2B PRINCIPLES OF ANTIMICROBIAL THERAPY(1).pdf

PRINCIPLES OF ANTIMICROBIAL THERAPY EDITED BY: MS EMILY  LEARNING OUTCOMES At the end of the lecture, students should be able to: 1. Identify characteristic features of bacteria 2. Describe laboratory techniques in the diagnosis of microbial diseases 3. Explain how a...

PRINCIPLES OF ANTIMICROBIAL THERAPY EDITED BY: MS EMILY  LEARNING OUTCOMES At the end of the lecture, students should be able to: 1. Identify characteristic features of bacteria 2. Describe laboratory techniques in the diagnosis of microbial diseases 3. Explain how antimicrobial agents would be choose 4. Describe empiric therapy, multiple antibiotic therapy and perioperative antibiotic prophylaxis 5. Explain factors affecting therapeutic effectiveness  PATHOGENS: Bacteria that cause disease are usually known as pathogens 3  CHARACTERISTIC FEATURES OF BACTERIA: SHAPE 3 forms of bacteria based on SHAPE: (a) Spherical or Ovoid bacteria occur as single cells (monococci), or in pairs (diplococci), clusters (staphylococci), chains (streptococci) or cubical groups (sarcinae) 4  CHARACTERISTIC FEATURES OF BACTERIA (b) Rod-shaped — bacteria are termed as bacilli, more oval ones are known as coccobacilli, and those forming a chain are called as streptobacilli (c) Spiral — bacteria are rigid (spirilla), flexible (spirochaetes) or curved (vibrios) 5 BACTERIAL SHAPE, ARRANGEMENT & DESCRIPTION 6 BACTERIAL SHAPE, ARRANGEMENT & DESCRIPTION 7 BACTERIAL SHAPE, ARRANGEMENT & DESCRIPTION 8  CHARACTERISTIC FEATURES OF BACTERIA: BACTERIAL GROWTH BASED ON OXYGEN REQUIREMENTS: Aerobes : Essentially require oxygen for their very existence and growth (E.g: M. tuberculosis) Anaerobes : Do not require oxygen for their existence and growth. e.g., most bacteria found in the GIT 9 Facultative : It can grow with or with out  CHARACTERISTIC FEATURES OF BACTERIA: BACTERIAL STAINING BASED ON STAINING: Gram–Positive microorganism stain Blue or Purple 10  CHARACTERISTIC FEATURES OF BACTERIA: BACTERIAL STAINING Gram-negative microorganisms stain red or rose-pink 11 LABORATORY TECHNIQUES FOR THE DIAGNOSIS OF MICROBIAL DISEASES 12  LABORATORY TECHNIQUES FOR THE DIAGNOSIS OF MICROBIAL DISEASES MICROBIOLOGIC CULTURES: To identify the specific causative agent, specimens of body fluids or infected tissue are collected for analysis SUSCEPTIBILITY TESTS: It determines the microbial susceptibility to a given drug. It is used to predict whether the drug will combat the infection effectively Includes microdilution method and Kirby -Bauer disk diffusion technique 13  MICRODILUTION METHOD The drug is diluted serially in various media containing the test microorganism MIC (Minimum Inhibitory Concentration): The lowest drug concentration that prevents microbial growth after 18-24 hrs of incubation MBC (Minimum Bactericidal Concentration): The lowest drug concentration that reduces bacterial density by 99.9 % 14 15  KIRBY-BAUER DISK DIFFUSION TECHNIQUE Less expensive and less reliable than the microdilution method Filter paper disks impregnated with specific drug quantities are placed on the surface of agar plates streaked with a microorganism culture After 18 hrs, the size of a clear inhibition zone is determined; drug activity against the test strain is then correlated to zone size 16  KIRBY-BAUER DISK DIFFUSION TECHNIQUE The Kirby-Bauer technique does not reliably predict therapeutic effectiveness against certain microorganisms E.g: Staphylococcus aureus, Shigella 17  CHOICE OF ANTIMICROBIAL AGENTS  Anti-infective agent should be chosen on the basis of: √ Pharmacologic properties of drug √ Spectrum of activity √ Patient factors - Age, Pregnancy and lactation - Underlying disease, immunologic status - Presence of a foreign body - Genetic traits 18 CHOICE OF ANTIMICROBIAL AGENTS: PATIENT FACTORS AGE: - Certain antibiotics causes ototoxicity in elderly patients - Decreased metabolism and excretion are common in young and very old patients PREGNANCY & LACTATION: - Most drugs including antibiotics appear in breast milk of nursing mothers may cause adverse effects in infants - e.g: Sulfonamides may lead to toxic bilirubin accumulation in a newborn’s 19 brain. CHOICE OF ANTIMICROBIAL AGENTS: PATIENT FACTORS UNDERLYING DISEASE: * Pre-existing liver or kidney disease increases the risk of hepatotoxicity or nephrotoxicity during the usage of some antibacterial drugs.  E.g: Patients with CNS disorders may suffer neurotoxicity (Motor seizure) during penicillin therapy. 20 CHOICE OF ANTIMICROBIAL AGENTS: PATIENT FACTORS IMMUNOLOGIC STATUS: A patient with impaired immune mechanisms may require a drug that rapidly destroys pathogens (bactericidal instead of bacteriostatic agents) PRESENCE OF A FOREIGN BODY: Effectiveness of anti-infective therapy is reduced in patients who have prosthetic joints 21 CHOICE OF ANTIMICROBIAL AGENTS: PATIENT FACTORS GENETIC TRAITS: * Sulfonamides may cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. * Patients who rapidly metabolize drugs (rapid acetylators) may develop hepatitis when receiving the anti-tubercular drug Isoniazid (INH). 