Treatment and Prophylaxis of Bacterial Infections¶
Chapter 149 | Part 5: Infectious Diseases
KEY CLINICAL POINTS¶
- Antibacterial agents target bacterial structures (cell wall, protein synthesis, DNA/RNA) and metabolic pathways to achieve bactericidal or bacteriostatic effects.
- Pharmacodynamic parameters like AUC/MIC and T > MIC are critical for optimizing therapeutic outcomes and minimizing resistance.
- Prophylaxis is indicated for surgical and high-risk nonsurgical infections, with timing and duration based on procedure type and patient risk factors.
- Antimicrobial stewardship programs reduce resistance, adverse effects, and costs through optimized prescribing and monitoring.
- Drug interactions and adverse effects (e.g., nephrotoxicity, ototoxicity, QT prolongation) require careful monitoring and dose adjustments.
1. DEFINITION & OVERVIEW¶
Antibacterial agents inhibit bacterial growth through mechanisms targeting cell wall synthesis, protein synthesis, DNA/RNA replication, or metabolic pathways. Pharmacodynamics (AUC/MIC, T > MIC) and pharmacokinetics (absorption, distribution, metabolism, excretion) determine efficacy and safety. Resistance development is influenced by drug exposure, bacterial virulence, and host factors.
Table 149-1: Risks of Antibacterial Use in Pregnancy and Lactation¶
| PREGNANCY CATEGORY | ANTIBACTERIAL DRUG | FETAL RISK RECOMMENDATION | BREASTFEEDING RISK RECOMMENDATION |
|---|---|---|---|
| B | Azithromycin | Limited human data; animal data suggest low risk. | Limited human data; probably compatible |
| C | Cephalosporins | Compatible | Compatible |
| C | Vancomycin | Compatible | Limited human data; probably compatible |
| D | Chloramphenicol | Compatible | Limited human data; potential toxicity |
| C | Fluoroquinolones | Human data suggest low risk. | Limited human data; probably compatible |
1.1 Mechanisms of Action¶
Key mechanisms include: (1) Cell wall synthesis inhibition ( β -lactams, glycopeptides), (2) Protein synthesis inhibition (macrolides, aminoglycosides), (3) DNA/RNA synthesis inhibition (fluoroquinolones, sulfonamides), and (4) Metabolic pathway disruption (sulfonamides, trimethoprim).
1.2 Resistance Development¶
Resistance arises from bacterial genetic mutations, efflux pumps, and enzymatic inactivation (e.g., β -lactamases). Resistance patterns vary by pathogen and region, necessitating local antibiograms for optimal therapy.
2. MECHANISMS OF ACTION¶
Antibacterial agents target bacterial structures and metabolic processes. Key mechanisms include cell wall synthesis inhibition ( β -lactams), protein synthesis inhibition (macrolides, aminoglycosides), DNA/RNA synthesis inhibition (fluoroquinolones), and metabolic pathway disruption (sulfonamides).
Table 149-2: Common Adverse Reactions to Antibacterial Agents¶
| ANTIBACTERIAL(S) | POTENTIAL ADVERSE EFFECTS | COMMENTS |
|---|---|---|
| b-Lactams | Hypersensitivity reactions (rash, anaphylaxis) | Cross-reactivity related to chemical structure |
| Vancomycin | Nephrotoxicity | Risk increases with trough levels >20 mg/mL |
| Telavancin | QT prolongation | Avoid with other QT-prolonging agents |
2.1 Cell Wall Synthesis Inhibition¶
β -lactams (penicillins, cephalosporins, carbapenems) inhibit transpeptidase activity, preventing peptidoglycan cross-linking. Glycopeptides (vancomycin, teicoplanin) bind D-alanine residues in cell wall precursors.
2.2 Protein Synthesis Inhibition¶
Macrolides (erythromycin, azithromycin) bind 50S ribosomal subunit. Aminoglycosides (gentamicin, tobramycin) bind 30S subunit, causing misreading of mRNA. Lincosamides (clindamycin) inhibit peptidyl transferase.
2.3 DNA/RNA Synthesis Inhibition¶
Fluoroquinolones inhibit DNA gyrase/topoisomerase IV, causing DNA strand breaks. Sulfonamides inhibit dihydropteroate synthase, disrupting folate synthesis.
