Antibiotic Therapy and Microbial Review

Introduction to Antibiotic Therapy

• Antibiotic therapy has no easy method of learning. It requires understanding three antibiotics per organism type, three bacterial types, the adverse effects of classes, and special features of specific antibiotics.

Review of Microbes

• Microbial identification is a three-part process:

  • Gram stain characteristics (Gram-positive, Gram-negative, Gram-variable)
  • Aerobic or anaerobic requirements (obligate aerobe, obligate anaerobe, facultative anaerobe, aerotolerant anaerobe, microaerophilic aerobe)
  • Microbial shape (rod, cocci, other shapes)

• Gram-positive cocci include Staphylococcus and Streptococcus.

• Gram-negative rods include E. coli, Klebsiella, and Pseudomonas.

• Gram-negative cocci include Neisseria and Moraxella.

• Gram-positive rods include Clostridium.

• Other shapes include spirochetes (Treponema and Borrelia).

Empiric Selection of Antibiotics

• The source of the infection influences antibiotic selection, including:
  • Urine
  • Wound
  • Lungs/Respiratory tract
  • Skin/Skin structure
  • Central Nervous System (CNS)
  • Blood
  • Abdomen/Pelvis
  • Bone/Joint
  • Foreign body

Patient Factors Influencing Selection

• Patient comorbidities, including cancer, COPD, and diabetes mellitus (DM), impact antibiotic choice.
• Patient immune status and overall condition are also considered.
• Patient allergies need to be taken into account.

Laboratory Tests

• Identifying pathogens, appropriate lab tests are needed:
  • Infectious disease (ID) monitoring parameters: cultures, complete blood count (CBC) with differential, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin,
• Antibiotic monitoring parameters: renal/liver function, CBC, and serum levels of antibiotics and certain other serum levels of interest.

General Mechanisms of Action

• Penicillin-binding proteins (PBPs) are bacterial enzymes involved in cell wall stabilization.
• Ribosomes are involved in protein synthesis.
• DNA gyrase is an enzyme involved in DNA replication.
• Folate synthesis is a crucial metabolic process.
• Other miscellaneous mechanisms of action are also important.

Antibiotic Classes/Common Drugs (Beta-Lactams)

• Penicillins -Mechanism of Action (MOA): Bind to penicillin-binding proteins (PBPs) inhibiting cell wall synthesis -Examples: penicillin, ampicillin, amoxicillin, ampicillin/sulbactam (Unasyn), amoxicillin/clavulanate (Augmentin), oxacillin, dicloxacillin, piperacillin/tazobactam (Zosyn)Adverse effects (AE) include rashes/allergic reactions, GI upset . Dosing and intervals based on patient, but use pharmacokinetic service where appropriate.

• Cephalosporins

  • MOA: Similar to penicillins, generally broader activity
  • Examples: cefazolin, cefprozil, ceftriaxone, cefotaxime, ceftazidime, cefepime
  • Divisions into generations based on activity against varied bacteria (Gram-positive vs Gram-negative)
  • AE: similar to penicillins (rashes, allergic reactions), others

• Carbapenems

  • MOA: Broad-spectrum; beta-lactam stable; broader activity than penicillins
  • Examples: ertapenem, imipenem, meropenem
  • AE: similar to penicillins, but imipenem may cause seizures in certain patients.

• Monobactams

  • MOA: Primarily anti-pseudomonal activity; only active against Gram-negative organisms
  • Example: aztreonam
  • Requires combination with Gram-positive antibiotic, as it alone may only combat a limited number of infections

Other Antibiotic Classes

• Aminoglycosides

  • MOA: bind irreversibly to 30S ribosomal subunit, inhibiting protein synthesis
  • Examples: gentamicin, tobramycin, amikacin
  • Synergistic with other antibiotics (beta-lactams, Vancomycin) in treating Gram-positive infections
  • Special consideration for dosage intervals based on creatinine clearance (CrCl)
  • AE: ototoxicity, nephrotoxicity, neuromuscular blockade, GI problems

• Macrolides

  • MOA: bind to 50S ribosomal subunit, impairing protein synthesis
  • Examples: azithromycin, clarithromycin, erythromycin
  • Broad-spectrum, often used for strep, atypical bacteria, H. influenza. Resistance is due to antibiotic pumps or alterations in ribosome
  • AE: GI upset, prolonged QT interval

• Glycopeptides

  • MOA: inhibit cell wall synthesis
  • Examples: vancomycin
  • Often used for serious Gram-positive infections, including those resistant to other antibiotics, but resistance is a growing concern
  • Specific dosing considerations based on creatinine clearance (CrCl)
  • AE: ototoxicity, nephrotoxicity, infusion reactions (red man syndrome)

• Sulfa Drugs

  • MOA: inhibit folic acid synthesis
  • Examples: sulfamethoxazole/trimethoprim (Bactrim)
  • Commonly used as 3-day therapy, active against a variety of bacteria, including MRSA
  • AE: Rash, elevated creatinine, anemia

• Fluoroquinolones

  • MOA: inhibit DNA gyrase
  • Examples: ciprofloxacin, levofloxacin, moxifloxacin
  • Active against Gram-negative organisms, including Pseudomonas
  • AE: connective tissue dysfunction, CNS effects (agitation, confusion, delirium), photosensitivity

• Tetracyclines

  • MOA: bind to 30S ribosomal subunit, impairing protein synthesis
  • Examples: doxycycline, tigecycline
  • Broad-spectrum; can be used against various bacterial infections, including atypical bacteria
  • AE: photosensitivity (avoid use in children <7)

• Oxazolidinones

  • MOA: inhibits bacterial protein synthesis; broad range of activity including Gram-positive organisms
  • Examples: linezolid
  • Effective against organisms resistant to other antibiotics.
  • Adverse effects: neuropathy, bone marrow toxicity, serotonin syndrome.

• Others

  • Metronidazole: active against anaerobic bacteria, used to treat intra-abdominal infections and some STIs.
  • Daptomycin: targets cell membranes, treats Gram-positive infections
  • Nitrofurantoin: treats UTIs but may have issues with effectiveness in men.
  • Fosfomycin: effective against bacterial infections.

Overview of antibiotic therapy, including microbial identification based on Gram stain, aerobic/anaerobic requirements, and shape. Covers empiric selection of antibiotics based on infection source and common microbes like Staphylococcus, Streptococcus, E. coli, and Pseudomonas.