Antibiotic Therapy Overview

Antibiotic Therapy

• Antibiotic therapy involves choosing the correct antibiotic and appropriate route, considering efficacy.
• Antimicrobial combinations are also used in certain circumstances.

Key Points

• Introduction to antibiotic therapy is presented.
• Selection of the appropriate antibiotic is a crucial step.
• Antimicrobial combinations are discussed.
• Choice of delivery method and assessing the treatment's effectiveness are important.

Sir A. Fleming

• Sir A. Fleming is credited with discovering penicillin.
• He won the Nobel Prize in 1945 for this discovery.

Antibiotics

• PCNS, Cephalosporins, Carbapenem, Monobactams, Glycopeptide, Aminoglycoside, and Fluoroquinolone are mentioned as examples of antibiotics.

PCN

• Several PCN types are listed, including PCN G, PCN V, Amoxicillin, Cloxacillin, Oxacillin, Ampicillin, Piperacillin, and Methicillin.

Choice of the Proper Agent

• Proper agent selection depends on organism identification, antimicrobial susceptibility, host factors (age, allergies, renal/liver function, site of infection, pregnancy, metabolic issues), and the narrowest effective spectrum.

Identification of the Organism

• Gram stains of samples (CSF, pleural fluid, synovial fluid, peritoneal fluid, urine, sputum) are used to identify the organism.
• Other methods include ELISA/latex agglutination and PCR.
• Cultures are crucial, preferably performed before antibiotic administration.
• Bacteriologic statistics are used to determine the most likely infecting organisms in a given clinical scenario.

Antimicrobial Susceptibility

• Disk diffusion and Epsilometer (E-test) methods are used.
• Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) are vital parameters.
• Specialized tests are used for fastidious organisms like obligate anaerobes, Haemophilus spp., pneumococci, and MRSA.
• Bacterial resistance mechanisms are considered (e.g., Staph. aureus, E. coli, Enterobacter).

Pharmacodynamic Profile

• Area under the curve (AUC)/ time curve to MIC, maximal serum concentration (Cmax)/ MIC, and time (t)/ MIC are important pharmacodynamic factors.

Concentration & Time-Dependent Dosing

• Concentration-dependent antibiotics (e.g., fluoroquinolones, aminoglycosides) exhibit faster bacterial death rates with increasing concentrations; thus, high doses at longer intervals are suitable.
• Time-dependent antibiotics (e.g., β-lactams, vancomycin) display bacterial density reduction proportional to the time the concentration is above the MIC. Therefore, consistent maintenance of drug concentrations above the MIC via appropriate intervals is crucial.

Resistance Selection

• Antibiotic use can promote antibiotic resistance in bacteria over time, potentially resulting in treatment failures.

Published Data

• Manuals like Sanford's and medical letters on drugs and therapeutics provide useful antibiotic information.
• This data should be used within the relevant context.

Host Factors

• Previous adverse reactions, neutrophil function (with neutropenia managed more aggressively), CLL, Multiple Myeloma, and asplenia are relevant considerations.
• The use of appropriate preventative measures is vital.

Age

• Relevant factors include renal function, absorption characteristics, and potential side effects like INH hepatotoxicity, nephrotoxicity, and ototoxicity.

Genetic/Metabolic Factors

• Hemolysis in G6PD deficiency can be a concern.
• Some antibiotics might worsen sulfonylurea hypoglycemia in patients with diabetes.
• Poor intramuscular absorption could be addressed with intravenous administration.

Pregnancy

• Certain antibiotics are safe during pregnancy (e.g., penicillin, cephalosporins, erythromycin), while others are not (e.g., tetracyclines, metronidazole).
• Careful consideration is required and antibiotic choices should be made judiciously.
• Fluoroquinolones are generally contraindicated in pregnancy.
• Antibody doses may need to be adjusted.

Renal and Liver Function

• Vancomycin and aminoglycosides can cause harm to the kidneys and liver, requiring careful monitoring.

