CEPHALOSPORINS

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Khushbu on Jul 23, 2012 Says :

great work on cephalosporins.

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Slide 1 :

Cephalosporin Akshaya Srikanth Pharm.D Internee

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Cephalosporin Cephalosphorin are bacteridal and work by interfering with bacterial cell wall synthesis. Active against gram-positives, gram-negatives or anaerobic bacteria. They do not against fungi and viruses.

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Cephalosporins are ß-Lactam antibiotics isolated from Cephalosporium spp. 3 inhibit wide variety of gram(+) and gram(-) bacteria Abraham and Newton, the suppliers of fungi cultures isolated three principal antibiotic components: Cephalosporin PI Cephalosporin N Cephalosporin C - a steroid with minimal antibacterial property - Identical with synnematin N ( also called penicillin N ) Resistant to S. aureus B-lactamase; antibacterial property is inferior to penicillin N.

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Cephalosporins Cephalosporin N or Penicillin N - the amino acid in the chain confers more activity against gram(-) bacteria particularly Salmonella spp. - less active against gram(+) organism - contains thiazolidine ring 4

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Cephalosporins Cephalosporin C - congener of Penicillin N - contains dihydrothiazide ring 5

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Generation Of Cephalosporins

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First Generation Cephalosporins First-generation cephalosporins are usually active against gram-positive and have limited activity against gram-negative bacteria. They are available both in parental and oral forms. Currently available first-generation cephalosporins include cefadroxil, cefazolin, cephalexin and cephradine.

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Action Bind to bacterial cell wall membrane, causing cell death. Therapeutic Effects Bactericidal action against susceptible bacteria. Spectrum Active against many gram-positive cocci including: Streptococci, Penicillinase-producing Staphylococci. Not active against: Methicillin-resistant Staphylococci, Bacteroides fragilis, Enterococcus. Active against some gram-negative rods including: Klebsiella Pneumoniae, Proteus mirabilis, Escbericbia coli.

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Second generation Second generation cephalosporins have coverage against gram-positive organisms similar to that of the first-generation cepalosporins but have enhance coverage against gram-negative bacteria. Both parenteral and oral formulation are available. Currently available second generation cephalosporin include cefoxitin and cefuroxime.

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Third-Generation Cephalosporins Drug included Ceftriaxone Ceftazidime Most potent of the first three generation in fighting gram-negative bacteria but less activity than the first and second drug against gram-positive organism.

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Fourth-generation cephalosporin There are currently three fourth-generation cephalosporin:cefdinir,cefepime,and cefditoren pivoxil. Some references classify these with the third generation drug. They have a broader spectrum of anti bacteria activity, especially against gram-positive bacteria, than the third generation drug.

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TYPE OF DRUG UNDER CEPHALOSPORINS FIRST GENERATION

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SECOND GENERATION

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THIRD GENERATION

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FOURTH GENERATION

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SIDE EFFECT OF DRUG UNDER CEPHALOSPORIN *Cns :Seizures(high doses) *GI :Diarrhea, nausea, and vomiting *Derm :Rashes, pruritis *Hemat :Hemolytic anemia, thrombocytopenia *Misc :Allergic reaction including anaphylaxis a serum sickness, super infection.

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Diagnosis Rashes related to side effect of cephalosporin medication as evidence by patient complain of red and itchy at his/her skin. Goal Reduce rashes of the patient

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INTERVENTION Asses the rashes such as location, level of pain, condition of rashes to develop medical treatment of the patient. Stop all the antibiotic related to cephalosporin group to avoid the rashes became bigger and more pain. Encourage patient to take bath frequently to increase patient hygiene and reduce the rashes. Avoid and note the patient from scratch the rashes area to prevent rashes from spread. Limited the visitor to avoid other from the rashes.

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Fifth generation cephalosporins were developed in the lab to specifically target against resistant strains of bacteria. In particular, ceftobiprole is effective against methicillin-resistant Staphylococcus aureus (MRSA). What are 5th generation Cephalosporins

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Ceftaroline is a beta-lactam of the cephalosporin class of antimicrobials with activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria associated with skin and respiratory infections. It also has activity against methicillin-resistant Staphylococcus aureus and Streptococcus pneumonia. Ceftraroline, a 5th generation cephalosporin

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FDA APPROVES CEFTAROLINE FOSAMIL On October 29th, FDA has approved Ceftaroline Fosamil, it is an antibiotic indicated for the treatment of adults with ACUTE BACTERIAL SKIN AND SKIN STRUCTURE INFECTIONS (ABSSSI) caused by susceptible Gram-positive and Gram-negative microorganisms, such as Staphylococcus aureus (including methicillin-susceptible and -resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Escherichia coli, Klebsiella pneumoniae, and Klebsiella oxytoca.

