History of Cephalosporins
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Cephalosporins are a class of β-lactam antibiotics originally derived from the fungus Acremonium. They are divided into generations based on their spectrum of activity. First generation cephalosporins such as cephazolin are effective against gram-positive and gram-negative bacteria. Second generation cephalosporins like cefuroxime have increased activity against Haemophilus influenzae and are used to treat respiratory tract infections. Third generation cephalosporins demonstrate better activity against gram-negative bacteria compared to prior generations and some like ceftriaxone have activity against Neisseria meningitidis making them useful for treating bacterial meningitis. Fourth generation cephalospor
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History of Cephalosporins
- 1. DAMRA HASSAN
- 2. History of Cephalosporins •Cephalosporin compounds were first isolated from cultures of Cephalosporium acremonium from a sewer in Sardinia in 1948 by Italian scientist Giuseppe Brotzu
- 3. •The cephalosporins (sg. /ˌsɛfəlɵˈspɔrɨn/) are a class of β-lactam antibiotics originally derived from the fungus Acremonium, which was previously known as "Cephalosporium". •First commercial Cephalosporin was Cephalothin launched by Eli Lily in 1964
- 5. They are divided into 3 groups: Cephalosporin N and C are chemically related to penicillin and Cephalosporin P a steroid antibiotic resembles fusidic acid. They are classified according to the chronological order in which they were produced.
- 6. Classification of Cephalosporins First generation •Cefazolin •Cephalothin •Cephapirin •Cephalexin •Cefadroxil •Cephradine Second Generation •Cefuroxime •Cefaclor •Cefoxitin (cephamycin) •Cefamandole •Cefotetan •Cefmetazole •Cefprozil •Cefpodoxime •loracarbef
- 7. Third Generation • Ceftriaxone • Cefotaxime • Ceftazidime • Ceftizoxime • Cefoperazone • Cefixime Fourth Generation • Cefipime Fifth Generation • Ceftobiprole Medocaril
- 8. Good activity v Staphs and Streps Increased activity v Gram Negatives Slightly less activity against Gram Positives Very good Gram negative coverage Reasonable against Gram Positives Ceftazidime has anti-pseudomonal activity Very broad spectrum activity including Pseudomonas
- 9. I. Indications 1. Effective alternative to Penicillins 2. Covers Gram Positive Cocci 3. Clinical Conditions a. Skin and Soft Tissue Infection b. Streptococcal Pharyngitis c. Not indicated for Otitis Media
- 10. • Good activity v Streps & Penicillin Resistant Staphs. • Surgical prophylaxis for cardiac and vascular surgery, insertion of orthopaedic prostheses, H&N surgery and most gynaecological surgery. • Treatment of Soft tissue infections, particularly in the outpatient setting. (not for bite wounds as poor activity against anaerobes and Pasteurella) Cephazolin
- 11. Cephamycins • Eg Cefoxitin, Cefotetan • Often grouped with 2nd generation cephalosporins • Have anaerobic activity (in particular Bacteroides) • Clinically useful in Surgical Prophylaxis for Colorectal Surgery
- 12. Cefaclor • Oral, good against URTIs & UTIs • Moderate activity in Soft Tissue Infections Cefuroxime • Increased activity v H. influenzae, M. catarrhalis • Used for Community Acquired Respiratory Tract Infections, Surgical prophylaxis for Colorectal Surgery. Treatment of post-operative wound infections.
- 13. First Generation Cephalosporins • Effective against gram(-) &gram (+) • Proteus Mirabilis • E coli • Krebsiella pneumonia Clinical Conditions a. Skin and Soft Tissue Infection b. Streptococcal Pharyngitis c. Not indicated for Otitis Media Example: Cephazolin Second Generation Cephalosporins • Effective against gram(-) • Less Effective against gram(+) • Haemophilus influenza • Proteus Mirabilis • E coli • Krebsiella pneumonia Clinical Conditions 1. Respiratory tract infections 2. Acute Sinusitis 3. Otitis Media Examples:Cephamycins, Cefaclor, Cefuroxime
- 14. Mechanism: Spectrum of Activity Gram Positive Cocci Less activity than First Generation Cephalosporins EKP Gram Negative Bacteria ESP Gram Negative Bacteria Better activity than First Generation Cephalosporins Better activity than Second Generation Cephalosporins No Pseudomonas activity
- 15. Fourth Generation Cephalosporin • The fourth generation cephalosporins have activity against gram-positive cocci and a broad array of gram- negative bacteria, including P. aeruginosa and many of the Enterobacteriaceae with inducible chromosomal - lactamases.
