Welcome, PharmD students, to this MCQ quiz focusing on the Principles of Important Gram-Negative Antimicrobials! Treating infections caused by Gram-negative bacteria requires a nuanced understanding of the antimicrobial agents available, their mechanisms of action, spectra of activity, pharmacokinetic/pharmacodynamic properties, and the common ways bacteria evade them. This quiz will test your knowledge on these critical principles for key antibiotic classes used against Gram-negative pathogens, helping you build a strong foundation for rational drug selection and antimicrobial stewardship. Let’s begin!
1. Extended-spectrum penicillins (e.g., piperacillin) are often combined with a beta-lactamase inhibitor (e.g., tazobactam) to:
- a) Enhance their activity against Gram-positive organisms only.
- b) Protect the penicillin from degradation by many beta-lactamases produced by Gram-negative bacteria, thus expanding their spectrum.
- c) Improve their oral bioavailability.
- d) Reduce their renal clearance.
Answer: b) Protect the penicillin from degradation by many beta-lactamases produced by Gram-negative bacteria, thus expanding their spectrum.
2. Which generation of cephalosporins generally offers the most reliable and broadest activity against Pseudomonas aeruginosa?
- a) First-generation (e.g., cefazolin)
- b) Second-generation (e.g., cefuroxime)
- c) Anti-pseudomonal third-generation (e.g., ceftazidime) and fourth-generation (e.g., cefepime)
- d) All generations have equivalent activity.
Answer: c) Anti-pseudomonal third-generation (e.g., ceftazidime) and fourth-generation (e.g., cefepime)
3. Carbapenems (e.g., meropenem, imipenem) are beta-lactam antibiotics known for their:
- a) Narrow spectrum of activity, limited to E. coli.
- b) Very broad spectrum of activity, including many Gram-negative rods (including P. aeruginosa for most), Gram-positives, and anaerobes.
- c) Exclusive activity against anaerobic bacteria.
- d) Inability to penetrate the outer membrane of Gram-negative bacteria.
Answer: b) Very broad spectrum of activity, including many Gram-negative rods (including P. aeruginosa for most), Gram-positives, and anaerobes.
4. Aztreonam, a monobactam, is unique because its spectrum of activity is primarily restricted to:
- a) Gram-positive cocci
- b) Anaerobic bacteria
- c) Aerobic Gram-negative bacteria (including many Enterobacterales and Pseudomonas aeruginosa)
- d) Fungi and viruses
Answer: c) Aerobic Gram-negative bacteria (including many Enterobacterales and Pseudomonas aeruginosa)
5. Aminoglycosides (e.g., gentamicin, tobramycin, amikacin) exhibit concentration-dependent bactericidal activity. This means their efficacy is best correlated with:
- a) The duration of time the concentration remains above the MIC (%T>MIC).
- b) Achieving a high peak concentration relative to the MIC (Cmax/MIC) or a high AUC/MIC.
- c) The trough concentration achieved.
- d) The frequency of dosing, regardless of peak levels.
Answer: b) Achieving a high peak concentration relative to the MIC (Cmax/MIC) or a high AUC/MIC.
6. Fluoroquinolones (e.g., ciprofloxacin, levofloxacin) exert their antibacterial effect by inhibiting:
- a) Bacterial cell wall synthesis.
- b) Bacterial protein synthesis at the 30S ribosome.
- c) Bacterial DNA gyrase (topoisomerase II) and topoisomerase IV.
- d) Folic acid synthesis.
Answer: c) Bacterial DNA gyrase (topoisomerase II) and topoisomerase IV.
7. The production of Extended-Spectrum Beta-Lactamases (ESBLs) by Gram-negative bacteria like E. coli and Klebsiella primarily confers resistance to:
- a) Carbapenems and aztreonam.
- b) Most penicillins and many cephalosporins (e.g., ceftriaxone, ceftazidime).
- c) Aminoglycosides and fluoroquinolones.
- d) Vancomycin and daptomycin.
Answer: b) Most penicillins and many cephalosporins (e.g., ceftriaxone, ceftazidime).
8. Trimethoprim/sulfamethoxazole (TMP/SMX) is effective against many Gram-negative bacteria by:
- a) Inhibiting bacterial cell wall cross-linking.
- b) Disrupting bacterial DNA replication.
- c) Sequentially inhibiting two enzymes in the bacterial folic acid synthesis pathway.
- d) Binding to the 50S ribosomal subunit.
Answer: c) Sequentially inhibiting two enzymes in the bacterial folic acid synthesis pathway.
