STEPTRACKERMICROBIOLOGY + PHARMACOLOGY | CELL WALL INHIBITORS | HIGH-YIELD REVIEW

β-Lactams I — Penicillins & Cephalosporins

All β-lactams bind penicillin-binding proteins (transpeptidases) and block peptidoglycan cross-linking — bactericidal. Spectrum widens as you move along each family.

FOCUS ON
Mechanism: bind PBPs → block transpeptidation → autolysins lyse the cell. Penicillin G/V: gram ⁺ cocci, T pallidum, Actinomyces, Neisseria meningitidis. Antistaphylococcal (nafcillin, oxacillin, dicloxacillin): bulky side chain resists penicillinase → MSSA. Aminopenicillins (ampicillin, amoxicillin): + some gram-negatives (H flu, E coli, Listeria, Proteus, Salmonella), Enterococcus. Antipseudomonal (piperacillin). β-lactamase inhibitors (clavulanate, sulbactam, tazobactam) extend coverage. Cephalosporins: 1st (cefazolin; surgical prophylaxis) → 2nd → 3rd (ceftriaxone: meningitis, gonorrhea; ceftazidime: Pseudomonas) → 4th (cefepime) → 5th (ceftaroline: MRSA). None cover Listeria, atypicals, Enterococcus. Toxicities: hypersensitivity, interstitial nephritis, hemolytic anemia, C difficile.
DRUG · CLASS
SPECTRUM
KEY USES
TOXICITY · NOTES
Penicillin G (IV/IM) · V (oral)
Streptococci, pneumococcus (if sensitive), meningococcus, T pallidum, Actinomyces, Clostridium (non-difficile)
Syphilis (benzathine), strep pharyngitis, rheumatic fever prophylaxis
Hypersensitivity; Jarisch-Herxheimer in syphilis
Nafcillin · oxacillin · dicloxacillin
Methicillin-sensitive S aureus (penicillinase-resistant)
MSSA bacteremia, endocarditis, cellulitis
Interstitial nephritis (classically methicillin) · nafcillin: hepatic excretion
Ampicillin · amoxicillin
+ H influenzae, E coli, Listeria, Proteus, Salmonella, Shigella, Enterococcus
Otitis, sinusitis, Listeria, enterococcal UTI, H pylori, Lyme (children)
Rash with EBV mono · C difficile · β-lactamase-sensitive
Piperacillin (+ tazobactam)
Broad gram ⁻ incl. Pseudomonas, anaerobes, gram ⁺
Hospital pneumonia, febrile neutropenia, intra-abdominal
—
β-lactamase inhibitors
Clavulanate, sulbactam, tazobactam, avibactam
Amoxicillin-clavulanate (bites, sinusitis), ampicillin-sulbactam (aspiration), ceftazidime-avibactam (CRE)
Sulbactam active against Acinetobacter
1st gen — cefazolin, cephalexin
Gram ⁺ cocci, Proteus, E coli, Klebsiella
Surgical prophylaxis, MSSA, skin, UTI
—
2nd gen — cefuroxime, cefoxitin, cefotetan
+ H flu, Enterobacter, Neisseria; cefoxitin/cefotetan cover anaerobes
Community pneumonia, PID (cefoxitin)
Cefotetan: disulfiram-like reaction, hypoprothrombinemia
3rd gen — ceftriaxone, cefotaxime, ceftazidime
Broad gram ⁻; ceftazidime → Pseudomonas
Meningitis, gonorrhea, Lyme meningitis/carditis, pyelonephritis, typhoid
Ceftriaxone: biliary sludge, avoid in neonates with calcium IV (precipitates), kernicterus
4th gen — cefepime
Gram ⁻ incl. Pseudomonas + gram ⁺; stable to AmpC
Febrile neutropenia, hospital infections
Neurotoxicity in renal failure
5th gen — ceftaroline
Gram ⁺ incl. MRSA; gram ⁻ (not Pseudomonas)
Skin infections, community pneumonia
Binds PBP2a
Cephalosporin gaps
Listeria, atypicals (Mycoplasma, Chlamydia), Enterococcus, MRSA (except 5th), C difficile
—
Add ampicillin for Listeria in meningitis
Allergy cross-reactivity
Shared β-lactam ring and similar side chains
Penicillin allergy → low risk with most cephalosporins (< 2%)
Anaphylaxis history → avoid or test · aztreonam safe (except ceftazidime side chain)

Picture it — where antibacterials act

DNA30S50SPABA → DHF → THFCell wallβ-lactams, vancomycinbacitracin, fosfomycinMembranedaptomycin, polymyxinsGyrase / topo IVfluoroquinolonesDNA damagemetronidazoleFolate synthesissulfonamides → TMP30Saminoglycosidestetracyclines50Smacrolidesclindamycin, linezolidchloramphenicolRNA polymeraserifampin
Antibacterial target mapWall and membrane drugs act at the envelope; fluoroquinolones and metronidazole attack DNA; rifampin blocks RNA polymerase; aminoglycosides and tetracyclines bind the 30S subunit; macrolides, clindamycin, linezolid and chloramphenicol bind the 50S subunit; sulfonamides and trimethoprim block two steps of folate synthesis.

Schematic diagrams, not to scale.

Mechanism — how β-lactams kill

β-lactam mimics D-Ala-D-Ala
→
Acylates PBP (transpeptidase)
→
No peptidoglycan cross-links
→
Autolysins → lysisBactericidal, growing cells

Cephalosporins by generation

GEN
EXAMPLE
GAINS
USE
1st
Cefazolin
Gram ⁺, Proteus, E coli, Klebsiella
Surgical prophylaxis
2nd
Cefoxitin
+ H flu, anaerobes
PID
3rd
Ceftriaxone
Broad gram ⁻, CNS
Meningitis, gonorrhea
4th
Cefepime
+ Pseudomonas
Neutropenic fever
5th
Ceftaroline
+ MRSA
Skin, pneumonia

How it's tested

COMMON CONFUSIONNafcillin covers MSSA but not MRSA; ceftaroline covers MRSA because it binds the altered PBP2a.
THE TRAPA morbilliform rash on amoxicillin during EBV mono isn't a true penicillin allergy.
YOUR APPROACHOrganism → does it make β-lactamase? altered PBP? → pick the narrowest β-lactam that covers it → check allergy and site (CNS penetration).

If you see… think…

Drug of choice for syphilis → penicillin G (benzathine)
MSSA endocarditis → nafcillin or cefazolin
Listeria meningitis → ampicillin
Rash on amoxicillin for sore throat → EBV mono
Single IM dose for gonorrhea → ceftriaxone
Pre-op antibiotic for clean surgery → cefazolin
Cephalosporin covering MRSA → ceftaroline
Cephalosporin covering Pseudomonas → ceftazidime, cefepime
Cephalosporin with disulfiram-like reaction → cefotetan
Fever, rash, eosinophiluria after nafcillin → acute interstitial nephritis