頭孢菌素類抗生素（英文）Cephalosporin Antibiotics

1、Cephalosporin AntibioticsFirst discovered in 1945 from a Cephalosporium fungiCommercial drugs derived semi-syntheticallyFrom 7-aminocephalosporanic acid - produced by fermentationSimilar to penicillins 4 GenerationsDerivatives acylated at the 7-amino groupReasons for synthetic modification include:I

2、ncreased acid stabilityImproved pharmacokinetics (oral absorption)Broaden antimicrobial spectrumIncreased activity (decreased resistance due to destruction)Improved penetrationIncreased receptor affinityDecreased allergenicityIncreased tolerance due to parenteral administration Transition from first

3、 generation to third generation agents reflectsBroadening of the Gram (-) organism spectrumLoss of efficacy against Gram (+) organismsGreater efficacy against resistant organisms (but increased cost)MOA: Inhibit cell wall synthesis osmotically induced cell lysisUsually bactericidal a function of dos

4、age, organism susceptibility, tissue concentrations, and growth rateCross allergenicity with penicillins is 5-16%Drug interactions:Alcohol use may produced a disulfiram like reaction - NMTTAminoglycoside nephrotoxicity can be increasedAnticoagulant effects can be potentiated - NMTTAntacids can decre

5、ase plasma concentrations of oral agentsLoop diuretic nephrotoxicity can be increasedMonitor renal function since all are renally excreted Cefoperazone the exceptionCephalosporin AntibioticsClassified by Generations - explosive advancesFirst GenerationEpitomized by cefazolinGood activity against Gra

6、m(+)Modest Gram(-) activitySecond GenerationIncreased Gram(-) activitySome active against baccillus fragilis (highly resistant anaerobe)Third Generation - cost vs. efficacy“Broad” spectrum with high penicillinase resistanceGreater Gram (-) spectrumLess active than G1 against most Gram(+)More active

7、than G1 against enterobacterFourth Generation - CefepimeExtended range of activity compared to G3 More Gram (+)Increased stability against b-lactamasesVERY useful for Gram(-) strains resistant to G3Cephalosporin AntibioticsCephalosporin AntibioticsG1PO: Cephalexin, Cephradine, CephadroxilParenteral:

8、 Cefapirin, CefazolinG2PO: Cefaclor, Loracarbef, Cefprozil, CefuroximeParenteral: Cefmetazole, Cefotetan, Cefonacid, Cefamandol, CefoxitinG3PO: Cefpodoxime, Cefixime, Cefdinir, CeftitbutenParenteral: Cefotaxime, Ceftizoxime, Ceftriaxone, Ceftazidime, CefaperazoneG4 - CefepimeCephalosporin Antibiotic

9、sCephalosporin DeactivationDeactivated Cephalosporin1st Generation CephalosporinsIndications: Respiratory tract infections, Otitis media, skin and skin structure infections, Bone infections, Gram (-) UTI. Used for staph or strep infection in patients with mild hypersensitivity to penicillins! Gram(+

10、) aerobic bacteria - limited Gram(-)Oral use only, 10% protein bound, 90% excreted renally unchangedOne of the Top 200Indications: Oral - Respiratory tract infections, Otitis media, skin and skin structure infections, Bone infections, GU infections, UTI; Parenteral Septicemia; pre-, post- or intraop

11、erative prophylaxisOral or IV/IM use, 17% protein bound, 90% excreted renally unchangedGenerally all are inactivated by b-lactamasesPartial hydrogenation1st Generation CephalosporinsGenerally all are inactivated by b-lactamasesIndications: UTI, pharyngitis and tonsillitis due to group A b-hemolytic

12、Streptococcus, skin and skin structure infections. Oral use only, 20% protein bound, 90% excreted renally unchangedProlonged half-life allows once-a-day dosingIndications: Respiratory tract infections, skin and skin structure infections, Osteomyelitis, UTI, Septicemia, pre-, post- or intraoperative

13、prophylaxis IV/IM use only, 50% protein bound, 70% excreted renally unchangedMethicillin substitute. Comparatively resistant to Staph. penicillinase 1st Generation CephalosporinsGenerally all are inactivated by b-lactamasesIndications: Respiratory tract infections, GU infections, skin and skin struc

