Antimicrobials Flashcards
What is the mechanism of action of metronidazole?
Metronidazole is a nitroimidazole that targets anaerobic microorganisms by forming cytotoxic free radicals that damage bacterial DNA, leading to strand breakage and cell death.
What is the antibacterial spectrum of metronidazole?
Active against anaerobic bacteria (Bacteroides spp., Clostridium difficile) and protozoa (Entamoeba histolytica, Giardia lamblia, Trichomonas vaginalis). No activity against aerobes.
What are the major uses of metronidazole?
Used for amebiasis, bacterial vaginosis, trichomoniasis, intra-abdominal infections, C. difficile colitis, and part of H. pylori treatment.
What are the major side effects of metronidazole?
GI distress, metallic taste, neurotoxicity (dizziness, vertigo, peripheral neuropathy), oral yeast infections, and Disulfiram-like reaction with alcohol.
What are the drug interactions of metronidazole?
Alcohol (Disulfiram-like reaction), CYP450 inducers (reduce efficacy), CYP450 inhibitors (increase toxicity), Warfarin (increased anticoagulation).
Which organisms commonly cause UTIs?
Escherichia coli (most common), Klebsiella spp., Enterococcus spp., Staphylococcus saprophyticus, Proteus spp., Pseudomonas aeruginosa.
What is the first-line oral therapy for UTIs in non-pregnant women?
Nitrofurantoin (Macrobid, Macrodantin), Trimethoprim-Sulfamethoxazole (Bactrim), and Fosfomycin.
What is the mechanism of action of nitrofurantoin?
Inhibits bacterial DNA and RNA synthesis by interfering with bacterial ribosomal proteins and enzymes.
What is the antimicrobial spectrum of nitrofurantoin?
Active against E. coli, Klebsiella spp., Enterococcus spp., Staphylococcus spp. Not effective against Proteus spp. or Pseudomonas aeruginosa.
Why should renal function be evaluated before nitrofurantoin use?
Nitrofurantoin requires renal excretion to reach therapeutic levels in urine. Poor renal function (GFR < 35 mL/min) can lead to inadequate levels and increased systemic toxicity.
What are the side effects of nitrofurantoin?
GI upset, pulmonary toxicity (acute pneumonitis, chronic fibrosis), peripheral neuropathy, autoimmune hepatitis (rare).
Is nitrofurantoin safe for use in children and pregnancy?
Safe in children >1 month. Generally safe in pregnancy except in the first trimester (birth defect risk) and near term (hemolytic anemia risk).
What are fungi and their characteristics?
Eukaryotic organisms with chitin-containing cell walls and ergosterol in their cell membranes. Includes yeasts, molds, and mushrooms.
What is the difference between systemic and superficial mycoses?
Superficial mycoses affect skin, nails, and mucosa (e.g., candidiasis, tinea infections). Systemic mycoses affect internal organs and deep tissues (e.g., cryptococcal meningitis, histoplasmosis).
What is the difference between opportunistic and non-opportunistic fungal pathogens?
Opportunistic fungi infect immunocompromised hosts (e.g., Candida, Aspergillus). Non-opportunistic fungi infect healthy individuals (e.g., Histoplasma, Coccidioides).
What are polyenes and their mechanism of action?
Polyenes (e.g., Amphotericin B, Nystatin) bind to ergosterol in fungal membranes, forming pores that cause cell leakage and death.
What are imidazoles and their mechanism of action?
Imidazoles (e.g., Ketoconazole, Clotrimazole) inhibit 14-alpha-demethylase, blocking ergosterol synthesis and disrupting fungal membrane function.
What are common side effects of azoles?
Hepatotoxicity, QT prolongation, CYP450 inhibition leading to drug interactions.
What is the structure of a virus?
Contains genetic material (DNA or RNA), a protein capsid, an optional lipid envelope, and surface proteins for host attachment.
What is the mechanism of action of acyclovir and valacyclovir?
