Antimicrobial Agents and Antibiotic Treatment

Introduction to Antimicrobial Agents

• Antimicrobial agents kill or inhibit the growth of susceptible organisms, encompassing anti-viral and anti-protozoal actions.
• Antibiotics are produced by microorganisms or chemically synthesized, capable of inhibiting microbial growth at low concentrations.
• Chemotherapy selectively targets invading microbes or abnormal cells.

History

• Fleming's 1945 Nobel Prize speech warned about the potential for antibiotic resistance if antibiotics became easily accessible and misused.

General Characteristics of Antimicrobial Agents

• Selective toxicity minimizes harm to the host while effectively targeting microbes.
• Therapeutic index (ratio of toxic dose to therapeutic dose) indicates the safety margin of an antibiotic; a larger index is preferable.
• Antimicrobials can be classified by range of effectiveness: narrow-spectrum (specific target) and broad-spectrum (variety of targets).
• Bactericidal agents kill microbes, while bacteriostatic agents inhibit their growth.

Measurement of Activity

• Minimum Inhibitory Concentration (MIC) is the lowest concentration that prevents microbe growth.
• Minimum Lethal Concentration (MLC) is the lowest concentration that kills microbes.
• Susceptibility testing methods include dilution tests and disk diffusion tests (e.g., Kirby-Bauer).

Factors Affecting Effectiveness

• Route of administration (oral, topical, parenteral) influences the drug’s effectiveness.
• The site of infection’s accessibility, drug stability in the body, and the pathogen’s susceptibility impact treatment success.
• Drug concentrations at the infection site must exceed the MIC for effectiveness.

Antibiotic Spectrum and Combinations

• Broad-spectrum antibiotics fight various gram-positive and gram-negative bacteria, while narrow-spectrum ones focus on specific organisms.
• Combination therapies can broaden the antibacterial spectrum, prevent resistant strains, and enhance killing effects through synergism.
• Antibiotic antagonism occurs when one drug reduces the effectiveness of another.

Classification of Antimicrobial Agents

• Antimicrobials are categorized based on therapeutic use (e.g., antibacterial, antifungal, antiviral), mechanism of action, spectrum of activity, and source.
• Common antibacterial agents include Penicillin, Chloramphenicol, and Tetracyclines; antifungals include Amphotericin B and Ketoconazole.

Mechanisms of Action

• Antimetabolite Action: Sulfonamides and trimethoprim interfere with folic acid synthesis in bacteria.
• Alteration of Cell Membranes: Polymyxins disrupt membrane integrity, mostly used topically due to toxicity.
• Inhibition of Protein Synthesis: Targets include the 30S and 50S ribosomal subunits; aminoglycosides and macrolides are key examples.
• Inhibition of DNA/RNA Synthesis: Rifampin and quinolones prevent bacterial replication by affecting RNA polymerase and DNA gyrase, respectively.
• Cell Wall Synthesis Inhibitors: Includes β-Lactam antibiotics like penicillins and cephalosporins, which disrupt peptidoglycan cross-linking.

Antimicrobial Resistance

• Antibiotic resistance arises when bacteria continue to multiply despite antibiotic treatment.
• Resistance mechanisms include drug inactivation, drug efflux, altered target sites, and decreased permeability.
• Resistance can be inherited or acquired through mutation, plasmids, or genetic transfer between bacteria.

Factors Contributing to Resistance

• Overuse of antibiotics and inappropriate prescriptions promote the survival of resistant strains.
• Suboptimal levels of antibiotics and the use of broad-spectrum drugs enhance selective pressure on pathogens.
• Poor hygiene, use of antibiotics in agriculture, and patient compliance issues also contribute to increased resistance.

Inappropriate Antibiotic Use

• Misuse includes using broad-spectrum antibiotics unnecessarily, inappropriate drug regimens, and not following established guidelines.
• Initiating therapy ideally involves culturing the infection site to determine the causative organism before prescribing antibiotics. Empiric therapy is commonly practiced when exact information is pending.

Current Situation and Challenges

• Misdiagnosis and underutilization of laboratory testing in Africa exacerbate antibiotic resistance issues.
• Factors beyond health worker control (e.g., over-the-counter antibiotics, counterfeit drugs) complicate the situation and promote improper use.
• Guidelines for antibiotic use are frequently ignored, leading to a higher risk of resistant infections.### Antibiotic Resistance Patterns
• Gentamicin demonstrates high effectiveness with resistance rates reaching 100% in some cases.
• Amikacin shows an overall resistance of 0% to Meropenem and persists at 100% effectiveness in certain contexts.
• Ciprofloxacin exhibits variable resistance, 53.1% in E. coli; lower in Klebsiella at 43.2%.
• Ceftriaxone shows high resistance in both E. coli (81.3%) and Klebsiella (78.5%).
• Ampicillin presents severe resistance levels of 97.8% in E. coli and 94.5% in Klebsiella, signifying limited treatment options.

Impact of Antimicrobial Resistance (AMR)

• AMR leads to longer illness duration, which complicates recovery and increases healthcare burdens.
• Patients infected with resistant strains face a higher mortality rate and require more expensive treatments.
• Technological advances in healthcare, like complex surgeries or transplants, are undermined due to resistant infections.
• Patients can act as reservoirs of resistant organisms, which may spread to the community and healthcare workers.

Strategies to Combat Antibiotic Resistance

• Avoid antibiotics for viral infections to prevent misuse and resistance development.
• Complete full doses of prescribed antibiotics to avoid incomplete treatment.
• Utilize combinations of drugs for bacterial infections to enhance effectiveness.
• Encourage reduction or elimination of preventive antibiotic use in livestock and crops.

Antimicrobial Stewardship

• A multi-disciplinary approach aims to reduce patient morbidity and the spread of AMR.
• Strategies include:
  • Education and guidelines for responsible antibiotic use.
  • Formulary restrictions to manage antibiotic prescriptions.
  • Audits with feedback to ensure compliance with antibiotic stewardship.

Importance of Preservation

• Recognizing antibiotics as a precious resource emphasizes the necessity for collective efforts in AMR management.
• Immediate action in combating AMR is crucial to ensure future treatment efficacy.

Quiz Questions

• Hearing impairment as a side effect is recognized for: A. Streptomycin
• Antibiotics affecting the cell wall include: A. Ceftriaxone
• Substances affecting bacterial cell walls encompass: C. Cephalosporins