principles in selection of antimicrobial therapy Flashcards

1
Q

aerobic gram-positive cocci

A

staphylococci (GPC in clusters)
-staphylococcus aureus - coagulase positive
-­S. epidermidis - coagulase negative
­-S. saprophyticus - coagulase negative
Streptococci (Lancefield, hemolysis pattern)
­-Streptococcus pneumoniae - GPC in pairs (diplococci)
-S. pyogenes - group A, B hemolytic
-S. agalactiae - group B hemolytic
-viridans streptococci - normal oral flora
Enterococci - GPC in pairs and chains
-enterococcis faecalis
-E. faecium - high prevalence of vancomycin resistance

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2
Q

alpha, beta, gamma hemolysis patterns

A

alpha - partial hemolysis
beta - complete hemolysis
gamma - no hemolysis

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3
Q

aerobic gram positive bacilli

A
non-spore-forming GPB
-listeria monocytogenes
-corynebacterium spp.
---C. diptheriae
---C. Jeikium
-Lactobacillus spp.
spore-forming GPB
-bacillus spp.
---B. cereus
---B. anthracis - causative agent in anrthrax
branching or filamentous GPB
-Nocardia spp. (N. asteroides)
-Erysipelothrix rhusiopathiae (rare)
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4
Q

aerobic gram-negative cocci and coccobacilli

A
cocci
-neisseria spp.
---N. gonorrhoeae
---N. miningitidis
coccobacilli
-moraxella catarrhalis
-haemophilus spp.
---H. influenzae
---H. parainfluenzae
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5
Q

aerobic gram-negative bacilli ***

A

enterobacteriaceae

  • Citrobacter (C. freundii, C. Koseri)
  • Enterobacter (E. aerogenes, E. cloacae)
  • Escherichia coli
  • Klebsiella (K. pneumoniae, K. oxytoca)
  • Morganella morganii
  • Proteus (P. mirabilis, P. vulgaris)
  • Providencia (P. rettgeri, P. stuartii)
  • Salmonella (S. enteritidis, S. typhi)
  • Serratia marcescens
  • Shigella dysenteriae
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6
Q

other aerobic gram-negative bacilli

A
  • aeromonas hydrophila
  • alcaligenes spp.
  • Acinetobacter baumannii
  • Bordetella spp.
  • Brucella spp.
  • Burkholderia cepacia
  • Campylobacter jejuni
  • Francisella tularensis
  • Helicobacter pylori
  • Pasturella multocida
  • Pseudomonas aerugnosa *
  • stenotrophomonas malkophilia
  • Vibrio cholerae
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7
Q

Lactose fermenters

A
CEEK
Citrobacter species
Escherichia coli
Enterobacter species
Klebsiella species
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8
Q

non-lactose fermenters

A
pseudomonas aeruginosa
acinetobacter species
stenotrophomonas maltphilia
burkholderia cepacia
proteus species
providencia species
serratia marcescens
morganella species
salmonella species
shigella species
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9
Q

anaerobic bacteria

A

gram positive cocci in chains
-microaerophilic streptococci
-peptostreptococcus spp. (P. anaerobius, P. intermedius, P. magnus)
gram positive bacilli
-non-spore forming: Propionibacterium acnes
-spore forming: Clostridium spp. (C. perfingens, C. tetani, C. difficile, C. botulinum)
-branching, filamentous: Actinomyces spp. (A. israelii)

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10
Q

anaerobic gram-negative bacilli

A

gram negative cocci
-Veillonella spp. (V. parvula)
gram negative bacilli
-Bacteroides spp. (B. fragilis, B. ovatus, B. distasonis, B. thetaiotaomicron) - common
-Prevotella spp. (P. melaninogenica, P. denticola, P. buccae, P. oralis) - oral
-Fusobacterium spp. (F. necroporum, F. nucleatum)

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11
Q

normal flora of the skin

A

diptheriods (i.e. Corynebacterium sp.)
staphylococci (esp. S. epidermidis)
Streptococci
P. acnes

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12
Q

Normal flora of the oropharynx (upper respiratory tract)

A
Haemophilus spp.
streptococci (virdans group)
diptherioids
Neisseria spp.
Oral anaerobes
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13
Q

Normal flora of the GI tract

A
Bacteroides spp.
Enterobacteriaceae
Enterococci
Fusobacterium spp.
Peptostreptococcus spp.
Clostridium spp.
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14
Q

Normal flora of the genital tract

A
Corynebacterium spp.
Enterobacteriaceae
Lactobacillus spp.
Mycoplasma spp.
Staphylococci
Streptococci
Anaerobes
Candida spp.
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15
Q

systematic approach for selection of antimicrobial agents

A

1) confirm the presence of infection: careful history and PE, s/sxs, predisposing factors
2) identification of the pathogen: collection of infected material, stains, serologies, culture and susceptibility testing
3) selection of empiric therapy: site of infection, likely pathogens, host factors, drug factors
4) de-escalate (directed therapy)
5) monitor therapeutic response: clinical assessment, laboratory tests, assessment of therapeutic failure

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16
Q

confirmation of infection

A

FEVER* - hallmark of infection
significant if oral temp over 38.0 C or 100.4 F
rectal temp generally 1 F higher; axillary temp generally 1 F lower
Non-infectious causes of fever (false positive) *
-malignancy, collagen vascular disease (autoimmune)
-Drug fever*: fever coincides temporarilly with administration of the offending agent and disappears promptly with w/d of agent; B-lactams, amphotericin, anticonvulsants, allopurinol, hydralazine, nitrofurantion, sulfonamides, phenothiazines
-blood transfusions
absence of fever in a patient with s/sxs consistent with an infection (false negative)
-antipyretics - discourage use during treatment, may mask poor therapeutic response
-corticosteroid therapy
-antimicrobial therapy (partial)
-overwhelming infection - BAD