Site of Infection

• Appropriate antibiotic selection depends on the infection's location, with optimal therapy requiring adequate antibiotic concentrations at the infection site.
• Specific conditions such as meningitis, endocarditis, osteomyelitis, chronic prostatitis, intraocular infections, abscesses, and foreign body infections are identified.

Immune System

• Immunosuppressed patients may experience more significant antibiotic-induced immune suppression.
• Some antibiotics suppress monocyte transformation, phagocytosis, chemotaxis, and antibody production.

Combinations

• Multiple antibiotic combinations are used sometimes due to issues of safety and/or efficacy.
• Synergism occurs when combining drugs enhances their efficacy, whereas antagonism means that combining them reduces efficacy.

Synergism

• Some combinations may be beneficial for resistant organisms.

Antagonism

• Some in vitro results indicate antagonism between certain antibiotic combinations.
• This is likely more relevant for immunosuppressed individuals.

Adverse Effects

• 5% of patients may experience side effects with antibiotic therapy.
• Combining antibiotics generally results in increased costs with an increased probability of adverse effects.

Anaphylaxis

• Beta-lactams are common causes of antibiotic-induced anaphylaxis.

• Penicillin has a low risk of anaphylaxis (0.01%) which rarely results in death(1 in 100,000 cases).

• Penicillins may cause allergic reactions (10-20%).

• Cross-reactions between penicillins, cephalosporins, and carbapenems are present in less than 1% of cases.

Route

• Oral antibiotics are appropriate for stable, mild infections.
• Intravenous delivery is essential for severe infections like sepsis and diabetes.

Monitoring the Response

• Regular monitoring, including clinical assessments, drug levels, and laboratory tests, are vital for evaluating treatment response.

Cost

• If other factors are equal, the least expensive appropriate antibiotic should be chosen.

Needle Stick

• Hepatitis B (30%), Hepatitis C (3%), and HIV (0.3%) are possible risks to healthcare workers exposed to needle sticks.

HBV Vaccine Recommendations

• Vaccination for hepatitis B is mandatory for healthcare workers in the US (since 1991).
• HBV vaccination does not transmit the virus and is completed with three shots.

HBV Vaccine

• There is a option to decline the HBV vaccination.
• If a healthcare worker is exposed to HBV or changes their mind about vaccination, they can still get the vaccination.
• HBV-vaccinated individuals and/or those with antibodies toward HBV may not receive this vaccination.

Response or no??

• Differentiating true non-response from waning antibody levels is crucial.
• A booster dose can be used.

To Boost or not to Boost??

• Current evidence does not support booster injections for routine use in many individuals after two vaccination doses.
• Further research is recommended.

Influenza Vaccine

• Influenza vaccination is performed annually during fall.
• Seasonal influenza vaccination includes two A and one B strains.
• Influenza vaccines do not protect against related viruses such as RSV or adenovirus.

Influenza Vaccine (Cont.)

• The occurrence of Guillain-Barré syndrome is not significantly higher following influenza vaccination (1/million).
• The vaccine's use is contraindicated in those with a previous history of Guillain-Barré syndrome or egg allergies.

Prevention - Rubella

• MMR vaccination should be considered to prevent rubella transmission, particularly during pregnancy.

Rubella risk

• Congenital rubella syndrome has a high risk of occurrence in the first few months of a pregnancy (up to 90%).

Congenital Rubella Syndrome

• Congenital rubella infection can result in severe problems such as growth retardation, heart, eye, or brain malformation, and hearing loss.
• Maternal rubella during the first two months of pregnancy can also result in the above issues.
• Other sites such as the spleen, liver, and bone marrow can be impacted as well.

Prevention - Varicella

• If you have no history of varicella or have antibodies, it is recommended to get the varicella vaccine.
• Individuals with varicella titers are considered immune.
• Two vaccination doses are administered with a 2-month apart interval.

Tetanus - Diphtheria Vaccine

• Tetanus-diphtheria vaccines are administered every 10 years.
• Toxoid vaccines are used in this case.

Pneumococcal Vaccine

• Pneumococcal vaccines are appropriate for immunocompromised individuals, those over 65, and situations requiring booster doses during outbreaks.