Cephalosporins: 1st Generation Overview

Study Notes

A class of β-lactam antibiotics derived from the fungus Cephalosporium acremonium
Similar in structure and mechanism to penicillin, but more resistant to bacterial β-lactamases
Classified into four generations based on their spectrum of activity
Each generation has a broader spectrum of activity against gram-negative bacteria moving from the 1st to the 3rd generation
While the 4th generation has the broadest spectrum of activity against gram-negative bacteria while maintaining comparable gram-positive coverage

Include: Cefadroxil, cephalexin, cephradine (oral), cefazolin (parenteral)
Sensitive to β-lactamases
Active against gram-positive cocci like Streptococci (except penicillin-resistant strains) and S.aureus (not MRSA), gram-negative rods including E.coli, K.pneumoniae, and Proteus mirabilis, and anaerobic gram-positive Peptostreptococci (not B.fragilis)
Used for uncomplicated community-acquired infections like UTIs, upper respiratory tract infections, cellulitis, skin infections, and prophylaxis before surgery

Include: Cefoxitin, cefuroxime axetil (oral), cefprozil (oral), cefaclor (oral)
More resistant to β-lactamases than 1st generation cephalosporins
Active against the same spectrum as 1st generation cephalosporins plus H.influenzae, Moraxella catarrhalis, and β-lactamase-producing K.pneumoniae
Cefoxitin is also active against anaerobic bacteria including B.fragilis
Cefuroxime is highly active against beta-lactamase-producing Moraxella catarrhalis
Used for URTIs, UTIs, pneumonia, intra-abdominal infection, peritonitis, and diverticulitis

Include: Cefotaxime, ceftazidime, ceftriaxone, cefdinir (oral), cefixime (oral)
Active against Serratia, beta-lactamase strains of Neisseria and H.influenzae, and P.aeruginosa (only ceftazidime)
Less active against gram-positive cocci than 1st generation except for S.pneumoniae
Used for sepsis, UTI, pneumonia, meningitis, and gonorrhea

Include: Cefepime (IM/IV) and cefpirome (IM/IV)
Comparable to 3rd generation with more resistance to some β-lactamases but sensitive to extended-spectrum beta-lactamases (ESBL)
Broad gram-negative coverage including Enterobacter and Citrobacter species
Similar gram-positive activity to 3rd generation
Have anti-pseudomonal activity
No anaerobic activity
Used for septicemia secondary to Enterobacteriaceae resistant to other drugs, febrile neutropenia, UTI, pneumonia, and meningitis

2nd generation: Cefuroxime, not typically used due to decreased efficacy against N.meningitidis and resistant strains of H.influenzae
3rd generation: Cefotaxime, agent of choice in neonatal meningitis, and ceftriaxone, agent of choice for adult meningitis but not in neonates due to potential elevated bilirubin levels
4th generation: Cefepime

Ceftaroline is classified as an advanced or 5th generation cephalosporin
Increased binding to PBP 2a, which mediates methicillin resistance in staphylococci
Similar activity to ceftriaxone, but with improved gram-positive activity against MRSA and penicillin-resistant S.pneumonia
Not active against enterococci, P.aeruginosa, ESBL-producing Enterobacterales bacteria, Acinetobacter baumannii, or B.fragilis
Used for acute bacterial skin and skin structure infections and community-acquired pneumonia

Include: Ertapenem, imipenem, and meropenem
Highly resistant to hydrolysis from β-lactamases, covering ESBL-producing bacteria
Susceptible to hydrolysis by bacteria producing metallo-β-lactamases and carbapenemases
Broad spectrum with coverage of most gram-positive bacteria (except MRSA), gram-negative bacteria including P.aeruginosa, and anaerobes
Ertapenem is less active against Pseudomonas or Acinetobacter species, two common nosocomial agents
Associated with higher incidence of seizures than other β-lactams
Used for mixed aerobic and anaerobic infections, resistant infections, and infections caused by Enterobacter, penicillin-susceptible strains of pneumococci, or extended-spectrum beta-lactamase producing gram-negative bacteria

Cilastatin, a peptidase inhibitor, blocks renal degradation of imipenem
Given only with imipenem (Primaxin®)
Has no β-lactamase inhibitory or antibacterial activity
Vaborbactam, a β-lactamase inhibitor, is combined with meropenem (Vabomere)
Vaborbactam is a new inhibitor with broader spectrum inhibition than older inhibitors
A good inhibitor of class C β-lactamases, chromosomally encoded and produced by gram-negative pathogens like Enterobacter, Citrobacter, Serratia, and P.aeruginosa
Resistant to hydrolysis by carbapenemases produced by K.pneumoniae