Rational Antimicrobial Selection Flashcards
The initial selection of antimicrobial therapy may be ___, prior to documentation and identification of the offending organism.
Empirical
Empirical antimicrobial therapy selection should be based on:
1) The patient’s history and physical examination
2) Results of Gram stains or other rapidly performed tests on specimens from the infected site
3) Knowledge of the most likely offending organism for the infection in question
4) Institution’s local microbial susceptibility patterns
What are the most important factors in determining the choice of antimicrobial therapy?
1) Identification of the pathogen
2) Its antimicrobial susceptibility
What are ‘infected materials’?
1) Blood
2) Sputum
3) Urine
4) Stool
5) Abscess, wound, or sinus drainage
6) Spinal fluid
7) Joint fluid
Infected materials must be sampled BEFORE starting antimicrobial therapy for two reasons:
1) A Gram stain might reveal positive or negative stain bacteria, and an acid-fast stain might detect mycobacteria
2) The premature use of antimicrobials can suppress the growth of pathogens = false-negative cultures results.
Blood cultures should be performed in which patient?
The acutely ill and febrile patient
What should be done when a pathogenic microorganism is identified?
1) Antimicrobial susceptibility testing should be performed
2) Specific definitive antimicrobial therapy should be administered ASAP
A variety of factors must be considered when selecting presumptive therapy:
1) The severity and acuity of the disease
2) Local epidemiology and antibiogram
3) Patient’s history and host factors
4) Factors related to the drug(s) to be used
5) The necessity for using multiple agents
Are antibiotic susceptibilities the same or different across hospitals?
Different
What is the most important part of the patient’s history when trying to find a suitable antibiotic?
The place where the infection was acquired
____ can be exposed to potentially more resistant organisms because they are often surrounded by ill patients who are receiving antibiotics.
Nursing home patients
Which host factors are taken into consideration when determining which antimicrobial to give?
1) Allergy
2) Age
3) Pregnancy
4) Metabolic or Genetic Variation
5) Organ Dysfunction
6) Concomitant Drugs
Which drugs should be avoided in patients allergic to penicillin for immediate or accelerated reactions (anaphylaxis, laryngospasm)?
Cephalosporins
Can we use Cephalosporins if a patient gets a mild rash when taking penicillins?
Yes
Why is age an important host factor?
1) For identification of the likely etiologic agent
2) In the ability to eliminate the drug
Which functions are NOT
well developed in neonates?
Hepatic and liver functions
Neonates (especially when premature) can develop ___ when given sulfonamides.
Kernicterus
Why can neonates (especially when premature) develop kernicterus when given sulfonamides?
Because of displacement of bilirubin from serum albumin
The major change in the elderly is:
Decreased renal function
Neonates (especially when premature) can develop kernicterus when given __.
Sulfonamides
How are aminoglycosides excreted?
Renally
The elderly has increased adverse effects of which antimicrobials?
Those eliminated by the kidney
During pregnancy, the fetus is at risk of:
Drug teratogenicity
Which drugs are cleared more rapidly during pregnancy?
1) Penicillins
2) Cephalosporins
3) Aminoglycosides
Why are certain drugs cleared more rapidly during pregnancy?
Because of increases in:
1) Intravascular volume
2) GFR
3) Hepatic metabolic activities
The maternal serum antimicrobial concentrations are ~ 50% __(higher/lower) than in the nonpregnant state.
Lower
__(Decreased/Increased) dosages of certain compounds might be necessary to achieve therapeutic levels during late pregnancy.
Increased
Patients with impaired blood flow may NOT absorb drugs given by ___ well.
Intramuscular injection
What will influence therapy of infectious diseases in a variety of ways?
Inherited or acquired metabolic abnormalities
Patients who are slow acetylators of __ are at greater risk for peripheral neuropathy
Isoniazid
Patients who are slow acetylators of isoniazid are at greater risk for ___.
Peripheral neuropathy
Patients with severe deficiency of ___ can develop significant hemolysis when exposed to dapsone, sulfonamides, nitrofurantoin, nalidixic acid, and antimalarials.
Glucose-6-phosphate dehydrogenase
Patients with severe deficiency of glucose-6-phosphate dehydrogenase can develop
significant hemolysis when exposed to which drugs?
