Infectious Disease - Pharmacology - Antibiotics Flashcards
What general type of antibiotic is only effective while the bacterium is replicating?
Inhibitors of cell wall synthesis
Name a few general types of test you might order in a patient with an infection of unknown etiology.
Stains (Gram, acid-fast, fungal);
cultures (blood, sputum, urine; aerobic, anaerobic);
molecular (NAAT, PCR)
When are inhibitors of bacterial cell wall synthesis effective?
When are inhibitors of cell metabolic activity / central dogma effective?
Only while the cell is replicating;
all the time
Name two quantitative methods by which antibiotic sensitivity can be measured in a culture.
Broth dilutions;
E-test
Name a qualitative method by which antibiotic sensitivity can be tested in a culture.
Disc diffusion
(Kirby-Bauer discs)
How does an E-test work in determining antibiotic sensitivity in culture?
Is it quantitative or qualitative?
A rod with antibiotic gradations is placed in culture;
quantitative
How can a minimum inhibitory concentration be determined for an antibiotic and a particular bacterial strain?
Dilutions
________-dependent killing agents kill gram-________ bacteria during the time at which the serum drug concentration is ________ than the MIC for the bacteria.
Time-dependent killing agents kill gram-negative bacteria during the time at which the serum drug concentration is higher than the MIC for the bacteria.
(The antibiotic must be present above MIC for a certain period of time. T > MIC)
________-dependent killing agents kill bacteria when the serum drug concentration is ________ than the MIC for the bacteria.
Concentration-dependent killing agents kill bacteria when the serum drug concentration is much higher than the MIC for the bacteria.
(The antibiotic must be well above MIC to have an effect.)
The post-antibiotic effect.
Some antibiotics continue ______ ______ for some time (≥ 1.5 hours) after serum levels drop below the _____.
The post-antibiotic effect.
Some antibiotics continue inhbiting growth for some time (≥ 1.5 hours) after serum levels drop below the MIC.
The ___________ effect.
Some antibiotics continue inhbiting growth for some time (≥ 1.5 hours) after serum levels drop below the MIC.
The post-antibiotic effect.
Some antibiotics continue inhbiting growth for some time (≥ 1.5 hours) after serum levels drop below the MIC.
Most antibiotics have significant post-antibiotic effects on Gram-___________ bacteria.
Only carbapenems and DNA/protein synthesis blockers have significant post-antibiotic effects on Gram-___________ bacteria.
Most antibiotics have significant post-antibiotic effects on Gram-positive bacteria.
Only carbapenems and DNA/protein synthesis blockers have significant post-antibiotic effects on Gram-negative bacteria.
Name a few things to keep in mind when prescribing medications:
History of ________ reactions, ______, renal function (________ clearance), ______ function, _______, critical illness, genomics (slow v. rapid acetylators, etc.), pregnancy, breast-feeding, G6PD deficiency, etc.
Name a few things to keep in mind when prescribing medications:
History of adverse reactions, age, renal function (creatinine clearance), hepatic function, weight, critical illness, genomics (slow v. rapid acetylators, etc.), pregnancy, breast-feeding, G6PD deficiency, etc.
Name a few things to keep in mind when prescribing medications:
History of adverse reactions, age, _______ function (creatinine clearance), hepatic function, weight, critical illness, _______ (slow v. rapid acetylators, etc.), ________, breast-feeding, G6PD deficiency, etc.
Name a few things to keep in mind when prescribing medications:
History of adverse reactions, age, renal function (creatinine clearance), hepatic function, weight, critical illness, genomics (slow v. rapid acetylators, etc.), pregnancy, breast-feeding, G6PD deficiency, etc.
Name a few organs or situations in which organs are difficult to reach with antibiotics BESIDES the blood-brain, blood-testis, or placental barriers.
Prostate (difficult to reach);
dead bone (no blood flow)
Determine if the following medications/classes are safe during pregnancy or not:
Penicillins
Cephalosporins
Tetracyclines
Clindamycin
Metronidazole
Azithromycin
All safe except tetracyclines
In order to treat intracellular bacteria (e.g. Salmonella spp., Chlamydia spp., Rickettsia spp., etc.), an antibiotic that is _______-soluble should be selected.
In order to treat intracellular bacteria (e.g. Salmonella spp., Chlamydia spp., Rickettsia spp., etc.), an antibiotic that is lipid-soluble should be selected.
Name three classes of β-lactam antibiotics.
Penicillins;
cephalosporins;
carbapenems
Penicillin ___ is for IV use.
Penicillin ___ is for oral use.