They are guanosine analogs phosphorylated by viral thymidine kinase, inhibiting viral DNA polymerase and causing chain termination.
What are the side effects of acyclovir?
GI upset, nephrotoxicity (especially IV formulation), headache, dizziness.
What drugs are used to treat influenza?
Neuraminidase inhibitors (Oseltamivir, Zanamivir), Adamantanes (Amantadine, Rimantadine - not recommended due to resistance).
What are the drug interactions of fluoroquinolones?
Inhibit CYP450 (increase warfarin, theophylline, caffeine levels). Absorption reduced by antacids, sucralfate, zinc, and iron supplements.
Why is ganciclovir the drug of choice for CMV?
Inhibits viral DNA polymerase, but causes severe neutropenia and is teratogenic (Black Box Warning: avoid in pregnancy).
What are the mechanisms of bacterial resistance?
Modification of target sites (MRSA), efflux pumps (tetracyclines), enzymatic inactivation (beta-lactamases).
What is the difference between empiric, therapeutic, and prophylactic antibiotic therapy?
Empiric: broad-spectrum, before culture results. Therapeutic: directed at identified pathogen. Prophylactic: prevents infection in high-risk patients.
What is the role of MIC in antibiotic selection?
MIC (Minimum Inhibitory Concentration) is the lowest antibiotic concentration that prevents bacterial growth, guiding dosage selection.
What is the post-antibiotic effect (PAE)?
Persistent bacterial suppression even after antibiotic levels drop below MIC. Seen in aminoglycosides and fluoroquinolones, allowing once-daily dosing.
What is the mechanism of macrolides?
Macrolides bind irreversibly to the 50S ribosomal subunit, inhibiting translocation in bacterial protein synthesis.
Are macrolides bactericidal or bacteriostatic?
Macrolides are bacteriostatic but can be bactericidal at higher doses.
What is the spectrum of activity of macrolides?
Gram-positive (Streptococcus, Staphylococcus), Gram-negative (H. influenzae, M. catarrhalis), Atypicals (Mycoplasma, Chlamydia, Legionella).
What are the most common side effects of macrolides?
GI distress, cholestatic jaundice, ototoxicity, QTc prolongation, liver toxicity.
How do erythromycin & clarithromycin affect other drugs via the P450 system?
Inhibit CYP3A4, increasing levels of statins, warfarin, theophylline, sildenafil.
What is the role of fidaxomicin (Dificid)?
Macrocyclic antibiotic for C. difficile; narrow spectrum, minimal systemic absorption, lower recurrence than vancomycin.
What is the spectrum of activity of clindamycin?
Gram-positive aerobes (Staph, Strep, MRSA), anaerobes (Bacteroides, C. perfringens).
What is clindamycin most commonly used for?
Skin/soft tissue infections, anaerobic infections, dental infections, osteomyelitis.
What is the most serious side effect of clindamycin and how is it treated?
Pseudomembranous colitis from C. difficile. Treat with oral vancomycin or metronidazole.
What are potential drug interactions with clindamycin?
Neuromuscular blockers (enhanced blockade), macrolides (antagonism), CYP3A4 interactions.
Why is the oxazolidinones class important in infection treatment?
Effective against drug-resistant Gram-positives: MRSA, VRE, penicillin-resistant Strep.
What is the spectrum of activity of linezolid?
Gram-positive bacteria including MRSA, VRE, Streptococci, Corynebacterium, Listeria.
What lab work should be done weekly for linezolid?
Monitor CBC weekly due to risk of thrombocytopenia, neuropathy, optic neuritis.
What drug interactions should be monitored with linezolid?
Linezolid is a weak MAO inhibitor; risk of serotonin syndrome with SSRIs, MAOIs, tyramine-rich foods.
What is Synercid’s (quinupristin/dalfopristin) spectrum of activity?
Active against VRE (except E. faecalis), MRSA, penicillin-resistant S. pneumoniae.
