Microbial Control Flashcards

Question

**Cell Wall Synthesis Inhibitors – Beta-lactams**

Answer 1

*Mechanism of Action* - **Inhibit peptidoglycan synthesis** by blocking **peptide cross-linking** between **NAG/NAM subunits** - Weakened wall → **osmotic lysis** of bacteria - Selectively toxic: humans lack peptidoglycan *Drug Classes* 1. **Penicillins** - Examples: *Amoxicillin, Ampicillin* - Natural (e.g. Penicillin G) targets Gram+ - Semi-synthetic forms like *ampicillin* broaden Gram– coverage - Resistance via **β-lactamase** common 2. **Cephalosporins** - Examples: *Cephalexin, Ceftriaxone* - Broader spectrum than penicillins - Common in hospital settings 3. **Monobactams** - Example: *Aztreonam* - Narrow spectrum: mostly Gram– aerobes - Often used when allergic to penicillins 4. **Carbapenems** - Examples: *Meropenem, Imipenem* - Very broad-spectrum - Resistant to many β-lactamases - Reserved for multi-drug resistant infections *Note*: All are **β-lactam antibiotics**, sharing a ring structure targeted by **β-lactamase enzymes**.

Answer 2

- **Bacitracin** - Blocks **peptidoglycan synthesis** - Inhibits transport of peptidoglycan **subunits out of the cell** - **Vancomycin** - A **glycopeptide** antibiotic - Prevents **peptide linkage formation** in the cell wall

Answer 3

*Mechanism of Action* - Target **70S ribosomes** in bacteria (unique to prokaryotes) - Prevent **translation** of bacterial proteins - Selectively toxic: do **not affect human 80S ribosomes** *Classes and Examples* 1. **Lincosamides** - Example: *Clindamycin* - Binds 50S subunit → blocks peptide bond formation - Effective against anaerobes and some Gram+ cocci - Risk of *C. difficile* superinfection 2. **Macrolides** - Example: *Azithromycin* - Binds 50S subunit → blocks translocation - Broad-spectrum: Gram+ and some Gram– - Often used for respiratory infections and STIs 3. **Tetracyclines** - Examples: *Tetracycline, Doxycycline* - Bind 30S subunit → prevent tRNA binding at A-site - Broad-spectrum: Gram+, Gram–, intracellular bacteria (e.g. *Rickettsia*, *Chlamydia*) - Can bind calcium → avoid in children/pregnancy

Answer 4

*Mechanism of Action* - Interfere with **bacterial DNA synthesis** - Disrupt **replication enzymes** or directly damage **DNA strands** *Classes and Examples* 1. **Fluoroquinolones** - Examples: *Ciprofloxacin, Levofloxacin, Ofloxacin* - Synthetic drugs - Bind to **DNA gyrase** (a type of topoisomerase) → prevent supercoiling relief → halt DNA replication - Broad-spectrum, especially effective against Gram– - *Side effects*: may weaken connective tissue (e.g., tendons) 2. **Nitroimidazoles** - Example: *Metronidazole* - Causes **strand breakage** by forming toxic intermediates in anaerobic cells - Effective against **anaerobic bacteria** and **protozoa** (*Giardia*, *Trichomonas*) - Often available **over the counter** in some countries

Answer 5

*Overview* - Target **folate biosynthesis**, essential for nucleotide and amino acid production - Humans obtain folate from diet → selective toxicity - Bacteria must **synthesize folate de novo** → vulnerable to these inhibitors *Drug Classes and Mechanisms* 1. **Sulfonamides** - Example: *Sulfamethoxazole* - Inhibits **dihydropteroate synthetase** (competes with PABA) - Blocks conversion of PABA → dihydropteroic acid 2. **Trimethoprim** - Inhibits **dihydrofolate reductase** - Prevents conversion of dihydrofolic acid → tetrahydrofolic acid *Clinical Strategy* - **Combination therapy** (e.g., TMP-SMX): - Synergistic effect → more effective - Decreases chance of **resistance**

Answer 6

- *Drug examples*: **Miconazole**, **Ketoconazole**, **Fluconazole** - *Target*: Inhibit **ergosterol synthesis**, disrupting fungal membrane structure - *Notes*: - Ergosterol is unique to fungi → basis for selective toxicity - Fluconazole has improved oral absorption and selectivity - Ketoconazole less selective, often topical only - Used for skin infections, yeast infections, systemic candidiasis

Answer 7

- *Drug example*: **Flucytosine** - *Target*: Inhibits **RNA synthesis** by acting as a false nucleotide - *Notes*: - Selectively toxic: fungi convert drug into active form, humans do not - Used in combination therapy (e.g., with Amphotericin B) - Effective for *Cryptococcus* infections (e.g., meningitis)

Answer 8

- *Drug example*: **Caspofungin** - *Target*: Inhibits **beta-glucan synthesis**, weakening fungal **cell wall** - *Notes*: - Effective against *Candida* and *Aspergillus* - Poor activity against fungi lacking β-glucan - Used IV for serious systemic infections

Answer 9

- *Drug example*: **Amphotericin B** - *Target*: Binds **ergosterol** in membrane → forms pores, disrupts membrane integrity - *Notes*: - Broad-spectrum, used for life-threatening fungal infections - High toxicity: can also bind human cholesterol - Often a last-resort treatment (e.g., for fungemia)

