VANCO PLUS INJECTION

Indications

• Bacterial infections
• Susceptible infections due to sensitive Gram-positive and Gram-negative bacteria
• Community-acquired pneumonia
• Hospital-acquired pneumonia
• Intra-abdominal infections
• Complicated urinary tract infections
• Severe diabetic foot infections
• Prophylaxis of infection from human and animal bites

Dosage

Adults: 1–2 g once daily, or 2 g every 8 hours for severe infections or hospital-acquired pneumonia.

Mechanism of action

Ceftriaxone works by inhibiting mucopeptide synthesis in the bacterial cell wall. Its beta-lactam structure binds to carboxypeptidases, endopeptidases, and transpeptidases located in the bacterial cytoplasmic membrane, which are crucial for cell wall synthesis and division. This binding leads to enzyme inactivity, resulting in the formation of defective cell walls and ultimately bacterial cell death.

Pharmacodynamics

Ceftriaxone is a beta-lactam antibiotic with bactericidal properties, primarily affecting the synthesis of bacterial cell walls. It exhibits activity against a variety of Gram-positive and Gram-negative organisms. The drug is stable against hydrolysis by many beta-lactamases, which enhances its effectiveness against resistant bacterial strains. However, it can still be subject to resistance mechanisms such as beta-lactamase production and alterations in penicillin-binding proteins.

Pharmacokinetics

Ceftriaxone has a long half-life, allowing for once-daily dosing in many cases. It is widely distributed in body tissues and fluids, including the central nervous system, making it effective for treating infections such as meningitis. The drug is primarily eliminated via the kidneys, with a portion excreted in the bile. Dose adjustments may be necessary in patients with renal impairment.

Contra-indications

• Hypersensitivity to ceftriaxone or any of its ingredients
• History of severe allergic reactions to penicillins or other beta-lactam antibiotics
• Newborns with hyperbilirubinemia
• Concurrent use with calcium-containing solutions in neonates

Adverse effects

• Diarrhea
• Nausea
• Vomiting
• Rash
• Thrombocytosis
• Thrombophlebitis at the injection site
• Antibiotic-associated colitis
• Acute kidney injury
• Jaundice
• Biliary sludge
• Neurotoxicity (rare, may include seizures)

Interactions

• Calcium-containing solutions (risk of precipitation)
• Probenecid (may increase plasma concentrations of ceftriaxone)
• Anticoagulants (may enhance anticoagulant effect)
• Other nephrotoxic agents (increased risk of renal impairment)

Precautions

• Use with caution in patients with renal impairment
• Caution in patients with hepatic impairment
• Monitor for signs of antibiotic-associated colitis
• Use with caution in patients with a history of gastrointestinal disease

Pregnancy

Not known to be harmful, but should be used only if clearly needed.

Breast-feeding

Present in milk in low concentrations, but generally considered appropriate to use.

Storage

Store in a cool, dry place away from light. Reconstituted solutions should be used immediately or stored at 2-8 degrees Celsius and used within 24 hours.

Formulations

• Powder for solution for injection: 500 mg, 1 g, 2 g vials

Indications

• Complicated skin and soft tissue infections
• Bone infections
• Joint infections
• Community-acquired pneumonia
• Hospital-acquired pneumonia, including ventilator-associated pneumonia
• Infective endocarditis
• Acute bacterial meningitis
• Bacteraemia
• Surgical prophylaxis for patients at high risk of bacterial endocarditis

Mechanism of action

Vancomycin exerts its bactericidal action by inhibiting cell wall biosynthesis. It specifically binds to the terminal D-alanyl-D-alanine residues of the peptidoglycan precursors, preventing their incorporation into the peptidoglycan matrix, which is vital for the structural integrity of Gram-positive bacteria. This leads to cell lysis and death. Additionally, vancomycin alters bacterial cell membrane permeability and affects RNA synthesis, contributing to its antimicrobial effects.

Pharmacodynamics

As a nonribosomal peptide antibiotic, vancomycin is often considered a drug of last resort and is used when other treatments have failed. It demonstrates activity against several significant pathogens, including Listeria monocytogenes, Streptococcus pneumoniae (including penicillin-resistant strains), and various enterococci. Vancomycin can synergistically enhance the effects of aminoglycosides against certain strains, leading to improved clinical outcomes in specific infections.

