Antibiotic Therapy Overview

Antibiotic Therapy

• Antibiotics began with penicillin, discovered by Alexander Fleming in 1945, earning him a Nobel Prize.
• Prior to penicillin, sulfa antibiotics were used but had numerous side effects, hindering their widespread use.
• Antibiotics have been widely used since the 1940s.

Key Points

• Introduction to antibiotic therapy
• Choosing the appropriate antibiotic
• Antimicrobial combinations
• Choosing the route of administration and assessing efficacy

Types of Antibiotics

• Penicillins (Penicillin G, Penicillin V, Amoxicillin, Cloxacillin, Oxacillin, Ampicillin, Piperacillin, Methicillin)
• Cephalosporins
• Carbapenems
• Monobactams
• Glycopeptides
• Aminoglycosides
• Fluoroquinolones

Choosing the Proper Agent

• Identifying the organism (e.g., Gram stain, culturing)
• Assessing antimicrobial susceptibility (e.g., disk diffusion, E-test)
• Selecting the narrowest effective spectrum
• Considering host factors (age, allergies, renal/liver function, infection site, pregnancy, metabolic disorders)

Identification of the Organism

• Gram stain and culturing are the most common methods of determining the causative microorganism.
• Biopsy, cerebrospinal fluid (CSF), sputum, pleural fluid, peritoneal fluid, urine or synovial fluid can be used to isolate microbes.
• For some bacteria or viruses, tests like ELISA or latex agglutination can be used to recognize the antibodies.
• PCR testing can be useful, especially when culturing is challenging.

Antimicrobial Susceptibility

• Disk diffusion and E-test are common methods to assess the effectiveness of antibiotics against the bacteria.
• The diameter of the inhibition zone determines whether bacteria are resistant or susceptible to the tested antibiotic.
• Minimum Inhibitory Concentration (MIC) is determined by applying different concentrations of an antibiotic to separate bacterial plates and measuring the effect.

Antimicrobial Susceptibility (continued)

• Specialized testing is vital for fastidious organisms (obligate anaerobes, Haemophilus species, pneumococci, and MRSA).
• Minimum bactericidal concentration (MBC) further determines the lowest antibiotic concentration needed to kill the bacteria.

Pharmacodynamic Profile

• Area under the curve / time curve to MIC (AUC/MIC) reflects the relationship between the drug's concentration in the body and the time it remains above the minimum inhibitory concentration (MIC).
• Maximal serum concentration / MIC (C_max/MIC) shows the peak drug concentration in the blood relative to the MIC.
• Time during dosing interval that plasma concentration exceeds the MIC (t/MIC) refers to the time concentration stays above the MIC.

Concentration and Time-Dependent Dosing

• Concentration-dependent antibiotics (e.g., fluoroquinolones, aminoglycosides) work best when the drug concentration is high.
• Time-dependent antibiotics (e.g., beta-lactams, vancomycin) act effectively over a sustained period above the MIC.

Organism Susceptibility

• Organism A is resistant
• Organism B is moderately susceptible
• Organism C is very susceptible

Host Factors

• Previous history of adverse reactions (allergies, drug reactions)
• Neutrophil function (neutropenia)
• Chronic conditions (CLL, MM, asplenia)

Three Types of Antibiotic Prescriptions

• Therapeutic: identify the specific microorganism
• Empirical: use clinical knowledge, choose likely bacterial causes
• Prophylactic: prevent infection in immunocompromised patients

Age

• Renal function decreases with age
• Absorption may change with age
• Some antibiotics (e.g., tetracyclines, INH) have age-related risks (hepatotoxicity, nephrotoxicity)

Genetic/Metabolic Factors

• Patients with G6PD deficiency should avoid sulfa drugs
• Patients with DM should be monitored for hypoglycemia when using sulfonylureas and for increased glucose levels due to a poor intramuscular absorption
• Intravenous (IV) route is preferred for some cases if oral administration is not recommended

Pregnancy

• Safe: Penicillins, cephalosporins, erythromycin base
• Dangerous: Tetracyclines, caution with metronidazole
• Contraindicated: Fluoroquinolones, clarithromycin, erythromycin
• Important to adjust antibiotic dosages in pregnancy due to altered metabolism

Renal and Liver Function

• Vancomycin and aminoglycosides need renal function monitoring

Site of Infection

• Maintaining optimal drug concentration at the infection site is crucial, especially for conditions like meningitis, endocarditis, infections in internal areas of the eye (intraocular)
• Some antibiotics may not be effective at particular sites

Immune System

• Antibiotics can suppress the immune system, particularly in immunosuppressed patients. This can impact monocyte transformation, phagocytosis, chemotaxis, and antibody production.