3. PHARMACOKINETICS & PHARMACODYNAMICS¶
Pharmacokinetic parameters (absorption, distribution, metabolism, excretion) and pharmacodynamic endpoints (AUC/MIC, T > MIC) guide dosing. Concentration-dependent agents (aminoglycosides, fluoroquinolones) require peak concentrations > MIC, while time-dependent agents ( β -lactams) require prolonged exposure above MIC.
Table 149-3: Antibacterial Drug Interactions¶
| ANTIBACTERIAL(S) | INTERACTING AGENT(S) | POTENTIAL EFFECT AND MANAGEMENT |
|---|---|---|
| Nafcillin | Warfarin | Decreased warfarin effect; monitor INR |
| ANTIBACTERIAL(S) | INTERACTING AGENT(S) | POTENTIAL EFFECT AND MANAGEMENT |
|---|---|---|
| Ceftriaxone | Calcium-containing solutions | Precipitation in neonates <28 days |
| Rifampin | Warfarin | Decreased warfarin levels; monitor INR |
3.1 Pharmacokinetic Considerations¶
Absorption varies by route (IV vs. oral). Distribution depends on tissue perfusion (e.g., CSF penetration for CNS infections). Renal/metabolic clearance affects dosing in patients with organ dysfunction.
3.2 Pharmacodynamic Parameters¶
Concentration-dependent agents (aminoglycosides, fluoroquinolones) require peak MIC ratios >10–20. Time-dependent agents ( β -lactams) require T > MIC >40%–50% of dosing interval.
4. THERAPY & PROPHYLAXIS¶
Empirical therapy targets likely pathogens based on clinical context, while directed therapy uses culture results. Prophylaxis is indicated for surgical and high-risk infections, with timing and duration based on procedure type and patient risk factors.
Table 149-5: Prophylaxis of Bacterial Infections in Adults¶
| CONDITION | ANTIBACTERIAL AGENTS | TIMING OR DURATION |
|---|---|---|
| Surgical Clean (cardiac, thoracic) | Cefazolin (vancomycin, clindamycin) | 1 hour before incision; re-dose for long procedures |
| Nonsurgical Dental procedures | Amoxicillin PO, ampicillin IM | Oral agents 1 hour before; injection 30 min before |
| Recurrent cystitis | Nitrofurantoin, TMP-SMX | After sexual intercourse or 3x/week for 1 year |
4.1 Empirical vs. Directed Therapy¶
Empirical therapy uses broad-spectrum agents for severe infections. Directed therapy selects narrow-spectrum agents based on culture and susceptibility data. Combination therapy may be required for multidrug-resistant organisms.
4.2 Prophylaxis Guidelines¶
Prophylaxis is indicated for surgical procedures (clean, contaminated, dirty) and nonsurgical infections (e.g., dental, bite wounds). Timing: 1 hour pre-procedure; duration: 24–48 hours post-procedure for surgical prophylaxis.
5. SPECIAL CONSIDERATIONS¶
Special populations (pregnancy, lactation, renal failure) require adjusted dosing and drug selection. Antimicrobial stewardship programs optimize use to reduce resistance and adverse effects.
Table 149-4: Drug Indications for Specific Infections¶
| ANTIBACTERIAL(S) | INFECTIONS | COMMON PATHOGENS (% SUSCEPTIBLE) |
|---|---|---|
| Penicillin G | Syphilis, leptospirosis | Neisseria meningitidis (60%), Streptococcus pneumoniae (97%) |
| Ceftriaxone | Gonococcal infections | Neisseria gonorrhoeae, S. pneumoniae (87%) |
| Vancomycin | MRSA infections | S. aureus (100%), E. faecalis (93%) |
5.1 Pregnancy and Lactation¶
Avoid drugs with high fetal risk (category D/X). Monitor for teratogenicity; some agents (e.g., tetracyclines) are contraindicated in pregnancy.
5.2 Renal/ Hepatic Impairment¶
Adjust doses for renal failure (e.g., vancomycin, aminoglycosides). Avoid drugs with hepatic metabolism (e.g., linezolid) in severe hepatic dysfunction.
6. KEY POINTS & CLINICAL PEARLS¶
- Optimize drug exposure using AUC/MIC and T > MIC for efficacy. 2. Monitor for nephrotoxicity (vancomycin, aminoglycosides) and ototoxicity (aminoglycosides). 3. Use prophylaxis for surgical and high-risk infections with timing based on procedure type. 4. Avoid drug interactions (e.g., rifampin with hormonal contraceptives). 5. Implement antimicrobial stewardship to reduce resistance and adverse effects.