1) Dapsone
2) Sulfonamides
3) Nitrofurantoin
4) Nalidixic acid
5) Antimalarials
Which antiretroviral drug is associated with severe hypersensitivity reaction (fever, rash, abdominal pain, and respiratory distress) in the presence of human leukocyte antigen allele HLAB*5701?
Abacavir
The antiretroviral drug Abacavir is associated with severe hypersensitivity reaction (fever, rash, abdominal pain, and respiratory distress) in the presence of:
Human leukocyte antigen allele HLAB*5701
Which antibiotics should be adjusted in severe liver disease?
1) Clindamycin
2) Erythromycin
3) Metronidazole
4) Rifampin
Significant accumulation can occur when both liver and renal dysfunction are present for which drugs?
1) Nafcillin
2) Sulfamethoxazole
3) Cefotaxime
4) Piperacillin
Administration of Isoniazid with phenytoin can result in phenytoin toxicity due to:
Inhibition of Phenytoin metabolism by Isoniazid
Administration of Isoniazid with Phenytoin can result in __ toxicity.
Phenytoin
Drugs that possess similar adverse effect profiles can produce ___ adverse effects.
Enhanced
Which drugs are aminoglycosides?
1) Gentamicin
2) Amikacin
3) Tobramycin
4) Neomycin
5) Streptomycin
Aminoglycosides have major drug interactions with:
1) Neuromuscular blocking agents
2) Nephro- and Oto-toxins
What happens if you give aminoglycosides with Neuromuscular blocking agents?
Additive NMJ block
Which drugs are nephro and oto toxic?
1) Amphotericin
2) Cisplatin
3) Cyclosporine
4) Furosemide
5) NSAIDs
6) Radiocontrast media
7) Vancomycin
Amphotericin B has major drug interactions with:
Nephrotoxins such as:
1) Aminoglycosides
2) Cidofovir
3) Cyclosporine
4) Foscarnet
5) Pentamidine
Chloramphenicol decreases metabolism of:
1) Phenytoin
2) Tolbutamide
3) Ethanol
Foscarnet given with ___ increases risk of severe nephrotoxicity/hypocalcemia.
Pentamidine IV
Foscarnet given with Pentamidine IV increases risk of:
Severe nephrotoxicity/hypocalcemia
Isoniazid decreases metabolism of:
1) Carbamazepine
2) Phenytoin
Isoniazid given with Carbamazepine/Phenytoin can cause:
1) Nausea
2) Vomiting
3) Nystagmus
4) Ataxia
Why shouldn’t Macrolides/azalides be given with Digoxin?
Increased Digoxin bioavailability
Macrolides/azalides should NOT be given with:
Digoxin
Metronidazole with ethanol (drugs containing ethanol) cause:
Disulfiram-like reaction
Metronidazole should not be given with ___ because of disulfiram-like reaction.
Ethanol (drugs containing ethanol)
Penicillins/Cephalosporins should NOT be given with:
1) Probenecid
2) Aspirin
Why should Penicillins/Cephalosporins NOT be given with Probenecid or Aspirin?
Blocked excretion of β-lactams
Quinolones have major drug reactions with:
1) Classes Ia and III antiarrhythmics
2) Multivalent cations (antacids, iron, sucralfate, zinc, vitamins, dairy products)
3) Citric acid
4) Didanosine
What happens if you give Quinolones with Classes Ia and III antiarrhythmics?
Increased QT interval
What happens if you give Quinolones with Multivalent cations (antacids, iron, sucralfate, zinc, vitamins, dairy products), Citric acid, or Didanosine?
Decreased absorption of Quinolones
Rifampin increases metabolism of:
1) Azoles
2) Cyclosporine
3) Oral contraceptives
4) Warfarin
5) Protease inhibitors
6) Methadone
7) Tacrolimus
8) Propranolol
Sulfonamides should not be given with:
1) Sulfonylureas
2) Phenytoin
3) Warfarin
Sulfonamides given with Sulfonylureas, Phenytoin, or
Warfarin cause:
Displacement from binding to albumin
Tetracyclines have major drug reactions with:
1) Antacids
2) Iron
3) Calcium
4) Sucralfate
5)Digoxin
Tetracyclines given with Antacids, iron, calcium, or sucralfate cause:
Decreased absorption of tetracycline.
Tetracyclines given with Digoxin cause:
Increased digoxin bioavailability
Important drug parameters to be considered are the:
1) Minimal Inhibitory Concentration (MIC)
2) Time the concentration is above MIC
Aminoglycosides exhibit ______, which allows a once-daily aminoglycosides administration.
