Revenge of the Ceph Cephalosporins

1.4 – “Revenge of the Cep Ceph”: h”: Cephalosporins • Cephalosporins (cephalopods). • β-lactam antibiotics contain a 4-membered β-lactam ring (ringed planet). Bacterial peptidoglycan cell wall is synthesized by repeating D-alanyl-D-alanine oligopeptides (coccoid Death Star with D-ALA scaffolding). PBPs remove terminal alanine in the process of forming crosslinks between peptides. β-lactams inhibit this transpeptidation reaction by covalently (irreversibly) binding PBPs, preventing bacterial cell wall synthesis. Effective in actively growing cells. • There are 5 generations of cephalosporins (5 cephalopod generals). Most activity against G+ bacteria in early generations, with increasing G- activity in progressive generations (4th generation and on are broad-spectrum). • β-lactamases ineffective (β-lactamase guns are deflected from headquarters). However, resistance can evolve, e.g. by altering PBPs. This can be counteracted with carbapenems • Adverse effects o Shared with other β-lactams. May also see cross-reactivity with penicillins. o Type 1 hypersensitivity (IgE mediated) o Drug induced autoimmune hemolytic anemia. Will have ⊕ direct coombs test o Cephalosporins are notorious for disrupting GI bacteria and causing downstream vitamin K disruption & coagulopathies (all antibiotics can do this) o Interstitial nephritis d/t mononuclear cells entering interstitium of the kidney. Blue cells on histology • 1st generation includes cephalexin (first general Lex with flexed arm) & cefazolin (wearing a fez) o Mostly G+ activity (coccoid purple station models). Some G- activity. E. coli, Klebsiella, proteus spp. are often sensitive (PEK bacteria) o Indications: ▪ Often effective in G- UTI proteus, E. coli, Klebsiella (PEcK on red bladder cup) ▪ Oral used for staph & strep, including • Cellulitis (patches on shirt) • Strep throat (2nd line) (red scarf) ▪ Cefazolin penetrates most tissue well. Used for surgical prophylaxis. (Tool rack behind general) • 2nd generation includes cefuroxime (2nd general is furious), cefotetan (drinking tea), cefoxitin o Same spectrum of activity as 1st gen + additional G- bugs (purple coccoid & red bacilli models). Not often used as first line agents. ▪ HENS (H. influenzae, Enterobacter aerogenes, Neisseria spp., & Serratia) (HENS PEcK bacteria - red hens on teapot) o Oral administration o Indications ▪ Sinusitis ▪ Otitis ▪ Lower respiratory infections, including against S. pneumoniae, Klebsiella, Moraxella, H. influenzae. ▪ Mixed anaerobic infections (peritonitis, diverticulitis) but not first line • 3rd generation, including ceftriaxone (3 axes), cefotaxime, ceftazidime (General Taz) o Extended G- coverage. No MRSA coverage. Good penetration of tissue. Ceftriaxone, cefotaxime penetrate BBB. Used to treat a wide variety of resistant infection o Indications: ▪ Meningitis (1st line for empiric treatment). Cross BBB & have activity against N. meningitidis, H. influenzae, S. pneumoniae, and a few other G- enteric bacteria (red mohawk; H. influenzae biplane). • Vancomycin is often added for resistant S. pneumoniae. • Ampicillin may be added for younger & older pts for better coverage. ▪ PNA (community & hospital acquired) (lung shaped rust marks) • Especially with ventilator acquired PNA, must consider pseudomonas (Mona Lisa – ceftazidime covers pseudomonas). ▪ Endocarditis including S. viridans & HECKS bacteria (miter-hatted emperor figurine) ▪ Activity against G- GI bugs, e.g. salmonella, shigella (colonic armor). Useful in hospital acquired infections ▪ 1st line treatment of gonorrhea: single dose of IM ceftriaxone (drippy chandelier) ▪ Lyme disease, especially with neuro involvement or arthritis (Robin of Ixodes poster) • 4th generation includes cefepime (4th General Prime) o Broad spectrum (prism). A big gun for serious systemic infections from MDR organisms, including Pseudomonas. Highly active against G- & G+. No MRSA coverage o Crosses BBB; can treat meningitis (headdress) • 5th generation includes ceftaroline fosamil (General Tara) o Broad spectrum (prism) including MRSA coverage (No Mercy, pharaoh figurine)