What is the major side effect of Synercid and how does it impact drug interactions?
Venous irritation, hyperbilirubinemia, arthralgia. Inhibits CYP3A4, increasing drug toxicity.
What is the antimicrobial mechanism of sulfonamides and trimethoprim?
Sulfonamides inhibit dihydropteroate synthetase; trimethoprim inhibits dihydrofolate reductase, blocking folate synthesis.
What are the primary uses of sulfonamides and trimethoprim?
TMP-SMX for UTIs, PCP, toxoplasmosis, Listeria, MRSA.
What serious disorders are linked to sulfonamides?
Stevens-Johnson Syndrome, hemolytic anemia (G6PD deficiency), kernicterus in neonates.
How does sulfonamide-induced crystalluria occur and how can it be prevented?
Acetylated metabolites precipitate in acidic urine. Prevent with hydration and urine alkalinization.
What is the mechanism of fluoroquinolones and their spectrum of activity?
Inhibit DNA gyrase (Gram-negative) and topoisomerase IV (Gram-positive).
What are the major adverse effects of fluoroquinolones?
Tendinitis, QTc prolongation, CNS toxicity, peripheral neuropathy, arthropathy.
What drug interactions are significant with fluoroquinolones?
CYP1A2/3A4 inhibition increases warfarin, theophylline, caffeine levels. Antacids reduce absorption.
What is the spectrum of activity and therapeutic use of daptomycin?
Gram-positive spectrum: MRSA, VRE, Streptococcus. Used for cSSSIs, bacteremia, right-sided endocarditis.
What are the major side effects and renal requirements for daptomycin?
Myopathy, rhabdomyolysis, eosinophilic pneumonia. Requires renal dose adjustment.
What lab monitoring is required for daptomycin?
Monitor creatine phosphokinase (CPK), renal function, WBC count.
What is the difference between microbial colonization and infection?
Colonization is the presence of bacteria without causing disease, whereas infection involves bacterial invasion and an immune response.
What are the key diagnostic methods for identifying an infection?
Patient history, physical examination, elevated WBC count, inflammatory markers, and culture growth.
What are common causes of antimicrobial treatment failure?
Incorrect antibiotic selection, poor drug penetration, noncompliance, inadequate dosing.
What are less common causes of antimicrobial treatment failure?
Immunosuppression, superinfections, biofilms, drug interactions.
What are the major mechanisms of action of antibiotics?
Cell wall inhibitors, protein synthesis inhibitors, nucleic acid synthesis inhibitors, folate metabolism inhibitors, membrane disruptors.
What are best practices for preventing antimicrobial resistance?
Use narrow-spectrum antibiotics, avoid unnecessary prescriptions, hand hygiene, patient education.
What is the mechanism of action and spectrum of natural penicillins?
Inhibits bacterial cell wall synthesis. Covers Gram-positive bacteria, some Gram-negatives, anaerobes, and spirochetes.
What is the mechanism of action and spectrum of extended-spectrum penicillins?
Similar to natural penicillins but with expanded Gram-negative coverage, including Haemophilus influenzae and E. coli.
What are the characteristics of first-generation cephalosporins?
Good for Gram-positive cocci (MSSA, Streptococci), used in surgical prophylaxis.
What are the characteristics of second-generation cephalosporins?
Better Gram-negative coverage, used for respiratory infections.
What are the characteristics of third-generation cephalosporins?
Excellent Gram-negative coverage, some cross the blood-brain barrier.
What are the characteristics of fourth- and fifth-generation cephalosporins?
Broad spectrum including Pseudomonas (fourth-gen), MRSA coverage (fifth-gen).
What are the indications and toxicities of aminoglycosides?
Used for severe Gram-negative infections; nephrotoxicity, ototoxicity.
What are the indications and toxicities of macrolides?
Used for respiratory infections, atypicals; GI disturbances, QT prolongation.
What are the indications and toxicities of sulfonamides?
