HW On Antibiotics: Answer The Following Questions ✓ Solved

HW on Antibiotics. Answer the following questions: 1. What a

HW on Antibiotics. Answer the following questions: 1. What are the main characteristics of penicillin? 2. State specifically how penicillins inhibit bacterial growth. 3. What is meant by natural and synthetic penicillin; give one example for each. 4. What are penicillinases? Is there any other term for that? 5. What is meant by the term VRE? 6. How do tetracyclines work? Why are they broad spectrum? 7. State two disadvantages of tetracyclines. 8. Why do antibiotics that act on the plasma membrane have low selective toxicity? 9. If an antibiotic is bacteriostatic, what does that mean? Would you recommend a bacteriostatic antibiotic to a patient? 10. Describe how sulfonamide drugs work. Do they affect human metabolic pathways? 11. What is therapeutic index (TI)? Is a low or high TI preferable for a good drug? 12. Choose the correct single property for an ideal antimicrobial: broad or selective toxicity; low or high potency; stable or unstable; soluble or insoluble in body fluids. 13. Can penicillin work against worms, Escherichia coli, or Mycoplasma? Explain. 14. If a drug is designed to impair mitochondria, would you prescribe it for Staphylococcal infection? Explain. 15. How does chloramphenicol work? Is it a drug of choice? When is it used? 16. Do amphotericin B and other polyenes act on eukaryotic or prokaryotic cells?

Paper For Above Instructions

Introduction

This document answers the set of questions on antibiotics with concise, evidence-based explanations and citations. The goal is to clarify mechanisms of action, clinical considerations, resistance issues, and selective toxicity for major antibiotic classes (Mandell et al., 2015; Katzung, 2018).

1. Main characteristics of penicillin

Penicillins are β-lactam antibiotics characterized by a β-lactam ring fused to a thiazolidine ring; they inhibit bacterial cell wall synthesis and are generally bactericidal against growing bacteria that possess peptidoglycan cell walls (Mandell et al., 2015; Bush & Jacoby, 2010).

2. How penicillins inhibit bacterial growth

Penicillins irreversibly bind to penicillin-binding proteins (PBPs), enzymes that catalyze the final stages of peptidoglycan cross-linking (transpeptidation). Inhibition weakens the cell wall, leading to osmotic instability and lysis of actively dividing bacteria (Mandell et al., 2015).

3. Natural vs synthetic penicillin (examples)

Natural penicillins are produced by Penicillium species; example: penicillin G (benzylpenicillin). Synthetic (semi-synthetic) penicillins are chemically modified to change spectrum or pharmacokinetics; example: ampicillin (expanded spectrum) or methicillin (β-lactamase resistant) (Katzung, 2018).

4. Penicillinases (other terms)

Penicillinases are enzymes produced by bacteria that hydrolyze the β-lactam ring, inactivating penicillins. The broader term is “β-lactamases,” which includes penicillinases, cephalosporinases, and extended-spectrum β-lactamases (ESBLs) (Bush & Jacoby, 2010).

5. VRE

VRE stands for vancomycin-resistant Enterococci—Enterococcus species with acquired resistance to vancomycin, often via alteration of the D-Ala-D-Ala target to D-Ala-D-Lac. VRE are significant nosocomial pathogens (CDC, 2019).

6. Tetracycline mechanism and broad spectrum

Tetracyclines bind reversibly to the 30S ribosomal subunit, blocking aminoacyl-tRNA entry into the A site and inhibiting protein synthesis. They are broad-spectrum because this mechanism targets a conserved step present in many Gram-positive and Gram-negative bacteria, atypicals, and some intracellular organisms (Chopra & Roberts, 2001).

7. Two disadvantages of tetracyclines

Common disadvantages: tooth and bone deposition leading to discoloration and growth effects in children and fetuses, and impaired absorption due to chelation with divalent cations (calcium, magnesium, iron). They also cause photosensitivity and gastrointestinal upset (Chopra & Roberts, 2001).

8. Low selective toxicity of plasma membrane–acting antibiotics

Agents that disrupt membranes (e.g., polymyxins, amphotericin B) can have low selective toxicity because membrane structure and lipid composition, while different between microbes and humans, share enough similarity that high concentrations or systemic exposure can damage host cell membranes (Falagas & Kasiakou, 2005; Gray et al., 2012).

