Antimicrobial Therapy Overview

Overview of Antimicrobial Therapy

• This presentation covers sulfonamide and quinolone antimicrobial therapy.
• Objectives include discussing antibacterial drug concepts for safety and effectiveness, listing antimicrobial classes, recognizing resistance, and discussing indications for drug combinations and prophylactic use.
• The presentation also discusses mechanisms of action, indications, and adverse effects of sulfonamides and fluoroquinolones.
• Antimicrobial drugs are effective because of their selective toxicity, harming invading microorganisms without harming the host.
• Bacteriostatic versus bactericidal drugs are discussed.
• Medically important microorganisms, including Gram-positive cocci, bacilli, and Gram-negative organisms, are also identified.

Objectives

• Discuss general concepts of antibacterial drugs for safety and effectiveness.
• List different antimicrobial classes.
• Recognize resistance development and methods for limiting it.
• Discuss antibacterial drug indications for drug combinations and prophylactic use
• Identify mechanisms of action and indications of sulfonamides and fluoroquinolones.
• Mention adverse effects of sulfonamides and fluoroquinolones.

Terms to Know

• Antimicrobial drugs are effective in treating infections due to selective toxicity, harming invaders without harming the host.
• Understanding bacteriostatic vs. bactericidal drugs is crucial.
• Key medically important microorganisms (e.g., Gram-positive cocci, Gram-negative rods, anaerobes) are classified.

Terms to Know (continued)

• Susceptibility testing is essential for determining drug sensitivity of pathogens.
• Antimicrobial prophylaxis prevents infection before it occurs (e.g., before dental extractions with implanted devices using Amoxicillin).
• Empiric therapy is the initial administration of a drug before knowing the pathogen.
• Combination antimicrobial drug therapy enhances efficacy compared to single-drug regimens.
• Minimum inhibitory concentration (MIC) is an estimate of the drug's sensitivity compared to predicted blood levels.
• Post-antibiotic effect (PAE) occurs when treatment effect persists after drug levels fall below the MIC.

Gram Stain for Bacterial Organisms

• Gram-positive bacteria stain purple, while Gram-negative stain pink.
• Atypical organisms (e.g., Chlamydia, Mycoplasma) may not stain well.
• Examples of Gram-positive Cocci and Rods are presented.
• Examples of Gram-negative Cocci and Rods are presented.
• Anaerobes are also highlighted in the Gram Stain.

Common Bacterial Pathogens

• Presentation of diseases and the bacteria responsible for infections in several body sites and systems is included (e.g., CNS, upper respiratory tract, heart, intra-abdominal, skin/soft tissue, bone/joint, and urinary tract).

Mechanism of Action of Antibacterial Agents

• Illustrates how various classes of antibiotics affect different bacterial targets.
• Inhibitors of bacterial metabolism, cell wall synthesis, protein synthesis, and nucleic acid function.

Selection of Appropriate Antimicrobial Agents

• Identifying the organism.
• Determining susceptibility to an agent.
• Understanding the infection site.
• Considering patient factors.
• Assessing drug safety and efficacy.
• Determining cost considerations.

Chemotherapeutic Spectra

• Defines narrow-spectrum (affecting a limited group of microorganisms), broad-spectrum (affecting various species), and extended-spectrum (effective against several gram-positive and negative bacteria) antibiotics.
• Gives examples of isoniazid, ampicillin, and tetracycline.

Frequency of Dosing

• Three critical factors influencing dosing frequency are concentration-dependent killing, and time-dependent (concentration-independent) killing, and post-antibiotic effect (PAE).
• PAE is a persistent suppression of bacterial growth even after drug levels are lower than the minimal inhibitory concentration (MIC).
• These factors influence treatment strategies, and proper dosing can improve outcomes and limit resistance development.

Mechanism of Action of Aminoglycosides

• Aminoglycosides demonstrate bactericidal effects with increasing concentration.

Antimicrobial Therapy Complications

• Hypersensitivity reactions (ranging from urticaria to anaphylactic shock).
• Direct toxicity (e.g., aminoglycoside ototoxicity and nephrotoxicity).
• Superinfections (resulting from broad-spectrum antimicrobials).

Drug Resistance Mechanisms

• Alterations in target sites (e.g., DNA gyrase mutations).
• Decreased accumulation (changes in permeability, efflux).
• Enzymatic inactivation (e.g. β-lactamases).

Minimizing Antibiotic Resistance

• Avoid indiscriminate use, emphasizing appropriate indication, dose, and duration.
• Employ antimicrobial combinations (e.g. tuberculosis).
• Monitor resistance patterns, modifying treatment as needed.
• Control infections (e.g. employing isolation methods, hand hygiene).
• Limit use of new agents.

Antibiotic Drug Combinations

• Synergistic combinations are more potent than individual agents, with examples like penicillin plus gentamicin for enterococcal endocarditis.
• Drug combinations can help prevent the development of resistance, particularly in chronic infections with multiple bacteria.
• Broader antibacterial activity and prevention of potential drug resistance are significant advantages
• Combining a bacteriostatic agent with a bactericidal one might interfere with the second drug's effects.

Prophylactic Antibiotics

• justifies prophylactic use in high-risk situations with numerous bacteria being operated on or in cases with potential disastrous outcomes and when prophylaxis with known agents could be effective.

Inhibitors of Bacterial DNA Replication

• Fluoroquinolones target bacterial topoisomerases II (DNA gyrase) and IV, inhibiting DNA replication and repair.

Fluoroquinolones Indications

• Fluoroquinolones are used for anthrax, urinary tract infections, and anaerobic infections.
• Used as treatment for resistant respiratory infections, gastroenteral infections

Fluoroquinolones Pharmacokinetics

• Absorption is affected by aluminum and magnesium antacids, or certain dietary items with high calcium content.
• Distribution in various tissues and fluids, except urine in specific cases.
• Extensive renal excretion is typical.

Fluoroquinolones Adverse Effects

• Phototoxicity, articular cartilage erosion, and adverse effects relating to pregnancy and lactation and in children under 18 are some of the side effects.

Trimethoprim

• Trimethoprim is a potent inhibitor of bacterial dihydrofolate reductase.
• Often used in combination (e.g., with sulfamethoxazole).
• Effective against UTIs and bacterial prostatitis, but can cause folate deficiency-related side effects.

Co-trimoxazole

• A combination of trimethoprim and sulfamethoxazole.
• Potent bactericidal effects due to synergistic action.
• Similar absorption and pharmacokinetics of the constituents allow for broader use.

Other Therapeutic Applications

• Various applications targeting specific bacterial infections, including those in the respiratory, urinary, and gastrointestinal systems, are illustrated.

Sulfonamides

• Sulfonamides are antagonists of folic acid in bacteria and exhibit a wide range of therapeutic uses.
• The therapeutic applications of sulfonamides involve bacterial infections, especially urinary tract, intestinal, and meningococcal infections, as well as topical uses like in the treatment of trachoma and burns.
• Adverse reactions and side effects are noted.