Cephalosporin

MECHANISM OF ACTION:
  • Binds to penicillin binding proteins and inhibition of formation of cell wall
  • Cephalosporin are Bacteriocidal
MECHANISMS OF RESISTANCE:
  • Changes in drug target of penicillin binding proteins - methicillin-resistant Staphylococcus aureus
  • Lack of access of the drug to the penicillin binding protein target
  1. Efflux pumps – MexAB-OprM efflux pump in Pseudomonas aeruginosa
  2. Decreased permeability of cell wall – less common for cephalosporins
  3. Alteration of drug itself by hydrolysis by beta-lactamases
  4. IIIrd generation are resistant to beta-lactamases from gram negative bacteria
  5. Numbers and types of beta-lactamases increasing
  6. Can be chromosomally or extra-chromosomally (more easily transmitted to other organisms) mediated
  • Resistance to one cephalosporin can result in resistance others depending on mechanism
  • Resistance to cephalosporins can confer resistance to other beta-lactam drugs like penicillins as well
  • Ureaplasma is naturally resistant to cephalosporin
  • ESBL are lactamases that mediate resistance (by hydrolyzing) to extended spectrum (third generation) cephalosporins, penicillins and monobactams (e.g. aztreonam).
GENERATION OF CEPHALOSPORINS:
  • Cephalosporin drugs fall into five classes or generations.
  • Each subsequent generation of these drugs demonstrates greater efficacy against gram-negative bacteria.

1st Generation 2nd Generation 3rd Generation 4th Generation 5th Generation
Cefacetrile
(cephacetrile)
Cefadroxil
(cefadroxyl
Duricef)
Cefalexin
(cephalexin
Keflex)
Cefaloglycin (cephaloglycin)
Cefalonium
(cephalonium)
Cefaloridine
(cephaloradine)
Cefalotin
(cephalothin;
Keflin)
Cefapirin
(cephapirin;
Cefadryl)
Cefatrizine
Cefazaflur
Cefazedone
Cefazolin(cephazolin;
Ancef, Kefzol)
Cefradine
(cephradine; Velosef)
Cefroxadine
Ceftezole
Cefaclor (Ceclor, Distaclor, Keflor, Raniclor)
Cefonicid (Monocid)
Cefprozil (cefproxil; Cefzil)
Cefuroxime (Zefu, Zinnat, Zinacef, Ceftin, Biofuroksym, Xorimax)
CefuzonamAntianaerobe activity
Cefmetazole
Cefotetan
Cefoxitin
The following cephems are also sometimes grouped with second-generation cephalosporins:
Carbacephems:
Loracarbef (Lorabid)
Cephamycins
Cefbuperazone
Cefmetazole(Zefazone)
Cefminox
Cefotetan(Cefotan)
Cefoxitin (Mefoxin)
Cefotiam (Pansporin)
Cefcapene
Cefdaloxime
Cefdinir (Sefdin, Zinir, Omnicef, Kefnir)
Cefditore(Fixx, Zifi, Suprax)
Cefmenoxime
Cefodizime
Cefotaxime (Claforan)
Cefovecin (Convenia)
Cefpimizole
Cefpodoxime (Vantin, PECEF, Simplicef)
Cefteram
Ceftamere (Enshort)
Ceftibuten (Cedax)
Ceftiofur (Naxcel, Excenel)
Ceftiolene
Ceftizoxime (Cefizox)
Ceftriaxone (parentral)(Rocephin)
Antipseudomonal activity:Cefoperazone (Cefobid)
Ceftazidime (Meezat, Fortum, Fortaz)
These cephems are also sometimes grouped with third-generation cephalosporins:
Oxacephems:
Latamoxef (moxalactam)
Cefclidine
Cefepime (Maxipime)
Cefluprenam
Cefoselis
Cefozopran
Cefpirome (Cefrom)
Cefquinome
These cephems are also sometimes grouped with fourth-generation cephalosporins
Oxacephems:
Flomoxef
Ceftobiprole
Ceftaroline
Ceftolozane
USES:
FIRST GENERATION:
  • First generation cephalosporins are active against Gram positive bacteria
  • Uncomplicated skin and soft-tissue infections
  • Uncomplicated urinary tract infections
  • Streptococcal pharyngitis
  • Surgical prophylaxis
  • Good alternatives to antistaphylococcal penicillins.