22  EMPIRIC THERAPY In serious or life threatening disease, anti-infective therapy must begin before the infecting organism has been identified The choice of drug (or drugs) is based on clinical experience, suggesting that a particular agent is effective in a given setting 23  EMPIRIC THERAPY A broad-spectrum antibiotic usually is the most appropriate choice until the specific organism has been determined. Culture specimens must be obtained before therapy begins 24  MULTIPLE ANTIBIOTIC THERAPY Combination of drugs should be given only when clinical experience has shown such therapy to be more effective than single-agent therapy in a particular setting A multiple-agent regimen can increase - The risk of toxic drug effects -Drug antagonism and therapeutic 25  INDICATIONS FOR MULTIPLE- AGENT THERAPY Need for increased antibiotic effectiveness: The synergistic (intensified) effect of two or more agents may allow dosage reduction or enhanced drug effect Treatment of an infection caused by multiple pathogens: (e.g., Intra-abdominal infection) Prevention of proliferation of drug-resistant organisms: (e.g., during treatment of tuberculosis) 26  DURATION OF ANTI-INFECTIVE THERAPY To achieve the therapeutic goal, anti-infective therapy must continue for a sufficient duration ACUTE UNCOMPLICATED INFECTION: Treatment generally should continue until the patient has been asymptomatic for at least 72 hrs 27  DURATION OF ANTI-INFECTIVE THERAPY To achieve the therapeutic goal, anti-infective therapy must continue for a sufficient duration CHRONIC INFECTION: Treatment may require a longer duration (4-6 weeks) with follow-up culture analyses to assess therapeutic effectiveness (e.g., endocarditis- inflammation of the endocardium, osteomyelitis- infection of bone and bone marrow) 28 MONITORING THERAPEUTIC EFFECTIVENESS To assess the patient’s response to anti- infective therapy, appropriate specimen should be cultured and the following parameters monitored * Fever curve * WBC count * Radiographic findings 29  MONITORING THERAPEUTIC EFFECTIVENESS Fever Curve – Important assessment tool, reliable indication of response to therapy. WBC count – In the initial stage of infection, the neutrophil count may raise above normal (neutrophilia) Radiographic findings – small effusions, abscesses or cavities that appear on radiographs indicate the focus of infection 30  MONITORING THERAPEUTIC EFFECTIVENESS Pain & Inflammation- May occur when the infection is superficial or within a joint or bone, also indicating a possible focus of infection ESR- Large elevation of ESR are associated with acute or chronic infection (e.g., endocarditis, chronic osteolmyelitis, intra abdominal infections) 31  LACK OF THERAPEUTIC EFFECTIVENESS DO’S & DONT’S: When an antibiotic drug regimen fails, instead of adding other drugs indiscriminately or changing the regimen, reassess the situation and intensify the diagnostic efforts Causes of therapeutic ineffectiveness include: * Misdiagnosis, Improper drug regimen, Inappropriate choice of antibiotic agent, microbial resistance, Unrealistic expectations, infection by two or more types of microorganisms. 32  CAUSES OF LACK OF THERAPEUTIC EFFECTIVENESS 1. Microbial resistance: Drug resistance is particularly common in geographic areas where a specific drug has been used excessively and improperly E.g., many gonococcal strains, now resist penicillin 33 CAUSES OF LACK OF THERAPEUTIC EFFECTIVENESS 2. Unrealistic expectations: Antibiotics are ineffective in certain circumstances Patients with conditions that require surgical drainage frequently cannot be cured by anti- infective drugs until the drain has been removed. E.g., The presence of necrotic tissue or pus in patients with pneumonia, renal calculi is a common cause of antibiotic failure. 34  PERIOPERATIVE ANTIBIOTIC PROPHYLAXIS It is a short course of antibiotic administered before there is clinical evidence of infection General Considerations: * Timing * Duration * Antibiotic spectrum * Route of administration 35 PERIOPERATIVE ANTIBIOTIC PROPHYLAXIS Timing: Initiation of prophylaxis is often at induction of anesthesia, just before the surgical incision. This ensures peak serum and tissue antibiotic levels. Duration: Prophylaxis should be maintained for the duration of surgery. Long surgical procedures (e.g., > 3 hrs) may require additional doses. 36  PERIOPERATIVE ANTIBIOTIC PROPHYLAXIS Antibiotic Spectrum: It should be appropriate for the usual pathogens 1) In general, 1st generation cephalosphorin (e.g., cefazolin) are the drugs of choice for most procedures and patients. It has an appropriate spectrum, favorable half- life, low cost and side effects. 37  Vancomycin is a suitable alternative in penicillin-sensitive patients and in situations where methicillin-resistant S.aureus is a concern ROUTE OF ADMINISTRATION: I.M or I.V routes are preferred to guarantee good serum and tissue levels at the time of incision 38  Q & A THANK YOU 39