14、ture infections, Biliary tract infections, bone and joint infections, Septicemia, endocarditits; pre-, post- or intraoperative prophylaxis. Used for staph or strep infection in patients with mild hypersensitivity to penicillins! NOT for meningitis (cant cross BBB).IM/IV use only, adjust dose as a fu

15、nction of creatinine clearance with 80% excreted renally unchanged, 86% protein boundLonger half-life than Cephapirin, less irritating on injection, heat/light unstable2nd Generation CephalosporinsIndications: Respiratory tract infections, Otitis media, skin and skin structure infections, UTIExtende

16、d release tabs: acute bacterial exacerbations of chronic bronchitis, secondary infections as a result of acute bronchitis, pharyngitis and tonsillitisOral use only, 25% protein bound, 85% excreted unchanged renally Refrigerate suspensionMOST susceptible to b-lactamases in its class!Carbon Isostere o

17、f cefaclorIndications: Secondary bacterial infection of acute bronchitits, pneumonia; Otitis media, acute maxillary sinusitis, pharyngitis, tonsillitis, skin and skin structure infection, UTI such as cystitis and pyelonephritisOral use only, 25% protein bound, 90% excreted unchanged in the urineStor

18、e suspension at room temperature Variable resistance to b-lactamase, more Gram (-) activity2nd Generation CephalosporinsVariable resistance to b-lactamase, more Gram (-) activityIndications: pharyngitis, tonsillitis, otitis media, acute sinusitis, acute and chronic bronchitis, uncomplicated skin and

19、 skin structure infectionsOral use only, 36% protein bound, 60% renal excretion unchanged - dosage adjustment necessary in renal failure - creatinine clearance 30 use 50% the usual dosageSimilar to Cefaclor with improved potencyTop 200 drugAmoxicillin like groupTrans form here imparts Gram(-) activi

20、ty2nd Generation CephalosporinsVariable resistance to b-lactamase, more Gram (-) activityIndications: Lower respiratory tract infections, UTI, intra-abdominal infections, GU infections, skin and skin structure infections, bone and joint infections, Septicemia, pre-, post- or intraoperative prophylax

21、isDo NOT mix in the same IV as aminoglycosides, stability of reconstituted solution is a function of the diluent used, IV use only, 73% protein bound, 85% excreted unchanged in the urineIndications: ORAL: Respiratory tract infections, UTI, early Lyme disease, uncomplicated gonorrhea, skin and skin s

22、tructure infections; PARENTERAL: As above plus septicemia, meningitis, bone and joint infections, mixed infections. Community acquired pneumoniaOral or IV/IM use, 50% protein bound, up to 100% excreted in the urine unchanged - reduce dosage in renal impairment based on creatinine clearance, may be t

23、aken with food, Do NOT mix in the same IV as aminoglycosides or use sodium bicarbonate injection as diluent, do NOT chew tablets due to very bad tasteswallow wholeTop 200 drugCan cross the BBB meningitisNot used as ceftriaxone & cefotaxime preferredCephamycin: Anaerobic activity2nd Generation Cephal

24、osporinsVariable resistance to b-lactamase, more Gram (-) activityIndications: UTI, lower respiratory infections, skin and skin structure infections, intra-abdominal infections, pre-operative prophylaxisIM/IV use only, 65% protein bound, 85% recovered unchanged in the urineDo NOT mix in the same IV

25、with aminoglycosides Indications: UTI, lower respiratory infections, skin and skin structure infections, intra-abdominal infections, peri-operative prophylaxis, GU infections, bone and joint infectionsWatch for nephrotoxicity when use with aminoglycosides - be sure to adjust dosage in renal failure

26、based on creatinine clearance and do NOT mix in the same IV IM/IV only, 90% protein bound, 81% recovered unchanged from the urine These agents + cefoxitin have reasonable anaerobic activity: Peritonitis & diverticulitis2nd Generation CephalosporinsVariable resistance to b-lactamase, more Gram (-) ac

