Cephalosporins and Antibiotics Overview

Cephalosporins (5th Generation)

• Inhibit bacterial cell wall synthesis, more resistant to penicillinases than earlier generations.
• Bactericidal effect, effective against broad gram-positive and gram-negative organisms.
• Treats infections caused by Listeria, atypical pathogens (Chlamydia, Mycoplasma), MRSA, and Enterococcus faecalis; does not cover Pseudomonas.
• Side effects include hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reactions, and vitamin K deficiency.
• Low cross-reactivity risk for penicillin-allergic patients; potential nephrotoxicity if used with aminoglycosides.

β-lactamase Inhibitors

• Added to penicillin antibiotics to prevent destruction by β-lactamase enzymes produced by some bacteria.
• Help maintain antibiotic efficacy against target bacteria by inhibiting the enzymes that render them ineffective.
• Examples include Clavulanic acid, Avibactam, Sulbactam, and Tazobactam.

Carbapenems

• Broad-spectrum antibiotics, resistant to β-lactamase.
• Binds to penicillin-binding proteins (PBPs) to inhibit bacterial cell wall synthesis.
• Always given with cilastatin to prevent renal inactivation of the drug.
• Effective against gram-positive cocci, gram-negative rods, and anaerobes; used for life-threatening infections when other options fail.
• Risks include significant adverse effects limiting their use.

Aminoglycosides

• Bactericidal antibiotics that irreversibly inhibit protein synthesis by binding to the 30S subunit.
• Mechanism includes misreading of mRNA and blocking translocation; effectiveness requires oxygen, thus not effective against anaerobes.
• Common usage for severe gram-negative rod infections and synergistic with β-lactam antibiotics.
• Notable examples include Gentamicin, Neomycin, Amikacin, Tobramycin, and Streptomycin.
• Side effects involve nephrotoxicity, ototoxicity (especially with loop diuretics), and neuromuscular blockade (caution in myasthenia gravis).

Tetracyclines

• Bacteriostatic antibiotics that prevent aminoacyl-tRNA attachment to the 30S ribosomal subunit.
• Limited penetration to the CNS; Doxycycline can be used in renal failure due to fecal elimination.
• Interaction with divalent cations (Ca²⁺, Mg²⁺) can hinder absorption in the gut.
• Effective against Borrelia burgdorferi, Mycoplasma, Rickettsia, and Chlamydia; also used for acne treatment.
• Side effects include GI distress, teeth discoloration in children, photosensitivity, and teratogenic effects.

Tigecycline

• Tetracycline derivative; bacteriostatic with broad-spectrum activity against anaerobic, gram-negative, and gram-positive bacteria, including multidrug-resistant organisms (MRSA, VRE).
• Side effects include nausea and vomiting.

Chloramphenicol

• Blocks peptidyltransferase at the 50S ribosomal subunit, acting bacteriostatically.
• Suggested uses include meningitis from Haemophilus influenzae, Neisseria meningitidis, and Rickettsial infections.
• Limited use in developed countries due to toxicity; notable side effects include dose-dependent anemia, dose-independent aplastic anemia, and gray baby syndrome in premature infants.

Clindamycin

• Bacteriostatic antibiotic that blocks peptide transfer at the 50S subunit.
• Effective for anaerobic infections (Bacteroides spp., Clostridium perfringens) particularly in aspiration pneumonia and lung abscesses; also treats invasive group A streptococcal infections.
• Side effects include pseudomembranous colitis (due to C. difficile overgrowth), fever, and diarrhea.

Linezolid

• Inhibits protein synthesis via binding to the 23S rRNA of the 50S subunit.
• Effective against gram-positive species, including MRSA and VRE.
• Side effects include myelosuppression (thrombocytopenia), peripheral neuropathy, and risk of serotonin syndrome.

Macrolides

• Bacteriostatic antibiotics that inhibit protein synthesis by blocking translocation on the 50S subunit.
• Mechanism of resistance includes methylation of the 23S rRNA-binding site to prevent drug binding.
• Effective against atypical pneumonia pathogens (Mycoplasma, Chlamydia, Legionella) and for treating STIs (Chlamydia).
• Side effects involve potential hemolysis in G6PD deficiency, methemoglobinemia, and agranulocytosis.

Trimethoprim

• Inhibits dihydropteroate synthase, disrupting folate synthesis and bacterial replication; bactericidal when combined with sulfonamides.
• Commonly used for urinary tract infections, Shigella, Salmonella infections, and Pneumocystis jirovecii prophylaxis.
• Side effects include hyperkalemia, megaloblastic anemia, leukopenia, and granulocytopenia.

Fluoroquinolones

• Bactericidal agents that inhibit topoisomerase II (DNA gyrase) and topoisomerase IV, critical for DNA replication.
• Oral absorption significantly reduced with concurrent use of divalent cations (e.g., dairy, antacids).
• Used for ear infections and a variety of gram-positive and gram-negative infections, including Pseudomonas aeruginosa.
• Side effects include GI upset, superinfections, skin rashes, tendonitis, or tendon rupture risks, and potential QT interval prolongation.

Rifamycin

• Inhibits DNA-dependent RNA polymerase, blocking mRNA synthesis.
• Resistance arises from mutations in the RNA polymerase gene.
• Rifabutin preferred in HIV patients due to less CYP450 induction.
• Uses include tuberculosis while noting minor hepatotoxicity and reddish discoloration of body fluids as a benign side effect.