9. Which of the following carbapenems has limited activity against Pseudomonas aeruginosa and Acinetobacter species, making it generally unsuitable for empirical treatment of infections caused by these organisms?
- a) Meropenem
- b) Imipenem/cilastatin
- c) Doripenem
- d) Ertapenem
Answer: d) Ertapenem
10. A common mechanism of resistance to aminoglycosides in Gram-negative bacteria is:
- a) Modification of penicillin-binding proteins (PBPs).
- b) Production of aminoglycoside-modifying enzymes that acetylate, adenylate, or phosphorylate the drug.
- c) Decreased affinity of DNA gyrase.
- d) Increased folic acid synthesis.
Answer: b) Production of aminoglycoside-modifying enzymes that acetylate, adenylate, or phosphorylate the drug.
11. Ciprofloxacin, a fluoroquinolone, generally has better activity against _______ compared to levofloxacin, which has enhanced activity against _______.
- a) Streptococcus pneumoniae; Pseudomonas aeruginosa
- b) Pseudomonas aeruginosa; Streptococcus pneumoniae and other Gram-positives
- c) Anaerobic bacteria; aerobic bacteria
- d) Fungi; bacteria
Answer: b) Pseudomonas aeruginosa; Streptococcus pneumoniae and other Gram-positives
12. The post-antibiotic effect (PAE) is a pharmacodynamic property where bacterial growth suppression continues even after the antibiotic concentration falls below the MIC. This is a prominent feature of which class active against Gram-negatives?
- a) Penicillins
- b) Cephalosporins
- c) Aminoglycosides and Fluoroquinolones
- d) Sulfonamides
Answer: c) Aminoglycosides and Fluoroquinolones
13. Fosfomycin is often used for uncomplicated urinary tract infections (UTIs). Its unique mechanism involves:
- a) Inhibition of the 30S ribosomal subunit.
- b) Inhibition of an early step in cell wall synthesis by inactivating MurA enzyme (enolpyruvyl transferase).
- c) Disruption of the bacterial outer membrane.
- d) Inhibition of DNA gyrase.
Answer: b) Inhibition of an early step in cell wall synthesis by inactivating MurA enzyme (enolpyruvyl transferase).
14. Nitrofurantoin is another agent used for UTIs. Its use is generally limited to cystitis because:
- a) It achieves high systemic concentrations but poor urine concentrations.
- b) It achieves therapeutic concentrations primarily in the urine but not significantly in blood or tissues.
- c) It is only active against Gram-positive bacteria.
- d) It is too toxic for systemic use.
Answer: b) It achieves therapeutic concentrations primarily in the urine but not significantly in blood or tissues.
15. Resistance to carbapenems mediated by carbapenemase enzymes (e.g., KPC, NDM, VIM, OXA-48-like) is a major concern because these enzymes:
- a) Only degrade penicillins.
- b) Can hydrolyze nearly all beta-lactam antibiotics, including carbapenems, penicillins, and cephalosporins.
- c) Are easily inhibited by standard beta-lactamase inhibitors like clavulanate.
- d) Only confer resistance to ertapenem.
Answer: b) Can hydrolyze nearly all beta-lactam antibiotics, including carbapenems, penicillins, and cephalosporins.
16. One of the primary targets for beta-lactam antibiotics in Gram-negative bacteria, located in the periplasmic space, are the:
- a) Ribosomes
- b) DNA gyrase enzymes
- c) Penicillin-binding proteins (PBPs) involved in cell wall synthesis
- d) Porin channels
Answer: c) Penicillin-binding proteins (PBPs) involved in cell wall synthesis
17. What is a potential adverse effect shared by many broad-spectrum antibiotics, including some that cover Gram-negatives, due to disruption of normal gut flora?
- a) Hypertension
- b) Clostridioides difficile-associated diarrhea
- c) Improved digestion
- d) Enhanced vitamin K synthesis
Answer: b) Clostridioides difficile-associated diarrhea
18. Polymyxins (e.g., colistin, polymyxin B) are older antibiotics that have re-emerged for treating multidrug-resistant Gram-negative infections. Their mechanism involves:
- a) Inhibiting protein synthesis.
- b) Disrupting the integrity of the bacterial outer and inner membranes.
- c) Inhibiting DNA replication.
- d) Blocking cell wall synthesis.
Answer: b) Disrupting the integrity of the bacterial outer and inner membranes.
19. A common counseling point for patients taking oral fluoroquinolones is to avoid co-administration with:
- a) Water
- b) Products containing divalent or trivalent cations (e.g., antacids, calcium, iron, zinc) due to chelation and reduced absorption.
