PCOL - Antibiotics

• Antibiotics are substances produced by microorganisms that have the capacity to inhibit or destroy other microorganisms
• All antibiotics are antibacterial, but not all antibacterial substances are antibiotics
• Antibiotics can be obtained from microbial sources or prepared synthetically
• According to spectrum of activity, antibiotics can be classified as:

  • Broad Spectrum: drugs that have a wide antimicrobial scope and can antagonize the growth or kill numerous pathogens
  • Narrow Spectrum: drugs that only act on one kind or one strain of bacteria
• According to action, antibiotics can be categorized as:

  • Bactericidal: drugs that kill bacteria at drug serum levels achievable in the patient
  • Bacteriostatic: drugs that arrest the growth and replication of bacteria at serum urine levels achievable in the patient
• The Chemotherapeutic Index (CI) is the ratio of median lethal dose (LD50) to median effective dose (ED50) of infective animals
• Minimal inhibitory concentration (MIC) is the minimum amount of a drug required to inhibit the growth of bacteria in vitro
• Minimal bactericidal concentration (MBC) is the minimum amount of a drug required to kill bacteria in vitro
• Antimicrobial resistance occurs when the effectiveness of antibiotics decreases due to the development or mutation of bacteria
• Cross resistance happens when bacteria show resistance to one drug and are also resistant to other drugs
• Antibiotics follow the principle of selective toxicity, targeting sites specific to the microorganism responsible for infection
• Cell wall synthesis inhibitors, such as beta-lactams, glycopeptides, and bacitracin, act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls
• Beta-lactam antibiotics have a beta-lactam ring in their structure, which inhibits cell wall synthesis by binding to penicillin-binding proteins (PBPs)

  
• Penicillins are derived from 6-aminopenicillanic acid and have a thiazolidine ring connected to a beta-lactam ring
• Natural penicillins like Pen G and Pen V are highly active against gram-positive cocci, gram-negative cocci, and non-beta-lactamase producing anaerobes
• Penicillins are lipophilic and highly protein-bound, with the acylamino side chain responsible for protein binding
• The four main types of beta-lactam antibiotics are penicillins, cephalosporins, carbapenems, and monobactams

  
• Antibiotics targeting bacterial ribosome subunits:

  • 30S subunit targeted by tetracyclines and aminoglycosides
  • 50S subunit targeted by macrolides, clindamycin, linezolid, chloramphenicol, and streptogramins

  
• Clindamycin, an antibiotic, is used to treat bacterial infections and prevent infections in high-risk individuals

  
• Penicillin G is usually combined with procaine (a local anesthetic) to prevent pain during injection
• Penicillin G is the drug of choice for streptococci, meningococci, enterococci, non-β lactamase producing staphylococci, and Treponema pallidum
• Ampicillin and amoxicillin are the most commonly associated with drug-induced rash and diarrhea
• Ampicillin is equivalent in activity to Penicillin G and is widely used for out-patients for uncomplicated community-acquired UTI
• Amoxicillin has better oral absorption due to being more acidic, leading to enhanced blood levels and less gastrointestinal disturbance
• Aminopenicillins like ampicillin and amoxicillin are orally active and have a broader spectrum than penicillin G, but are quite susceptible to beta lactamase
• Antipseudomonal penicillins, like carbenicillin and ticarcillin, are effective against Pseudomonas, Enterobacter, Proteus sp., Klebsiella sp., and other gram-negative microorganisms
• Beta-lactamase inhibitors are used to produce synergistic activity against resistant strains by inhibiting the enzymes that inactivate or hydrolyze the lactam ring
• Cephalosporins are derivatives of 7-amino-cephalosporanic acid and are closely related in structure to penicillin, isolated from Cephalosporium sp.
• Cephalosporins inhibit bacterial cell wall synthesis, reducing cell wall stability and causing membrane lysis

  
• Cephalosporins are considered broad-spectrum antibiotics
• Cephalosporins exhibit uniquely potent activity against most species of Klebsiella pneumoniae
• The activity of cephalosporins against gram-negative bacteria increases as the generation increases
• First-generation cephalosporins include Cefalexin, Cefadroxil, and Cefazolin
• Second-generation cephalosporins include Cefuroxime, Cefaclor, and Cefoxitin
• Third-generation cephalosporins include Cefotaxime, Ceftriaxone, and Ceftazidime
• Fourth-generation cephalosporins include Cefepime and Cefpirome
• Cephalosporins are resistant to beta-lactamase, with Cephalothin and Cefoxitin being the most resistant
• Cephalosporins can be hydrolyzed by beta-lactamases, with some being more efficient at hydrolyzing cephalosporins than penicillin itself
• Allergic reactions are less common in cephalosporins compared to penicillins, but cross-sensitivity with penicillin can occur
• Cephalosporins are taken orally, with Cephradine being the only cephalosporin derivative available in oral and parenteral preparations