Beta-Lactams and Macrolides Antibiotics

• β-Lactam antibiotics inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), preventing transpeptidation.
• β-Lactams are bactericidal, except against enterococcus.
• Efficacy of β-lactams depends on the duration of time that the drug concentration remains above the minimum inhibitory concentration (MIC).
• β-Lactams are dosed frequently because they have a short half-life.
• Macrolides bind to the 50S ribosomal subunit, thus inhibiting protein synthesis.
• Azithromycin is the only macrolide that does not interact with CYP enzymes.
• Macrolides are commonly used for respiratory infections, STDs, Mycobacterium avium, and Bordetella infections.
• A major cardiac side effect of macrolides is QT prolongation.
• Erythromycin carries the highest risk of QT prolongation among macrolides.
• Allergic reactions to β-lactams include maculopapular rash, hives, and anaphylaxis.
• β-Lactams are associated with the highest incidence of anaphylaxis among antibiotic classes.
• The estimated cross-reactivity between penicillins and cephalosporins is 1-10%.
• Antimicrobial desensitization is a controlled process used to induce temporary tolerance in allergic patients.
• Benzodiazepines are the first-line treatment for antibiotic-induced seizures.
• Carbapenems and especially imipenem, have the highest seizure risk among antibiotic classes.
• Antibiotics with the highest risk for QT prolongation include macrolides, fluoroquinolones, azole antifungals, and pentamidine.
• Risk factors for antibiotic-induced QT prolongation include female sex, electrolyte abnormalities, cardiac disease, and drug interactions.
• Antibiotics used for multidrug-resistant gram-positive infections include vancomycin, linezolid, daptomycin, and tigecycline.
• Antibiotics used for multidrug-resistant gram-negative infections include colistin, ceftolozane/tazobactam, and ceftazidime/avibactam.
• Vancomycin is primarily used to treat MRSA and serious gram-positive infections.
• Vancomycin inhibits cell wall synthesis by binding to D-Ala-D-Ala in peptidoglycan precursors.
• Vancomycin resistance in enterococci is mediated by the replacement of D-Ala-D-Ala with D-Ala-D-Lac.
• "Red Man Syndrome" involves histamine release that causes flushing and hypotension during rapid vancomycin infusion.
• Red Man Syndrome can be prevented by slowing vancomycin infusion and premedication with antihistamines.
• Major toxicities of vancomycin include nephrotoxicity and ototoxicity.
• Daptomycin disrupts bacterial cell membranes via depolarization.
• Daptomycin is not used for pneumonia because it is inactivated by pulmonary surfactant.
• The major toxicity associated with daptomycin is myopathy and rhabdomyolysis.
• Linezolid binds to the 50S ribosome, inhibiting protein synthesis.
• Linezolid is used for MRSA, VRE, and drug-resistant gram-positive infections.
• A major adverse effect of linezolid is bone marrow suppression, specifically thrombocytopenia.
• Linezolid is a weak MAOI that can increase the risk of serotonin syndrome.
• Tigecycline inhibits protein synthesis by binding to the 30S ribosome.
• Tigecycline is used for complicated skin, intra-abdominal infections, and multidrug-resistant bacterial infections.
• Major side effects of tigecycline include nausea, vomiting, and increased mortality in severe infections.
• Colistin is primarily used for multidrug-resistant gram-negative infections.
• The major toxicities of colistin are nephrotoxicity and neurotoxicity.
• Aminoglycosides bind to the 30S ribosome, inhibiting protein synthesis.
• Aminoglycosides primarily target gram-negative aerobic bacteria.
• Commonly used aminoglycosides include gentamicin, tobramycin, and amikacin.
• Major toxicities of aminoglycosides are nephrotoxicity and ototoxicity.
• Aminoglycosides are typically dosed using extended-interval dosing to optimize peak concentrations.
• Tetracyclines bind to the 30S ribosome, inhibiting protein synthesis.
• Tetracyclines are commonly used for atypical pneumonia, Lyme disease, acne, and MRSA infections.
• Divalent cations such as calcium, magnesium, and iron reduce the absorption of tetracyclines.
• A major side effect of tetracyclines in children is tooth discoloration.
• Demeclocycline, a tetracycline, is used for SIADH.
• Sulfonamides inhibit folic acid synthesis.
• Trimethoprim-sulfamethoxazole (TMP-SMX) is used for UTIs, Pneumocystis pneumonia, MRSA, and Nocardia infections.
• Major side effects of TMP-SMX include hyperkalemia, hemolysis in G6PD deficiency, and Stevens-Johnson syndrome.
• Metronidazole forms free radicals that damage bacterial DNA.
• Metronidazole is used for anaerobic infections, C. difficile, bacterial vaginosis, and trichomoniasis.
• A major side effect of metronidazole is a disulfiram-like reaction with alcohol.
• Rifampin inhibits RNA polymerase.
• Rifampin is a strong inducer of CYP450 enzymes reducing drug efficacy.
• A unique side effect of rifampin is red/orange discoloration of body fluids
• Clindamycin binds to the 50S ribosome, inhibiting protein synthesis.
• A major side effect of clindamycin is an increased risk of C. difficile infection.
• Clindamycin is commonly used for anaerobic infections, MRSA, and toxin suppression in necrotizing fasciitis.
• Fosfomycin inhibits bacterial cell wall synthesis by blocking the MurA enzyme.
• Fosfomycin is primarily used for uncomplicated urinary tract infections.
• Nitrofurantoin damages bacterial DNA.
• Nitrofurantoin is commonly used for uncomplicated lower UTIs.
• Nafcillin, oxacillin, ceftriaxone, and cefoperazone are β-lactam antibiotics that are NOT renally eliminated.
• The most common mechanism of resistance to β-lactams is β-lactamase production.
• The four mechanisms of β-lactam resistance are β-lactamase production, PBP modification, impaired penetration, and efflux pumps.
• β-Lactamase inhibitors help β-lactams by inhibiting β-lactamases that degrade β-lactam antibiotics.
• β-Lactam structure includes a fused thiazolidine and β-lactam ring ("house and garage").

Overview of beta-lactam and macrolide antibiotics, including mechanism of action focusing on inhibition of cell wall & protein synthesis. Explains efficacy, common uses for respiratory infections and STDs. Highlights side effects like allergic reactions and QT prolongation.