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Also for the treatment of community-acquied bacterial pneumonia (CABP) caused by susceptible Gram-positive and Gram-negative bacteria, such as Streptococcus pneumoniae (including cases with concurrent bacteremia), Staphylococcus aureus (methicillin-susceptible isolates only), Haemophilus influenzae, Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli.

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Ceftaroline is a broad-spectrum cephalosporin. Ceftaroline has the ability to bind to penicillin-binding protein (PBP) 2a , an MRSA-specific PBP that has low affinity for most other ß-lactam antibacterial. The high binding affinity of ceftaroline to PBP 2a (median inhibitory concentration 0.90?µg/mL) correlates well with its low minimum inhibitory concentration for MRSA. How ceftaroline works

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ADVANTAGES OF CEFTAROLINE The high affinity of ceftaroline for penicillin-binding proteins is responsible for the potent activity observed against clinically relevant pathogens. With respect to the treatment of CABP, the activity of ceftaroline against pathogens such as S. pneumoniae, S. aureus, Haemophilus influenzae and Moraxella catarrhalis demonstrates coverage across a broad range of pathogens typically encountered in clinical practice. Ceftaroline is also very active against common pathogens seen in ABSSSIs such as S. aureus (methicillin-susceptible S. aureus and methicillin-resistant S. aureus) and Streptococcus pyogenes.

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Ceftaroline was developed by modifying the structure of the fourth-generation cephalosporin cefozopran. The prodrug, ceftaroline fosamil, which contains a phosphono group to increase water solubility, is rapidly converted in plasma into the bioactive agent, ceftaroline The 1,3-thiazole ring attached to the 3-position of the cephalosporin nucleus and the oxime group in the C7 acyl moiety are responsible for the enhanced anti-MRSA activity observed with ceftaroline. MECHANISM OF ACTION OF CEFTAROLINE

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CEFTAROLINE IS ACTIVE ON Ceftaroline is active in vitro against Gram-positive cocci, including MRSA, methicillin-resistant Staphylococcus epidermidis, penicillin-resistant Streptococcus pneumoniae and vancomycin-resistant Enterococcus faecalis (not E. faecium). The broad-spectrum activity of ceftaroline includes many Gram-negative pathogens but does not extend to extended-spectrum ß-lactamase-producing or AmpC-derepressed Enterobacteriaceae or most nonfermentative Gram-negative bacilli.

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Ceftaroline has been shown to have synergistic activity against Gram-negative species in combination with an aminoglycoside. In an in vitro study, ceftaroline plus amikacin was synergistic against 90% of isolates tested, including Pseudomonas aeruginosa, extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli, ESBL-producing Klebsiella pneumoniae and AmpC-derepressed Enterobacter cloacae. Synergy was also demonstrated for ceftaroline in combination with meropenem against all E. coli isolates tested CEFTAROLINE HAS SYNERGISTIC ACTION

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Fifth generation Ceftobiprole has been described as "fifth generation",] though acceptance for this terminology is not universal. Ceftobiprole (and the soluble prodrug medocaril) are on the FDA fast-track. Ceftobiprole has powerful antipseudomonal characteristics and appears to be less susceptible to development of resistance. FIFTH GENERATION CEFTOBIPROLE

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CEFTOBIPROLE IS A Ceftobiprole is a 5th generation cephalosporin antibiotic with activity against methicillin-resistant STAPHYLOCOCCUS AUREUS, PENICILLIN-RESISTANT STREPTOCOCCUS PNEUMONIAE, PSEUDOMONAS AERUGINOSA, AND ENTEROCOCCI. It was discovered by Basilea Pharmaceutica and was developed by Johnson & Johnson Pharmaceutical Research and Development. It has been shown to be statistically non-inferior to the combination of vancomycin and ceftazidime for the treatment of skin and soft tissue infections.

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Ceftobiprole inhibits the 2a penicillin-binding protein (pbp) of Methicillin-resistant Staphylococcus aureus and the 2x pbp of Streptococcus pneumoniae as well as the classic PBP-2 of MSSA. Ceftobiprole is resistant to staphylococcal ß-lactamase PHARMACOLOGY OF CEFTOBIPROLE

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HOW CEFTOBIPROLE DIFFERS FROM OTHER BETA LACTAMS Ceftobiprole can be distinguished from other beta-lactams by its increased binding to penicillin-binding protein 2a. Penicillin-binding proteins, the targets of beta-lactam antibiotics, are enzymes found in the membrane that are the last step of peptidoglycan biosynthesis. Penicillin-binding protein 2a is the enzyme most directly related to methicillin-resistant staphylococci. Activity of ceftobiprole has been studied against both the community-acquired MRSA strains and hospital-acquired MRSA

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Thank you

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