Pharm Week 10 Objectives Hard

Bactericidal vs. Bacteriostatic

• Bactericidals are agents that kill bacteria/microorganisms.
• Penicillins, cephalosporins, and aminoglycosides are examples of bactericidals.
• Bactericidals destroy the bacterial cell wall, interfere with essential cellular processes or disrupt the bacterial membrane, leading to cell death.
• Bacteriostatics inhibit bacteria growth and reproduction without killing them.
• Tetracyclines, macrolides, and sulfonamides are examples of bacteriostatics.
• Bacteriostatic action allows the immune system to clear the infection and is not as aggressive as bactericidal.
• Bacteriostatics interfere with protein synthesis or metabolic pathways.

Broad-Spectrum vs. Narrow-Spectrum Antibiotics

• Broad-spectrum antibiotics target a wide variety of bacteria, including both gram-positive and gram-negative types.
• They are often started after a culture is taken but before the exact organism is identified.
• Broad-spectrum antibiotics can disrupt the balance of normal, beneficial bacteria, leading to GI disturbances or superinfections (GI infections, yeast infections, C.Diff).
• Use can lead to antibiotic resistance by affecting a larger pool of bacteria.
• They are often chosen when the exact causative pathogen is unknown, making them useful in empiric therapy.
• Narrow-spectrum antibiotics target specific types or families of bacteria.
• Use is preferred when the pathogen is identified, allowing for targeted treatment.
• It starts after culture results are available to provide specific coverage and decrease the organism's risk of becoming resistant to the antibiotics.
• They are reserved for severe infections from gram-positive organisms (esp. staph aureus, MRSA).
• Use leads to less disruption to normal bacterial flora, reducing the likelihood of side effects.
• Use helps minimize the selection pressure for resistance among non-target bacteria.
• Blood levels of ABXs, CBC, and WBC are monitored to determine effectiveness.

Mechanisms of Antibiotic Resistance

• Genetic mutations in bacteria DNA can alter target sites for antibiotics, reduce drug binding, or modify metabolic pathways, making the drug less effective.
• The organism can change the structure of channels or pores for antibiotic entry, leading to resistance.
• Enzymatic inactivation occurs when bacteria produce enzymes (e.g., β-lactamases) that degrade or modify antibiotics, deactivating them.
• Haemophilus influenzae produces beta-lactamase enzyme that destroys penicillin and ampicillin.
• Efflux pumps are systems that Gram-negative bacteria can develop or enhance to pump antibiotics out of the cell; preventing accumulation of antibiotic.
• Reduced permeability happens when changes in the bacterial cell wall or membrane reduces antibiotic uptake, limiting the access to internal targets.
• Gram-negative bacteria are surrounded by an outer lipopolysaccharide membrane which presents a barrier for many antibiotics.
• Resistant strains of bacteria have less permeable outer membranes or porin channels.
• Pseudomonas aeruginosa is resistant to gentamycin for this reason.
• Alteration of the target site happens when the bacteria produces a different protein target site where the antibiotic normally binds, preventing binding and killing the bacteria.
• MRSA has altered penicillin binding protein, so methicillin can no longer bind with Staph. aureus and will no longer kill the bacteria.

Pseudomembraneous Colitis

• Pseudomembranous colitis is an inflammatory condition of the colon associated with the overgrowth of Clostridioides difficile, previously known as Clostridium difficile.
• Clostridioides difficile (C. difficile) is the primary pathogen, producing toxins (toxin A and toxin B) that damage the colonic mucosa and form of pseudomembranes.
• The most common clinical signs are watery diarrhea and abdominal pain and cramping, which may be severe.
• Common clinical manifestations include fever and leukocytosis; ↑ WBC.
• Nausea, loss of appetite, and in severe cases, complications like toxic megacolon or perforation are among other clinical manifestations.
• Broad-spectrum antibiotics such as clindamycin, cephalosporins, fluoroquinolones, and penicillins are frequently implicated risk factors.
• Risk increase with the use cephalosporins (especially IV use) but c.diff is seen in up to 20% of patients on oral cephalosporins .
• Additional risk factors include the disruption of normal flora, hospitalization with healthcare exposure, advanced age, immunocompromised status, and underlying comorbidities.

Antibiotic Selection Processes

• Identification of the likely pathogen and its susceptibility is the first step.
• Empiric therapy is based on clinical presentation, patient history, and local epidemiological data.
• A culture and sensitivity laboratory tests (e.g., cultures, PCR) are used to identify the exact pathogen and determine its susceptibility profile
• Consideration of Antibiotic Spectrum and Resistance Patterns follows.
• Choosing an antibiotic with the appropriate range of action is essential.
• Broad-spectrum agents may be used initially when the pathogen is unknown, but the goal is often to switch to a narrow-spectrum antibiotic once the pathogen is identified
• De-escalation involves narrowing the antibiotic spectrum based on clinical response and microbiological data to minimize antibiotic resistance and reduce adverse effects.
• Factors such as age, weight, organ function (liver, kidney), allergies, pregnancy status, and other comorbid conditions influence the selection and dosing of an antibiotic.
• Host factors: defenses→primarily the immune system and phagocytics cells (macrophages, neutrophils).
• To be effective, an antibiotic must be present at the site of infection in a concentration greater than the MIC.
• Duration of Therapy involves determining the appropriate length of antibiotic treatment is essential to ensure the infection is fully eradicated while minimizing the risk of resistance and side effects
• Appropriate duration is based on the type and severity of infection

Client Factors for Antibiotic Selection

• Dosage and choice of antibiotic affects pediatric and geriatric patients differently due to metabolism and organ function.
• Weight-based dosing ensures the drug reaches therapeutic levels without causing toxicity.
• Prior allergic reactions to antibiotics (e.g., penicillin allergies) necessitates the use of alternative agents.
• Some antibiotics are contraindicated during pregnancy or while breastfeeding due to potential risks to the fetus or infant.
• Impaired kidney or liver function can affect drug clearance, requiring dosage modifications to prevent toxicity.
• Focus drug selection on some antibiotics that are primarily metabolized by the liver or excreted by the kidneys for patients with organ dysfunction.
• Conditions like diabetes, immunosuppression, or cardiovascular disease might affect drug selection, dosing, or potential drug interactions.
• Review the client's medication list to avoid adverse interactions.
• The chosen antibiotic should have good penetration to the infection site.
• More aggressive infections may require broader-spectrum or higher-dose therapies initially.
• Client's ability to adhere to the prescribed regimen (oral vs. intravenous) can influence the choice of antibiotic.
• Outpatient versus inpatient care may dictate which routes of administration and antibiotic forms are most practical.

Client Factors for Antibiotic Compliance

• The nature and severity of the infection play a crucial role; A mild skin infection might require a different antibiotic than a severe systemic infection.
• Review affordability, taste, convenience, and adverse reactions.
• Client education is very important to educate patients to complete the full course of antibiotics.
• Failing to complete the full course may result in the development of resistant infections, which might be passed on to family members.