Penicillin G is for IV use.
Penicillin V is for oral use.
What are the two natural penicillins?
Penicillin G;
penicillin V
Name a few penicillins that are β-lactamase resistant.
Methicillin;
oxacillin;
nafcillin
Name two aminopenicillins.
Ampicillin;
amoxicillin
Name two anti-pseudomonal penicillins.
Piperacillin;
ticarcillin
Name three β-lactamase inhibitors.
Clavulinic acid;
tazobactam;
sulbactam
Name a carbapenem.
Meropenem
Name a monobactam.
Aztreonam
How are cephalosporins identified via nomenclature?
What is an example?
Prefix: Cef- or ceph-
e.g. ceftriaxone
What type of medication is vancomycin?
Name another medication in this category.
Glycopeptide;
bacitracin
What suffix is given to macrolides?
Give an example.
-thromycin
azithromycin
What are the two main aminoglycosides?
Gentamicin;
tobramycin
What suffix is typically given to tetracyclines?
What is a common example?
-cycline
doxycycline
What prefix or suffix is given to fluoroquinolones?
What is an example?
-floxacin
levofloxacin
Name the antibiotic class (and two example medications) that inhibit general peptidoglycan synthesis.
Glycopeptides;
vancomycin, bacitracin
Name an antibiotic that inhibits mRNA synthesis by blocking bacterial RNA polymerase.
Rifampin
Name a specific medication and an alternate drug class that both inhibit bacterial folic acid synthesis.
Trimethoprim;
sulfonamides
(sulfamethoxazole, sulfadizine, sulfasoxazole)
Name an antibiotic that decreases DNA integrity by increasing free radical formation.
Metronidazole
Name two medication classes that both inhibit bacterial DNA gyrase (topoisomerase II).
Fluoroquinolones;
quinolones
Name two antibiotic classes that both inhibit the bacterial 30S subunit.
Aminoglycosides;
tetracyclines
Name three medications and two antibiotic classes that all inhibit the bacterial 50S subunit.
Medications: chloramphenicol, clindamycin, linezolid;
classes: macrolides, streptogramins
Name five antibiotic classes that all inhibit peptidoglycan cross-linking.
Penicillins;
antipseudomonals;
cephalosporins;
carbapenems;
monobactams
Describe the method of action of the following medication(s):
Glycopeptides
(vancomycin, bacitracin)
Inhibition of general peptidoglycan synthesis
Describe the method of action of the following medication(s):
Rifampin
Inhibition of bacterial RNA polymerase
Describe the method of action of the following medication(s):
Trimethoprim;
sulfonamides (sulfamethoxazole, sulfadizine, sulfasoxazole)
Inhibit bacterial folic acid synthesis
Describe the method of action of the following medication(s):
Metronidazole
Decreases DNA integrity by increasing free radical formation
Describe the method of action of the following medication(s):
Fluoroquinolones;
quinolones
Inhibit bacterial DNA gyrase (topoisomerase II)
Describe the method of action of the following medication(s):
Aminoglycosides;
tetracyclines
Inhibit the bacterial 30S subunit
Describe the method of action of the following medication(s):
Medications: chloramphenicol, clindamycin, linezolid;
classes: macrolides, streptogramins
Inhibit the bacterial 50S subunit
Describe the method of action of the following medication(s):
Penicillins;
cephalosporins;
carbapenems;
monobactams
Inhibit peptidoglycan cross-linking
Are tetracyclines bactericidal or bacteriostatic?
Bacteriostatic
Is metronidazole bactericidal or bacteriostatic?
Bactericidal
Are macrolides bactericidal or bacteriostatic?
Bacteriostatic
Are β-lactams (penicillins, cephalosporins, carbapenems) bactericidal or bacteriostatic?
Bactericidal
Is vancomycin bactericidal or bacteriostatic?
Bactericidal
Is trimethoprim bactericidal or bacteriostatic?
Bacteriostatic
Are fluoroquinolones bactericidal or bacteriostatic?
Bactericidal
Are sulfonamides bactericidal or bacteriostatic?
Bacteriostatic
How do beta-lactams damage the bacterial cell walls?
Inhibition of peptidoglycan cross-linking
(via binding of penicillin-binding proteins)
What enzyme type performs the final steps of peptidoglycan cell wall formation for bacteria?
Penicillin-binding proteins
Fill in the blanks for the three main mechanisms by which bacteria can resist beta-lactam activity.
- Altered ______ability.
- Production of _____________.
- Alterations to _____________ proteins.
Fill in the blanks for the three main mechanisms by which bacteria can resist beta-lactam activity.