Answer 10

- *Drug example*: **Acyclovir** - *Target*: Inhibits **viral nucleic acid synthesis** - *Mechanism*: Mimics normal nucleosides → incorporated into viral DNA → chain termination - *Notes*: - Selective for virus-infected cells (e.g., HSV-infected) - Commonly used for **herpes** virus infections

Answer 11

- *Drug example*: **Oseltamivir (Tamiflu)** - *Target*: Inhibits **release of virions** from infected cells - *Mechanism*: Blocks influenza neuraminidase → prevents virus spread to other cells - *Notes*: - Must be taken early - Shortens **flu** duration, not a cure

Answer 12

- *Drug examples*: **Ritonavir**, **Tipranavir** - *Target*: Inhibits **HIV protease** enzyme - *Mechanism*: Prevents cleavage of viral polyproteins → non-infectious viral particles - *Notes*: - HIV protease is a **unique viral enzyme** - Used in **combination antiretroviral therapy (cART)**

Answer 13

- *Drug examples*: **Tenofovir**, **Etravirine** - *Target*: Inhibits **reverse transcriptase** - *Mechanism*: Blocks conversion of viral RNA → DNA - *Notes*: - Effective against **HIV** - Can be nucleoside or non-nucleoside analogs

Answer 14

- *Drug examples*: **Raltegravir**, **Elvitegravir** - *Target*: Inhibits **HIV integrase** - *Mechanism*: Prevents integration of viral DNA into host genome - *Notes*: - Crucial for **preventing permanent infection** - Used in **HIV combination therapy**

Answer 15

lowest concentration of a drug that inhibits visible microbial growth - Standard method to assess susceptibility of microbes to antibiotics - Reported in µg/mL; lower MIC = higher potency against the organism **Susceptibility Testing – Broth Dilution** - Series of tubes with increasing concentrations of drug - Inoculated with target microbe and incubated - **MIC = lowest concentration where no visible growth (clear broth)** - Produces precise, quantitative MIC value **Susceptibility Testing – E-Test** - Plastic strip with **concentration gradient** placed on agar with lawn of bacteria - Drug diffuses from strip → creates elliptical zone of inhibition - **MIC = point where zone edge intersects the scale on strip** - Combines qualitative ease of disk diffusion with quantitative MIC data

Answer 16

- An **antibiogram** is a report that summarizes how susceptible (or resistant) bacterial isolates are to a panel of antibiotics at a specific institution (usually a hospital or clinic). - It is based on lab testing of **clinical isolates** (e.g., *E. coli* from patient urine cultures) against a variety of antibiotics using methods like MIC or disk diffusion. --- *What information does it give?* - The **percentage** of isolates that are **susceptible** to each antibiotic. - Example: If 95% of *E. coli* are susceptible to ciprofloxacin, it means ciprofloxacin is a good choice empirically. - If only 40% are susceptible, it’s likely a poor first choice unless susceptibility is confirmed. --- *Why is it useful?* 1. **Guides empiric therapy**: Helps clinicians choose the best initial antibiotic while waiting for culture results. 2. **Tracks resistance trends**: Detects increases in antibiotic resistance over time. 3. **Improves stewardship**: Encourages use of narrow-spectrum antibiotics when possible. --- *How to interpret it?* - **Higher % = more effective** - **Lower % = less reliable** (may indicate resistance is common) - Clinicians aim to use drugs where susceptibility is consistently high (e.g., >85–90%) unless culture results suggest otherwise. *Note:* Antibiograms are **local**, meaning patterns vary by hospital, region, or unit (e.g., ICU vs outpatient).

Answer 17

1. **Prevent Drug Entry** - Example: *Pseudomonas aeruginosa* alters porins to block β-lactams. 2. **Target Modification** - Example: Mutation in **DNA gyrase** → prevents fluoroquinolone (e.g., ciprofloxacin) binding. 3. **Enzymatic Destruction** - Example: **β-lactamase** breaks the β-lactam ring in penicillins and cephalosporins. 4. **Enzymatic Alteration** - Example: Bacteria add chemical groups (e.g., acetyl, phosphate) to inactivate **aminoglycosides**. 5. **Target Mimicry** - Example: Bacteria produce decoy molecules that sequester drugs before they reach the real target. 6. **Enzymatic Bypass** - Example: Alternative enzymes that bypass sulfonamide- or trimethoprim-inhibited steps in folic acid synthesis. 7. **Efflux Pumps** - Example: **Tetracycline** resistance via pumps that expel the drug from bacterial cytoplasm (e.g., in *E. coli*). 8. **Target Overproduction** - Example: Overproduction of folate pathway enzymes to overwhelm **trimethoprim** inhibition. *These mechanisms can arise from mutation or horizontal gene transfer, and they often combine in multidrug-resistant organisms.*

Answer 18

*Multidrug Resistance (MDR)* - **Definition**: Resistance to multiple drugs using **multiple distinct mechanisms** - **Example**: A bacterium may use an efflux pump for one drug and an enzyme for another - **Common in**: *Nosocomial pathogens* and healthcare-associated infections (HAIs) - *Treatment is harder because multiple targets must be overcome* *Cross Resistance* - **Definition**: Resistance to multiple drugs due to a **single mechanism** - **Example**: - *Efflux pump* expels multiple unrelated drugs - *Extended-spectrum β-lactamases (ESBLs)* degrade multiple β-lactam antibiotics - **Also seen in**: HAIs and nosocomial infections - *One genetic mutation or enzyme can disable entire drug classes*

Microbial Control Flashcards

(43 cards)