Cephalosporin
INTRODUCTION:
- β-lactam antibiotics having 7-aminocephalosporinic acid nucleus.
MECHANISM OF ACTION:
- Binds to penicillin binding proteins & inhibites cell wall formation.
- Bacteriocidal in action.
GENERATION OF CEPHALOSPORINS:
- Fall into five classes or generations.
- Each subsequent generation drugs demonstrates greater efficacy against gram-negative bacteria.
- No cephalosporin is active against MRSA, listeria monocytogenes, & Enterococcus fecalis.
| 1st Generation | 2nd Generation | 3rd Generation | 4th Generation | 5th Generation |
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Antianaerobe activity:
The following cephems are also sometimes grouped with second-generation cephalosporins: Carbacephems:
Cephamycins:
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Antipseudomonal activity:
These cephems are also sometimes grouped with third-generation cephalosporins: Oxacephems:
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These cephems are also sometimes grouped with fourth-generation cephalosporins: Oxacephems:
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USES:
FIRST GENERATION:
- Active against gram-positive bacteria.
- Cefazolin – DOC for surgical prophylaxsis.
- Uncomplicated skin & soft-tissue infections
- Uncomplicated urinary tract infections
- Streptococcal pharyngitis
- Surgical prophylaxis
- Good alternatives to antistaphylococcal penicillins.
SECOND GENERATION:
- Upper & lower respiratory tract infections
- Acute sinusitis
- Otitis media
- Uncomplicated urinary tract infections
- Cephamycins – Mixed aerobic/anaerobic infections of skin & soft tissues, intra-abdominal, gynecologic infections, and surgical prophylaxis.
- Cefotetan, cefmetazole & cefoxitin – Active against anaerobes like Bacteroides fragilis.
- Cefuroxime – High CSF levels achieved, hence used in bacterial meningitis.
- Note: Ceftriaxone preferred.
THIRD GENERATION:
- Gram-negative bacillary meningitis.
- Meningococcal infection.
- Due to high BBB penetrability, except Cefperazone & Cefixime.
- Serious infections of Enterobacteriaceae
- Upper & lower respiratory tract infections
- Otitis media
- Pyelonephritis
- Skin & soft tissue infections.
Drugs:
- Cefotaxime, ceftazidime, ceftriaxone, ceftizoxime & Moxalactam – Excellent penetration into cerebrospinal fluid.
- Ceftazidine: DOC for meliodiosis.
Anti-pseudomonal cephalosporins:
- Third-generation drugs.
- Ceftazidime (Fortaz, Tazicef, Tazidime)
- Cefoperazone.
- Doesn’t require dose reduction for renal impairment.
- Cefobid.
Ceftriaxone:
- Indicated for Lyme disease, gonorrhea, salmonellosis, E.coli sepsis, Proteus, Serratia & Hemophilus.
- Long-term use (>2g/dl) causes “Biliary sludging syndrome” & cholelithiasis, due to bile precipitation.
- Long plasma half-life
FOURTH GENERATION:
- Cefepime & cefpirome –
- Highly active against nosocomial pathogens.
- Cefepime penetrates CNS, used in meningitis treatment.
FIFTH GENERATION:
- Ceftaroline, Ceftobiprole – Acts against multidrug-resistant Staphylococcus aureus, including MRSA & VRSA and for community-acquired pneumonia.
- Ceftaroline – ONLY beta-lactam with MRSA activity.
- Also active against Enterococcus.
SIDE EFFECTS:
Gastrointestinal:
- Diarrhea, mild stomach cramps & upset, nausea, and vomiting.
- Hematologic abnormalities (rare):
- Hypoprothrombinemia common with cefoperazone, cefamandole, cefotetan, cefmenoxime
- Thrombocytopenia, Neutropenia & Leukopenia – Mainly by Ceftazidime.
Disulfiram-like reaction:
- Occurs with methylthiotetrazole-containing cephalosporins (cefoperazone, cefamandole, cefotetan.
- Flushing, sweating, headache, tachycardia on concomitant alcohol use.
- Hepatic toxicity occurs rarely and usually manifests as elevations in transaminase levels.
- More serious but infrequent reactions include:
- Black, tarry stools;
- Painful or difficult urination;
- Antibiotic-induced colitis:
- Severe watery diarrhea, severe stomach cramps, fever, & weakness.
Allergic reactions:
- Rashes (maculopapular, urticaria),
- Eosinophilia, drug fever.
- More serious hypersensitivity reactions – Anaphylaxis, serum sickness-like reaction, angioedem occur rarely.
- Durg cross-reactivity also occurs.
- Overgrowth of fungus normally present in body.
MECHANISMS OF RESISTANCE:
- Changes in drug target of penicillin-binding proteins – methicillin-resistant Staphylococcus aureus
- Lack of drug access to penicillin-binding protein target:
- Efflux pumps – MexAB-OprM efflux pump in Pseudomonas aeruginosa.
- Decreased cell-wall permeability less common for cephalosporins.
- IIIrd generation is resistant to beta-lactamases from gram-negative bacteria.
- Resistance to cephalosporins can confer resistance to other beta-lactam drugs like penicillins as well.
- Ureaplasma – naturally resistant to cephalosporin.
- ESBL are lactamases mediating resistance (by hydrolyzing) to extended spectrum (third generation) cephalosporins, penicillins and monobactams (e.g. aztreonam).
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
- Cefoperazone 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 the patient with any degree of renal impairment is Cefoperazone
- Cephalosporin is 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 is resistant to beta-lactamases from gram-negative bacteria
- Ceftriaxone is administered parenterally
- Cefamandole 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
Don’t Forget to Solve all the previous Year Question asked on Cephalosporin
