MED 2207 – Antimicrobials

In Class Quiz – Answers

1. A. 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 small fraction of these patients will have a serious reaction when challenged with another beta-lactam antibiotic in the future.B. Beta-lactams can rarely produce this potentially life-threatening type of reaction (less than 0.04% of drug administrations), but it is not the most commonly observed side effect. There is a BETTER answer option.

2. A. 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).B. No. This is not a beta-lactam, It is not effective against gram-negative bacteria (such as E. coli), and disrupts bacterial membranes.C. No. Fosfomycin is not a beta-lactam. It is a structural analog of phosphoenolpyruvate, and inhibits an enzyme (enolypyruvate transferase) involved in a very early intracellular stage of cell wall synthesis. It is used for treating uncomplicated UTIs (and not pyelonephritis). D. No. Nitrofurantoin is not a beta-lactam, so it doesn't fit the characteristics of the drug you are being asked about. Nitrofurantoin is used to uncomplicated treat bladder infections (vs more serious kidney infections). Because of its limited tissue permeability & pharmacokinetic properties, it remains localized to the urine, and has little systemic effect. Your patient Susan has an infection of her kidney tissue, and effective treatment would require a drug that can penetrate into kidney tissue, vs being trapped in the urine. E. This drug is not a beta-lactam. Glycopeptides (vancomycin) is a large bulky molecule that can't cross the outer membrane of gram-negative bacteria, such as E. coli. A really lousy choice.

3. A. Arguably not the best choice? Ampicillin is still a penicillin, and (fact alert) it is structurally identical to amoxicillin except for removal of a hydroxyl group. If Will had a bonafied allergic reaction to amoxicillin, then he "might" react to ampicillin too. (Lets not find out). There is a safer therapeutic option with a <1% predicted incidence of cross-reactivity with amoxicillin. B. Correct!. 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% cross-reactivity. This risk of cross-reactivity is acceptable when the patient has a history of a minor allergic-like reaction, but isNOT an acceptable risk if the patient has a history of an anaphylactic reaction to another beta-lactam antibiotic.C. This drug is not a beta-lactam, does not directly affect cell wall synthesis, and has an intracellular mechanism of action. D. This drug is not a beta-lactam, does not directly affect cell wall synthesis, and has an intracellular mechanism of action.

4. A. This is a penicillin, which has a high enough risk in cross-reacting to another beta-lactam to be considered "not worth the risk" when treating a sore throat in a patient with a history of anaphylactic reaction to another type of beta-lactam antibiotic. B. This is a 1st generation cephalosporin, which has a high enough risk in cross-reacting with a 2nd generation cephalosporin (cefaclor) to be considered "not worth the risk"

when treating a sore throat in a patient with a history of anaphylactic reaction to another beta-lactam antibiotic. C. Good choice. 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. D. This is a carbapenem. Carbapenems are structurally related to beta-lactams, and do show asmall incidence (<1%) of cross-reactivity in those patients with a truely confirmed sensitivity to beta-lactams. Treatment with a carbapenem is considered not advisable (they are contraindicated) in patients with a history of anaphylatoid reactions to beta-lactam antibiotics.E. This is a type of penicillin resistant to beta-lactamases produced by most staphlococci. Treatment with nafcillin is not advisable in a patient with a history of anaphylatic reaction to a beta-lactam antibiotic.

5. A. Correct! 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.B. Not the best choice listed. These penicillins (ampicillin, amoxicillin, piperacillin) have been given this classification based upon their ability to penetrate through the outer membrane of gram-negative bacteria, providing greater activity against these organisms compared to the natural (narrow spectrum) penicllins (Pen G & Pen V). The combination of an extended pencillin plus a beta-lactamase inhibitor (e.g. piperacillin + tazobactam) has been used to treat ESBL infections in the past, but due to the development of resistance, the outcomes are not typically as favorable as when using another drug option listed here. C. ESBLs will inactivate all cephalosporins.D. ESBLs will inactivate monobactams.E. ESBLs will inactivate all narrow spectrum penicillins (e.g. Pen V & Pen G).

6. A. This penicillin is given orally, and would not be the most likely candidate for producing this type of reaction. Possible, yes, but likely, no. B. This monobactam can occassionally produce skin rashes, but this reaction sounds a bit different. There is a more likely answer option. C. This antibiotic is known for affecting skeletal muscle, producing myalgia & weakness with increased CPK levels. But this is not what is being observed here.D. Not likely. This drug can inhibit monoamine oxidase (MAO) and produce a serotonin-excess or tyramine-excess type reaction when drugs or foods are consumed that elevate these compounds. However, this reaction would elevate blood pressure, and would not cause the flushing type response.E. Correct! 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. Remember this one. Its a classic side effect for a relatively commonly used drug.

7. A. Correct! 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).

8. A. these drugs inhibit the 30 S ribosomal subunit at different locations.

B. No, these drugs are dissimilar and have different mechanisms of action, including effects on the 50S ribosome (chloramphenicol), RNA polymerase (rifamycins), and DNA gyrase (fluoroquinolones). C. Correct! This mechanism of resistance is of great clinical relevance when considering the appropriate therapy for infections by S. aureus, including MRSA.D. No. These drugs have different mechanisms of action, including the bacterial cell membrane (daptomycin & polymyxins) and folic acid synthesis (sulfonamides). E. No. These drugs have different mechanisms of action including causing DNA strand breaks (metronidazole), tRNA synthetase (mupirocin), and biosynthesis of mycolic acids (isoniazid)

9. DF10. A. Aminoglycosides are notorious for having 3 major types of side effects: 1)

Ototoxicity - both reversible auditory & irreversible vestibular toxicity due to damage of hair cells; 2) nephrotoxicity - caused by damage to the renal proximal convoluted tubule, and 3) neuromuscular blockade - more rare & most commonly seen in patients with myasthenia gravis.B. No. While fluroquinolones can cause QT prolongation, they are not protein synthesis inhibitors, and aren't known for P-450 interactions. C. Correct! These dose-dependent drug effects are more commonly observed with erythromycin (especially when its given IV), followed by clarithromycin. D. No. These drugs interfere with RNA polymerase, and are notorious inducers of P-450 (mainly rifampin). They don't inhibit P-450, and aren't known for their cardiac effects.E. No. These drugs are known for their effects on bone and teeth, and for causing some degree of increased photosensitivity.