β-LACTAMS

  • β-Lactams include penicillins, cephalosporins, monobactams and carbapenems
  • β-Lactams, as a drug class, are the MOST reported cause of drug-related adverse effects
  • Site of action: cell wall → bactericidal

Generic Name

Penicillins

  • Pregnancy Category B
Dosing & Formulations

* Antibiotic dosing quite variable, for further reading/details: refer to a pharmacology book

Mechanism of Action
  • β-lactam ring binds bacterial enzyme DD-transpeptidase 🡪 inhibits peptidoglycan cross-links in cell wall 
  • 1st generation (natural) Penicillin G and V: gram-positive, gram-negative cocci and anaerobes
  • 1st generation (synthetic) Dicloxacillin and Oxacillin: MSSA and gram-positive cocci and rods; gram-negative cocci; anaerobes
  • 2nd generation (aminopenicillins) – ampicillin and amoxicillin: as above plus gram negative bacilli
  • 3rd generation (carboxypenicillins) carbenicillin and ticarcillin
  • 4th generation (ureidopenicillins) – Piperacillin: 3rd and 4th generation + cover Pseudomonas
Indications
  • Skin infections by S. Aureus such as SSSS (MSSA only) and Strep. spp. 
  • STBBIs: syphilis, chlamydia, erysipeloid, cutaneous anthrax, Lyme disease, actinomycosis, listeriosis, gas gangrene, gingivostomatitis and leptospirosis

Contraindications:

  • Type 1 hypersensitivity reaction or severe allergy
Adverse Effects
  • Hypersensitivity reactions: morbilliform, urticaria, angioedema, anaphylaxis (of note, of the reported ‘allergies’ to penicillins, only 5-10% have had true IgE-mediated hypersensitivity reactions), Steven Johnson/toxic epidermal necrolysis, vasculitis, acute generalized pustular dermatoses, symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) with amoxicillin most common
  • Administration of ampicillin (and other penicillins) in mononucleosis (or lymphocytic leukemia or when co-administered with allopurinol) can lead to a morbilliform eruption 7-10 days after onset; however, this is not a true allergic reaction
  • Other cutaneous: shore nails (transverse leukonychia and onychomadesis) and photo-onycholysis
  • Other systemic: interstitial nephritis, C. Difficile infection, cholestatic jaundice, diarrhea/gastrointestinal effects, hemolytic anemia, neutropenia and platelet dysfunction 
  • Drug interactions: β-lactams can alter levels of warfarin (monitor INR); probenecid prolongs excretion of β-lactams
Other
  • Hydrolysis by β-lactamases renders the drugs ineffective (can be combined with β-lactamase inhibitors)
  • SSSS: empiric treatment includes combination with penicillin and clindamycin
  • Syphilis: 1st line treatment is with penicillin G benzathine
  • Mechanisms of resistance
    1. Hydrolysis by β-lactamases (produced by Staph. aureus, Enterobacter spp.) 
    2. Modification of Penicillin-binding sites 
    3. Reduction in outer membrane permeability preventing drug from reaching target site (gram negatives
  • Cross-reactions with β-lactams: all penicillins cross react; ~5% with cross-reaction between penicillins and cephalosporins; much less between penicillins and carbapenems/ monobactams)

Generic Name

β-lactamase inhibitors

Dosing & Formulations
  • Clavulanate, sulbactam, tazobactam
Mechanism of Action
  • β-lactamase inhibitors alone have no inherent antibacterial effects 
  • Examples of combinations of β-lactam with β-lactamase inhibitor include: amoxicillin-clavulanate, ampicillin-sulbactam, ticarcillin-clavulanate, piperacillin-tazobactam
Indications
  • Many uses in dermatology
  • Examples include polymicrobial infections; human bites, diabetic foot ulcers, infected decubitus ulcers and burn wounds
Adverse Effects
  • Gastrointestinal: including diarrhea (less when taken with food), transaminitis; hematologic: hemolytic anemia, thrombocytopenia, eosinophilia; hypersensitivity
Other

* For further reading/details: refer to a pharmacology book

Generic Name

Cephalosporins

  • Pregnancy Category B
Dosing & Formulations
  • Cefadroxil 500mg BID
  • Cephalexin 500mg QID
  • Cefuroxime 500mg BID
  • Cefixime 200mg BID
Mechanism of Action
  • 1st generation cefadroxil (p.o.), cephalexin (p.o.), cefazolin (IV): gram positive cocci (no MRSA coverage)
  • 2nd generation cefaclor, cefuroxime, cefprozil: similar to 1st but more gram-negative coverage (good for H. influenza, Moraxella, N. meningitides/gonorrhoeae)
  • 3rd generation cefixime, ceftriaxone, cefotaxime, ceftazidime: more gram-negative but less gram-positive coverage compared to previous generations (ceftazidime only 3rd gen that covers pseudomonas)
  • 4th generation cefepime: broad-spectrum coverage (covers pseudomonas)
  • 5th generation ceftaroline, ceftobiprole: cover MRSA, VRSA, weak pseudomonas
Indications
  • Skin and soft tissue infections, impetigo, folliculitis, furunculosis, paronychia, necrotizing fasciitis; diabetic foot ulcers, Lyme disease; also pseudomonal infections, ecthyma gangrenosum, 
  • Sexually transmitted and blood-borne infections: gonorrhea
Adverse Effects
  • Hypersensitivity reactions (1-3%); maculopapular eruption, pruritus, urticaria, angioedema, anaphylaxis (<0.1%), serum-sickness-like reactions (especially cefaclor); can also lead to other severe cutaneous drug eruptions (rare); SDRIFE
  • Other systemic: Gastrointestinal (nausea, vomiting, diarrhea, C. Difficile infection, disulfiram-like reactions with alcohol), vaginal candidiasis, transaminitis, hematologic (hemolytic anemia, eosinophilia, neutropenia, hemopoietic changes), sleep disturbances
  • Drug interactions:
    1. Warfarin: warfarin inhibits production of vitamin K-dependent clotting factors leading to increased INR with warfarin 
    2. Probenecid: probenecid competes with renal excretion, leading to increased levels of cephalosporin
Other
  • Caution in breastfeeding as can cause diarrhea and candida infections in nursing infants
  • Cross-reactions with penicillins occur in approximately 5-10% of cases