9. Bacteriostatic meaning and clinical recommendation

Bacteriostatic antibiotics inhibit bacterial growth but do not directly kill; they rely on host defenses to clear the infection. Bacteriostatic agents are appropriate in many situations, though bactericidal drugs may be preferred for life-threatening infections or immunocompromised patients (Pankey & Sabath, 2004).

10. Sulfonamide mechanism and effects on human pathways

Sulfonamides are structural analogues of para-aminobenzoic acid (PABA) and competitively inhibit dihydropteroate synthase (DHPS) in the folate synthesis pathway of bacteria, blocking folate and nucleotide synthesis. Humans do not synthesize folate (we obtain it from diet), so DHPS is not present in humans; however, downstream enzymes differ and some sulfonamide metabolites can have off-target effects (Mandell et al., 2015).

11. Therapeutic index (TI)

TI = toxic dose in 50% of subjects (TD50) ÷ effective dose in 50% (ED50) or similarly a safety margin. A high TI indicates a larger safety window and is preferable for clinical drugs (Katzung, 2018).

12. Ideal antimicrobial property (single best choices)

The ideal antimicrobial should have selective toxicity (harm pathogen, spare host), high potency, stability, and good solubility in body fluids. If only one choice is permitted: selective toxicity is the single most important property (Mandell et al., 2015).

13. Penicillin activity against worms, E. coli, Mycoplasma

Penicillin is ineffective against worms (helminths) because they are eukaryotes without peptidoglycan. Mycoplasma lack a cell wall and therefore are intrinsically resistant to β-lactams. Some Gram-negative rods like E. coli may be susceptible to certain penicillins (e.g., ampicillin), but many strains produce β-lactamases or have limited permeability to classic penicillin G (Mandell et al., 2015; Bush & Jacoby, 2010).

14. Mitochondria-targeting drug—would you prescribe?

No. A drug designed to impair mitochondria is likely toxic to human cells because mitochondria are essential eukaryotic organelles. Although prokaryotes lack mitochondria, human toxicity would be unacceptable; thus it should not be prescribed (Alberts et al., 2015).

15. Chloramphenicol mechanism and role

Chloramphenicol binds the 50S ribosomal subunit and inhibits peptidyl transferase, blocking protein synthesis. It is not a first-line drug in many settings because of serious adverse effects (aplastic anemia, bone marrow suppression), but it is used when alternatives are unavailable or for life-threatening infections (e.g., certain meningitis cases or rickettsial diseases) where benefits outweigh risks (Mandell et al., 2015).

16. Amphotericin B and polyenes—eukaryotic or prokaryotic target?

Amphotericin B and other polyenes target ergosterol in fungal (eukaryotic) membranes, forming pores that lead to cell death. They preferentially affect fungal membranes because fungi use ergosterol; however, they can bind human cholesterol and cause toxicity (renal and infusion-related), reflecting imperfect selectivity (Gray et al., 2012).

Conclusion

Understanding mechanisms and selective toxicity is critical for appropriate antibiotic selection and stewardship. Resistance mechanisms such as β-lactamases and target modification (e.g., van genes in VRE) underscore the need for prudent use and for continued drug development (Payne et al., 2007; WHO, 2020).

References

• Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 8th ed. Elsevier; 2015.
• Katzung BG, Masters SB, Trevor AJ. Basic & Clinical Pharmacology. 14th ed. McGraw-Hill; 2018.
• Chopra I, Roberts M. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev. 2001;65(2):232–260.
• Bush K, Jacoby GA. Updated functional classification of β-lactamases. Antimicrob Agents Chemother. 2010;54(3):969–976.
• Centers for Disease Control and Prevention (CDC). Vancomycin-Resistant Enterococci (VRE). CDC website; 2019. Available from: https://www.cdc.gov/hai/organisms/vre
• Pankey GA, Sabath LD. Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of gram-positive bacterial infections. Clin Infect Dis. 2004;38(6):864–870.
• Falagas ME, Kasiakou SK. Toxicity of polymyxins: a systematic review of the evidence from old and recent studies. Clin Infect Dis. 2005;40(9):1333–1341.
• Payne DJ, Gwynn MN, Holmes DJ, Pompliano DL. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat Rev Drug Discov. 2007;6(1):29–40.
• World Health Organization (WHO). Antimicrobial resistance. WHO website; 2020. Available from: https://www.who.int/antimicrobial-resistance
• Gray KC, Palacios DS, Dailey I, Endo MM, Uno BE, Wilcock BC, Burke MD. Amphotericin primarily kills yeast by simply binding ergosterol. Proc Natl Acad Sci U S A. 2012;109(7):2234–2239.