Antibiotics Quiz: Beta-Lactams and Cephalosporins

Antimicrobial Therapy

• Used to treat infectious diseases.
• 190 million antibiotic doses are administered in hospitals daily.
• Modern antimicrobials developed in the 1930s and 1940s.
• Significantly reduced infection-related morbidity and mortality.

Antimicrobial Therapy: General Terms

• Antimicrobial therapy is a form of chemotherapy.
• Antimicrobial: Any agent harming a microbe.
• Antibiotic: Any substance produced by a microbe that harms another microbe.
• Anti-infective: Agent reducing or eliminating infection (includes antibiotics, antivirals, and even things like cranberry juice).

Basic Principles of Antimicrobial Therapy

• Selective toxicity: Targets the pathogen, not the host.
• Achieved by:
  • Disrupting the bacterial cell wall (e.g., penicillin).
  • Disrupting bacterial protein synthesis (e.g., clindamycin).
  • Inhibiting bacterial-specific enzymes (e.g., sulfonamides).

Classification of Antimicrobials

• Classified by mechanism of action and susceptible organisms (Gram-positive, Gram-negative, resistant/non-resistant).
• Understanding both classification systems enables targeted therapy.
• Bacteriostatic drugs slow bacterial growth without killing them.
• Bactericidal drugs directly kill bacteria.

Innate Resistance to Antimicrobial Therapy

• Four primary mechanisms of microbial resistance:
  • Decreasing drug concentration entering the cell.
  • Altering target molecules to prevent drug-receptor interaction.
  • Producing antagonist compounds.
  • Inactivating the drug.

Acquired Resistance to Antimicrobial Therapy

• Spontaneous mutation: Random DNA changes resulting in slow, specific drug resistance.
• Conjugation: Transfer of DNA between bacteria, often with multiple drug resistance.

How Antibiotics Promote Resistance

• Broad-spectrum antibiotics promote resistant microbes.
• Increased antibiotic use leads to faster emergence of drug-resistant organisms.
• Antibiotic stewardship is crucial.

Terms to Know

• Nosocomial infections (healthcare-associated infections).
• Superinfection: New infection arising during treatment of a primary infection, often caused by resistant organisms.

Basic Principles of Antimicrobial Therapy (Continued)

• Selecting the appropriate antibiotic:
  • Identifying the organism through culture and sensitivity testing.
  • Considering drug sensitivity and host factors (e.g., immunocompromised patients).
  • Accounting for drug allergies and limited drug penetration.
  • Assessing renal and hepatic function.

Empiric Therapy

• Empiric therapy: Antibiotic therapy initiated before causative organism is identified.
• Drug selection based on clinical evaluation and knowledge of likely pathogens.

Other Factors to Consider

• Host defenses: A competent immune system is critical for some antimicrobials.
• Site of infection: Drug must reach the site of infection, including potential barriers (e.g., abscesses).
• Previous drug reactions and genetic factors (e.g., G6PD deficiency with sulfonamides).
• Dosage and duration: Adequate presence at infection site and sufficient time are crucial. Premature discontinuation can be problematic.

Combination Therapy

• Antibiotic combinations can be:
  • Additive (1 + 1 = 2).
  • Synergistic (1 + 1 > 2).
  • Antagonistic (1 + 1 < 2).
• Indications: Mixed infections, resistance prevention, and toxicity reduction.
• Disadvantages: Potential interactions, increased cost.

Prophylactic Use of Antimicrobials

• Prophylaxis: Administered before a procedure to prevent infection, not treat infection.
• Indications:
  • Surgery.
  • Bacterial endocarditis (for certain high-risk patients).
  • Neutropenia (for immunocompromised).
  • Other situations (e.g., travel-related infections).

Inappropriate Use of Antimicrobials

• Avoid using antibiotics for viral infections.
• Improper/inadequate dosing.
• Treatment of fever of unknown origin (FUO) unless life-threatening.
• Treatment without proper bacteriologic information.
• Antibiotics must reach infection site (e.g., draining abscesses).

Penicillins: Key Concepts

• Active against various bacteria; generally low toxicity; primary adverse effect is allergy.
• All penicillins contain a beta-lactam ring.

Penicillins: Mechanism of Action

• Weaken the bacterial cell wall, leading to bacterial death.
• Effective only against dividing bacteria.

Penicillins: Resistance Mechanisms

• Inability to reach target.
• Inactivation by bacterial enzymes (e.g., beta-lactamases).
• Altered penicillin-binding proteins (e.g., MRSA).

Penicillins: Classification

• Narrow-spectrum (penicillin G, V).
• Penicillinase-resistant (nafcillin, oxacillin).
• Broad-spectrum (ampicillin, amoxicillin).
• Extended-spectrum (antipseudomonal: ticarcillin, piperacillin).

Penicillins: Adverse Effects

• Allergic reactions: Anaphylaxis (Type I hypersensitivity) and other allergic reactions (e.g., rashes).
• Anaphylaxis is more common with penicillin than with other drugs; avoid in patients previously exhibiting anaphylaxis.

Penicillins: Drug Interactions

• Aminoglycosides: Do not mix in the same IV solution or administer within several hours.
• Probenecid: Delays PCN excretion and should be used with caution in renal dysfunction.

Penicillin Combinations

• Beta-lactamase inhibitors (e.g., clavulanate, sulbactam) augment antibiotic spectrum against penicillinase-producing bacteria and can reduce resistance.

