second-generation cephalosporin

**Members (mnemonic "Fed Fox Tets Cur Pro Cla" or similar):** cefoxitin, cefotetan, cefuroxime, cefaclor, cefprozil (also cefamandole, cefmetazole, loracarbef in some lists). Cefoxitin and cefotetan are technically cephamycins and have anaerobic activity (B. fragilis).

**Mechanism:** Bind penicillin-binding proteins (PBPs/transpeptidases) and block peptidoglycan cross-linking, which causes cell wall lysis. They are bactericidal and time-dependent. Like all beta-lactams, they are not active against organisms without a cell wall (Mycoplasma) or with altered/absent PBPs (MRSA, Enterococcus, Listeria, atypicals such as Chlamydia and Legionella).

**Spectrum:** - Gram-positive: Less than 1st generation, but still good against methicillin-sensitive staph and strep. - Gram-negative: Increased coverage. Mnemonic **HEN PEcKS**: H. influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E. coli, Klebsiella pneumoniae, Serratia marcescens. - Anaerobes: Cefoxitin and cefotetan cover B. fragilis. - Not active against Pseudomonas.

**Clinical uses:** - Community-acquired pneumonia (cefuroxime, cefaclor), sinusitis, otitis media, and bronchitis (H. influenzae, M. catarrhalis, S. pneumoniae). - Cefuroxime: Lyme disease (early, including erythema migrans; alternative to doxycycline and used in children and pregnancy), and some meningitis coverage is no longer recommended (it was inferior to 3rd generation). - Cefoxitin/cefotetan: Surgical prophylaxis (colorectal, gynecologic), intra-abdominal infections, PID (with doxycycline).

**Adverse effects:** - Hypersensitivity: Roughly 1-2% cross-reactivity with penicillin allergy (lower than once thought, and related to similar R1 side chains rather than the beta-lactam ring). Type I reactions, rash, and hemolytic anemia (type II) can occur. - Cefotetan (NMTT side chain): **Disulfiram-like reaction** with ethanol, and **hypoprothrombinemia/vitamin K deficiency** leading to bleeding. - Cefaclor: **Serum sickness-like reaction** in children. - Nephrotoxicity, particularly when combined with aminoglycosides. Also increased risk of C. difficile infection. - Positive direct Coombs test, which is sometimes associated with hemolysis.

**Pharmacokinetics:** Mostly renally excreted, so dose adjust in renal failure. Exception: ceftriaxone (3rd generation) is biliary. Second-generation agents do not reliably cross the BBB (cefuroxime does so poorly and is not used for meningitis).

**Resistance:** Beta-lactamase production (many are more resistant than 1st generation but are hydrolyzed by ESBLs), altered PBPs (MRSA), and reduced porin permeability.

**Generation comparison (high-yield):** - 1st (cefazolin, cephalexin): Gram-positive cocci, plus PEcK (Proteus, E. coli, Klebsiella). Used for surgical prophylaxis and skin infections. - 2nd: Gram-positive plus HEN PEcKS, anaerobes with cephamycins. - 3rd (ceftriaxone, cefotaxime, ceftazidime): Serious gram-negative infections and meningitis. Ceftazidime covers Pseudomonas. - 4th (cefepime): Pseudomonas, gram-positive coverage. - 5th (ceftaroline): MRSA and Enterococcus faecalis coverage.

**Test pearl:** If a question describes bleeding or alcohol intolerance after a cephalosporin, think of cefotetan (and also cefoperazone). If it describes a child with Lyme disease who cannot take doxycycline, think of cefuroxime. If the question describes a patient undergoing colorectal surgery needing anaerobic coverage, cefoxitin or cefotetan is the answer.