- Altered permeability.
- Production of beta-lactamases.
- Alterations to penicillin-binding proteins.
Bacteria are characterized by a high _________ (internal/external) osmotic pressure.
So defects in the integrity of their peptidoglycan can have major deleterious effects.
Bacteria are characterized by a high internal osmotic pressure.
So defects in the integrity of their peptidoglycan can have major deleterious effects.
Which penicillin group is made of moderate-spectrum penicillins?
Aminopenicillins
(amoxicillin, ampicillin)
Which Gram-negative organisms are commonly treated with penicillin?
Is it typically used for Gram-negatives or Gram-positives?
- Neisseria meningitidis*,
- Treponema pallidum*
Gram-positives
Penicllin G and V are associates with what type(s) of adverse event?
Hypersensitivity reactions
What bacterial defense mechanism confers resistance against penicillin G and penicillin V?
Penicillinases
(a type of beta-lactamase)
True/False.
Penicillin use can result in IgE-mediated anaphylaxis in a hypersensitive individual (~1 / 10,000 administrations). Penicillin use can also result in diarrhea, nephritis, hematologic effects, or other adverse events.
True.
___% of patients who report an allergy to penicillin either were never allergic or had an earlier allergy that has since resolved.
90% of patients who report an allergy to penicillin either were never allergic or had an earlier allergy that has since resolved.
A woman in your clinic presents with syphilis. You learn that she is also 22 weeks pregnant. She reports being allergic to penicillin.
What do you give for treatment?
Penicillin
(following testing and desensitization — temporary state of desensitization)
In addition the the hypersensitivity reactions that sometimes accompany penicillin, what other adverse events are associated with the aminopenicillins (amoxicillin, ampicillin)?
Rash;
pseudomembranous colitis
What medication type is given for enterococcal infections (e.g. an enterococcal endocarditis)?
Aminopenicillins
(ampicillin, amoxicillin)
True/False.
Penicillin is often used in treating Streptococcus pyogenes infections.
True.
Besides penicillins G and V, what other medication type is sensitive to penicillinases?
Aminopenicillins
(ampicillin, amoxicillin)
Which penicillinase-resistant penicillin is given PO?
Which penicillinase-resistant penicillin is given IV?
Which other penicillinase-resistant penicillin is given IV?
Dicloxacillin;
nafcillin,
oxacillin
Name some major organisms treated with aminopenicillins (amoxicillin, ampicillin).
E. coli
Enterococcus spp.
L. monocytogenes
- H. influenzae*
- P. mirabilis*
- Shigella spp.*
- Salmonella spp.*
- H. pylori*
What organisms are treated with penicillinase-resistant penicillins (dicloxacillin, nafcillin, oxacillin)?
Oxacillin-sensitive S. aureus (formerly MRSA)
(narrow-spectrum antibiotics)
What types of adverse event are seen with nafcillin, oxacillin, and dicloxacillin?
Hypersensitivity;
interstitial nephritis
How do organisms build up resistance to penicillinase-resistant penicillins (dicloxacillin, nafcillin, oxacillin)?
Altered penicillin-binding protein
(E.g. ORSA — formerly MRSA)
How often do penicillins need to be given for serious infections (e.g. bacteremia)?
Every ~four hours
(time-dependent killing)
Pipercillin is associated with what adverse reaction(s)?
Is it penicillinase-sensitive or -resistant?
Hypersensitivities only;
sensitive
What is pipercillin used to treat?
What is administered with it?
Pseudomonas spp.;
tazobactam (a beta-lactamase inhibitor)
Name the beta-lactamase inhibitor commonly administered with ampicillin.
Sulbactam
Name the beta-lactamase inhibitor commonly administered with amoxicillin.
Clavulinic acid
Name the beta-lactamase inhibitor commonly administered with pipercillin.
Tazobactam
What medication(s) should be used for beta-lactamase producing strains of E. coli, Enterobacter spp., Klebsiella spp., and Bacteroides spp.?
What zoonotic disease is it used for?
Ampicillin-sulbactam;
P. multocida
Name a few infection types (locations and/or organisms) that pipercillin-tazobactam might be used to treat.
(Empiric therapy for a variety of infections where a broad-spectrum agent is needed, including sepsis)
What penicillin combo is used for sinusitis and animal bites (humans, dogs, cats, etc.)?
Amoxicillin-clavulinic acid
Name two first generation cephalosporins.
Cephalexin — PO (Keflex);
cefazolin — IV (Ancef)
Name two few third generation cephalosporins.
