Abx Principles I Flashcards
Selection of abx therapy
- ID infecting organism
- Organism’s drug susceptibility
- Site of infection
- Patient factors
- Safety of antimicrobial agent
- Cost
ID Infecting organism
Gram Stain (Blood, serum, CSF, pleural fluid, synovial fluid, peritoneal fluid, urine)
Gram+ - PG cell wall layer –> Purple
Gram - Thin PC layer –> Pink
Common Gram + Cocci
STAPHYLOCOCCUS S. aureus S. epidermidis STREPTOCOCCUS S. pneumoniae S. pyogenes S. agalactiae ENTEROCOCCUS E. faecalis E. faecium
Common Gram + Bacilli
Listeria monocytogenes Corynebacterium Nocardia sp. Bacillus anthracis Clostridium sp.
Common Gram - Cocci/Coccobacilli
COCCI Neisseria meningitidis COCCOBACILLI Haemophilus influenza Moraxella catarrhalis
Common Gram - Bacilli (non-lactose fermenters)
Providencia stuartii Proteus mirabilis Pseudomonas aeruginosa Morganella morganii Actinobacter baumannii Stenotrophomonas maltophilia Burkholderia cepacia
Common Gram - Bacilli (lactose fermenters)
Escherichia coli Klebsiella spp Citrobacter spp Enterobacter spp Serratia marcescens
Culture to ID pathogen
R/O pathogenic vs. normal flora
Contaminant
Susceptibility Testing
Sensitivity to selected abx (MIC)
Minimum Inhibitory Concentration (MIC)
Lowest concentration of abx that prevents visible growth of organism in vitro
Quantitative value (micrograms/ml)
Bacteria is interpreted as susceptible (S), intermediate (I), resistant (R) to abx tested
Steps to Abx selection
- ID abx pathogen is susceptible to
- Check MIC (lower not necessarily better)
- Consider infection site/drug’s ability to reach site
- Consider abx’s PK/PD
- Make final decision based on pt specific factors (allergy, kidney fxn, comorbid conditions)
Minimum bactericidal concentration (MBC)
Lowest concentration of abx that will kill 99.9% of organisms in vitro rather than concentration that inhibits growth (MIC)
Rarely determined in clinical practice due to time and labor
Infection site
Empiric therapy –> organisms known to cause infection in question
Other influences of empiric therapy: patient factors, previous infections, recent travel history, place where infection acquired: Hospital, SNF, community
Narrow-spectrum abx
Poor for empiric therapy
Abx that acts on a single or limited group of microorganisms
(e.g. nafcillin and MSSA; isoniazid and Mycobacterium tuberculosis)
Extended-spectrum abx
Good for empiric therapy
Abx effective against GP organisms and significant # GN organisms
(e.g. ampicillin and amoxicillin)
Broad-spectrum abx
Excellent for Empiric Therapy
Abx that affect wide variety of microbial species
(e.g. quinolones, tetracycline, carbapenems)
MUST USE WITH CAUTION: altering normal bacterial flora can ppt superinfection from organisms like Clostridioides difficile or yeast
Combination Abx
Broaden abx coverage for empirical therapy (e.g. treat mixed infection w/ 2 abx to cover aerobic and anaerobic bacteria)
Achieve synergistic activity against known pathogen (e.g. nosocomial infection P. aeruginosa w/ two anti-pseudomonal abx; enterococcal endocarditis treated w/ combo of PCN abx and gentamicin)
Prevent emergence of resistance (Isoniazid and rifampin for TB)
RISKS: Superinfection, cost, drug toxicity
Empiric therapy once microbial results are known
Continue current abx therapy if appropriate based on C/S report
Narrow spectrum of coverage or # of abx to avoid risk of superinfection and drug resistance
Natural barriers to abx delivery
Capillary permeability may inhibit drug delivery in prostate, testes, eye, CNS, through placenta, blood brain barrier
Blood brain barrier
tight junctions of endothelium lining vessels at brain interface prevent large, non-lipid soluble stuff from crossing the basement membrane and entering the brain
Most abx cannot corss BBB unless…
brain becomes inflamed (e.g. meningitis) which allows abs to enter CSF
Abx characteristics determine empiric therapy
Lipid solubility (poor lipid solubility - beta-lactams)
ROA: Oral for mild infections/outpt
Parenteral admin for drugs poorly absorbed from GI tract/treatment of serious infections (e.g. oral vanco not absorbed)
Patient factors in abx selection
Immune system, kidney function, liver function, poor perfusion, age, pregnancy, allergies, risk factors for multi-drug resistant organisms
Patient Immune system factors in abx selection
INTACT IMMUNE SYSTEM REQUIRED TO ELIMINATE INFECTING ORGANISMS
Potenital immunocompromised pt: elderly, EtOH disorder, malnutrition, DM, HIV+, autoimmune disease, pregnancy, CA pt, transplant recipients, taking immunosuppressive meds
USE higher doses of bactericidal abx OR longer courses of treatment. AVOID bacteriostatic abx
Patient kidney function factors
Poor function may lead to accumulation abx and increase SE risk
Monitor Scr and CrCl to adjust abx therapy
Monitor drug levels w/ aminoglycosides and vancomycin to maximize therapy and avoid SE
Most common adjustment: keep dose (mg) same, extend dosing interval
Patient liver function factors
Avoid or reduce dose for abs eliminated by liver to reduce accumulation risk
(Erythromycin, clindamycin, metronidazole, rifampin)
Patient poor perfusion factors
Changes in peripheral blood make infections more difficult to treat (e.g. DM or PAD wounds)
Patient age factors
Selection of abx therapy (pathogen, formulation, taste!)
Abx dosing/organ function (neonates, elderly)
Patient pregnancy and breastfeeding factors
May require dosage increase d/t increased clearance (aminoglycosides, beta-lactams)
Many abx cross placenta and are expressed in breast milk
Category A abx risks
No human fetal risk or remote possibility of fetal harm
Category B abx risks
No controlled studies demonstrate human risk (or haven’t been conducted)
Animal studies do not demonstrate fetal risk or potential toxicity noted but not confirmed in controlled studies in women
(Beta-lactams, Clindamycin, erythromycin, azithromycin, metronidazole, nitrofurantoin, sulfonamides)
Category C abx risks
Animal fetal toxicity demonstrated
Human risk undefined d/t lack of controlled studies
DRUGS SHOULD ONLY BE GIVEN IF POTENTIAL BENEFIT JUSTIFIES POTENTIAL RISK TO FETUS
(Quinolones, Clarithromycin, Trimethoprim, TMP/Sulfa, Vanco, Gentamicin)
Category D abx risks
Positive evidence of human fetal risk, but benefits may outweigh risks
(Tetracyclines, aminoglycosides)
Category X abx risks
Human fetal risk clearly outweighs benefits
Contraindicated in women who are or may become pregnant
