Aggressive Treatment in Medicine

Antibiotic Therapy

• Antibiotics began with penicillin's discovery by Sir Alexander Fleming in 1945, earning him a Nobel Prize.
• Before penicillin, sulfa antibiotics were used, but they had numerous adverse effects, limiting their success.
• Antibiotics have been widely used since the 1940s.

Key Points

• Introduction to antibiotic therapy
• Choosing the correct antibiotic
• Antimicrobial combinations
• Selecting the right route and assessing effectiveness

Types of Antibiotics

• Penicillins (e.g., Penicillin G, Penicillin V, Amoxicillin, Cloxacillin, Oxacillin, Ampicillin, Piperacillin, Methicillin)
• Cephalosporins
• Carbapenem
• Monobactams
• Glycopeptide
• Aminoglycosides
• Fluoroquinolones

Choosing the Proper Agent

• Identify the organism causing the infection.
• Determine antimicrobial susceptibility.
• Use the narrowest effective spectrum.
• Consider host factors (allergies, age, organ function, site of infection, pregnancy, metabolic disorders like diabetes).

Identification of the Organism

• Gram stain and culturing are the best methods for identifying bacteria.
• Biopsies, cerebrospinal fluid (CSF), pleural fluid, synovial fluid, peritoneal fluid, urine, or sputum are sources for sample collection.
• ELISA/Latex agglutination tests can detect bacteria that might not grow in cultures.
• PCR tests are useful for organisms difficult to culture, such as COVID-19.

Antimicrobial Susceptibility

• Disk diffusion method (common): Bacteria are cultured and antibiotic disks are placed on the plate.
• Epsilometer (E-test): An antibiotic strip with different concentrations is placed on the plate. The inhibition zone indicates the minimum inhibitory concentration (MIC).

Antimicrobial Susceptibility Continued

• Minimum bactericidal concentration (MBC): Specialized testing is necessary for fastidious organisms (e.g., obligate anaerobes, Haemophilus, pneumococci, and MRSA).
• Organisms' resistance mechanisms (e.g., Staphylococcus aureus, E. coli, Enterobacter).

Pharmacodynamic Profile

• Area under the curve/time curve to MIC (AUC/MIC): It indicates the time the drug's concentration is above the MIC for effective bacterial killing.
• Maximal serum concentration/MIC (Cmax/MIC): It shows the relationship between the drug's peak blood concentration and MIC.
• Time during dosing interval that plasma concentration exceeds the MIC (t/MIC): The longer the concentration stays above the MIC, the more effective the treatment.

Concentration and Time-Dependent Dosing

• Concentration-dependent (e.g., fluoroquinolones): Higher concentrations result in faster bacterial death. Larger doses are required.
• Time-dependent (e.g., beta-lactams, vancomycin): Drug effectiveness is proportional to the duration of time the concentration remains above the MIC. Sufficient dosage intervals are critical. Concentration graphs show the efficacy of the drug.

Resistance Selection

• Initial population: Bacteria population includes some already resistant to an antibiotic (marked visually).
• Exposure to antibiotic: The antibiotic kills susceptible bacteria.
• Resistant bacteria survive: Resistant bacteria survive and reproduce, increasing in the population.

Published Data Sources

• Medical and scientific manuals (e.g., Sanford's)
• Medical literature on drugs and therapeutics provide valuable information on drug dosing, choice, and interactions.

Host Factors

• Previous history of adverse reactions (e.g., drug allergies, gastrointestinal upset)
• Neutropenia
• Other conditions (e.g., chronic lymphocytic leukemia, multiple myeloma, asplenia)

Types of Antibiotic Prescriptions

• Therapeutic: The causative microorganism is known and the treatment is targeted (resistant or moderately susceptible).
• Empirical: The causative organism is unknown and the treatment targets the most probable/likely microorganism (typically a broad-spectrum antibiotic).
• Prophylactic: Antibiotics are given to patients with known immunodeficiencies to prevent infections.

Age

• Renal function decreases with age.
• Absorption changes with age (e.g., tetracyclines are not recommended for children under 8).
• Certain drugs' toxicity (e.g., hepatotoxicity with INH, nephrotoxicity in elderly, cochlear damage/hearing loss from aminoglycosides) increases with age.

Genetic/Metabolic Factors

• G6PD deficiency: Avoid sulfa drugs or other unspecified drugs.
• Diabetes mellitus: Sulfa drugs potentially increase hypoglycemic events. Dextrose load may increase glucose, and IM absorption from micro-angiopathy might be poor in diabetes.

Pregnancy

• Safe antibiotics: Penicillins, cephalosporins, erythromycin
• Dangerous antibiotics (teratogenic potential): Metronidazole has been reclassified (is now B rather than C), but tetracyclines and others should still be avoided. Should not be used if possible during pregnancy and should be critically considered.

