Part 4 Carbapenems, Cephalosporins, Fluoroquinolones

Curbing Opponents: Understanding Carbapenems and Cephalosporins

Overview of Carbapenems

• Carbapenems are a new class of broad-spectrum antibiotics effective against both gram-positive and gram-negative bacteria, with meropenem being a notable example.

• The first drug discussed has limited use due to severe risks for potentially fatal gastrointestinal (GI) toxicity; it is bactericidal and treats serious infections.

• Indications for this antibiotic include serious infections in intra-abdominal, urinary tract, skin, joint, and gynecological areas.

• Contraindications include known allergies, seizure disorders, and caution during pregnancy; regular urine function tests are necessary.

• Pseudomembranous colitis is a significant concern associated with antibiotic therapy leading to severe diarrhea and dehydration.

Adverse Effects and Drug Interactions

• Antibiotics can disrupt normal intestinal flora leading to Clostridium difficile infections causing nausea and vomiting.

• CNS effects such as dizziness, headaches, altered mental states, and seizures have been reported when combined with other drugs.

• Probenecid should not be combined with meropenem due to the risk of toxic levels; alternative antibiotics may be needed if patients are on anticonvulsants like valproic acid.

Introduction to Cephalosporins

• Following carbapenems, cephalosporins were introduced; they share structural similarities with penicillin but differ in effectiveness across generations.

• First-generation cephalosporins are largely effective against gram-positive bacteria while second-generation shows reduced efficacy against them but remains potent against gram-negative bacteria.

Generational Differences in Cephalosporins

• Third-generation cephalosporins are effective against previously mentioned strains but weaker against gram-positive bacteria. Fourth generation is still developing with cephepene as an active drug.

• Notable examples include cefalexin (first), cefuroxime (second), ceftazidime (third), and cefepime (fourth).

Therapeutic Actions & Pharmacokinetics

• All cephalosporins exhibit bactericidal actions; their selection depends on the sensitivity of the involved organism determined through culture tests.

• Pharmacokinetics involve liver metabolism with excretion via urine; they cross the placenta and breast milk. Absorption varies by generation.

Indications and Cautions for Antibiotic Use

Key Considerations in Antibiotic Administration

• Known allergies to cephalosporins and penicillins should be assessed due to their similarities.

• Adverse effects on the gastrointestinal (GI) tract are common, including nausea, vomiting, diarrhea, and abdominal pain.

• Monitor for nephrotoxicity and superinfections; intravenous administration may lead to injection site reactions.

• Patients on oral anticoagulants face an increased risk of bleeding; monitor for signs like easy bruising.

• Educate patients to avoid alcohol for 72 hours post-antibiotic treatment to prevent disulfiram-like reactions.

Fluoroquinolones: Overview and Usage

Characteristics of Fluoroquinolone Antibiotics

• Ciprofloxacin is a widely used fluoroquinolone with broad-spectrum activity against gram-negative bacteria.

• Effective in treating urinary tract infections, respiratory infections, and even anthrax prevention.

• Pharmacokinetics include absorption from the GI tract, metabolism in the liver, and excretion via urine; crosses the placenta.

• Levofloxacin is preferred for severe infections when oral intake isn't possible; finafloxacin is used as otic drops for ear infections.

Safety Concerns with Fluoroquinolones

• Not recommended for patients under 18 years due to potential cartilage development issues.

• Common adverse effects include CNS symptoms like headache and dizziness, along with GI disturbances such as nausea and diarrhea.

Risks Associated with Fluoroquinolone Use

Potential Complications

• Increased risk of tendinitis and tendon rupture in patients over 60 or those on corticosteroids; instruct patients to report any pain or weakness.

• Drug interactions can decrease therapeutic effects when taken with iron salts or antacids; separate doses by at least four hours.