Beta-Lactam Antibiotics

• Beta-lactams, cephalosporins, carbapenems, and monobactams are types of antibiotics.

Beta - Lactams

• Penicillins are a subgroup that inhibit cell wall synthesis to kill bacteria.
• Older penicillins have a narrow spectrum, with Penicillin G & V as key examples.
• Aminopenicillins like Ampicillin and Amoxicillin target penicillin-binding proteins and have a broad spectrum of activity.
• Beta-lactamase-resistant antibiotics, such as Cloxacillin, are designed to overcome bacterial resistance.
• Some are poorly absorbed orally and are broken down by HCL, like Penicillin G, others like Penicillin V, Ampicillin, and Amoxicillin are well absorbed orally.
• Allergic reactions, GI and Blood disorders are adverse reactions.
• Bacteria produce beta-lactamases, decrease cell membrane penetration, resist the target, and use efflux pumps, all as mechanisms of resistance.
• Used for respiratory and GI infections, UTIs, soft tissue infections, mastitis, and endocarditis.
• Beta-lactamases are enzymes that deactivate the drug by hydrolyzing the beta-lactam ring.
• Beta-lactamase inhibitors like clavulanate and sulbactam are co-administered with beta-lactam antimicrobials to combat resistance.

Cephalosporins

• First-generation cephalosporins (Cephalexin, Cephadroxil, Cephapirin, Cefazolin) inhibit cell wall synthesis and are bactericidal with a wider spectrum.
• Active against gram-positive bacteria
• But also some gram - negative bacteria
• Unstable in gastric acid and need to be administered parenterally
• First and Second generation drugs are well absorbed orally
• They are distributed well in fluids and tissues, except for the cerebrospinal fluid (CSF).

Sulfonamides

• Sulfonamides and potentiated sulfonamides block folic acid synthesis, preventing DNA formation, and mainly administered orally
• Have a broad spectrum of activity, effective against Gram-positive and Gram-negative bacteria, as well as protozoa, and are widely distributed in tissues and fluids.
• Crystaluria (renal obstruction), keratoconjunctivitis sicca (in dogs), hepatic necrosis, blood clotting, and GI tract reactions are adverse side effects
• Overproduction of PABA, efflux pumps, decreased permeability, and changes in target enzyme are mechanisms of resistance for bacteria
• Used for UTIs, respiratory and GI infections, and skin and soft tissue infections.
• Potentiated Sulfonamides are combined with to treat coccidiosis and toxoplasmosis, frequently prescribed for dogs and cats.
• Teratogenic effects and transferable resistance are other considerations.

Quinolones

• Quinolones and Fluoroquinolones inhibit DNA replication
• First-generation quinolones like Nalidixic Acid target DNA gyrase, while second-generation drugs (Difloxacin, Enrofloxacin) also inhibit topoisomerase.
• They exhibit a narrow to broad spectrum of activity and are bactericidal.
• They display good oral absorption, administered once or twice per day, and accumulate in inflammatory cells
• Tendinopathy and retinal degeneration in cats are adverse reactions.
• Decreased permeability, increased efflux, altered target enzymes, and mutations are bacterial resistance mechanisms.
• Used for respiratory, UTIs, and GI infections, and resistance is maintained even after stopping treatment.

Aminoglycosides

• Aminoglycosides (Kanamycin, Neomycin, Gentamycin, Amikacin) inhibit bacterial protein synthesis by binding to 30S ribosomes and are bactericidal
• Active against Gram-negative aerobes
• Useful with Beta-lactams which can act synergistically on Gram-positive pathogens
• Aminoglycosides are not absorbed from the GI tract and are highly polar; only used IM or SC for systemic infections or oral for GI disorders
• Have affinity for renal and otic tissue, cause autotoxicity and nephrotoxicity (why NMB blocking agents are needed) + Allergic reactions (but only at dermal level)
• Secrete enzymes to degrade the antibiotic, natural resistance in anaerobes
• Used for severe aerobic Gram-negative bacterial infections.

Tetracyclines

• Tetracyclines (Oxytetracycline, Chlortetracycline, Tetracycline, Doxycycline, Minocycline) inhibit bacterial protein synthesis by binding to 30S ribosomes reversibly and are bacteriostatic
• Have a broad spectrum against Gram-positive and Gram-negative bacteria, aerobes, anaerobes, atypical, and intracellular bacteria, as well as protozoa.
• Impaired absorption (avoid salts, milk, antacids 3 hours before and atfer)
• Chelates calcium which can impair the healing process
• Superinfections and hepatotoxicity
• Binds important cations
• Efflux pumps, decreased cell permeability, and target alteration are resistance mechanisms
• Used for respiratory infections, tick-borne diseases, GI infections, UTIs, skin and reproductive infections, and ocular infections.

Phenicols

• Phenicols (Chloramphenicol, Florphenicol) inhibit bacterial protein synthesis by binding to 50S ribosomes reversibly and Can NOT be used in food producing animals
• Are broad in spectrum, but can act on eurokayotic ribosomes
• Cause: Bone marrow suppression, GI issues, and neurological effects
• Restricted in food producing animals as it causes Aplastic Anemia
• Should not be used close to vaccination periods as they are immunosuppressive
• Bacteria causes Cross resistance to Macrolides as they inhibit same site of action
• Used to treat severe Aerobic bacteria and MRSA's (resistant strands of the staphylococcus bacteria) in the: respiratory system, in the CNS & eyes including Salmonellas

Macrolides

• (Erythromycin, Oleandomycin, Troleandomycin, Azithromycin, Gamithromycin, Spiramycin, Josamycin, Tylosin, and Tilmicosin)
• According to the Macrolide rings they
• Inhibit bacterial protein synthesis, and are bacteriostatic or bactericidal in high concentrations
• Are absorbed orally, but are sensitive to stomach acid
• Highly Cardiotoxic
• High Accumilation in the microphages
• Efflux-pumps action
• Alteration of subunits
• Used where patient is allergic to penicillins (Second choice for the bacterial infections)
• Good for: Respiratory, Mastitis, Enteritis, pyrometra, & conjunctivitis

Polypeptides

• Polymyxin B, Polymyxin E are Polypeptides
• Alter the cell membrane
• Can result in bacterial lysis
• High integrity for gram NEGATIVE cell membrane
• Use both topically or as last resort for resistant strands of Gram negotive bacteria.
• Can cause reactions at application site/ infections and may be nephortoxic and neurotoxic
• For Topicall applications: Ear infections, Skin infections & eye infections

Lincosamides

• Lincomycin, Clindamycin
• Inhibits synthesis by linking into bacterial cell
• Both good to use against broad infections
• Both cause disturbance and have cross resistance
• Diffuse across Placent
• Good alternative to Pennicillan ( used to treat general infections, dental areas etc...)