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CEPHALOSPORINS, Oral
Cefixime
Cefpodoxime proxetil
Cefdinir
…
CEPHALOSPORINS
FIRST GEN :check:
CEFAZOLIN
- Prototype
SPECTRUM: :check:
- Most PnG sensitive org.
- Strep. pyogenes/viridans, gonococci, meningococci, C. diphtheriae, H.influenzae, Clostridia, Actinomyces
- Klebsiella, Moraxella, E.coli action high
- Susceptible to staph. ß lactamase
- Parenteral use: IM-mildly painful, IV
- Longer T½ & slow Tub. secrn.
- Higher conc. in plasma & bile
Use :check: : Surgical prophylaxisDose: :check: 0.5-2g, IV 8hrly
CEPHALEXIN
SPECTRUM :check:
- Similar spectrum
- Less active against penicillinase producing staph. & H.influenzae
- Low PPB
- High conc in bile
- Excr. unchanged in urine
CEFADROXIL
- Close congener of cephalexin
- Oral
- Good tissue penetration→
○ More sustained action at inf. site
○ Hence given 12 hrly despite a T½ of 1 hr
- Excr. unchanged in urine
○ Dose redn. if creatinine clearance <50ml/min
PHARMACOKINETICS & DOSAGE
:check:
A. ORAL
- Urine conc. ↑
- Tissue levels variable
- Excrn. via GF & TS
- Drugs that block TS→ probenecid ↑ serum levels
- Dose redn. in renal impairment
B.PARENTERAL
- IM, IV admn
- Excrn. via kidney
- Dose adjustment n renal impairment
CLINICAL USES :check: ORAL
- UTIs
- Staph. & Strep infections
Cellulitis, soft tissue abscess
- Not for serious systemic illness
PARENTERAL
- DOC→ surgical prophylaxis
- Strep & Staph inf. requiring IV therapy
- Does not penetrate CNS⮽
- Better tolerated than anti-staph. penicillins
SECOND GEN :check:
- More active against G-ve
- Wider spectra
CEFUROXIME
SPECTRUM :check:
- Resistant to G-ve ß lactamases
- PPNG, ampicillin resistant H.influenzae
- G+ cocci & certain anaerobes
- IM admn.
- High CSF levels attained
Use: :check:
- Single dose IM therapy of gonorrhea d/t PPNG
CEFUROXIME AXETIL
- Ester ppn
- Oral admn. but incomplt. abs.
- Activity depends on in vivo hydrolysis & release of cefuroxime
Dose: :check: 250-500mg BD
CEFACLOR
- Oral admn
- Against H.infuenzae, E.coli, P. mirabilis, some anaerobes
- Highly susceptible to ß lactamases
CEFPROZIL
- >90% oral abs.
- Augmented action against
→
○ Strep. puogenes/pneumoniae, Staph. aureus (not MRSA), H.influenzae, Moraxella, Klebsiella
- Excrn. → kidney
Use :check:
- Bronchitis, ENT, skin inf.
SPECTRUM :check:
- Extended G-ve coverage
- Klebsiella(incl. resistant), H.influenzae, etc
- Improved stability with ESBL produced by E.coli, Klebsiella
- Cefoxitin, cefotetan→ against anaerobes
PHARMACOKINETICS & DOSAGE
:check:
Heterogenous group with individual differences in activity, PK, toxicity
A. ORAL
- MC used: cefuroxime axetil
- Not active against penicillin non-susceptible pneumococci
B. PARENTERAL
- IM painful & to be avoided
- Doses & dosing intervals vary ~agent
- Dose dep. difference in T½, PPB & dosage interval.
