Antimicrobial Selection and Prophylaxis 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.
t
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
Increasing and Broadening the Spectrum of coverage of antimicrobial therapy is necessary in which cases?
- In mixed infections where multiple organisms are likely to be present (in intra-abdominal and female pelvic infections), in which a variety of aerobic and anaerobic bacteria can produce disease.
- For critically ill patients with health care associated infections. These infections are frequently caused by multidrug resistant pathogens.
In mixed infections where multiple organisms are likely to be present (in intra abdominal and female pelvic infections) which antimicrobial should be selected?
A combination of a drug active against aerobic Gram-negative bacilli (aminoglycoside) and a drug active against anaerobic bacteria (metronidazole or
clindamycin) are selected.
In mixed infections and critically ill patients with health care associated infections, why should you use Combination therapy?
Combination therapy is used in this setting to ensure that at least one of the antimicrobials will be active against the pathogen(s).
what are the Rationale For Combination Antimicrobial Therapy
1- Synergism
2-Preventing Resistance
when should you use synergistic Combination Antimicrobial Therapy?
This is necessary for infections caused by enteric Gram-negative bacilli in immunosuppressed patients.
(Traditionally, combinations of aminoglycosides and β-lactams have been used because these drugs together generally act synergistically
against a wide variety of bacteria. )
Synergistic combinations may produce better results in infections caused by ________________ and ______________.
Pseudomonas aeruginosa, Enterococcus species
how do we use Synergistic combinations in the treatment of enterococcal endocarditis ?
The causative organism is usually only inhibited by penicillins, but it is killed rapidly by the addition of streptomycin or gentamicin to a penicillin
what is the best example of The use of antimicrobial combinations to prevent
the emergence of resistance?
in the treatment of tuberculosis, Combinations of drugs with different
mechanisms should be used in this case.
Disadvantages of Combination Therapy
- Increased cost.
- Greater risk of drug toxicity (nephrotoxicity) with aminoglycosides, amphotericin, and vancomycin.
- Superinfection with more resistant bacteria.
- Antagonistic effects: when one drug induces βlactamase production and the other is susceptible to β-lactamase.
________ and __________are capable of inducing β-lactamases and may result in more rapid inactivation of penicillins.
Cefoxitin, imipenem
when Antimicrobial prophylaxis should be used ?
in circumstances in which efficacy has been demonstrated and benefits outweigh the risks of prophylaxis.
Risk factors for postoperative wound infections
a) operations on the abdomen.
b) operations lasting more than 2 hours.
c) contaminated or dirty wound.
d) at least three medical diagnoses.
what are the Surgical procedures that carry a significant risk of postoperative site infection and necessitate the use
of antimicrobial prophylaxis?
a) contaminated and clean-contaminated operations.
b) selected operations in which postoperative infection may be catastrophic such as open heart surgery.
c) clean procedures that involve placement of prosthetic materials.
d) any procedure in an immunocompromised host.
what are the General principles of antimicrobial surgical prophylaxis?
- The antibiotic should be active against common surgical wound pathogens; unnecessary broad coverage should be avoided.
- The antibiotic should have proved efficacy in clinical trials.
- The antibiotic must achieve concentrations greater than the MIC of the suspected pathogens, and these concentrations must be present at the time of incision.
- The shortest possible course — ideally a single dose — of the most effective and least toxic antibiotic should be used.
- The newer broad-spectrum antibiotics should be reserved for therapy of resistant infections.
- If all other factors are equal, the least expensive agent should be used.
The antibiotic must achieve concentrations _______ than the MIC of the suspected pathogens, and these concentrations must be
present ________ of incision
greater, at the time
The ________ broad-spectrum antibiotics should be reserved for therapy of resistant infections.
newer
when The selection of vancomycin over cefazolin may be necessary?
in hospitals with high rates of
methicillin-resistant S. aureus or S. epidermidis infections
The antibiotic should be present in adequate concentrations at the operative site ______ incision and ________ the procedure.
before, throughout
Parenteral agents should be administered during the interval beginning _______ before incision up to the ____________.
60 minutes, time of incision
In cesarean section, the antibiotic is administered ____________
after umbilical cord clamping
If short-acting agents such as ________ are used, doses should be repeated if the procedure exceeds ________ in duration.
cefoxitin, 3–4 hours
_______________ prophylaxis is effective for most procedures and results in decreased toxicity and decreased antimicrobial resistance.
Single-dose
Common errors in antibiotic prophylaxis
a) Selection of the wrong antibiotic.
b) Administering the first dose too early or too late.
c) Failure to repeat doses during prolonged procedures.
d) Excessive duration of prophylaxis.
e) Inappropriate use of broad-spectrum
antibiotics.
when Nonsurgical prophylaxis is indicated ?
a) Individuals who are at high risk for selected virulent pathogens
b) Immunocompromised hosts.
What does nonsurgical prophylaxis involve?
a) The administration of antimicrobials to prevent colonization and asymptomatic infection.
b) The administration of drugs following colonization by or inoculation of pathogens but before the development of disease.
Tigecycline spectrum
1-Staphylococcus aureus including coagulase-negative, methicillin-resistant and vancomycin-resistant strains.
2- Streptococci including penicillin-resistant strains.
3-Enterococci including vancomycin-resistant strains.
4-Gram positive rods and Enterobacteriaceae
5- Acinetobacter sp
6-Gram positive and gram negative anaerobes.
7-Atypical agents, rickettsiae, chlamydia and Legionella and rapidly growing Mycobacteria.
Tigecycline side effect
Hypersensitivity reactions including drug fever and skin rash, and anaphylaxis.
GIT: nausea, vomiting and diarrhea.
Superinfections: Pseudomonas, Proteus, Staphylococcus aureus, Coliforms, Clostridia and Candida.
Bone & teeth:
a) Fetal teeth: fluorescence, discoloration, and enamel dysplasia.
b) Fetal bone: deformity or growth inhibition.
c) Similar changes occur in children below 8 years of age.
Liver toxicity: hepatic necrosis and impairment of hepatic function.
Pancreatitis.
Kidney toxicity: renal tubular acidosis and other renal injury.
Local tissue toxicity: Thrombophlebitis after IV administration, local pain after IM administration.
Photosensitivity.
Vestibular reactions: dizziness, vertigo, nausea, vomiting.
