Beta-lactam Definitions

Beta-lactam mechanism of action

Binds PBPs to inhibit the transpeptidation step of peptidoglycan synthesis.

Major resistance mechanisms for beta-lactams

Decreased permeability, efflux pump extrusion, target site alteration, and beta-lactamases.

PBP alteration in MRSA

PBP2 alters to PBP2a.

PBP alteration in penicillin-resistant Strep pneumoniae

PBP2 alters to PBP2x or PBP2b.

PBP alteration in resistant Enterococcus

PBP5 alteration.

Beta-lactam resistance mechanism unique to Gram-negatives

Decreased permeability (porin mutations) and efflux pump extrusion.

Ampicillin/sulbactam (IV)

Aminopenicillin combined with a beta-lactamase inhibitor.

Amoxicillin/clavulanic acid (PO)

Aminopenicillin combined with a beta-lactamase inhibitor.

Amoxicillin vs. Ampicillin PO absorption

Amoxicillin has more complete oral absorption and less frequent dosing.

Ambler Class A beta-lactamase resistant genes: tem and shv

Confer resistance to ampicillin; treat with cephalosporins or BL/BLIs.

Ambler Class A beta-lactamase resistant gene: ctx-m

Confers resistance to penicillins and cephalosporins (ESBL); treat with carbapenems.

Ambler Class A beta-lactamase resistant gene: kpc

Confers resistance to penicillins, cephalosporins, and carbapenems (CRE).

Drugs of choice for KPC-producing CRE

Ceftazidime-avibactam, meropenem-vaborbactam, or imipenem-relebactam.

Natural Penicillins spectrum of activity

Gram-positive cocci (Streptococci, Enterococci), Gram-positive rods, Spirochetes (Treponema pallidum).

Drug of choice for Syphilis (Treponema pallidum)

Penicillin G (IV) or Benzathine Penicillin (IM).

Penicillinase-resistant penicillins (IV)

Oxacillin and Nafcillin.

Penicillinase-resistant penicillin (PO)

Dicloxacillin.

Drug of choice for MSSA infections

Nafcillin, oxacillin, or dicloxacillin.

Piperacillin/tazobactam spectrum

Broad Gram-negative (HNPEK, CAPES, Pseudomonas), Gram-positive cocci, and anaerobes (B. fragilis).

Benzathine penicillin (Bicillin L-A) dosing frequency for Syphilis

Every week.

Benzathine penicillin (Bicillin L-A) dosing frequency for GAS infection

Every month.

Penicillins that do NOT require renal dose adjustment

Nafcillin, oxacillin, and dicloxacillin.

Adverse effect of high-dose Penicillin G or Imipenem

Seizures (especially in renal failure or CNS history).

Nafcillin-specific adverse effect

Thrombophlebitis.

Counseling for oral penicillin and dicloxacillin

Take on an empty stomach (1 hour before or 2 hours after meals).

Counseling for oral amoxicillin/clavulanate

Take with food to increase absorption and decrease stomach upset.

1st generation cephalosporins

Cefazolin (IV), Cephalexin (PO), Cefadroxil (PO).

1st generation cephalosporin spectrum

Gram-positive (MSSA, Strep pyogenes) and Gram-negative PEK (Proteus, E. coli, Klebsiella).

2nd generation cephalosporins

Cefuroxime (IV, PO), Cefaclor (PO).

Cephamycins

Cefoxitin (IV) and Cefotetan (IV).

Unique coverage of Cephamycins (cefoxitin, cefotetan)

Additional activity against anaerobes like Bacteroides fragilis.

Clinical use for Cephamycins

Surgical prophylaxis in colorectal procedures and intra-abdominal infections.

3rd generation oral cephalosporins

Cefixime, Cefpodoxime, Cefdinir.

3rd generation IV cephalosporins

Ceftriaxone and Ceftazidime.

Ceftriaxone spectrum of activity

Excellent Strep (S. pneumoniae), HNPEK, and CAPES; no Pseudomonas activity.

Ceftazidime spectrum of activity

Antipseudomonal Gram-negative coverage; no Gram-positive or anaerobic activity.