- c) Vitamin C
- d) Protein-rich meals
Answer: b) Products containing divalent or trivalent cations (e.g., antacids, calcium, iron, zinc) due to chelation and reduced absorption.
20. Which of these antimicrobials relies on an oxygen-dependent transport system to enter bacterial cells, making it largely ineffective against anaerobic Gram-negative bacteria?
- a) Metronidazole
- b) Clindamycin
- c) Aminoglycosides
- d) Piperacillin/tazobactam
Answer: c) Aminoglycosides
21. Porin channel mutations or downregulation in Gram-negative bacteria can contribute to resistance against:
- a) Vancomycin
- b) Daptomycin
- c) Beta-lactams (like carbapenems) and fluoroquinolones by reducing their entry into the periplasmic space or cell.
- d) Linezolid
Answer: c) Beta-lactams (like carbapenems) and fluoroquinolones by reducing their entry into the periplasmic space or cell.
22. The development of newer beta-lactam/beta-lactamase inhibitor combinations like ceftolozane/tazobactam or ceftazidime/avibactam was primarily driven by the need to combat:
- a) Methicillin-resistant Staphylococcus aureus (MRSA).
- b) Vancomycin-resistant enterococci (VRE).
- c) Multidrug-resistant Gram-negative bacteria, including those producing ESBLs and some carbapenemases (for ceftazidime/avibactam).
- d) Atypical bacteria like Mycoplasma.
Answer: c) Multidrug-resistant Gram-negative bacteria, including those producing ESBLs and some carbapenemases (for ceftazidime/avibactam).
23. For antibiotics whose efficacy is related to %T>MIC, such as beta-lactams, which dosing strategy is often employed to optimize this parameter?
- a) Once-daily high doses.
- b) More frequent administration or continuous/prolonged infusions.
- c) Co-administration with food only.
- d) Administering the drug via the topical route.
Answer: b) More frequent administration or continuous/prolonged infusions.
24. Which statement is TRUE regarding the medicinal chemistry principle of beta-lactam antibiotics?
- a) The beta-lactam ring is extremely stable and resistant to hydrolysis.
- b) The strained beta-lactam ring is crucial for their mechanism of action (mimicking D-Ala-D-Ala and acylating PBPs).
- c) All beta-lactams have identical side chains.
- d) They are all orally bioavailable.
Answer: b) The strained beta-lactam ring is crucial for their mechanism of action (mimicking D-Ala-D-Ala and acylating PBPs).
25. A key principle when considering treatment for an infection caused by Stenotrophomonas maltophilia is its:
- a) High susceptibility to imipenem.
- b) Intrinsic resistance to carbapenems and frequent susceptibility to trimethoprim/sulfamethoxazole.
- c) Preference for anaerobic environments.
- d) Gram-positive staining characteristic.
Answer: b) Intrinsic resistance to carbapenems and frequent susceptibility to trimethoprim/sulfamethoxazole.
26. The pharmacodynamic goal for aminoglycosides is typically to achieve a high Cmax/MIC ratio (e.g., 8-10). This supports the use of:
- a) Low, frequent doses.
- b) Once-daily (extended-interval) dosing for many indications.
- c) Continuous infusion.
- d) Oral administration.
Answer: b) Once-daily (extended-interval) dosing for many indications.
27. Efflux pumps in Gram-negative bacteria contribute to resistance by:
- a) Preventing antibiotic entry through porins.
- b) Actively transporting antibiotics out of the bacterial cell.
- c) Chemically modifying the antibiotic.
- d) Altering the antibiotic’s target site.
Answer: b) Actively transporting antibiotics out of the bacterial cell.
28. Which of the following beta-lactams has the most reliable activity against Pseudomonas aeruginosa when used as a single agent (among common choices)?
- a) Ampicillin
- b) Cefazolin (a first-generation cephalosporin)
- c) Piperacillin (often with tazobactam) or Ceftazidime or Cefepime
- d) Amoxicillin
Answer: c) Piperacillin (often with tazobactam) or Ceftazidime or Cefepime
29. The “penicillin-binding proteins” (PBPs) targeted by beta-lactam antibiotics are essential bacterial enzymes involved in:
- a) Protein synthesis.
- b) DNA replication.
- c) Peptidoglycan cell wall synthesis (transpeptidation).
- d) Folic acid metabolism.
Answer: c) Peptidoglycan cell wall synthesis (transpeptidation).
