principles in selection of antimicrobial therapy Flashcards

Question

factors predisposing to infection

Answer 1

``` alteration in normal flora disruption of natural barriers -skin/mucus membrane -cilia of respiratory tract - smoking -pH, motility and integrity of the GI tract age immunosuppression -malnutrition -underlying diseases (hereditary or acquired) -hormones (pregnancy, corticosteroids) -drugs (chemo) ```

Answer 2

collect infected material for direct exam, culture and susceptibility testing -BEFORE* initiating antimicrobial therapy - could kill organism - exceptions? meningitis -aspiration of infected fluids (sputum, blood, urine, CSF, abscesses, bone, etc.) -must be properly obtained and promptly submitted to microbiology lab -MUST* avoid contamination (i.e. sputum with saliva) -contamination - introduction of an organism into the clinical specimen during sample collection or processsing direct examination: gram stain, ziehl-nielsen strain, india ink, KOH culture, susceptibilty testing, rapid diagnostic tests -aerobic, anaerobic cultures -blood cultures - collect 2 sets (aerobic and anaerobic) from different sites, 1 hour apart if possible -sputum, urine, CSF, etc isolation of an organism from a clinical specimen does not always represent the presence of infection and vice versa (neg. culture doesn't always mean no infection) colonization versus infection

Answer 3

colonization: -a potentially pathogenic organism is present at a body site but is not invading host tissues or eliciting a host immune response -example: isolation of P. aeruginosa from a sputum culture in a patient with a chronic tracheostomy but no fever, cough or infiltrate on CXR infection: -a pathogenic* organism is present at a body site and is damaging host tissues and eliciting host responses and symptoms consistent with infection -example: isolation of S. pneumoniae in the sputum of a patient with fever, SOB, cough, sputum production, and evidence of consolidation on CXR

Answer 4

antibody or antigen detection -advantage - rapid turnaround time with acceptable sensitivity and specificity -sensitivity* - positive result in the presence of disease/infection -specificity - negative result in the absence of disease/infection -primary methods - detection and quantification of antibodies directed against a specific pathogen or detection of components of pathogen -immunofluorescence, latex agglutination, ELISA detection of microorganisms -nucleic acid amplification -hybridization DNA probes

Answer 5

drug allergy or hx of ADR - SE vs allergy patient age, weight, sex -age and sex related differences in PK -obesity - increase antibiotic doses? -different bacteria in meningitis based on age pregnancy, lactation - teratogenicity, PK changes, excretion into breast milk? genetic or metabolic abnormalities - G6PD deficiency, acetylator status, abacavir - fatal hypersensitivity in pt s HLA-B*5701 (requires screening) renal or hepatic dysfxn - calculate CrCl for EVERY* patient, dose adjustment? toxicity?, augmented Cr clearance over 130 site of infection - can antibiotic get there and at what conc? concomitant drug therapy, nutritional supplements - drug-drug interactions, drug-food interactions concomitant disease states (CF, HIV, cancer) prior antibiotic use - may increase risk of resistant bacteria

Answer 6

depends on the urgency of the situation, specific infection, and infection severity critically ill patients (septic shock, febrile neutropenia, bacterial meningitis) -initiate antibiotic therapy immediately after or concurrently with collection of diagnostic specimens -sepsis** - increased mortality with every hour delay in effect antibiotic therapy bacterial endocarditis, osteomyelitis** -withhold antibiotic therapy until multiple sets of blood cultures obtained in endocarditis -withhold antibiotic therapy until bone biopsy obtained in osteomyelitis

Answer 7

empiric therapy: -initiation of broad-spectrum antimicrobial therapy BEFORE** pathogen identification and susceptibility results are known -may require multiple antibiotics -importance of selecting empiric antibiotics with in vitro activity against infecting pathogens - significant decrease in mortality directed or definitive therapy -after ID of pathogen and susceptibility results are known -de-escalate to agent with narrowest effective spectrum of activity** -IV to PO conversion (except: CNS infection, endocarditis)

Answer 8

knowledge of likely pathogens known to cause specific infections and severity of infection -knowledge of most likely pathogen from Hx and PE, gram stain results -body site involves (CSF, urine, blood, sputum) -location where infection began (comm., nursing home, hospital) anticipated antimicrobial susceptibility pattern -antibiogram* - summary susceptibility report in a given institutions -local patterns: city v hospital, hospital v specific care area -large scale studies from literature information from hx and PE -where did the infection begin? other people sick at home? -prior knowledge of colonization or infections -prior antimicrobial use -recent hospitalizations -work-related exposures -smoking, DM, COPD, HIV, CF -travel hx -pets