Isoniazid

• Inhibits mycolic acid synthesis vital for mycobacterial cell walls.
• Requires conversion by the catalase-peroxidase enzyme for activation; resistance often due to mutations in the katG gene.
• Given with vitamin B6 to prevent peripheral neuropathy; risks include hepatotoxicity and drug interactions.

Pyrazinamide

• Works best at acidic pH; mechanism of action remains uncertain.
• Used primarily for tuberculosis treatment, with risks of hepatotoxicity and hyperuricemia.

Ethambutol

• Inhibits arabinosyltransferase leading to decreased cell wall synthesis.
• Used in tuberculosis treatment, associated side effects include optic neuropathy, leading to red-green color blindness.

Cephalosporins (5th Generation)

• β-lactam antibiotics that inhibit cell wall synthesis, more resistant to penicillinases.
• Mechanism: Bactericidal, primarily targeting penicillin-binding proteins.
• Broad coverage against gram-positive and gram-negative organisms, including Listeria and MRSA, but not Pseudomonas.
• Side effects: Hypersensitivity reactions, nephrotoxicity (with aminoglycosides), autoimmune hemolytic anemia, and vitamin K deficiency.

β-lactamase Inhibitors

• Protect β-lactam antibiotics from being inactivated by β-lactamases.
• Include agents such as clavulanic acid and tazobactam.
• Important for preserving the effectiveness of penicillins and cephalosporins against resistant bacteria.

Carbapenems

• Broad-spectrum antibiotics that are resistant to β-lactamases; bind to penicillin-binding proteins.
• Administered alongside cilastatin to prevent renal inactivation.
• Used for serious infections caused by gram-positive cocci, gram-negative rods, and anaerobes.
• Side effects: Nephrotoxicity, potential for seizures with imipenem.

Aminoglycosides

• Bactericidal drugs that irreversibly bind to the 30S ribosomal subunit, causing misreading of mRNA.
• Require oxygen for uptake; ineffective against anaerobes.
• Commonly used for severe gram-negative infections and synergistic with β-lactam antibiotics.
• Side effects: Nephrotoxicity, ototoxicity, and neuromuscular blockade.

Tetracyclines

• Bacteriostatic agents that bind to the 30S ribosomal subunit, preventing tRNA attachment.
• Effective against a variety of bacteria including Borrelia and Mycoplasma.
• Doxycycline is suitable for patients with renal failure and has fecal elimination.
• Side effects include gastrointestinal distress, photosensitivity, and potential effects on bone growth in children.

Tigecycline

• A derivative of tetracyclines with broad-spectrum activity against gram-positive, gram-negative, and anaerobic bacteria.
• Generally bacteriostatic; used against multidrug-resistant organisms.
• Side effects primarily include nausea and vomiting.

Chloramphenicol

• Inhibits bacterial protein synthesis by blocking peptidyltransferase at the 50S ribosomal subunit.
• Used for meningitis and rickettsial diseases despite toxicity.
• Side effects: Anemia, aplastic anemia, and gray baby syndrome in neonates.

Clindamycin

• Blocks peptide transfer at the 50S ribosomal subunit, rendering it bacteriostatic.
• Effective for anaerobic infections and invasive streptococcal infections.
• Side effects can include pseudomembranous colitis due to C. difficile overgrowth.

Linezolid

• Binds to the 50S ribosomal subunit, inhibiting protein synthesis.
• Effective against gram-positive species including MRSA and VRE.
• Side effects: Myelosuppression, peripheral neuropathy, and risk of serotonin syndrome.

Macrolides

• Inhibit protein synthesis by blocking translocation at the 50S ribosomal subunit.
• Treat atypical pneumonias and some gram-positive cocci infections.
• Side effects: Gastrointestinal motility issues and interactions with cytochrome P-450 substrates.

Polymyxins

• Disrupt the cell membrane integrity of gram-negative bacteria by binding to phospholipids.
• Used for multidrug-resistant infections and included in topical preparations.
• Side effects: Nephrotoxicity and neurotoxicity.

Sulfonamides

• Inhibit dihydropteroate synthase, leading to impaired folate synthesis and bacteriostatic action.
• Effective against a variety of gram-positive and gram-negative bacteria.
• Side effects include hypersensitivity reactions, hemolysis in G6PD deficiency, and potential for Stevens-Johnson syndrome.

Dapsone

• Functions similarly to sulfonamides but is a structurally distinct agent.
• Inhibits dihydropteroate synthase, leading to inhibition of bacterial replication.

Antimicrobial Prophylaxis

• Meningococcal exposure: Ceftriaxone, Ciprofloxacin, Rifampin.
• Infective endocarditis: Amoxicillin for at-risk patients.
• Recurrent UTIs: TMP-SMX.
• Malaria prophylaxis: Atovaquone-proguanil, Doxycycline among others.
• Group B strep in pregnancy: Intrapartum penicillin G or ampicillin.
• Gonococcal conjunctivitis prevention: Erythromycin ointment for newborns.
• Prevent postsurgical S. aureus infections: Cefazolin, possibly vancomycin if MRSA positive.
• Strep pharyngitis prophylaxis: Benzathine penicillin G or oral penicillin V.