27、tivityIndications: Lower respiratory infection, UTI, skin and skin structures, septicemia, bone and joint infections, pre-operative prophylaxisIV/IM use only, 90% protein bound, 99% excreted unchanged in the urine-dosage adjustment necessary in renal failureAdmix incompatibility with aminoglycosides

28、Longer half-life than other G2, lower Gram(+) potencyIndications: Lower respiratory infection, UTI, peritonitis, skin and skin structures, septicemia, bone and joint infections; pre-, intra- and post-operative prophylaxisAdmix incompatibility with aminoglycosidesIV/IM use only, dosage reduction nece

29、ssary based on renal functionNMTT bleeding and disulfuram problemsNMTTDiester prodrug!-extended spectrum agentIndications: acute community-acquired pneumonia, chronic bronchitis, acute otitis media, pharyngitis, tonsilllitis, acute uretheral, cervical or rectal gonorrhea but NOT pharyngeal disease;

30、skin and skin structure infections, UTIUseful in cirrhosis patientsno dosage adjustment needed, renal failure necessitates dosage adjustmentOral use only, 29% protein bound, 33% excreted unchanged in the urineIndications: UTI, otitis media, pharyngitis, tonsillitis, acute and acute chronic bronchiti

31、s, cervical or urethral gonorrheaOral use only, 65% protein bound, 50% excreted unchanged in the urineDOC gonorrhea single 400mg dose3rd Generation Cephalosporins Indications: Community acquired pneumonia, acute exacerbation of chronic bronchitits, acute maxillary sinusitis, pharnygitis, tonsillitis

32、, skin and skin structure infections, acute otitis mediaOral use only, 70% protein bound, 17% excreted unchanged in the urine but dosage still needs reduced in renal failureIndications: acute bacterial exacerbations of chronic bronchitis, acute bacterial otitis media caused by H. influenza, pharyngi

33、tis and tonsillitits caused by S. pyogenesOral use only, 65% protein bound, 56% excreted unchanged in the urine - dosage adjustment as a function of creatinine clearance3rd Generation CephalosporinsCeftibutenIndications: Lower respiratory infection, UTI, gynecological infection, bacteremia/septicemi

34、a, skin and skin structure infections, intra-abdominal infections, bone or joint infections, meningitis or other CNS infections, perioperative prophylaxisCDC recommended treatment for gonorrheaIM/IV, 40% protein bound, 60% renal excreted unchanged adjust with renal fx3rd Generation CephalosporinsInd

35、ications: Lower respiratory infection, UTI, gonorrhea and PID, septicemia, skin and skin structure infections, intra-abdominal infections, bone or joint infections, meningitisIM/IV use only, 30% protein bound, 80% excreted unchanged in the urine-dosage reduction necessary in renal failureIndications

36、: Lower respiratory infection, UTI, gonorrhea and PID, septicemia, skin and skin structure infections, intra-abdominal infections, bone or joint infections, meningitis, surgical prophylaxis, effective in treating Lyme disease infection causing neurological complications, arthritis and carditits refr

37、actory to PenGDOC Gonorrhea single injectionIM/IV use only, 95% protein bound, 67% excreted unchanged in the urine3rd Generation CephalosporinsIndications: Lower respiratory infections, skin and skin structure infections, UTI, bacterial septicemia, bone and joint infections, gynecological infections

38、, intra-abdominal infections, CNS infections, concomitant antibiotic therapy in immunocompromised patientsRenal excretion-adjust dosage as a function of GFR90% unchangedSodium bicarbonate solution is NOT recommended as a diluent, do NOT mix with aminoglycosidesIM/IV use only, 10% protein boundIndica

39、tions: Respiratory tract infections, peritonitits and other intra-abdominal infections, bacterial septicemia, skin and skin structure infections, PID, endometritis, UTI IM/IV only, 93% protein bound, 30% excretion unchanged in the urineExtensively excreted in the bilemonitor serum concentrations in high doses in the case of hepatic disease or biliary obstructionRenal failure-no dose adjustment except in high doses3rd Generation Cephalosporins4th Generation CephalosporinsIndications: UTI, skin and skin structure infections, pneumonia (moder