OIA1015 CEPHALOSPORINS & CARBAPENEMS

Cephalosporins

β-lactam antibiotics similar to penicillins, inhibiting bacterial cell wall synthesis.

Carbapenems

Broad-spectrum β-lactam antibiotics, highly resistant to β-lactamases.

Monobactams

Single-ring β-lactam antibiotics, primarily effective against Gram-negative bacteria.

Penicillin-Binding Proteins (PBPs)

Enzymes involved in bacterial cell wall synthesis, inhibited by β-lactams.

Cell Wall Synthesis Inhibition

Binds PBPs, blocking peptidoglycan cross-linking, leading to cell lysis.

Bactericidal Action

Kills bacteria only during active cell division.

β-Lactamase Resistance

Cephalosporins and carbapenems are more stable to β-lactamases than penicillins.

1st Generation Cephalosporins

Cefazolin, Cephalexin

Good Gram-positive activity (Staph, Strep), limited Gram-negative.

2nd Generation Cephalosporins

Cefuroxime, Cefotetan

Better Gram-negative coverage, including H. influenzae, Neisseria.

3rd Generation Cephalosporins

Ceftriaxone, Cefotaxime, Ceftazidime

Strong Gram-negative coverage, best CSF penetration.

4th Generation Cephalosporins

Cefepime

Resistant to β-lactamases, used for serious infections.

5th Generation Cephalosporins

Ceftaroline, Ceftolozane

Active against MRSA and multi-drug resistant bacteria.

1st Generation

Skin infections, surgical prophylaxis, UTIs.

2nd Generation

Respiratory infections, intra-abdominal infections.

3rd Generation

Meningitis, pneumonia, gonorrhea, nosocomial infections.

4th Generation

Serious hospital-acquired infections, febrile neutropenia.

5th Generation

MRSA infections, community-acquired pneumonia (CAP).

Administration

Most require IV or IM due to poor oral absorption.

Distribution

All cephalosporins distribute well in body fluids.

Only 3rd and 4th generation penetrate CSF.

Excretion

Mostly renal elimination, except ceftriaxone (biliary excretion).

β-Lactamase Production

Some bacteria produce β-lactamases that degrade cephalosporins.

Altered PBPs

MRSA modifies PBPs, reducing cephalosporin binding.

Efflux Pumps

Actively remove antibiotics from bacterial cells.

Porin Mutations

Gram-negative bacteria reduce entry of cephalosporins.

Hypersensitivity Reactions

Rash, anaphylaxis, cross-reactivity with penicillins.

Nephrotoxicity

First-generation cephalosporins may cause kidney damage.

Pseudomembranous Colitis

C. difficile overgrowth leading to diarrhea.

Hematologic Effects

Leukopenia, thrombocytopenia.

Carbapenems Examples

Imipenem, Meropenem, Ertapenem, Doripenem.

Carbapenems Spectrum of Activity

Broadest β-lactam spectrum, covering Gram-positive, Gram-negative, and anaerobes.

Imipenem & Cilastatin Combination

Imipenem is inactivated by renal dehydropeptidase, requiring cilastatin to prevent breakdown.

Meropenem & Bacterial Meningitis

Meropenem penetrates CSF well, treating bacterial meningitis.

Carbapenems Administration

IV only (destroyed by stomach acid).

Carbapenems Elimination

Renal excretion, requiring dose adjustment in renal failure.

Carbapenems Adverse Effects

Seizures (especially imipenem at high doses).

GI upset, nausea, rash.

Monobactams (Aztreonam) Spectrum

Only Gram-negative activity, including Pseudomonas aeruginosa.

Aztreonams Clinical Use

Patients allergic to penicillins and cephalosporins.

Aztreonams Resistance to β-Lactamases

Stable against most β-lactamases.

Aztreonams Pharmacokinetics

IV administration, renal elimination.

Aztreonams Adverse Effects

Minimal hypersensitivity, occasional liver enzyme elevation.