(Bold the one that has anti-Pseudomonas activity)
Ceftriaxone;
ceftazamine
What third generation cephalosporin is used for its anti-Pseudomona activity?
What fourth generation cephalosporin is used for its anti-Pseudomona activity?
Ceftazidime;
cefepime
Name one fifth generation cephalosporin.
Ceftaroline
What generation of cephalosporins are useful against Gram-positive organisms?
First generation
True/False.
Penicillins and cephalosporins have virutally the same mechanism of action.
True.
True/False.
Some of the adverse effects associated with cephalosporins are hypersensitivity, hemolysis, fomepizole-like effects, and hypercoagulability.
False.
Some of the adverse effects associated with cephalosporins are hypersensitivity, hemolysis, disulfiram-like effects, and vitamin K deficiency.
What generations of cephalosporins are useful against Gram-negative organisms?
Third and fourth generations
What bacterial alteration leads to increased resistance to cephalosporins?
Altered penicillin-binding proteins
Which generation (and specific) cephalosporin is very broad-spectrum?
Is it effective against MRSA?
How about Pseudomonas?
5th generation (ceftaroline);
yes,
no
What medication is frequently used for pre-op due to its solid staph coverage?
Cefazolin
Which cephalosporin is typically a part of treatment for UTIs, community-acquired pneumonia, meningitis, and gonorrhea?
Ceftriaxone
What is the broadest spectrum class of beta-lactam antibiotics?
Carbapenems
What beta-lactam class has the smallest likelihood of cross-sensitivity reactions?
Monobactams
(aztreonam)
Which of the following carbapenams must be administered with cilastatin (to improve efficacy)?
Which only needs to be administed once per day?
Which is not useful against Pseudomonas?
Meropenem
Imipenem
Ertapenem
Doripenem
Imipenem
Ertapenam
Ertapenam
What type of organisms can monobactams (e.g. aztreonam) be used to treat?
Gram-negatives only
True/False.
Aminoglycosides (e.g. gentamycin, streptomycin) are generally used in treating severe infection with Gram-positive organisms.
False.
Aminoglycosides (e.g. gentamycin, streptomycin) are generally used in treating severe infection with Gram-negative organisms.
Carbapenems can be used to treat what types of bacteria?
Strep. and staph.;
Gram-negative rods;
anaerobes
(broad-spectrum)
Some Gram-negative bacteria produce ESBLs. What are ESBLs?
What beta-lactam antibiotic could be used to attempt to treat these infections?
Extended-spectrum beta-lactamases
(very high resistance to beta-lactams such as penicillins and cephalosporins);
carbapenems
What beta-lactam class has been known to lower the seizure threshold in suceptible patients at high plasma levels?
Carbapenems
How does vancomycin inhibit peptidoglycan synthesis?
What do vancomycin-resistant bacteria do to get around this?
By binding D-alanine residues;
switch to D-lactate
What type of bacteria can be treated with vancomycin?
Gram-positive only
Vancomycin can damage what organ system in particular?
The kidneys (nephrotoxic)
Soon after starting an IV antibiotic treatment for a MRSA infection, you notice the patient’s BP dropping and a pruritic, erythematous rash forming on the patient’s face, neck, and upper torso.
What medication did you give and what is happening?
Vancomycin;
red-man syndrome
(anaphylactoid reaction)
True/False.
PO vancomycin is not absorbed and so remains in the gut until it is excreted.
True.
(Making it useful for treating C. difficile)
Vancomycin should always be dosed according to what?
The patient’s creatinine clearance
In what situations should you use vancomycin to treat an E. coli infection?
How about Pseudomonas spp.?
How about Bortadella spp?
Never.
Vancomycin doesn’t treat Gram-negatives.
Why doesn’t vancomycin treat infections with Gram-negatives?
It’s too bulky to fit through the outer membrane porins to access the cell wall peptidoglycan
What antibiotic attacks the bacterial cell membrane?
Daptomycin
Daptomycin targets what part of bacteria?
The cell membrane
Daptomycin can be used to treat what types of bacteria?
Gram-positive only
Daptomycin (an antibiotic against Gram-positive organisms) is associated with a risk of damage to what tissue?
Muscle
(myopathies; rhabdomyolysis)
(check CK before use)
Name a few infections that daptomycin is used to treat.
MRSA skin infections;
right-sided endocarditis;
vancomycin-resistant Enterococcus spp.
What are some of the severe effects that can arise from linezolid use?
(E.g. in treating vancomycin-resistant Enterococcus spp. or MRSA)
Bone marrow suppression (leading to thrombocytopenia);
serotonin syndrome (when given concurrently with SSRIs)
Macrolides bind the ___s rRNA of the ___s ribosomal subunit.