30. A principle of using fosfomycin for UTIs is its ability to achieve very high concentrations in the _______ after a single oral dose.
- a) Cerebrospinal fluid
- b) Urine
- c) Lungs
- d) Bile
Answer: b) Urine
31. One mechanism of resistance to trimethoprim/sulfamethoxazole in Gram-negative bacteria involves:
- a) Production of beta-lactamases.
- b) Mutations in DNA gyrase.
- c) Overproduction of para-aminobenzoic acid (PABA) or mutations in dihydrofolate reductase or dihydropteroate synthase.
- d) Modification of the 30S ribosomal subunit.
Answer: c) Overproduction of para-aminobenzoic acid (PABA) or mutations in dihydrofolate reductase or dihydropteroate synthase.
32. Why is cilastatin co-administered with imipenem?
- a) To inhibit bacterial beta-lactamases.
- b) To inhibit renal dehydropeptidase I, an enzyme in the kidney that metabolizes and inactivates imipenem.
- c) To enhance imipenem’s oral absorption.
- d) To reduce imipenem’s CNS toxicity.
Answer: b) To inhibit renal dehydropeptidase I, an enzyme in the kidney that metabolizes and inactivates imipenem.
33. A common side effect concern with fluoroquinolones, particularly in older adults or those on corticosteroids, is:
- a) Severe hepatotoxicity.
- b) Tendinitis and tendon rupture.
- c) Red man syndrome.
- d) Bone marrow suppression.
Answer: b) Tendinitis and tendon rupture.
34. Which of the following antibiotics is NOT a beta-lactam but still targets the bacterial cell wall (different mechanism than beta-lactams)?
- a) Gentamicin
- b) Ciprofloxacin
- c) Vancomycin (primarily Gram-positive, but illustrates cell wall target)
- d) Fosfomycin
Answer: d) Fosfomycin (Vancomycin is also cell wall active but mainly for G+; Fosfomycin directly targets cell wall synthesis in a unique way for G- UTIs).
35. The choice between different fluoroquinolones for Gram-negative infections often depends on:
- a) Their color.
- b) Their specific spectrum of activity (e.g., anti-pseudomonal activity) and pharmacokinetic properties.
- c) Patient preference for brand names.
- d) Their cost only.
Answer: b) Their specific spectrum of activity (e.g., anti-pseudomonal activity) and pharmacokinetic properties.
36. A key principle in antimicrobial therapy is to use the narrowest spectrum agent effective against the identified pathogen to:
- a) Ensure all bacteria in the body are killed.
- b) Minimize disruption to the patient’s normal flora and reduce the selection pressure for resistance.
- c) Make the therapy more expensive.
- d) Increase the chance of superinfection.
Answer: b) Minimize disruption to the patient’s normal flora and reduce the selection pressure for resistance.
37. For which of these Gram-negative pathogens is combination therapy often recommended for serious infections to prevent resistance and enhance killing?
- a) Escherichia coli in uncomplicated cystitis
- b) Pseudomonas aeruginosa in hospital-acquired pneumonia
- c) Haemophilus influenzae in otitis media
- d) Neisseria gonorrhoeae in uncomplicated urethritis (though resistance is driving combinations here too)
Answer: b) Pseudomonas aeruginosa in hospital-acquired pneumonia
38. A patient with a true, severe IgE-mediated penicillin allergy should generally avoid which other class of antibiotics due to potential cross-reactivity (though the risk varies)?
- a) Aminoglycosides
- b) Fluoroquinolones
- c) Cephalosporins and Carbapenems (cross-reactivity is possible, especially with early-gen cephalosporins or those with similar side chains)
- d) Sulfonamides
Answer: c) Cephalosporins and Carbapenems (cross-reactivity is possible, especially with early-gen cephalosporins or those with similar side chains) (Aztreonam is often an exception with low cross-reactivity).
39. The ability of some Gram-negative bacteria to modify their LPS structure can contribute to:
- a) Increased susceptibility to polymyxins.
- b) Resistance to polymyxins and evasion of host immune responses.
- c) Enhanced beta-lactamase production.
- d) Improved porin function.
Answer: b) Resistance to polymyxins and evasion of host immune responses.
40. What is a major limiting toxicity for polymyxins like colistin when used systemically?
- a) Hepatotoxicity and cardiotoxicity.
- b) Nephrotoxicity and neurotoxicity.
- c) Bone marrow suppression.
- d) Severe gastrointestinal upset.
Answer: b) Nephrotoxicity and neurotoxicity.
