N333: Antibiotics Affecting the Cell Wall

(I) Beta-Lactam Antibiotics

• Contain a beta-lactam ring

• Inhibit penicilling-binding proteins (PBPs)

• Prevent peptidoglycan synthesis, causing bacterial cell lysis

• Examples: Penicillins, Cephalosporins, Carbapenems, Monobactams

Penicillin Overview

• Definition: Beta-lactam antibiotics effective mainly against gram-positive bacteria

• MOA: Inhibits penicillin-binding proteins (PBPs), disrupting bacterial cell wall synthesis and causing lysis

• Spectrum:

  • Narrow-spectrum (gram-positive)

  • Broad and Extended-spectrum (e.g., amoxicillin, piperacllin) covers some gram-negative bacteria

• Pharmacokinetics: Rapid kidney excretion (adjust for renal impairment); short half-life requires frequent dosing

• Cost & Use: Affordable and widely used for bacterial infections

• Examples: Penicillin G, Amoxicillin, Piperacillin

• Nursing Considerations:

  • Check for allergies (cross-reactivity with cephalosporins)

  • Monitor renal function; adjust doses if needed

  • Stress completing the entire course of therapy

Natural Penicillins

E.g., Penicillin G, Penicillin V

• Spectrum:

  • Primarily effective against gram-positive bacteria (e.g., Streptococcus)

  • Limited gram-negative cocci (e.g., Neisseria meningitidis)

• Uses: Strep throat, syphillis, meningitis, and mild skin infections

• Resistance: Significant resistance in some organisms (e.g., MRSA)

• Notes: Monitor for allergies and administer on an empty stomach for better absorption

Penicillin G

• Class: Natural Penicillin; Beta-lactam; Cell wall inhibitor

• MOA: Binds to penicillin-binding proteins (PBPs), inhibiting bacterial cell wall synthesis by preventing peptidoglycan cross-linking, leading to cell lysis

• Indication(s): Strep throat, syphillis, meningitis, mild skin infections

• ADR(s):

  • Urticaria (hives), rash, and severe hypersensitivity reactions (e.g., anaphylaxis)

  • Risk of neurotoxicity at high doses (e.g., seizures)

  • Hyperkalemia with potassium salt forms

• Contraindication(s):

  • Known penicillin allergy (and cross-reactivity with cephalosporins)

  • Renal impairment (CKD)

  • Hyperkalemia

• Nursing Consideration(s):

  • Monitor for allergic reactions

  • Monitor serum-creatinine levels, especially in patients with CKD

  • Stress the importance of completing full course of therapy

  • Administer IM or IV (inactivated when taken orally)

Broad-Spectrum Penicillin

Aka Aminopenicillin

E.g., Amoxicillin, Ampicillin

• Spectrum:

  • Enhanced gram-negative activity, covering organisms including:

    • Haemophilus influenzae

    • Escherichia coli

    • Proteus mirabilis

    • Salmonella and Shigella (ampicillin)

  • Retains activity against gram-positive bacteria, but slightly less potent than natural penicillins

• Uses: Sinusitis, otitis media, respiratory infections, urinary tract infections (UTIs), endocarditis prevention

• Resistance: Susceptible to beta-lactamases unless combined with a beta-lactamase inhibitor (e.g., amoxicillin + clavulanate = Augmentin)

Ampicillin

• Class: Aminopenicillin; Beta-lactam; Cell wall inhibitor

• MOA: Binds to penicillin-binding proteins (PBPs), inhibiting bacterial cell wall synthesis by disrupting peptidoglycan cross-linking, leading to bacterial cell lysis

• Indication(s): Gram-negative bacteria (Haemophilus influenzae, Escherichia coli, Proteus mirabilis, Salmonella and Shigella); sinusitis, otitis media, respiratory infections, UTIs, endocarditis prevention

• ADR(s):

  • Rash

  • Diarrhea (risk of pseudomembranous colitis caused by C. diff)

  • Hypersensitivity reaction (anaphylaxis)

• Contraindication(s):

  • Allergy to penicillin or cephalosporins

  • Severe renal impairment (CKD; requires dose-adjustment)

  • History of severe hypersensitivity to beta-lactams

• Nursing Consideration(s):

  • Administer on an empty stomach (1 hour before or 2 hours after meals) for optimal absorption