Macrolides bind the 23s rRNA of the 50s ribosomal subunit.
Macrolides are often used for what infection types?
__________ pneumonias;
__________ __________ (STI);
non-____ mycobacteria
Atypical pneumonias;
Chlamydia** **trachomatis;
non-TB mycobacteria
What is the main adverse effect of macrolides?
GI upset
What type of infections is clindamycin typically used to treat?
Above-the-waist anaerobic infections (e.g. Bacteroides spp.; C. perfringens);
severe group A strep. / toxic shock syndrome
___________ is typically used for anaerobic infections above the diaphragm.
___________ is typically used for anaerobic infections below the diaphragm.
Clindamycin is typically used for anaerobic infections above the diaphragm.
Metronidazole is typically used for anaerobic infections below the diaphragm.
What is the main adverse side effect of aminoglycosides?
Nephrotoxicity
(also, ototoxicity, neuromuscular blockade)
Fluoroquinolones (levofloxacin, ciprofloxacin, moxifloxacin) are typically used to treat what types of infection?
Gram-negative rods in GI and urinary tracts
Fill in the blanks for the following fluoroquinolones and their respective functions:
Levofloxacin — Gram-___________
Ciprofloxacin — Gram-___________
Moxifloxacin — only ___________ (Gram-negatives and Gram-positives)
Fill in the blanks for the following fluoroquinolones and their respective functions:
Levofloxacin — Gram-negatives AND Gram-positives (VERY broad-spectrum)
Ciprofloxacin — Gram-negative rods
Moxifloxacin — only respiratory (Gram-negatives and Gram-positives)
Which fluoroquinolone is often used to treat Pseudomonas infection?
Ciprofloxacin
True/False.
Fluoroquinolones have very few side effects.
False.
GI upset, rashes, superinfections, headaches, dizziness;
prolonged QT;
tendonitis (in the elderly)
Which fluoroquinolone is very broad-spectrum?
Levofloxacin
While beta-lactam antibiotics remain one of the most commonly prescribed types of antibiotics, they have side effects that can range from mild to life-threatening in nature. What type of side effect is most commonly observed?
A. allergic reaction
B. anaphylactoid reaction
C. aplastic anemia
D. cartilage toxicity
E. disulfiram reaction
F. hearing loss
G. hemolytic anemia
H. Stevens-Johnson syndrome
I. red/orange colored urine or tears
? yellowing of teeth
A. allergic reaction
‘Up to 5-10% of patients have been reported to experience “allergic like” side effects. Most of these reactions are minor (e.g. mild rash, itching or skin flushing). Only a small fraction of these patients will have a serious reaction when challenged with another beta-lactam antibiotic in the future.’
Susan H arrives at the emergency department with complaints of high fever, malaise, painful urination and severe flank pain. Lab tests indicate the presence of white blood cells and E.coli in her urine. A diagnosis of kidney infection (pyelonephritis) is made, and the decision is made to use a beta-lactam antibiotic that has both an appropriate antibacterial spectrum of activity, and good tissue penetration, yet is more resistant to beta-lactamases than narrow spectrum penicillins. The drug that best fits these characteristics is:
A. ceftriaxone
B. daptomycin
C. fosfomycin
D. nitrofurantoin
E. vancomycin
A. ceftriaxone
Ceftriaxone is a “3rd generation” cephalosporin that fits the characteristics described. Parenteral, broad spectrum beta-lactams such as ceftriaxone are the preferred antibiotics for initial empiric therapy of pyelonephritis caused by most pathogens (e.g. E. coli, Proteus, Klebsiella).
Will, a 14 year-old boy develops a bad case of otitis media a few days after swimming in Hideaway Lake, MS. Will’s previous medical history is unremarkable except for having had a minor skin rash two years ago after being treated with amoxicillin for a sore throat. Which of the following shares a common mechanism, but would be very unlikely to produce a similar allergic reaction (e.g. ~1-2% or lower chance)?
A. ampicillin
B. cefaclor
C. clarithromycin
D. clindamicin
E. gentamicin
B. cefaclor
Drugs that start with “cef” or “ceph” are cephalosporins. These drugs have a 6-membered ring structure fused to the beta-lactam ring (as compared to penicillins that have a 5-member ring attached to the beta-lactam core). Cephalosporins are structurally different enough than penicillins to have only ~1-2% cross-reactivity. This risk of cross-reactivity is acceptable when the patient has a history of a minor allergic-like reaction, but the risk is generally considered NOT acceptable if the patient has a history of an anaphylactic reaction to another beta-lactam antibiotic.