Concentration-dependent bactericidal effects
Which drugs are given as a single large daily dose to maximize the peak/MIC ratio?
Aminoglycosides
Aminoglycosides possess a what kind of effect?
Post-antibiotic
What is the Post-antibiotic effect?
Persistent suppression of organism growth after concentrations decrease below the MIC
What appears to contribute to the success of high-dose, once-daily administration of aminoglycosides?
Post-antibiotic effect
Fluoroquinolones exhibit:
Concentration-dependent killing activity
Optimal killing by Fluoroquinolones appears to be characterized by:
The AUC/MIC ratio
β-Lactams display ___ effects.
Time-dependent bactericidal
The important pharmacodynamic relationship for β-Lactams is:
The duration that drug concentrations exceed the MIC
How can you administer β-lactams in ways that appear to be correlated with positive outcomes?
1) Frequent small doses
2) Continuous infusion
3) Prolonged infusion
One important factor in treating an infection is:
The presence of the antimicrobial agent in an active form and at adequate concentration at the site of infection
Drugs that have low biliary fluid concentrations are NOT useful in the treatment of:
1) Cholecystitis
2) Cholangitis
Drugs that do NOT reach significant concentrations in the CSF should NOT be used in
treatment of:
Bacterial meningitis
Which factors can high
concentrations of certain drugs?
1) Acidic pH
2) WBC products
3) Various enzymes
Body fluids where drug concentration data are
clinically relevant include:
1) CSF
2) Urine
3) Synovial fluid
4) Peritoneal fluid
Parenteral therapy is indicated in:
1) Febrile neutropenia
2) Meningitis
3) Endocarditis
4) Osteomyelitis
Severe pneumonia often is treated initially with __(oral/IV) antibiotics then switched to __(oral/IV) therapy with clinical improvement.
IV; Oral
Which patient illnesses treated in the ambulatory setting can receive oral therapy?
1) URTIs (pharyngitis,
bronchitis, sinusitis, and otitis media)
2) Lower respiratory tract infections
3) Skin and soft-tissue
infections
4) Uncomplicated UTIs
5) Selected STDs
Antibiotics associated with CNS toxicities, when not dose-adjusted for renal function, include:
1) Penicillins
2) Cephalosporins
3) Quinolones
4) Imipenem
Reversible nephrotoxicity is classically associated with:
1) Aminoglycosides
2) Vancomycin
Irreversible ototoxicity can occur with:
Aminoglycosides
Hematologic toxicities occur with prolonged use of:
1) Nafcillin (Neutropenia)
2) Piperacillin (Platelet
dysfunction)
3) Cefotetan (Hypoprothrombinemia)
4) Chloramphenicol (Bone marrow suppression, both idiosyncratic and dose-related toxicity)
5) Trimethoprim (Megaloblastic anemia)
Prolonged use of Nafcillin causes:
Neutropenia
Prolonged use of Piperacillin causes:
Platelet dysfunction
Prolonged use of Cefotetan causes:
Hypoprothrombinemia
Prolonged use of Chloramphenicol causes:
Bone marrow suppression
Prolonged use of Trimethoprim causes:
Megaloblastic anemia
Which drugs cause photosensitivity?
1) Azithromycin
2) Quinolones
3) Tetracyclines
4) Pyrazinamide
5) Sulfamethoxazole
6) Trimethoprim
Many antibiotics have been implicated in causing
diarrhea and colitis secondary to ___ superinfection!!!!!!
Clostridium difficile
Which drugs cause QT prolongation?
1) Macrolides/azalide
2) Fluoroquinolones
Which drugs cause Stevens-Johnson syndrome?
1) Fluoroquinolones
2) Sulfonamides and trimethoprim
Patients who fail to respond to antimicrobial therapy over 2-3 days require:
A thorough reevaluation
Causes of antimicrobial therapy failure?
1) The disease is NOT infectious or is nonbacterial in origin
2) There is an undetected pathogen in a polymicrobial infection
3) Factors directly related to drug selection, the host, or the pathogen
4) Laboratory error in identification, susceptibility testing, or both
Antimicrobial therapy failures caused by Drug Selection?