  • Monitor for diarrhea; watch for signs of C. diff-associated diarrhea

  • Regularly assess renal function, especially in patients with CKD

  • Advise patients to complete the full course of therapy, even if symptoms improve

Penicillinase-Resistant Penicillins

E.g., Nafcillin, Dicloxacillin, Oxacillin

• Penicillinase: Bacterial enzyme (type of beta-lactamase) that breaks down penicillin, rendering it ineffective

• Spectrum:

  • Resist breakdown by penicillinase

  • Effective against penicillinase-producing Staphylococcus aureus (MSSA) and some Streptococcus species

• Uses: Skin and soft tissue infections, endocarditis, osteomyelitis caused by MSSA

• Resistance: Limited to bacteria producing penicillinase; ineffective against beta-lactamase from gram-negative bacteria

• Notes: Monitor for hypersensitivity and potential liver toxicity

Extended-Spectrum Penicillins

E.g., Piperacillin, Ticarcillin

• Spectrum:

  • Broad gram-negative coverage, including Pseudomonas aeruginosa, Enterobacter, and Klebsiella

  • Effective against many gram-positive organisms, though less potent than natural penicillins

• Uses: Severe hospital-acquired infections, such as pneumonia, sepsis, UTIs, and intra-abdominal infections

• Resistance: Susceptible to beta-lactamases; often used with inhibitors to combat resistance

• Notes: Monitor renal function and for hypersensitivity reactions

Cephalosporins Overview

Similar to penicillins, but with a six-member dihydrothiazine ring

• Definition: Broad-spectrum beta-lactam antibiotics divided into five generations, progressively enhancing activity against gram-negative organisms, beta-lactamase resistance and CNS penetration

• MOA: Inhibits PBPs, preventing bacterial cell wall synthesis

• Spectrum:

  • 1st Gen: Gram-positive (e.g., cefazolin)

  • 2nd Gen: Adds some gram-negative coverage (e.g., cefuroxime)

    • Used for lyme disease

  • 3rd Gen: Broad gram-negative, less gram-positive (e.g., ceftriaxone)

  • 4th Gen: Gram-positive and gram-negative, including Pseudomonas (e.g., cefepime)

  • 5th Gen: Effective against MRSA (e.g., ceftaroline)

• Uses: Respiratory infections, UTIs, skin infections, and surgical prophylaxis

• Nursing Considerations:

  • Assess for cross-allergies (penicillins)

  • Monitor renal function for dose adjustments

  • Watch for C. diff risk

Cefazolin

• Class: 1st Gen Cephalosporin; Cell wall inhibitor

• MOA: Inhibits penicillin-binding proteins (PBPs), preventing bacterial cell wall synthesis, leading to cell lysis

• Indication(s): Gram-positive bacterial infections of the skin, bone, joint, genitals, blood, heart valves, respiratory tract, biliary tract, and UTIs

• ADR(s):

  • Rash

  • Phlebitis at the infection site

  • Nephrotoxicity (increased risk with renal impairment)

• Contraindication(s):

  • Allergy to cephalosporins or penicillins

  • Use with caution in CKD or renal impairment

• Nursing Consideration(s):

  • Monitor creatinine and BUN levels

  • Assess for allergies to cephalosporins or beta-lactam antibiotics

  • Monitor for signs of superinfection (e.g., C. diff diarrhea)

  • Administer slowly to prevent phlebitis

  • Advise patients to report diarrhea, rashes, or allergic reactions immediately

Carbapenems Overview

• Definition: Broad-spectrum beta-lactam antibiotics resistant to beta-lactamases

• MOA: Inhibits PBPs, disrupting bacterial cell wall synthesis

• Spectrum: Effective against gram-positive, gram-negative, anaerobes, and MDRO pathogens (e.g., ESBL-producing bacteria)

• Uses: Severe or MDRO infections, such as intra-abdominal infections, pneumonia, septicemia, and complicated UTIs

• Examples: Imipenem/cilastatin, Meropenem, Ertapenem

• Nursing Considerations:

  • Monitor for cross-allergies (penicillins/cephalosporins)

  • Adjust dose for renal impairment

  • Watch for C. diff infections

Imipenem-Cilastatin

• Class: Carbapenem Antibiotic; Cell wall inhibitor

• MOA: Inhibits penicillin-binding proteins (PBPs), disrupting bacterial cell wall synthesis; Cilastatin prevents renal degradation of imipenem

• Indication(s): Severe or MDRO infections; intra-abdominal infections, pneumonia, septicemia, complicated UTIs

