-β-lactamases gene. It does not induce the production of AmpC type class C beta- lactamases. Synergistic action CEFTECT SB containing cefepime and sulbactam is a synergistic antimicrobial combination with marked in vitro antibacterial activity against a broad spectrum of ESBL (Extended-spectrum beta-lactamase) organisms. Sulbactam not only potentiates the antibacterial activity by inhibiting beta-lactamases,