Aminoglycosides Antibiotics

• Protein synthesis inhibitors are antibiotics

Aminoglycosides

• Specific antibiotics include gentamycin, amikacin, tobramycin, neomycin, and streptomycin
• Mechanism: blocks translocation of peptide chain, causes mRNA misreading, leading to cell death
• Aminoglycosides bind to the 30S at the start codon (AUG) of mRNA causing the ribosome to incorrectly assemble
• Premature termination of translation can occur and abnormal ribosomal complexes known as streptomycin monosomes form
• The mistranslated proteins are nonfunctional or abnormal, which can disrupt various cellular processes
• Bactericidal, but concentration-dependent
• Special uses: Often used with penicillins to enhance penetration of aminoglycosides
• Tobramycin inhalation is indicated for cystic fibrosis patients who acquire pseudomonas
• Tobramycin and gentamicin peak levels are 4 - 10 mcg/mL
• Troughs level are 0.5 - 2 mcg/mL for serious infections
• Spectrum of activity: primarily gram negative (BLP E. coli, kleb. pneumoniae, H. influenzae, SPACE, ESBL, CRE, and pseudomonas)
• Synergistic activity against staphylococcus, streptococcus, or enterococcus with vancomycin and penicillin
• Resistance occurs through methylation of ribosome binding site and decreased permeation to target due to active efflux
• Side effects: nephrotoxicity (especially with cyclosporine, cisplatin, NSAIDs, and vancomycin), ototoxicity (with diuretics), neuromuscular blockade (contraindicated with myasthenia gravis), teratogenicity
• Mechanism: Bind to 30S ribosomal subunit

Tetracyclines

• Specific antibiotics: doxycycline, tetracycline, minocycline, demeclocycline
• Mechanism: inhibits peptide elongation by blocking the tRNA from binding to the A site, thereby inhibiting protein synthesis (bacteriostatic)
• Spectrum of activity: gram positives (especially streptococcus and MSSA), gram negatives (like H. influenzae), atypical organisms (chlamydia pneumoniae, Legionella, and Mycoplasma pneumoniae)
• Doxycycline is effective against community-acquired MRSA and is the drug of choice for Lyme disease
• Demecycline is used to treat Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
• Tetracycline can be used in four-drug regiment for H. pylori
• Effective against Rickettsia
• Contraindications: children under 8 years old and pregnant/breast-feeding women due to permanent teeth discoloration and impaired bone/teeth growth.
• Use after expiration date can cause Fanconi syndrome
• Adjust dose for all, except doxycycline, in renal impairment
• Resistance occurs through active drug efflux/decreased uptake
• Side effects: photosensitivity, intracranial hypertension (pseudotumor cerebri), hepatitis, pill esophagitis, gray teeth, and inhibition of bone growth in fetus
• Interactions: absorption decreases with antacids, dairy products containing iron, magnesium, aluminum, calcium, or zinc
• May increase risk of bleeding when taken with warfarin
• Mechanism: Bind to 30S ribosomal subunit

Macrolides

• Specific antibiotics: erythromycin, clarithromycin, and azithromycin
• Mechanism: blocks peptide chain exit by inhibiting the translocation step so that the nascent peptide chain temporarily residing at the A site fails to move to the P, or donor, site (bacteriostatic)
• Spectrum of activity: gram positives (streptococcus and MSSA), atypical organisms (chlamydia pneumoniae, Legionella, and Mycoplasma pneumoniae).
• Azithromycin and clarithromycin are active against mycobacteria
• Effective against bordetella pertussis
• Special uses: azithromycin and clarithromycin are good alternatives for patients allergic to penicillin
• Azithromycin or erythromycin preferred in pregnancy
• Erythromycin can be used to treat diabetic gastroparesis
• Resistance occurs through methylation of the 23S rRNA-binding site, preventing the binding of the drug
• Side effects: hypersensitivity rxns (nausea, vomiting, diarrhea), prolonged QT intervals and increased risk of torsade de pointes with other drugs that prolong QT intervals, gastrointestinal motility issues, acute cholestatic hepatitis, eosinophilia, and increased levels of many drugs (cytochrome P450 metabolism inhibitor through clarithryomycin and erythromycin)
• Increased risk of bleeding with warfarin and may increase risk of digoxin toxicity
• Mechanism: Bind to 50S ribosomal subunit