• ADR(s):

  • Nausea, diarrhea, rash

  • Seizures (higher risk in renal impairment or CNS disorders)

  • Superinfections (e.g., C diff)

• Contraindication(s):

  • Allergy to carbapenems or beta-lactams

  • Caution in renal impairment or seizure disorders

• Nursing Consideration(s):

  • Monitor renal function and adjust dosing as needed

  • Assess for allergies to carbapenems or beta-lactams

  • Watch for CNS effects (e.g., seizures) and signs of superinfection

  • Administer IV infusion over recommended time to minimize side effects

  • Advise patients to report severe diarrhea, rash, or neurological symptoms immediately

  • Complete the full antibiotic course

Monobactams Overview

• Definition: Narrow-spectrum beta-lactam antibiotics effective primarily against Gram-negative bacteria

• MOA: Inhibits penicillin-binding proteins (PBPs), disrupting bacterial cell wall synthesis

• Spectrum: Effective against Gram-negative bacteria, including Pseudomonas aeruginosa, but lacks activity against Gram-positive bacteria and anaerobes

• Uses: Treatment of severe or multidrug-resistant infections such as:

  • Complicated UTIs

  • Lower respiratory tract infections

  • Intra-abdominal infections

  • Sepsis caused by susceptible Gram-negative organisms

• Examples: Aztreonam (prototype)

• Nursing Considerations:

  • Monitor for hypersensitivity reactions (potential cross-reactivity with penicillin, but generally well-tolerated)

  • Adjust dose for renal impairment

  • Ensure proper monitoring for potential C. diff-associated diarrhea

(II) Glycopeptides

• MOA:

  • Inhibit bacterial cell wall synthesis by binding to the D-Ala-D-Ala terminus of peptidoglycan precursors, preventing cross-linking and elongation of the cell wall

  • Bactericidal for most susceptible organisms

• Spectrum: Effective primarily against gram-positive bacteria, including:

  • MRSA, Enterococcus faecium and Enterococcus faecalis (vancomycin-sensitive strains), Clostridium difficile (oral vancomycin)

• Examples: Vancomycin and long-acting agents: Dalbavancin, Oritavancin

• Uses: Treat serious Gram-positive infections, including:

  • Skin and soft tissue infections and osteomyelitis

  • Bacteremia and endocarditis caused by MRSA or Enterococcus

  • Clostridium difficile-associated diarrhea

Vancomycin

• Class: Glycopeptide; Cell wall synthesis inhibitor

• MOA: Inhibits bacterial cell wall synthesis by binding to D-Ala-D-Ala of peptidoglycan precursors, preventing elongation and cross-linking

• Indication(s):

  • IV: Serious Gram-positive infections (MRSA, Enterococcus, Streptococcus)

  • Oral: First-line therapy for C. diff-associated diarrhea

• ADR(s):

  • Phlebitis, nausea rash

  • Nephrotoxicity

  • Ototoxicity

  • Infusion-related “Red man syndrome” — flushing and hypotension

• Contraindication(s):

  • Hypersensitivity to the medication

  • Use cautiously in patients with renal impairment

• Nursing Consideration(s):

  • Regularly monitor peak and trough levels to ensure therapeutic dosing

  • Monitor BUN and creatinine frequently during therapy

  • Infuse IV over at least 60 minutes to avoid Red man syndrome

  • Advise patients to report hearing loss, ringing in the ears, or reduced urinary output

  • Stress adherence to prescribed therapy duration to prevent resistance

(III) Fosfomycin

• Class: Urinary tract antiseptic, phosphonic acid derivative; Cell wall synthesis inhibitor

• MOA:

  • Inhibits bacterial cell wall synthesis by blocking enolpyruvyl transferase

  • Reduces bacterial adhesion to uroepithelial cells

• Indication(s):

  • Acute uncomplicated cystitis in women

  • Effective against resistant strains, including ESBL-producing organisms and VRE

• ADR(s):

  • Diarrhea, nausea, headaches, vaginitis

  • Hypersensitivity reactions

  • Liver enzyme elevation

• Contraindication(s):

  • Hypersensitivity to the medication

  • Caution in severe renal impairment (CrCl < 30 mL/min)

• Nursing Consideration(s):

  • Dissolve powder in water; take immediately on an empty stomach

  • Monitor symptom resolution within 2-3 days

  • Educate patients about single-dose administration