Renal and Liver Function

• Vancomycin and aminoglycosides (gentamicin, amikacin) can cause renal issues; monitor renal function.

Site of Infection

• Optimal therapy requires an antibiotic concentration above the MIC at the infection site (particularly important for meningitis, endocarditis, osteomyelitis, chronic prostatitis, intraocular infections, abscesses, foreign bodies, or UTIs).

Immune System

• Antibiotics can cause immunosuppression in immunocompromised patients, suppressing monocyte transformation, phagocytosis, chemotaxis, and antibody production.

Combinations of Antibiotics

• Some clinicians believe combinations are beneficial, but antagonism and increased toxicity might outweigh the benefit.
• Combinations may be helpful for infections like TB, endocarditis, abdominal sepsis, and for initial treatment like aminoglycosides + piperacillin.

Synergism and Antagonism for Combinations

• Synergism: When two antibiotics work together to enhance effectiveness (e.g., penicillin and amino-glycosides).
• Antagonism: When two antibiotics decrease each other's effectiveness (e.g., penicillin and tetracycline).

Adverse Effects

• 5% of patients experience adverse effects when taking antibiotics.
• Combining antibiotics often leads to more cost and adverse effects.

Anaphylaxis

• Beta-lactams (e.g., penicillin) are frequent causes of anaphylaxis.
• Cross-reactions are possible (e.g., between penicillin and cephalosporins).
• Aztreonam (a monobactam) generally does not cross-react with other Beta-lactams.

Route of Administration

• Oral: Suitable for stable patients with mild infections.
• IV: Essential for serious infections like sepsis or diabetes.

Monitoring Response

• Monitor patient's clinical condition after antibiotic administration.
• Monitor drug levels (e.g., vancomycin).
• Perform lab tests (e.g., WBC count, liver enzymes, kidney function tests)

Cost

• If all other factors are equal, choose the least expensive antibiotic.

Needle Stick Injuries

• Common in healthcare.
• Potential for transmission of Hepatitis B virus (30%), Hepatitis C virus (3%), and HIV (0.3%).

Hepatitis B Vaccine Recommendations

• Vaccination should be offered to all healthcare workers annually.
• Declination forms can be used if someone chooses not to be vaccinated.
• People can be vaccinated later if exposures or changes in mind occur.

HBV Vaccine (Continued)

• The vaccine comprises the HBV surface antigen and cannot transmit the virus.
• A vaccination schedule (3 shots over a specific time) is followed.
• Booster shots may be given during outbreaks.
• HBV immunoglobulin can be administered if needed after exposure.

HBV Vaccine (Additional Considerations)

• Employees may not offer vaccination if patients already have antibodies or if the vaccine is contraindicated for the healthcare worker.
• Patients should not accept the vaccine if they do not want to.

Responder vs. Non-Responder (HBV)

• Check antibody titers one month after the last dose.
• A titer >10 IU/L indicates a responder; <10 IU/L indicates a non-responder.
• Non-responders can benefit from a booster dose to improve vaccination.

To Boost or Not to Boost (Vaccines)

• Booster injections are not always necessary within the first two decades of successful immunization.

Influenza Vaccine for Healthcare Workers

• Annual administration in the fall.
• Injected inactivated (killed) virus vaccine with 3 or 4 strains
• Does not prevent other viral infections, like RSV
• Risk of Guillain-Barré syndrome is low.

Influenza Vaccine Contraindications

• Prior history of Guillain-Barré syndrome
• Egg allergies (with caution) and allergic reactions to the vaccine components.

Rubella Infection

• MMR vaccine prevention is offered to children.
• A titer check and booster dose can be recommended in case the initial protection is weak or lacking.

Rubella Risk in Pregnancy

• High risk of congenital rubella syndrome.
• Termination is considered in Western countries for early pregnancy infections.
• The risk of congenital rubella drops for pregnancies starting beyond the third trimester.

Congenital Rubella Syndrome

• Growth retardation.
• Malformations include heart, eyes, or brain.
• Deafness, and/or liver/spleen/bone marrow problems.
• Prevention/vaccination is recommended.

Prevention -Chickenpox (Varicella)

• History of chickenpox or positive IgG indicates immunity.
• Prevention is crucial, as chickenpox affects adults more severely than children.

Prevention - Tetanus

• Toxoid vaccine (national program).
• Waning immunity over time.
• Healthcare workers have a higher risk from exposure.

pneumococcal vaccine

• Indicated for immunocompromised adults and those over 65 years of age.
• Not part of the routine vaccination protocol for healthcare workers.

This quiz explores the reasons for providing aggressive treatment in certain patient populations, the concept of empirical versus therapeutic antibiotic prescriptions, and specific conditions that require such interventions. Participants will evaluate various scenarios and conditions in the context of treatment protocols.