Penicillins: Pharmacokinetics

• Absorption: Varies depending on the specific penicillin (e.g., IM, IV, or PO).
• Distribution: Varies, generally good distribution, but with poor penetration in some situations (inflammation promotes penetration).
• Metabolism: Minimal.
• Excretion: Primarily renal excretion; adjust dosage in renal disease.

Cephalosporins, Carbapenems, Vancomycin, and Aztreonam: Key Concepts

• Active against various bacteria; generally low toxicity; primary adverse effect is allergy (less than for penicillin)
• All contain a beta-lactam ring (except vancomycin).

Cephalosporins: General Concepts

• Five generations; each generation has improved properties.

Cephalosporins: Mechanism of Action

• Similar to penicillin: Targets penicillin-binding proteins.

Cephalosporins: Classification

• Classified by generation, with increasing Gram-negative and anaerobic coverage and improved CSF penetration with each generation.

Cephalosporins: Therapeutic Uses

• First generation: Primarily Gram-positive.
• Second generation: Variable Gram-negative activity; not for Pseudomonas.
• Third generation: Increased Gram-negative activity; Ceftazidime active against Pseudomonas.
• Fourth generation: Very broad spectrum, highly active against Pseudomonas and effective in CSF.
• Fifth generation: Broad spectrum, active against MRSA

Cephalosporins: Kinetics

• Absorption: PO and IV common formulations.
• Distribution: Good tissue penetration; first and second generations generally poor CSF penetration.
• Elimination: Primarily renal, except ceftriaxone.

Cephalosporins: Adverse Effects

• Primarily allergic (rash more common than anaphylaxis; less common than with penicillin).
• Bleeding with some cephalosporins; use caution with aspirin/NSAIDs or anticoagulants.
• Thrombophlebitis.

Cephalosporins: Interactions

• Probenecid can delay excretion
• Alcohol intolerance with some cephalosporins

Carbapenems

• Very broad spectrum (except MRSA).
• Parenteral administration only.
• Imipenem: Effective against Gram-positives and -negatives, anaerobes; fixed dose of cilastatin is included to inhibit renal degradation.

Carbapenems: Adverse Effects

• Nausea, vomiting, diarrhea, superinfections, and seizures (rare).
• Allergies: Possible but uncommon.
• Drug interactions (e.g., valproate).

Vancomycin

• Cell wall synthesis inhibitor; NOT a beta-lactam.
• Widely used; primary indications are C. difficile and MRSA; given IV slowly to prevent red-man syndrome.

Vancomycin: Kinetics/Adverse Effects

• Poor GI absorption, IV only, slow IV infusion.
• Distributed to most tissues; unreliable CSF penetration.
• Renal excretion; adjust dosage for renal insufficiency.
• Ototoxicity; thrombophlebitis; rare immune-mediated thrombocytopenia. No cross-reactivity with penicillin.

Aztreonam

• Monobactam not a beta-lactam, inhibits cell wall production.
• Highly resistant to beta-lactamases, narrow spectrum active only against Gram-negative aerobic bacteria (e.g., Pseudomonus, Neisseria, Enterobacter).

Aztreonam: Kinetics

• No GI absorption; IV and IM, also inhaled.
• Distributed to tissues and fluids, including CSF.
• Renal excretion; adjust dosage with renal problems

Aztreonam: Adverse Effects

• Pain at injection site, thrombophlebitis.
• Safe for penicillin-allergic patients.

Acute Otitis Media (AOM), Otitis Externa, Otomycosis

Ear Anatomy

• External ear (collects sound).
• Middle ear (transmits sound).
• Inner ear (hearing and balance).
• Eustachian tube: connects middle ear to nasopharynx and aids in fluid/pressure exchange.

Acute Otitis Media (AOM)

• Middle ear infection; fluid, otalgia common; onset, effusion, and inflammation are all required signs.
• Common pathogens: Strep pneumoniae , H. influenza (part of the normal respiratory flora), Moraxella catarrhalis).
• Treatment: Analgesics and antibiotics (amoxicillin , clavulanate, cefdinir are all commonly utilized).
• Observation is recommended in certain cases (e.g. less severe symptoms in older children ).

Otitis Externa

• Infection of the external auditory canal (swimmer's ear).
• Causes: Bacteria, abrasions, excessive moisture.
• Treatment: Topical (ear drops containing e.g., acetic acid) or oral (Ciprofloxacin or Cephalexin) antibiotics depending on severity.

Necrotizing Otitis Externa

• Complication of AOE.
• Risk factors: Elderly, diabetics, immunocompromised.
• Common pathogen: Pseudomonas aeruginosa.
• Treatment: Anti-Pseudomonal drugs including drops (ofloxacin) and tablets (ciprofloxacin); even IV imipenem if severe.

Fungal Otitis Externa

• Caused by fungi (e.g., Aspergillus, Candida).
• Symptoms: Intense pruritus and erythema.
• Treatment: Acidifying ear drops, and if not effective then antifungal drops like 1% clotrimazole can be utilized.

Complementary/Alternative Therapy

• Complementary and alternative medicine (CAM) refers to treatment options not widely accepted by mainstream medicine (e.g., herbal products, vitamins, prayer, acupuncture, and others.)
• Dietary supplements: Vitamins/minerals/herbs/botanicals, etc., intended to support the diet, often not rigorously evaluated for safety and efficacy before being released to the public.
• Regulations differ from conventional drug products; use caution with interactions.
• Careful drug history is crucial when also utilizing complementary/alternative therapies - be sure to note the herbal therapies the patient is taking.