41. Understanding the principles of antimicrobial PK/PD helps in designing dosing regimens that:
- a) Ensure subtherapeutic concentrations to avoid toxicity.
- b) Maximize the probability of achieving the target PK/PD index associated with efficacy and minimize resistance development.
- c) Are the same for all patients regardless of infection type or site.
- d) Use the lowest possible dose to save money.
Answer: b) Maximize the probability of achieving the target PK/PD index associated with efficacy and minimize resistance development.
42. Which of the following is NOT a primary mechanism of bacterial resistance to antimicrobials targeting Gram-negative bacteria?
- a) Enzymatic inactivation of the drug.
- b) Modification of the drug target site.
- c) Decreased drug uptake due to porin loss.
- d) Increased host immune response clearing the drug.
Answer: d) Increased host immune response clearing the drug.
43. The addition of avibactam (a non-beta-lactam beta-lactamase inhibitor) to ceftazidime primarily extends its activity against Gram-negative bacteria producing:
- a) Only simple penicillinases.
- b) ESBLs, AmpC beta-lactamases, and some carbapenemases (like KPC).
- c) Metallo-beta-lactamases.
- d) VanA type resistance.
Answer: b) ESBLs, AmpC beta-lactamases, and some carbapenemases (like KPC).
44. The principle of “source control” in managing infections, particularly those involving Gram-negative bacteria, refers to:
- a) Choosing the correct antibiotic source (manufacturer).
- b) Physical measures to eradicate the focus of infection (e.g., draining an abscess, removing an infected catheter) in addition to antibiotic therapy.
- c) Using only locally sourced antibiotics.
- d) Controlling the source of hospital funding.
Answer: b) Physical measures to eradicate the focus of infection (e.g., draining an abscess, removing an infected catheter) in addition to antibiotic therapy.
45. Pharmacists applying principles of Gram-negative antimicrobials must consider the site of infection because:
- a) All antibiotics achieve the same concentration in all body tissues.
- b) Drug penetration to certain sites (e.g., CSF, prostate, bone) can be limited for some agents, affecting efficacy.
- c) Gram-negative bacteria only infect external surfaces.
- d) The MIC of an organism changes based on infection site.
Answer: b) Drug penetration to certain sites (e.g., CSF, prostate, bone) can be limited for some agents, affecting efficacy.
46. For many beta-lactams, maintaining drug concentrations above the MIC for at least _______ of the dosing interval is often targeted for optimal efficacy against Gram-negative pathogens.
- a) 10-20%
- b) 20-30%
- c) 40-70% (or higher for some infections/pathogens)
- d) 100% (often ideal but not always achievable or necessary for all beta-lactams/bugs)
Answer: c) 40-70% (or higher for some infections/pathogens)
47. The medicinal chemistry of fluoroquinolones involves modifications to the basic quinolone structure to:
- a) Only improve taste.
- b) Enhance spectrum of activity, pharmacokinetic properties, and reduce toxicity.
- c) Only increase water solubility.
- d) Make them resemble beta-lactams.
Answer: b) Enhance spectrum of activity, pharmacokinetic properties, and reduce toxicity.
48. When considering antimicrobial therapy for an Enterobacterales species known to produce an inducible AmpC beta-lactamase (e.g., Enterobacter cloacae), there is a risk of resistance developing during therapy if treated with:
- a) A carbapenem initially.
- b) A third-generation cephalosporin (e.g., ceftriaxone), as it can select for derepressed mutants.
- c) Vancomycin.
- d) An aminoglycoside.
Answer: b) A third-generation cephalosporin (e.g., ceftriaxone), as it can select for derepressed mutants.
49. A key principle of antimicrobial therapy for serious Gram-negative infections in immunocompromised patients is often to:
- a) Use bacteriostatic agents only.
- b) Select bactericidal agents and potentially combination therapy to ensure adequate killing.
- c) Delay therapy until the patient’s immune system recovers.
- d) Use the lowest possible doses to avoid side effects.
Answer: b) Select bactericidal agents and potentially combination therapy to ensure adequate killing.
50. The overall understanding of the principles of antimicrobials active against Gram-negative bacteria is essential for pharmacists to:
- a) Perform surgery.
- b) Contribute effectively to antimicrobial stewardship, optimize patient-specific regimens, and educate patients and other healthcare providers.
- c) Only manage the pharmacy inventory of these drugs.
- d) Diagnose the specific species of Gram-negative bacteria without lab tests.
Answer: b) Contribute effectively to antimicrobial stewardship, optimize patient-specific regimens, and educate patients and other healthcare providers.