- All renal cleared→ dosage adj. in RF
CLINICAL USES :check:
A. ORAL
B. PARENTERAL
- Cefoxitin, cefotetan→ mixed anaerobic inf. & peritonitis
- Cefuroxime→ CAP
- Not used in meningitis though it crosses BBB
THIRD GEN :check:
CEFOTAXIME
SPECTRUM :check:
- Aerobic G-ve & G+ bacteria
- Not active with anaerobes, Staph. aureus, Ps. aeruginosa
PK :check:
- Deacetylated→ metabolite→ weaker but synergistic action
- Plasma T½ of metabolite > parent drug
Dose: :check: 1-2g IM/IV 6-12hrlyINDICATIONS :check:
- Meningitis by G-ve bacilli
- Resistant HAI, septicemias, inf. in immunocompromised
- Typhoid
○ Alt. to Ceftriaxone
- Single dose therapy for PPNG urethritis
CEFTIZOXIME
- Similar AMA & indications, Parenteral
- Inhibits Bacteroides fragilis also
- Not metabolised→ exc. by kidney slowly
Dose : :check: 0.5-2g IM/IV 8-12 hrly
CEFTRIAXONE
- Longer duration of action
○ Once daily/ twice daily dosing
- Penetration to CSF good
- Elmn. via urine & bile
- Parenteral
INDICATIONS :check:
- High efficacy in→
○ Bacterial meningitis (esp. children)
○ Multiresistant typhoid fever
○ Complicated UTIs
○ Abdominal sepsis
○ Septicemias
- Meningitis
○ 4g followed by 2g IV OD for 7-10dy
- Typhoid
○ 4g IV OD x2days followed by 2g/day till 2 days after fever subsides
- Single 1g IM dose→ curative for gonorrhea(incl. PPNG) & chancroid
- Alt. drug for syphilis
○ 1g IM x7days→ Early
○ 1g x15 days→ Late
ADVERSE EFFECTS :warning:
- Hypoprothrombinemia
- Bleeding
CEFTAZIDIME
- High activity against Pseudomonas aeruginosa
- Less active against Staph. aureus, other G+ cocci, anaerobes like Bacteroides
INDICATIONS :check:
- Febrile neutropenic patients with hematological malignancies, burns, etc
ADVERSE EFFECTS :warning:
- Neutropenia, thrombocytopenia
- Rise in plasma transaminaes, blood urea↑
Dose : :check: 0.5-2g IM/IV every 8 hr
CEFOPERAZONE
- Stronger action against Pseudomonas
- S. typhi, B. fragilis inhibited
- Susceptible to ß lactamases
- Excr. in bile
INDICATIONS :check:
- Severe urinary, biliary, resp., skin-soft tissue infections, typhoid & septicemias
ADVERSE EFFECTS :warning:
- Hypoprothrombinemic action
- No bleeding
- Disulfiram-like reaction with alcohol
CEFIXIME
SPECTRUM : :check:
- Highly active against Enterobacteriaceae, H. influenzae, Strep. pyogenes, resistant to ß lactamases
- Not active on Staph. aureus, most pneumococci, Pseudomonas
INDICATIONS : :check:
- Resp/ urinary/ biliary inf.
○ 200-400mg BD
ADVERSE EFFECTS :warning:
CEFPODOXIME PROXETIL
- Orally active Ester prodrug
- Highly active against Enterobacteriacease & Streptococci, inhibits Staph aureus
INDICATIONS :check:
- Resp., urinary, skin, soft tissue inf.
Dose : :check: 200mg BD
CEFDINIR
- Orally active
- Activity against many ß lactamase producing org.
- Most resp. pathogens, G+cocci are susceptible
INDICATIONS :check:
- A/c exacerbation of c/c bronchitis
- Pneumonia
- ENT, skin inf.
Dose: :check: 300mg BD
CEFTIBUTEN
- Oral
- Active against G+ & few G-ve
- Not against Staph. aureus
- Stable to ß lactamases
INDICATIONS :check:
CEFTAMET PIVOXIL
- Ester prodrug
- High activity against G-ve esp. Enterobacteriaceae, N. gonorrhea
INDICATIONS :check:
- Resp, skin & soft tisue inf.