Ceftazidime-avibactam (Avycaz) spectrum

Ceftazidime spectrum plus AmpC-producing Pseudomonas, ESBL, and CRE.

4th generation cephalosporin

Cefepime (IV).

Cefepime spectrum of activity

Ceftriaxone coverage plus Pseudomonas; stable against AmpC beta-lactamases.

Anti-MRSA cephalosporins

Ceftaroline (IV) and Ceftobiprole (IV).

Ceftaroline spectrum

MRSA, Gram-positive cocci (including PCN-R Strep), HNPEK; no Pseudomonas activity.

Ceftobiprole spectrum

MRSA, Gram-positive cocci (including E. faecalis), Gram-negatives (including Pseudomonas).

Ceftolozane-tazobactam (Zerbaxa) spectrum

Strep, HNPEK, CAPES, AmpC, ESBL, and multidrug-resistant (MDR) Pseudomonas.

Cefiderocol (Fetroja) spectrum

Broad Gram-negative rods (including MDR Pseudomonas, ESBL, CRE, and Stenotrophomonas).

Organisms that ALL cephalosporins lack activity against (except Ceftobiprole)

Enterococci, Listeria, Clostridium difficile, and atypical organisms.

Cephalosporins that penetrate the CSF (with inflamed meninges)

Ceftriaxone, ceftazidime, and cefepime.

Cephalosporin that does NOT require dose adjustment in renal dysfunction

Ceftriaxone (eliminated partly via biliary route).

Cefepime-specific serious adverse effect

Neurotoxicity (encephalopathy, agitation, seizures), especially in renal dysfunction.

Cephalosporins with activity against Bacteroides fragilis

Cefotetan, cefoxitin, and ceftolozane/tazobactam.

Cephalosporins with activity against Pseudomonas

Ceftazidime, cefepime, ceftazidime/avibactam, ceftolozane/tazobactam, cefiderocol, and ceftobiprole.

Carbapenem drugs

Imipenem, Meropenem, Ertapenem, Meropenem/vaborbactam, Imipenem/relebactam.

Carbapenems spectrum of activity

Very broad Gram-positive, Gram-negative (including ESBL and Pseudomonas), and anaerobes (B. fragilis).

Ertapenem spectrum limitations

Lacks activity against Pseudomonas, Acinetobacter, and Enterococcus.

Reason Imipenem is combined with Cilastatin

Prevents metabolism by renal dehydropeptidase I to maintain therapeutic levels.

Carbapenem seizure risk ranking

Imipenem > Meropenem > Ertapenem.

Ertapenem IM contraindication

Hypersensitivity to amide-type local anesthetics (e.g., lidocaine).

Carbapenem and Valproic acid drug interaction

Carbapenems rapidly decrease valproic acid levels; avoid co-administration.

Imipenem and Ganciclovir drug interaction

Avoid due to increased risk of generalized seizures.

Monobactam drug

Aztreonam (IV).

Aztreonam spectrum of activity

Aerobic Gram-negative rods (including Pseudomonas); no Gram-positive or anaerobic activity.

Aztreonam clinical indication

Patients with IgE-mediated penicillin/cephalosporin allergies requiring Gram-negative coverage.

Aztreonam cross-reactivity risk

High cross-reactivity with Ceftazidime due to identical R1 side chains.

Beta-lactam PK/PD efficacy parameter

Time above Minimum Inhibitory Concentration (T > MIC).

Strategy to maximize T > MIC for beta-lactams

Prolonged infusion (3 to 4 hours) instead of intermittent (30 minutes).

Percentage of reported PCN allergies that are true allergies

Only 10% to 20%.

Type I hypersensitivity reaction mechanism and onset

IgE-mediated mast-cell activation; onset

Type I hypersensitivity symptoms

Urticaria, angioedema, bronchospasm, hypotension, anaphylaxis.

Type IV hypersensitivity reaction mechanism and onset

T-cell mediated, delayed; onset days to weeks.

Primary driver of beta-lactam cross-reactivity

R1 side-chain similarity.

Preferred tool for low-probability, remote penicillin allergy history

Direct oral challenge in a monitored setting.