Answer 9

bactericial* - kill the organism by acting on the cell wall (B lactams), cell membrane (daptomycin) or bacterial DNA (fluoroquinolones) bacteriostatic* - inhibit bacterial replication without killing the organism by inhibiting protein synthesis (macrolides, tetracyclines) - immune system can then kill not always a clear distincation - some bactericial drugs may be static against some organisms and vice versa bactericidal therapy required** in certain infections (meningitis - no host defense, endocarditis, osteomyelitis, immunocompromised hosts)

Answer 10

broaden spectrum coverage for empiric therapy in polymicrobial infections or infections potentially caused by organisms not adequately covered by 1 agent achieve synergistic bactericidal activity against a pathogen to improve outcomes prevent emergence of resistance

Answer 11

increased cost greater risk of toxicity superinfection with resistant bacteria antagonism

Answer 12

efficacy, in vitro microbiologic activity, PK, PD, AEs, drug interactions, cost

Answer 13

clinical (cure rate) and bacteriologic (eradication rate) efficacy FDA-approved and non-approved indications problems with clinical trials: -lack of comparative trials -extremely ill patients excluded -small sample size -infrequent pathogen isolation at baseline -exclusion of resistant orgainsms

Answer 14

spectrum of activity* susceptibility tests - MIC, Disc, Etest resistance trends and mechanisms - enzymatic activation (B-lactamases), altered target site, decreased entry of drug into organism

Answer 15

Absorption - may be impaired by disease state, surgery, drug therapy Distribution - conc in bloodstream, conc at site of infection, protein binding, tissue conc do not always correlate with efficacy Metabolism Elimination - biliary and renal - glomerular filtration or tubular secretions tissue distribution -preferred: microdialysis (measure ECF conc) -tissue samples collected, pulverized, weighed, drug extracted and conc determined -tissue conc = (conc in supernatant) x volume of supernatant / weight of tissue -tissue conc represent the mean extracellular and intracellular conc

Answer 16

the study of the biochemical and physiological effects of drgs and their MOA, including correlation of drug actions and effects with the drug conc in vitro effects - conc dependent bactericidal activity, time dependent bactericial activity in vivo effects -time above MIS - B-lactams -AUC/MIC - FQs, vanc, macrolides, linezolid -peak/MIC or Cmax/MIC - predicts outcomes for AGs

Answer 17

risk/benefit analysis problems w pre-marketing date - small sample size for AEs with low incidence of occurance -trovafloxacin - 140 cases of severe hepatotoxicity in 2.5 million patients (0.056%) problems w post-marketing data -underreporting -difficult to determine causality due to incomplete information -affected by length of time drug has been on market, publication bias, marketing trends

Answer 18

reported in literature predicted based on known effects of the drug potential mechanisms: effects on protein binding, induction or inhibition of cytochrome P450 isoenzymes, complexation

Answer 19

acquisition costs - least useful, most used administrative costs - supplies, personnel, storage/inventory monitoring costs - TDM, lab tests cost of toxicity - extended length of stay, additional treatment costs cost of poor clinical response total cost of care

Answer 20

drugs of choice: guidelines, not rules common misuse(s) of antibiotics: -prolonged empiric therapy with no clear evidence of infection -treatment of a positive culture in the absence of infection -failure to narrow empiric therapy when pathogen is identified -prolonged prophylactic therapy -excessive use of certain antimicrobial agents

Answer 21

clinical assessment - hows the patient doing?*** - PE - resolution of s/sxs of infection - non-invasive techniques (xray, scans) - AEs? - evaluate route of administration daily - switch to oral therapy

Answer 22

``` overall clinical improvement lack of fever for 8-24 hours decreasing WBC count functioning GI tract duration of treatment: not well defined, individualize based on clinical response, recent emphasis on shorter courses of therapy ```

Answer 23

culture and susceptibility reults -narrowest effective spectrum of activity based on results -repest cultures to document eradication of the pathogen WBC, differential therapeutic drug monitoring

Answer 24

``` re-evaluate therapy after 2-3 days due to incorrect diagnosis? due to antibiotic selection? -wrong drug/dose/route -enhanced drug clearance -drug interactions due to host factors? -immunosuppression -foreign bodies -abscess requiring surgical drainage due to microorganism? -resistance? -emergence of resistance -mixed (polymicrobial) infection due to lab error? -incorrect identification of pathogen -error in susceptibility test results ```