Lincosamides

• Specific antibiotics: clindamycin
• Mechanism: blocks peptide bond formation (bacteriostatic)
• Spectrum of activity: community-acquired MRSA, staph epi (coag -), streptococcus pneumoniae, anaerobic infections (bacteroides species, clostridium perfringes)
• Treats anaerobic infections above the diaphragm versus metronidazole which treats anaerobic infections below the diaphragm.
• Resistance occurs through methylation at ribosome binding site
• Side effects: diarrhea, including clostridium difficile colitis (psuedomembranous colitis, highest incidence)
• Mechanism: Bind to 50S ribosomal subunit

Streptogramins

• Specific antibiotics: quinupristin-dalfopristin
• Mechanism: block peptide chain exit (usually bacteriostatic but bactericidal when used in combination with other drugs)
• Spectrum of activity: gram positive organs (vancomycin-resistant enterococcus faecium [VRE], MSSA, MRSA, staphylococcus epi/coag negative, resistant streptococcus pneumoniae)
• Indicated for SSTIs. Mostly used for VRE
• Side effects: arthralgias/myalgias and increase in bilirubin levels
• Resistance occurs through methylation at ribosome binding site
• Mechanism: Bind to 50S ribosomal subunit

Oxazolidinones

• Specific antibiotics: linezolid and tedizolid
• Mechanism: inhibit the initiation of peptide synthesis (bacteriostatic)
• Side effects: myelosuppression (especially thrombocytopenia), peripheral and optic neuropathy (more common with more than 4 weeks of use, seizures, and serotonin syndrome inpatients also taking SSRIs and other medications that affect serotonin levels (partial monoamine oxidase inhibition).
• Have to monitor blood count with CBC weekly if in therapy for over two weeks
• Spectrum of activity: gram positive organs (vancomycin-resistant enterococcus faecium [VRE], MSSA, MRSA, staphylococcus epi/coag negative, resistant streptococcus pneumoniae)
• Contraindications: concurrent or recent within 2 weeks use of MAOI (weak MAOI), concurrent use of SSRI, TCAs, triptans, meperidine, or bisiprone
• Resistance occurs through methylation at ribosome binding site

Chloramphenicol

• Specific antibiotics: chloramphenicol
• Mechanism: inhibits ribosomal transpeptidation (ribosomal peptidyl transferase, bacteriostatic)
• Spectrum of activity: meningitis (H. influenzae, neisseria meningitidis, and streptococcus pneumoniae), beta-lactam producing E. coli, Kleb. pneumoniae, and H. influenzae, anaerobes (bacteroides), Rickettsia rickettsii (AKA rocky mountain spotted fever)
• Only used for life-threatening infections due to toxicity
• Contraindications: neonates due to increased risk of gray baby syndrome
• Resistance occurs through plasmid-encoded acetyltransferase inactivates the drug
• Side effects: anemia (dose-dependent), aplastic anemia (dose-independent), gray baby syndrome (in premature infants because they lack liver UDP-glucuronosyltransferase, causes vomiting, lethargy, respiratory depression, and death)

Mupirocin

• Specific antibiotics: mupirocin
• Mechanism: reversibly binds to isoleucyl-tRNA synthetase, inhibiting protein synthesis (monoxycarbolic acid)
• Spectrum of activity: staphylococci (including methicillin-resistant strains), beta-hemolytic streptococci, and streptococcus pyogenes
• Indicated for tropical bacterial infections (e.g., impetigo) caused by gram positive bacteria (like staphylococcus aureus or staphylococcus pyogenes)
• Acts on gram positive cocci
• Side effects: superinfection with prolonged inappropriate use
• Blocks isoleucyl tRNA synthetase

Glycylcyclines

• Specific antibiotics: tigecycline (structurally similar to tetracyclines)
• Mechanism: binds to the 30S of the ribosome and inhibits translation (bacteriostatic)
• Spectrum of activity: gram positives (MSSA, MRSA, vancomycin-resistant enterococcus faecalis [VRE], and most other gram positives), gram negatives (E. coli, enterobacter, H. infleunzae, klebsiella + BLP), anaerobics, SPACE, ESBL, CRE
• NO ACTIVITY against the three P’s: pseudomonas, proteus, and providencia
• Indicated for complicated SSTIs, complicated intra-abdominal infections, and community-acquired pneumonia
• Contraindications: children under 8 years old and pregnant/breast-feeding women due to permanent teeth discoloration and impaired bone/teeth growth
• DO NOT USE for bloodstream infections (such as sepsis) as it does not achieve sufficient blood levels, as it is very lipophilic