Roxanne, a 23-year-old medical student arrives in the student health clinic complaining of difficulty in swallowing, sore throat, and chills. Upon examination, she is found to be running a fever, and has white patches on her tonsils. A throat swab is positive for Streptococcus pyogenes (group A). A diagnosis of acute pharyngitis is made. Her past medical history is unremarkable except for an anaphylactic reaction to cefaclor two years ago. Which of the following would be a safe alternative for treating Roxanne’s condition?
A. amoxicillin, oral
B. cephalexin, oral
C. clindamycin
D. meropenem
E. nafcillin
C. clindamycin
*This is chemically different type of antibiotic (a lincosamide) that inhibts protein synthesis, and is effective against beta-lactamase producing bacteria such as group A strep.
The objective of this question was for you to identify a drug that would NOT cross-react with a beta-lactam in a patient with a history of beta-lactam induced anaphylaxis.*
One of the most challenging types of infections to treat are those produced by gram-negative enteric bacteria that produce Extended-Spectrum Beta-Lactamases (ESBLs). Which type of beta-lactam drug (circa 2015) is structurally different enough to other beta-lactams to remain effective in treating most infections caused by this type of bacteria?
A. carbapenems
B. extended-spectrum pencillins
C. fourth generation cephalosporins
D. monobactams
E. narrow-spectrum penicillins
A. carbapenems
Carbapenems (imipenem, meropenem, doripenem, ertapenem) currently produce the best outcomes in terms of bacteriologic clearance. Carbapenems are one of the “drugs of last resort” against bacteria resistant to multiple antibiotics. ESBLs are resistant to the other answer options listed.
A 47 year old patient with a severe bacterial infection is given a drug by i.v. infusion. Because the drug is administered too rapidly, the patient develops hypotension, as well as marked flushing and itching over the upper portion of his chest, neck and face. The antibiotic most likely responsible for producing this reaction is:
A. amoxicillin
B. aztreonam
C. daptomycin
D. linezolid
E. vancomycin
E. vancomycin
The signs & symptoms described are those commonly referred to as “red man syndrome” or sometimes “red neck syndrome”. These symptoms result from histamine release when vancomycin is infused too rapidly.
A. Antibiotic A
Drug A has the largest “zone of inhibition”. As the drug diffuses out of the disc, the concentration decreases as a function of distance. A larger zone of inhibition indicates that the antibiotic is inhibiting bacterial growth even at low concentrations. Small zones of inhibition indicate relative resistance to the antibiotic. Absence of a zone of inhibition indicates total resistance (lack of drug effect).
Three different types of antibiotics inhibit bacterial protein synthesis by targeting the peptidyl transferase center within the 50S ribosomal subunit. Bacterial expression of a methyltransferase that modifies a specific adenine residue in the 23S rRNA renders all of these drugs ineffective. Hence resistance to one of these antibiotics frequently means that the bacteria will be resistant to all three drug types. These three drug types include:
A. aminoglycosides, tetracyclines & tigecycline
B. chloamphenicol, rifamycins, fluorquinolones
C. clindamycin, macrolides, streptogramins
D. daptomycin, polymyxins, sulfonamides
E. metronidazole, mupirocin, isonaizid
C. clindamycin, macrolides, streptogramins
This mechanism of resistance is of great clinical relevance when considering the appropriate therapy for infections by S. aureus, including MRSA.
A. This strain of S. aureus most likely expresses a macrolide-indicible plasmid that confers resistance to clindamycin. Therefore use of clindamycin should be avoided.
The lack of growth in zone 1 is consistent with the bacteria expressing an erythromycin-inducible methylase (iMLS-B) that is encoded by a plasmid-borne gene (erm). When this methylase is induced (e.g. by a macrolide) it alters the binding site on the 23S ribosomal subunit that both erythromycin and clindamycin bind to, making both antibiotics ineffective. When a positive D test is obtained, clindamycin should not be used for treatment because it may select for constituitive erm mutants already present in the S aureus population, resulting in a failure of clindamycin to exert an antibiotic effect.
Amongst those antibiotics that act by inhibiting protein synthesis, several members this drug class are known to produce side effects related to both drug interactions caused by inhibition of P-450 and cardiac effects (QT prolongation/Torsade de pointes). Which drug class is this?
A. Aminoglycosides
B. Fluoroquinolones
C. Macrolides
D. Rifamycins
E. Tetracyclines
C. Macrolides
These dose-dependent drug effects are more commonly observed with erythromycin (especially when its given IV), followed by clarithromycin.