SECOND GENERATION:
  • Upper and lower respiratory tract infections
  • Acute sinusitis
  • Otitis media
  • Uncomplicated urinary tract infections
  • Cephamycins are useful for mixed aerobic/anaerobic infections of the skin and soft tissues, intra-abdominal, and gynecologic infections, and surgical prophylaxis.
 THIRD GENERATION:
  • Gram-negative bacillary meningitis
  • Meningococcal infection
  • Serious infections of Enterobacteriaceae
  • Upper and lower respiratory tract infections
  • Otitis media
  • Pyelonephritis
  • Skin and soft tissue infections
  • Ceftriaxone is indicated for Lyme disease and gonorrhea.
  • Cefotaxime, ceftazidime, ceftriaxone, ceftizoxime, and moxalactam have excellent penetration into the cerebrospinal fluid.
  • AntiPseudomonal Cephalosporins
  • Ceftazidime (Fortaz, Tazicef, Tazidime) and Cefoperazone (not require dose reduction in patient with any degree of renal impairment )(Cefobid) are the two third generation cephalosporins with antipseudomonal activity.
FOURTH GENERATION:
  • Cefepime and cefpirome are highly active against nosocomial pathogens and are primary used for nosocomial infections
  • Cefepime penetrates the CNS and can be used in the treatment of meningitis.
FIFTH GENERATION:
  • Ceftaroline,Ceftobiprole is unique in its activity against multidrug-resistant Staphylococcus aureus, including MRSA, VRSA, and VISA.
  • Ceftaroline is the ONLY beta-lactam with MRSA activity.
  • It is also active against Enterococcus.
SIDE EFFECTS:
  • Gastrointestinal side effects:
  1. Common side effects involve mainly the digestive system: diarrhea, mild stomach cramps or upset, nausea, and vomiting.
  • Hematologic abnormalities (rare):
  1. Hypoprothrombinemia (deficiency of prothrombin in the blood) is common with cefoperazone, cefamandole, cefotetan, cefmenoxime
  2. Thrombocytopenia (low number of platelets):Ceftazidime
  3. Neutropenia (low number of neutrophils).
  4. Leukopenia (reduced number of white blood cells).
  • Disulfiram-like reaction (flushing, sweating, headache, tachycardia) may occur with concomitant use of alcohol and methylthiotetrazole-containing cephalosporins (cefoperazone, cefamandole, cefotetan).
  • Hepatic toxicity occurs rarely and usually manifests as elevations in transaminase levels.
  • More serious but infrequent reactions include: black, tarry stools;
  1. painful or difficult urination;
  2. antibiotic-induced colitis (severe watery diarrhea, severe stomach cramps, fever, and weakness).
  • Allergic reactions occur mostly in the form of
  1. Rashes (maculopapular, urticarial),
  2. Eosinophilia, drug fever.
  3. More serious hypersensitivity reactions, such as anaphylaxis, serum sickness-like reaction, or angioedema, occur rarely.
  • Cephalosporins can also cause overgrowth of fungus normally present in the body.
Exam Question
  • Strain i.e beta lactamase producing and resistant to chloramphenicol, of H. influenzae isolated from CSF in a known case of meningitis can be treated with Third generation cephalosporin.
  • Ceftazidime, Cefodizime & Cefoperazone belongs to third generation Cephalosporin
  • Cephoperazone has got antipseudomonal effect
  • Cephalosporin act by inhibiting cell wall
  • Cefepime,Cefpirome belongs to fourth generation Cephalosporin
  • Cephalosporin that does not require dose reduction in patient with any degree of renal impairment is Cefoperazone
  • Cephalosporin are Bacteriocidal agents
  • A third generation cephalosporin, such as ceftriaxone or ceftazidime is DOC for the treatment of meningococcal infections.
  • Ureaplasma is naturally resistant to cephalosporin
  • When allergic to penicillin Cephalosporins is contraindicated
  • ESBL are lactamases that mediate resistance (by hydrolyzing) to extended spectrum (third generation) cephalosporins, penicillins and monobactams (e.g. aztreonam).
  • IIIrd generation are resistant to beta-lactamases from gram negative bacteria
  • Ceftriaxone is administered parenterally
  • Cefamendole can cause Disulfiram like reaction
  • Cephalosporins with antipseudomonal activity :- Ceftazidime, Cefoperazone, Cefepime
  • Cephalosporin causing thrombocytopenia is Ceftazidime
  • Ceftobiprole has activity against MRSA (Methicillin Resistant Staphylococcus Aureus)
  • First generation cephalosporins are active against Gram positive bacteria
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