Pharmacokinetics

Vancomycin is administered intravenously or intramuscularly, with its pharmacokinetics influenced by renal function. The drug is distributed widely in body tissues and fluids, with a volume of distribution of approximately 0.4 to 1 L/kg. It is primarily eliminated via the kidneys, necessitating dosage adjustments in patients with renal impairment. Trough concentrations should be monitored to ensure efficacy while preventing toxicity, especially during prolonged therapy.

Contra-indications

• Previous hearing loss
• Hypersensitivity to vancomycin or any component of the formulation

Adverse effects

• Nephrotoxicity
• Ototoxicity
• Red man syndrome
• Thrombophlebitis
• Hypersensitivity reactions
• Skin rash

Interactions

• Increased risk of nephrotoxicity when used with other nephrotoxic drugs (e.g., aminoglycosides, nonsteroidal anti-inflammatory drugs)
• Potential interactions with muscle relaxants and anesthetics

Precautions

• Monitor renal function and auditory function during prolonged treatment
• Use with caution in patients with renal impairment
• Assess for potential allergic reactions prior to administration

Pregnancy

Vancomycin is classified as category B. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Vancomycin is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

Store in a cool, dry place. Protect from light. Do not freeze.

Formulations

• Solution for injection
• Powder and solvent for solution for injection

Mechanism of action

Ceftriaxone works by inhibiting the mucopeptide synthesis in the bacterial cell wall. The beta-lactam moiety of ceftriaxone binds to carboxypeptidases, endopeptidases, and transpeptidases in the bacterial cytoplasmic membrane. These enzymes are involved in cell-wall synthesis and cell division. Binding of ceftriaxone to these enzymes causes the enzyme to lose activity; therefore, the bacteria produce defective cell walls, causing cell death.

Pharmacodynamics

Ceftriaxone is a cephalosporin/cephamycin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. Ceftriaxone has <i>in vitro</i> activity against gram-positive aerobic, gram-negative aerobic, and anaerobic bacteria. The bactericidal activity of ceftriaxone results from the inhibition of cell wall synthesis and is mediated through ceftriaxone binding to penicillin-binding proteins (PBPs). Ceftriaxone is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended-spectrum beta-lactamases. However, resistance to ceftriaxone usually occurs through beta-lactamase hydrolysis, altered PBPs, or reduced bacterial cell permeability. Ceftriaxone should not be mixed with or giving in the same IV line as diluents/products containing calcium as they may cause ceftriaxone to precipitate. Ceftriaxone use may also cause biliary sludge or gallbladder pseudolithiasis.

Mechanism of action

The bactericidal action of vancomycin results primarily from inhibition of cell-wall biosynthesis. Specifically, vancomycin prevents incorporation of N-acetylmuramic acid (NAM)- and N-acetylglucosamine (NAG)-peptide subunits from being incorporated into the peptidoglycan matrix, which forms the major structural component of Gram-positive cell walls. Vancomycin forms hydrogen bonds with the terminal D-alanyl-D-alanine moieties of the NAM/NAG-peptides, preventing the incorporation of the NAM/NAG-peptide subunits into the peptidoglycan matrix. In addition, vancomycin alters bacterial-cell-membrane permeability and RNA synthesis. There is no cross-resistance between vancomycin and other antibiotics. Vancomycin is not active in vitro against gram-negative bacilli, mycobacteria, or fungi. Vancomycin is bactericidal and appears to bind to the bacterial cell wall causing blockage of glycopeptide polymerization. This effect, which occurs at a site different from that affected by the penicillins, produces immediate inhibition of cell wall synthesis and secondary damage to the cytoplasmic membrane. Magnesium, manganese, calcium, and ferrous ions reduce the degree of adsorption of vancomycin to the cell wall, but the in vivo importance of this interaction is unknown. The bactericidal action of vancomycin results primarily from inhibition of cell-wall biosynthesis. In addition, vancomycin alters bacterial-cell-membrane permeability and RNA synthesis.

Pharmacodynamics

Vancomycin is a branched tricyclic glycosylated nonribosomal peptide often reserved as the "drug of last resort", used only after treatment with other antibiotics has failed. Vancomycin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections: <i>Listeria monocytogenes</i>, <i>Streptococcus pyogenes</i>, <i>Streptococcus pneumoniae</i> (including penicillin-resistant strains), <i>Streptococcus agalactiae</i>, <i>Actinomyces</i> species, and <i>Lactobacillus</i> species. The combination of vancomycin and an aminoglycoside acts synergistically in vitro against many strains of Staphylococcus aureus, Streptococcus bovis, enterococci, and the viridans group streptococci.