A 47 year old man who presents in the ED with symptoms of fever, nausea, neck stiffness and severe headache is diagnosed with bacterial meningitis caused by Haemophilus influenzae. Which of the following is a beta-lactam antibiotic that could adequately cross the blood brain barrier and be used to treat this type of infection?
A. Chloramphenicol
B. Ceftriaxone (3rd Gen cephalosporin)
C. Cephalexin (1st Gen cephalosporin)
D. Clofazimine
E. Tazobactam
B. Ceftriaxone (3rd Gen cephalosporin)
3rd generation cephalosporins are commonly used as drugs of choice for treating bacterial meningitis. Both 3rd & 4th generation cephalosporins can cross the BBB and penetrate into tissues, which makes them useful for treating CNS infections involving susceptible bacteria.
A 34 year old HIV-positive man with a persistent cough and chest pain has a positive response to a Mantoux tuberculin skin test. Blood tests confirm the presense of TB infection, and the patient is started on combination drug therapy. A few months later, the patient develops a bilateral numbness and tingling of his upper and lower extremities, attributed to drug-induced peripheral neuropathy. Which agent is most likely responsible?
A. Clindamycin
B. Ethambutol
C. Isoniazid
D. Pyrazinamide
E. Rifampin
C. Isoniazid
Isoniazid causes peripheral neuropathy in 10-20% of patients. This side effect is attributed to a functional pyridoxine deficiency that results from isoniazid binding to pyridoxine, as well as inhibiting the enzyme pyridoxine phosphokinase (an enzyme necessary for converting pyridoxine to its active form that is a cofactor in many “pyridoxine-dependent” reactions).
A 24 year old African American woman with a history of anaphylaxis to amoxicillin is treated with an oral antibiotic for cystitis (urinary tract infection). A few days later she develops a fever, weakness, dark-colered urine, and a yellow discoloration of her eyes. Lab tests confirm that she is suffering from hemolytic anemia, and that she also has a mild deficiency in glucose-6-phosphate dehydrogenase (a genetic condition that was previously undiagnosed). The most likely cause for her anemia is:
A. Ceftriaxone (3rd Gen cephalosporin)
B. Imipenem (a carbapenem)
C. Nitrofurantoin
D. Piperacillin + Tazobactam
C. Nitrofurantoin
Nitrofurantoin is a drug of first choice for emperic treatment of cystitis (bladder infection) because: a) it is cleared by the kidney, and appears in the urine, b) is effective against most organisms commonly causing UTIs (e.g. E. coli), and has few systemic side effects in normal patients. However, it is on the list of agents known to produce hemolytic anemia in patients with G-6-PD deficiency.
A 52 year old man with a 3 month history of stomach pain is diagnosed with a stomach ulcer after undergoing an upper gastric biopsy, followed by a positive urea breath test. After a week of combination drug therapy, he arrives in the local emergency room suffering from a severe disulfiram-like reaction (tachycardia, sweating, nausea, flushed skin) after consuming two beers while watching a football game. Which drug most likely is responsible for causing this reaction?
A. Ampicillin
B. Azithromycin
C. Bismuth subsalicylate
D. Clarithromycin
E. Levofloxacin
F. Metronidazole
F. Metronidazole
H. pylori is leading cause for stomach ulcer, and there are case reports indicating that metronidazole can produce a “disulfiram-like” reaction when patients ingest alcohol, although the mechanism remains unclear (e.g. metronidazole does not inhibit alcohol metabolism in the liver and does not increase acetaldehyde production). Nevertheless case reports of this “disulfiram like” reaction exist, and you should be aware of it. The drug manufacturer recommends not consuming alcohol within 48 hours after taking metronidazole. Since the conventional treatment for ulcers combines a PPI and two or more antibiotics for a treatment period of 14 days, he should probably just avoid alcohol until several days after completing his therapy.
A neonate suffering from a severe methicillin and vancomycin-resistant infection is given a “rarely used antibiotic” in a last-ditch effort to save its life. After 5 days of antibiotic therapy, the child develops hypothermia, hypotension, irregular respiration, and develops an ashen gray skin color. What drug was the baby most likely given?
A. Ampicillin (a Penicillin)
B. Cefatoxin (a Cephalosporin)
C. Chloramphenicol
D. Doripenem (a Carbapenem)
C. Chloramphenicol
The side effects described here are associated with the “Gray Baby Syndrome”. Chloramphenicol is rarely used because of the risk for producing a potentially fatal aplastic anemia, but now and then it is used for treating bacterial infections that are resistant to all other available drugs. It is also a drug being used in developing countries, so familiarity with its toxicity is still relevant.
