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Lecture 1
Introduction to Chemotherapy of Infectious Diseases
| Question | Answer |
|---|---|
| Selection of Agent Based Upon | identity of organism, susceptibility, site of infection, patient factors, safety and efficacy of agent, cost of therapy |
| Identification of infecting organism | gram stain (useful in sterile body fluids), culture, prior to starting antimicrobial agents |
| Empiric Antimicrobial Therapy | initiating treatment prior to knowing identity of infecting organism |
| Empiric Antimicrobial Therapy | factors influencing medication choice: site, history, local susceptibility data, known associations of organisms |
| Empiric Antimicrobial Therapy | broad spectrum therapy |
| Determination of antimicrobial susceptibility | cultures; predictable susceptibility; unpredictable susceptibility seen with most gram negative bacilli, enterococci, staphylococcal species; minimum inhibitory and minimum bactericidal concentrations |
| Determination of antimicrobial susceptibility: minimum inhibitory concentration (MIC) = lowest antimicrobial concentration that _____of pathogen after incubation period of 24 hours | prevents visible growth |
| Determination of antimicrobial susceptibility: minimum bactericidal concentration (MBC) = lowest antimicrobial concentration causing 99.9% ____after overnight broth dilution incubation; rarely done in practice (time and labor requirements) | decrease in colony count |
| Determination of antimicrobial susceptibility: bacteriostatic | antibiotics stop the growth and replication of bacteria |
| Determination of antimicrobial susceptibility: bactericidal | antibiotics effectively kill > 99.9% within 18 to 24 hours of incubation |
| Effect on Site of Infection on Therapy: Blood Brain Barrier | capillaries carry drugs to tissues; structures of capillaries provide natural barriers for drug delivery |
| Blood Brain Barrier: entry and concentration of antibacterials into CSF influenced by | lipid solubility, molecular weight, protein binding, susceptibility to transporters or efflux pumps |
| Blood Brain Barrier: lipid solubility | allows for penetration into CNS; drugs ionized at physiologic pH and have low lipid solubility do not readily cross B-lactam antibiotics-penicillins |
| Blood Brain Barrier: molecular weight | low molecular weight drugs vs. high MW drugs; low MW drugs better able to cross BBB |
| Blood Brain Barrier: protein binding | highly protein bound drugs restricted entry into CSF; amount of free drug, not total, important in CSF entry |
| Blood Brain Barrier: Susceptibility to Transporters or Efflux Pumps | antibiotics with affinity for transporter mechanisms have better CNS penetration; those without an affinity for efflux pumps have better CNS penetration |
| Patient Factors | immune system, renal function, hepatic function, perfusion, age, pregnancy and lactation, risk factors for multi drug resistant organisms |
| Immune System: conditions affecting immunocompetency | bactericidal agents and longer courses of treatment |
| Renal Dysfunction | accumulation; dosage adjustment; serum creatinine |
| Patient Factors: hepatic dysfunction | use caution with antibiotics that concentrated or eliminated by liver; erythromycin, doxycycline |
| Patient Factors: poor perfusion | decreased circulation and perfusion |
| Patient Factors: age | newborns and elderly |
| Patient Factors: pregnancy/lactation | review product labeling; total dose to infant possibly detrimental |
| Safety of the Agent | penicillins less toxic; agents with less specificity reserved for life-threatening infections |
| Route of Administration: oral | mild infections and outpatient |
| Route of Administration: parenteral | poorly absorbed medications (vancomycin, aminoglycosides), serious infections needing higher antibiotic serum concentrations |
| Route of Administration: converting____ patients to ___ agents | hospitalized and oral |
| Determinants of Rational Dosing: Factors influencing frequency of dosing | concentration-dependent killing; time-dependent (concentration-independent) killing; post antibiotic effect (PAE) |
| Concentration-Dependent Killing: as drug concentration increases, the rate of bacterial killing ____ | increases; aminoglycosides |
| Time-dependent Killing: concentration-____; time drug concentrations; time drug concentrations remain above MIC; beta-lactams, gylcopeptides, macrocodes, linezolid | independent |
| Postantibiotic Effect (PAE)** | Suppression of microbial growth occurring after antibiotic levels below MIC |
| Antimicrobial Spectrum | Range of different microorganisms that an antimicrobial agent inhibits or kills |
| Antimicrobial Spectrum: types | narrow, extended, broad |
| Narrow-Spectrum Antibiotics | act only on a single or limited group of microorganisms |
| Narrow-Spectrum Antibiotics | isoniazid=mycobacterium tuberculosis |
| Extended-Spectrum Antibiotics | gram positive organisms; some gram-negative bacteria; ampicillin |
| Broad-Spectrum Antibiotics | affect wide variety of microbial species; tetracycline, fluoroquinolone; carbapenems |
| Combinations of Antimicrobial Drugs: typically, best to treat patients with _____agent | single |
| Combinations of Antimicrobial Drugs: combinations sometimes necessary and advantageous | infection of unknown origin and organisms with variable sensitivity |
| Disadvantages of combo therapy | coadministration may cause interference between the drugs; antibiotic resistance |
| Drug Resistance: resistance=maximal level of antibiotic tolerated by host does not halt ___ | bacterial growth |
| Drug Resistance | natural resistance and mutations or acquired resistance |
| Drug Resistance: genetic alterations | acquired resistance requires gain or alteration of bacterial genetic info; DNA spontaneously mutates or moves from one organism to another |
| Drug Resistance: Altered Expression of Proteins | altered target sites; decreased accumulation; enzymatic inactivation |
| Prophylactic Use of Antibiotics | used for prevention rather than treatment; benefits outweigh risks; duration |
| Complications of Antibiotic Therapy: hypersensitivity | inappropriate immune responses can lead to extensive tissue damage |
| Complications of Antibiotic Therapy: hypersensitivity | penicillin=hives to anaphylactic shock |
| Complications of Antibiotic Therapy: hypersensitivity | vancomycin=red man syndrome |
| Complications of Antibiotic Therapy: direct toxicity | high serum levels may cause toxicity by directly affecting cellular processes in host |
| Complications of Antibiotic Therapy: direct toxicity | aminoglycosides = ototoxicity |
| Complications of Antibiotic Therapy: direct toxicity | fluoroquinolones=effects on cartilage and tendons; tetracyclines=bones |
| Complications of Antibiotic Therapy: superinfections, candidiasis, interaction with OCs | C. difficile |
| Antimicrobial Action: Antimicrobials classified | 1. chemical structure=beta-lactams, aminoglycosides. 2. MOA=cell wall synthesis inhibitors. 3. Activity against certain types of organisms |
| Nosocomial Infections: healthcare-associated infections =not present at ____. | admission |
| Nosocomial Infections: risk factors | increasing age, length of hospital stay, overuse/incorrect use of broad-spectrum antibiotics, number of procedures/invasive devices |
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bluedolphin7
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