- 16. • Cefipime • Broad spectrum including Pseudomonas / Anti-Pseudomonal (including ceftazidime resistant isolates) • Enhanced activity against certain Gram negative bacilli, including Enterobacter, Citrobacter and Serratia. • Uses. Severe Community Acquired Pneumonia requiring Intensive Care. • Not effective v ESBL producing organisms. • Good gram-positive & gram-negative coverage • Penetrates CSF • Limited anaerobic coverage • Trade Name: Maxipime ®
- 17. • Gram Positive Cocci • Less activity than First Generation Cephalosporins • EKP Gram Negative Bacteria • ESP Gram Negative Bacteria • Better activity than First Generation Cephalosporins • Better activity than Second Generation Cephalosporins • No Pseudomonas activity • active against gram- positive cocci • gram-negative bacteria • P. aeruginosa Example:Cefipime Trade Name: Maxipime Third Generation Cephalosporins Fourth Generation Cephalosporins
- 18. 5th Generation…. Ceftobiprole Medocaril • Activity v MRSA & PRP. • Has completed Phase III trials for treatment of soft tissue infections and HAP. Licensing probably imminent.
- 19. Generally distributes well into the lung; kidney; urine; synovial, pleural, and pericardial fluids. Penetration into the cerebral spinal fluid (CSF) of some 3rd generation cephalosporins(cefotaxime, ceftriaxone, and ceftazidime) is adequate to effectively treat bacterial meningitis. Elimination is primarily via the kidneys, though a few exceptions include cefoperazone and ceftriaxone which have significant biliary elimination. Metabolized in the liver
- 20. •Peak: 30-60 min •Duration:8-10 hrs.
- 21. • Allergies to cephalosporin, food dyes, preservatives • Hepatic impairment • Renal impairment • Pregnant • Lactating patient Contraindications and cautions:
- 22. • Nausea • Vomiting • Diarrhea • Rash • Dizziness • Superinfection • Bone marrow depression • Abdominal pain • Headache • Lethargy Adverse reactions:
- 23. Cephalosporin prescribing in Renal Impairment • Most, apart from Ceftriaxone, need dose adjustment. • Don’t guess, consult with Pharmacist regarding correct dosing. • With exception of Cefipime, should not be used for treatment of Enterobacter, Serratia, Citrobacter infections due to induction of chromosomal Amp C beta-lactamases in these bacteria. • Not effective against Enterococci.
- 24. Drug to drug interaction: • Cephalosporin with aminoglycosides increase the risks of nephrotoxicity • Cephalosporin in addition to anticoagulants experience increase bleeding • Alcohol while receiving cephalosporin or 72 hrs. after receiving cause disulfiram-like reaction
- 25. Nursing considerations: • Allergies to cephalosporin, • Hepatic impairment • Renal impairment • Pregnant • Lactating patient
- 26. o Assess for known allergies o Assess for history of renal and hepatic diseases o Performed physical assessment o Assess the vital signs o Assess the renal function test result including the creatinine clearance o Examine the injection site Assessment:
- 27. • Acute pain related to GI, CNS effect of drug • Deficient fluid volume and imbalance nutrition: less than body requirement, related to diarrhea • Deficient knowledge regarding drug therapy • Risk for infection related to repeated injection Diagnoses:
- 28. Implementation: • Check culture and sensitivity reports • Monitor renal function • Ensure the the patienr receive the full course of cephalosporin as prescribed • Monitor the site of infection and presenting signs and symptoms throught out the course of the therapy • Provide small,frequent meals as tolerated, frequent mouth care, and chips or sugarless candy to suck if stomatitis and sore mouth are problems • Ensure that the patient is hydrated • Ensure that the patient is instructed about the appropriate dosage regimen and possible adverse effect.
- 29. Evaluation: • Patient response to the drug • Adverse effects • Effectiveness of the teaching plan • Effectiveness of comfort and safety measures and compliance with the therapeutic regimen.