A 5 year old boy develops a serious infection that requires antibiotic therapy. Assuming the bacteria causing the infection were sensitive to any of the drugs listed below, which would be contraindicated due to the age of the patient?
A. Aminoglycosides (e.g. gentamicin)
B. Carbapenems (e.g. doripenem)
C. Cephalosporins (e.g. cephalexin)
D. Macrolides (e.g. clarithromycin)
E. Tetracyclines (e.g. doxycycline)
E. Tetracyclines (e.g. doxycycline)
Tetracyclines can cause staining of teeth, and should not be given to patients who have not formed their adult teeth (the first permanent molars typically erupt between ages 6 & 7). Drug manufacturers state that tetracyclines should not be used in patients younger than age 8, while some other sources state that age 10 is the cutoff. Whether or not all adult teeth have come through in the patient in question is probably more relevant.
Amy, a 35 year old woman develops a gram-negative soft tissue infection below the waist. Which of the following antibiotic classes, based upon basic antibiotic principles alone, would be “most likely” ineffective, and therefore contraindicated for empiric treatment of this type of infection?
A. Aminoglycosides
B. Antipseudonomal Carbapenems
C. Beta lactam + beta-lactamase inhibitors
D. Fluoroquinolones
E. Glycopeptides (e.g. vancomycin)
F. Third Generation Cephalosporins (e.g. moxifloxacin)
E. Glycopeptides (e.g. vancomycin)
Glycopeptides such as vancomycin have a molecular mass that is much too large to fit through porins in the outer membrane of gram-negative bacteria, making such bacteria resistant to their effects. Smaller antibiotics (e.g. penicillins, quinolones) are able to diffuse through porins, making them effective drugs (unless other mechanisms of resistance are in effect).
After successful treatment for her skin infection with a broad spectrum cephalosporin (cefotaxime), Amy’s condition improves for several days, and then suddenly declines. A second set of cell cultures confirmed the presence of a superinfection by a new organism: Bacteroides fragilis, a beta-lactamase producing obligate anaerobic gram-negative rod-shaped bacteria. Based upon basic principles of antibiotic action, which of the following would be contraindicated for treating this infection?
A. a carbapenem (e.g. meropenem)
B. a macrolide (e.g. clarithromycin)
C. a tetracycline derivative (tigecycline)
D. an aminoglycoside (e.g. gentamicin)
E. metronidazole
D. an aminoglycoside (e.g. gentamicin)
Aminoglycosides are ineffective against anaerobes because they depend upon an oxygen sensitive transport mechanism to cross through the cell membrane and reach their intended molecular target, the 30S ribosome.
A 30 year old male soldier who was seriously injured by an IED while on patrol in Afghanistan develops a life-threatening infection by Acinetobacter baumannii, a gram-negative bacterium that is an opportunistic pathogen that commonly lives in the soil. The infection proves to be resistant to a wide spectrum of available antibiotics, and a decision is made to treat the infection with i.v. infusion of a drug that exerts its on the bacterial cell membrane, and can also produce serious nephrotoxicity and neurotoxicity. Which drug was given?
A. Daptomycin
B. Fosfomycin
C. Mupirocin
D. Nitrofurantoin
E. Polymyxin
E. Polymyxin
- Note: daptomycin has no Gram-negative activity.*
- Polymyxins are drugs with significant toxicity that were traditionaly used only in topical ointments, but have become increasingly used in treating infections resistant to most other available antibiotics. Its a drug of last resort, used when other drugs are ineffective or contraindicated.*
Johnny is a 5 year old boy hospitalized for a severe infection who has been treated with a parenteral antibiotic having bactericidal properties. Two days after the onset of therapy he complains of “ringing in the ears”, and appears to have difficulty walking normally. Which of the following antibiotics was Johnny most likely given?
A. a macrolide (e.g. azithromycin)
B. a tetracycline (e.g. minocycline)
C. an aminoglycoside (e.g. tobramycin)
D. an oxazolidinone (linezolid)
E. clindamycin
C. an aminoglycoside (e.g. tobramycin)
These drugs can only be given parenterally, which typically means they are given in a hospital or clinic setting only. They bind irreversibly to the 50S ribosome (a unique characteristic for protein synthesis inhibitors), making their effect bactericidal. They are known to produce ototoxicity (vestibular & cochlear), nephrotoxicity, and rarely neuromuscular paralysis (primarily in patients with myasthenia gravis).