Combinations of Antibiotics

• Some clinicians advocate antibiotic combinations for broader pathogen coverage, but potential antagonism and increased toxicity must be considered

Indications for Combination Therapy

• Prevention of resistance
• Treating polymicrobial infections
• Initial therapy (e.g., combining aminoglycosides and piperacillin)
• Enhancing effectiveness (synergism)

Synergism for Resistant Organisms

• Examples include penicillin (PCN) + aminoglycosides for enterococcal or staphylococcal endocarditis; and anti-pseudomonal β-lactam + aminoglycosides for Pseudomonas bacteremia.

Antagonism

• Some antibiotic combinations can be antagonistic, leading to reduced effectiveness.
• Examples include penicillin and tetracycline, or combining two beta-lactam antibiotics
• This is especially important for immunosuppressed patients.

Adverse Effects

• 5% of patients experience adverse effects from antibiotics
• Antibiotic combinations lead to higher cost and more adverse effects

Anaphylaxis

• Beta-lactams are the most frequent cause of anaphylaxis.
• Penicillin has a very low risk (0.01% risk).
• Cross-reactions can occur with cephalosporins and carbapenems
• Not all alleged allergies are actual clinical allergies. The actual incidence is much lower than many patients report.

Route of Administration

• Oral route is preferred if patient is stable and has mild infection
• IV route is often preferred for serious infections like sepsis or patients with DM.

Monitoring the Response

• Clinically monitor improvement or worsening after administration
• Measure drug levels
• Check laboratory tests (White Blood Cell count, liver enzymes, and kidney function tests)

Cost

• Choose the least expensive antibiotic if all other factors are similar

Needle Stick Injuries

• Risks of transmission through needle stick injuries include hepatitis B virus (30%), hepatitis C virus (3%), and HIV (0.3%).

HBV Vaccine

• HBV vaccine should be offered to all healthcare workers.
• Decline and sign a declination form is possible
• Vaccination is possible after exposure or change of mind
• Employers may not offer a vaccination for those already immune, vaccinated, or if contraindicated.
• HBV vaccine contains the surface antigen and does not transmit the virus.
• This vaccine is administered once and is not needed to repeat administration.

Responder vs. Non-Responder to HBV Vaccine

• Check antibody titer (e.g., > 10 IU/L) one month after the final HBV vaccine dose.
• If antibody titer is <10 IU/L, consider a booster dose.
• Most people respond to HBV vaccine (95%)

Boost or Not to Boost Vaccine

• There is no evidence of need for periodic booster injections within the first two decades after immunization.

Influenza Vaccine

• Annual vaccination with an injectable, inactivated virus vaccine, containing 3-4 strains, depending on availability.
• This vaccine does not protect against other similar illnesses.
• Small risk of association with Guillain-Barré syndrome

Influenza Vaccine (Contraindications)

• Previous Guillain-Barré Syndrome
• Egg allergy (monitor for mild reactions).

Prevention - Rubella

• MMR vaccine is used to prevent infection, but rubella immunity can diminish over time in some people
• Pregnancy should be avoided for 2 months after MMR vaccination
• Individuals who test negative on rubella immunity testing may need an MMR booster.

Rubella-Risk

• Risk of congenital infection is substantial in first 2 trimesters (e.g., 90% in first two months)
• 3rd month risk is lower but still exists
• Termination is typical recommendation in the first two months of suspected exposure
• Risk declines significantly after the second trimester (12-16 weeks)

Congenital Rubella Syndrome

• Symptoms include growth retardation, malformations of the heart, eyes, or brain, deafness, and liver, spleen, and bone marrow problems.

Prevention - Varicella

• History of chickenpox, or a positive IgG titer indicates immunity.
• Chickenpox prevention is important, as chickenpox is more severe and has a wider spread for adults
• Vaccination through two doses administered two months apart
• Two-month pregnancy avoidance postpartum is recommended

Tetanus - Diphtheria Vaccine

• Protection from tetanus is provided by toxoid vaccine, part of the national immunization program, but immunity can diminish over time.
• Workers face an increased risk of tetanus through sharp injuries
• Countries may require documented immunity

Pneumococcal Vaccine

• Indicated for immunocompromised adults or those over 65 years.
• Not part of the routine HCW vaccination program.

Explore the fundamentals of antibiotic therapy, including the history of antibiotics, key types, and methods for selecting the appropriate agent. This quiz covers essential concepts such as antimicrobial combinations and the factors that influence treatment decisions.