Used for UTIs, pneumocystis pneumonia; hypersensitivity reactions, crystalluria.
What is the mechanism of action of quinolones?
Inhibits DNA gyrase and topoisomerase IV, broad Gram-negative activity.
What is the mechanism of action of tetracyclines?
Binds to 30S ribosomal subunit, inhibiting protein synthesis.
How do penicillins and cephalosporins inhibit bacterial cell wall synthesis?
Bind to PBPs, preventing peptidoglycan cross-linking, leading to bacterial lysis.
Which beta-lactams can penetrate Gram-negative bacteria?
Aminopenicillins (ampicillin, amoxicillin) and extended-spectrum cephalosporins (ceftriaxone, ceftazidime, cefepime).
What are the four main classes of penicillins and their coverage?
Penicillin G (narrow, sensitive), Nafcillin (staph coverage), Aminopenicillins (broader Gram-negative), Piperacillin (Pseudomonas).
What are the four generations of cephalosporins and their characteristics?
First-gen (Gram-positive), second-gen (more Gram-negative), third-gen (broad Gram-negative), fourth-gen (Pseudomonas), fifth-gen (MRSA).
Why are beta-lactams vulnerable to beta-lactamase inactivation?
Beta-lactamases hydrolyze the beta-lactam ring, inactivating the drug.
What are the major allergic reactions associated with penicillins and cephalosporins?
Immediate (anaphylaxis), accelerated (urticaria), delayed (maculopapular rash).
What is the role of beta-lactamase inhibitors?
Beta-lactamase inhibitors bind to and inactivate beta-lactamases, preserving antibiotic activity.
Why are IV penicillins often used with aminoglycosides?
Beta-lactams weaken the cell wall, enhancing aminoglycoside penetration.
What are common resistance mechanisms to penicillins and cephalosporins?
Beta-lactamase production, porin mutations, altered PBPs.
What are common drug interactions with penicillins and cephalosporins?
Probenecid inhibits excretion, warfarin enhances anticoagulation, aminoglycosides increase nephrotoxicity.
What is the spectrum and indications of carbapenems?
Broad spectrum, covering Gram-positive, Gram-negative, and anaerobes. Used for multi-drug resistant infections.
What is the spectrum and indications of monobactam (Aztreonam)?
Effective against Gram-negative aerobes, safe for penicillin-allergic patients.
When is vancomycin the drug of choice?
DOC for MRSA, C. difficile (oral form), severe beta-lactam-allergic infections.
How does vancomycin treat C. difficile infections?
Oral vancomycin is used because it remains in the gut and is not systemically absorbed.
What are the most serious side effects of vancomycin?
Nephrotoxicity, ototoxicity, Red-Man Syndrome.
Why is therapeutic drug monitoring necessary for vancomycin?
Trough levels are critical for efficacy and preventing toxicity.
What is the difference between vancomycin and telavancin?
Telavancin is more potent, disrupts membrane potential, but causes more nephrotoxicity and QT prolongation.
What is the mechanism of action and clinical uses of tetracyclines?
Binds 30S ribosomal subunit, inhibiting protein synthesis; used for acne, MRSA, atypicals.
What are common adverse effects of tetracyclines?
Photosensitivity, esophagitis, hepatotoxicity, tooth discoloration in children.
How do macrolides interact with CYP450 enzymes?
Inhibit CYP450, increasing levels of warfarin, statins, theophylline.
What is the spectrum and clinical use of linezolid?
Covers Gram-positive bacteria including MRSA and VRE.
What are key drug interactions of linezolid?
Risk of serotonin syndrome with SSRIs, hypertensive crisis with sympathomimetics.
What is the mechanism of action of azole antifungals?
Inhibit ergosterol synthesis, disrupting fungal cell membranes.
What is the mechanism of action of neuraminidase inhibitors for influenza?
Block neuraminidase, preventing viral release.
What is the role of ganciclovir in CMV infections?
Used for CMV infections, but causes bone marrow suppression.