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17
Q

systemic signs and symptoms of infection

A
fever
increase WBC count
chills, rigor
tachycardia (over 90 bpm)
tachypnea (over 20 bpm)
hypotension (SBP under 90 or MAP under 70)
mental status change - elderly
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18
Q

WBC count as s/sxs of infection

A
normal WBC 4500-10500
normal WBC differential
-granulocytes ("phils"):
---mature neutrophils: 50-70%
---immature neutophiles (bands): 0-5%
---eosinophils: 0-5%
---basophils: 0-2%
-agranulocytes:
---lymphocytes: 15-40%
---monocytes: 2-8%
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19
Q

leukocytosis as s/sxs of infection

A

leukocytosis -increased WBCs
bacterial infection - associated with increased neutrophils + immature neutrophils (bands) = left shift *
presence of bands indications an increased bone marrow response to infection
may be elevated due to non-infectious causes (leukemia, stress) or drug therapy (steroids, lithium)
absent in neutropenic host; blunted in elderly**
leukopenia (abnormally low WBC count) may be sign of an overwhelming infection; poor prognostic sign**

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20
Q

lymphocytosis as s/sx of infection

A

lymphocytosis - increase lymphocytes
-associated with viral, tuberculosis or fungal infections
-B-lymphocytes: proliferate into plasma cells which produce antibodies involved in humoral* immunity
-T-lymphocytes: involved in cell-mediated* immunity
—T-helper/inducer cells (CD4) - regulation of the immune system; help with antibody production and secrete lymphokines to help protect against viral infections and tumors
—T suppressor (CD8) - bind to and directly kill tumor cells; help with regulation of humoral and cell-mediated immunity
monocytosis - associated with tuberculosis or lymphoma
eosinophilia - associated with allergic reactions or protozoal/parasitic infections

21
Q

pain and inflammation as s/sx of infection

A

pain and inflammation: swelling, erythema, tenderness, purulent drainage, easily detected in superficial infections or infections of the bone/joint
inflammation in deep-seated intections (pneumonia, menegitis, UTI) - must examine tissues/fluids (sputum, CSF, urine)
may be absent in neutropenic patients (WBCs)
symptoms referable to specific organ system

22
Q

additional lab tests - erythrocyte sedimentation rate and C-reactive protein

A

ESR and CRP
elevated in presence of inflammatory process but does not confirm the presence of enfection
normal values:
-ESR: 0-15 mm/hr in males; 0-20 mm/hr in females
-CRP: 0-0.5 mg/L
often elevated in the presence of infection
serial measurements may be useful in assessing response to treatment of deep-seated infections(i.e. osteomyelitis, endocarditis)

23
Q

additional lab tests - procalcitonin

A

PCT
precursor of calcitonin, a calcium regulatory hormone
normal value: less than 0.05 mcg/L
more specific marker from bacterial infections that ESR or CRP
-released when macrophages exposed to bacteria and endotoxin, increases 3-12 hours after stimulation and declines over 24-72 hours, levels correlate to bacterial load and severity of illness
magnitude of PCT elevation may provide diagnostic information
-PCT over 10 - sepsis/systemic infection
-PCT 2-10 - suggects sepsis
-PCT 0.25-2 - other condition or localized infection
may be useful for assessing response to therapy and when to stop antibiotic therapy

24
Q

radiographic test

A

xrays
computed tomography (CT)
magnetic resonance imaging (MRI) - more sensitive in detecting soft tissue infections, acute osteomyelitis and CNS infections
nuclear imaging - bone scans, WBC-labeled scans, etc
echocardiograpy - TTE or TEE, useful to detect vegetations on heart valves (endocarditis)

25
Q

factors predisposing to infection

A
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)
26
Q

identification of the pathogen

A

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

27
Q

colonization versus infection

A

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

28
Q

immunologic and molecular methods of testing

A

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

29
Q

host factors

A

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-B5701 (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

30
Q

timing of initiation of antimicrobial therapy

A

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

31
Q

empiric vs directed therapy

A

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)

32
Q

empiric therapy should be based on:

A

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

33
Q

bactericidal vs bacteriostatic therapy

A

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)

34
Q

Is combo therapy needed? 3 main reasons for it

A

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

35
Q

disadvantages of combo therapy

A

increased cost
greater risk of toxicity
superinfection with resistant bacteria
antagonism

36
Q

criteria for selecting antimicrobial therapy

A

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

37
Q

selecting antimicrobial therapy - efficacy

A

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

38
Q

selecting antimicrobial therapy - in vitro activity

A

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

39
Q

selecting antimicrobial therapy - PK

A

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

40
Q

selecting antimicrobial therapy PD

A

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

41
Q

selecting antimicrobial therapy AEs

A

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

42
Q

selecting antimicrobial therapy drug-drug interactions and drug-food interactions

A

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

43
Q

selecting antimicrobial therapy cost

A

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

44
Q

criteria for selecting antimicrobial therapy

A

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

45
Q

monitoring clinical response

A

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
46
Q

criteria to switch to oral therapy

A
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
47
Q

laboratory test to monitor clinical response

A

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

48
Q

assessment of clinical features

A
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