1) Inappropriate selection of drug, dosage, or route of administration
2) Reduced absorption of a drug, resulting in subtherapeutic concentrations
3) Accelerated drug elimination = low concentrations
4) Poor penetration into the site of infection
5) Chemical inactivation of the drug at the site of infection
Which “diseases” can cause accelerated drug elimination?
1) Cystic fibrosis
2) Pregnancy
Which sites have poor penetration into the site of infection?
1) CNS
2) Eye
3) Prostate gland
Reduced absorption of a drug, resulting in subtherapeutic concentrations, can be caused by:
1) GI disease (short-bowel syndrome)
2) Drug interactions
Antimicrobial therapy failures caused by Host Factors?
1) Immunosuppression
2) The need for surgical drainage of abscesses or removal of foreign bodies, necrotic tissue, or both.
Which infections will NOT be effectively treated without surgical procedures?
1) Abscesses
2) Removal of foreign bodies, necrotic tissue, or both.
What is Intrinsic resistance?
When the antimicrobial agent never had activity against the bacterial species. (Naturally resistant)
Bacteria that lack ___ will not respond to βlactam antibiotics.
Cell wall
What is Acquired resistance?
When the antimicrobial agent was originally active against the bacterial species but the genetic makeup of the bacteria has changed so the drug can NO longer be effective.
What are the mechanisms of acquired bacterial resistance?
1) Alteration in the target site
2) Change in membrane permeability
3) Expression of an efflux pump
4) Drug inactivation through either β-lactamases or aminoglycoside-modifying enzymes is the predominant mechanism of resistance!!
The expression of β-lactamases can be:
1) Induced
2) Constitutive
The increased resistance results from:
1) Continued overuse of antimicrobials in the community and in hospitals
2) Long-term suppressive antimicrobials for the prevention of infections in immunosuppressed patients
Enterococci with multiple resistance patterns may be resistant to:
1) β-lactams
2) Vancomycin
3) Aminoglycosides
4) Tetracyclines
5) Ciprofloxacin
6) Clindamycin
7) Erythromycin
8) Quinupristin-dalfopristin
Resistance to β-lactams can be caused by:
1) β-lactamase production
2) Altered penicillin-binding proteins [PBPs]
3) Both
Resistance to Vancomycin can be caused by:
Alterations in peptidoglycan synthesis
Resistance to Aminoglycosides can be caused by:
High levels of AGs-degrading enzymes
Penicillin-Resistant Enterococci treatment?
Vancomycin + Gentamicin or Streptomycin
Vancomycin-Resistant Enterococci (VRE) treatment?
1) Linezolid
2) Daptomycin
3) Tigecycline
4) Nitrofurantoin for UTI
Enterococci with multiple resistance patterns treatment are susceptible to:
1) Imipenem
2) Teicoplanin
Resistant Pneumococci are usually susceptible to:
1) Vancomycin
2) New Fluoroquinolones:
a) Moxifloxacin
b) Trovafloxacin)
3) Cefotaxime/Ceftriaxone
Which antimicrobial agents have been used for resistant gram-positive bacteria?
1) Linezolid
2) Daptomycin
3) Telavancin (Semi-synthetic
derivative of Vancomycin)
4) Tigecycline (New Tetracycline)
Enterobacter, Citrobacter, Serratia, and P. aeruginosa usually retain susceptibility to:
1) Fluoroquinolones
2) Aminoglycosides
3) Carbapenems
Which patients are at high risk for drug failure?
Debilitated patients with:
1) Pulmonary infections
2) Abscesses
3) Osteomyelitis
True or False: Antimicrobial combinations are often overused in clinical practice.
TRUE
The unnecessary use of antimicrobial combinations may cause:
1) Increases toxicity
2) Increases costs
3) Reduced efficacy due to antagonism of one drug by another
Antimicrobial combinations should be selected for one or more of the following reasons:
1) To provide broad-spectrum empiric therapy in seriously ill patients.
2) To treat polymicrobial infections
3) To decrease the emergence of resistant strains–tuberculosis.
4) To obtain enhanced inhibition or killing
5) To decrease dose-related toxicity by using reduced doses of one or more components of the drug regimen.
Antimicrobial combinations chosen should cover:
The most common known or suspected pathogens but NOT cover all possible pathogens.
The use of Flucytosine in combination with Amphotericin B for the treatment of Cryptococcal meningitis in non HIV-infected patients allows for:
A reduction in amphotericin B dosage with decreased Amphotericin B induced nephrotoxicity