FOURTH GEN :check:
- Non-susceptibility to inducible chromosomal ß lactamases
- High potency against Enterobacteriaceae & spectrum ~ 3rd gen
Dose: :check: 1-2g/12hrly
CEFEPIME
- Highly resistant to ß lactamases
- Active against Ps. aeruginosa, Strep.pneumoniae, H.influenzae,Staph. aureus ( but not MRSA)
- High potency, extended spectrum
- Higher conc. in CSF
- Excr. by kidney
INDICATIONS :check:
- HAI, febrile neutropenia
- Bacteremia
- Septicemia
CEFPIROME
- Zwitterion character→ better penetration into G-ve bacteria
- Resistant to many ß lactamases
- Inhibits Type I producing Enterobacteriaceae
- More potent
INDICATIONS :check:
- Serious & resistant HAI
- Septicemias & LRTIs
FIFTH GEN :check:
- Distinguished by ability to kill MRSA & other bacteria with penicillin resistance d/t altered PBP
CEFTAROLINE FOSAMIL
- Prodrug → IV inf.→ active Ceftaroline**→ cidal**
SPECTRUM :check:
- G+ & G-ve bacteria incl. MRSA, penicillin resistant Strep. pneumoniae, Enterococcus faecalis
- Ability to bind to altered PBPs
○ HA for PBP2a in MRSA
○ PBP2b & PBP2x in penicillin resistant Strep. pneumoniae
- Susceptible to ESBL
INDICATIONS :check:
- Complicated skin & soft tissue infections
- CAP→ MRSA res. Strep. pneumonia
ADVERSE EFFECTS :warning:
- Headache/ dizziness/ itching
- Rashes/ fever/ diarrhea/ irritation of inj. vein
CEFTOBIPROLE MEDOCARIL
- Prodrug→ active ceftobiprole by type A esterases
- Minimal metabolism→ excr. in urine
- No accumulation occurs
SPECTRUM :check:
- Active against MRSA, G-ve (HAP & CAP)
- Binds to PBP2a in MRSA
- PBP2x in penicillin resistant Strep. pneu
- PBP5 in resistant Enterococcus fecalis
INDICATIONS :check:
- Monotherapy for HAP & severe CAP
- Complicated skin/soft tissue infections
ADVERSE EFFECTS :warning:
- Nausea, diarrhea, infusion site infections
- Rise of hepatic transaminases, hyponatremia
Dose: :check: 500mg over 2hrs every 8hrly
ADVERSE EFFECTS 1. Pain after IM inj.
- Many cephalosporins
- Thrombophlebitis can occur
2. Diarrhea
- D/t alteration of gut ecology/ irritation
- MC with oral admn- Cephalexin, cefixime
- And Parenteral Cefoperazone→ excr. in bile
3. HS reactions
- Lower incidence
- Rashes, anaphylaxis, angioedema, asthma & urticaria
- Positive Coomb's test in many patients
4. Nephrotoxicity
- Low grade toxicity
- Accentuated by preexisting renal disease, concurrent admn of AG/LD
5. Bleeding
- CS having Methylthiotetrazole/ similar substitution at 3rd position
○ Cefoperazone, ceftriaxone
6. Neutropenia, thrombocytopenia
7. Disulfiram like reaction with alcohol
USES 1. Alt. to Penicillin
- ENT/ URTI/ cutaneous inf.
- 1st gen
2. Resp/ urinary/ soft tissue inf. by G-ve
- Klebsiella, Proteus, Enterobacter, Serratia
- Cefuroxime, cefotaxime, ceftriaxone
- CAP d/t resi. Strep pneumoniae→ Ceftaroline fosamil
- HAP→ Ceftobiprole medocaril
3. Penicillinase producing Staph. inf.
- MRSA→ Ceftaroline fosamil
4. Septicemias d/t G-ve org.
5. Surgical Prophylaxis
6. Meningitis
- Empirical therapy before diagnosis
○ Cefotaxime/ ceftriaxone + Ampicillin/ Vancomycin/ both
- Pseudomonal meningitis→ Ceftazidime + gentamicin
- 3rd gen CS→ not useful
7. Gonorrhea
- Cefuroxime, cefotaxime
- Chancroid & syphilis also
8. Typhoid
- Ceftriaxone & cefoperazone IV
○ Fastest drugs
- Preferred over FQs
- Advantages
○ Quick defervescence→2-3 days
○ Early abetment of symptoms
○ Low risk of relapse & complications
○ Prevent carrier state→ cidal action
○ Treat typhoid carriers
9. Mixed aerobic-anaerobic inf.
10. HAI
- cefotaxime, ceftizoxime, 4th gen cephalosporin+ vancomycin
- ceftobiprole medocaril-alt.
11. Prophylaxis & treatment of infections in Neutropenic patients
-
2nd Gen Parenteral
Oral
- Cefaclor
- Cefuroxime axetil
- Cefprozil
3rd Gen Parenteral
- Cefotaxime
- Ceftizoxime
- Ceftriaxone
- Ceftazidime
- Cefoperazone
-
5th Gen
- Ceftaroline fosamil
- Ceftibiprole medocaril
Oral
- Cefixime
- Cefpodoxime proxetil
- Cefdinir
- Ceftibuten
- Ceftamet pivocil