Ceftazidime

Uses

Sidobac Injection is used for the treatment of patients with infections caused by susceptible strains of the designated organisms in the following diseases:

Lower Respiratory Tract Infections, including pneumonia, caused by Pseudomonas aeruginosa and other Pseudomonas spp., Haemophilus influenzae, including ampicillin-resistant strains; Klebsiella spp.; Enterobacter spp.; Proteus mirabilis; Escherichia coli; Serratia spp.; Citrobacter spp.; Streptococcus pneumoniae; and Staphylococcus aureus (methicillin susceptible strains).

Skin and Skin Structure Infections caused by Pseudomonas aeruginosa; Klebsiella spp.; Escherichia coli; Proteus spp., including Proteus mirabilis and indole-positive Proteus, Enterobacter spp.; Serratia spp.; Staphylococcus aureus (methicillin susceptible strains); and Streptococcus pyogenes (group A beta-hemolytic streptococci).

Urinary Tract Infections, both complicated and uncomplicated, caused by Pseudomonas aeruginosa; Enterobacter spp.; Proteus spp., including Proteus mirabilis and indole-positive Proteus, Klebsiella spp.; and Escherichia coli.

Bacterial Septicemia caused by Pseudomonas aeruginosa, Klebsiella spp., Haemophilus influenzae, Escherichia coli, Serratia spp., Streptococcus pneumoniae, and Staphylococcus aureus (methicillin susceptible strains).

Bone and Joint Infections caused by Pseudomonas aeruginosa, Klebsiella spp., Enterobacter spp., and Staphylococcus aureus (methicillin susceptible strains).

Gynecologic Infections, including endometritis, pelvic cellulitis, and other infections of the female genital tract caused by Escherichia coli.

Intra abdominal Infections, including peritonitis caused by Escherichia coli, Klebsiella spp., and Staphylococcus aureus (methicillin susceptible strains) and polymicrobial infections caused by aerobic and anaerobic organisms and Bacteroides spp.

Central Nervous System Infections, including meningitis, caused by Haemophilus influenzae and Neisseria meningitidis, Pseudomonas aeruginosa and Streptococcus pneumoniae.

Ceftazidime is also used to associated treatment for these conditions: Bacteremia, Bacterial Infections, Bloodstream Infections, Bone and Joint Infections, Bronchopulmonary Infection, Central Nervous System Infections, Complicated Intra-Abdominal Infections, Complicated Skin and Soft Tissue Infection, Complicated Urinary Tract Infection, Complicated Urinary Tract Infections caused by susceptible Gram-negative microorganisms, Fever caused by susceptible bacteria, Gynaecological infection, Intra-Abdominal Infections, Lower Respiratory Tract Infection (LRTI), Meningitis, Bacterial, Nosocomial Pneumonia, Peritoneal Dialysis-associated Peritonitis, Urinary Tract Infection, Ventilator-associated Bacterial Pneumonia caused by susceptible Gram-negative microorganisms, Chronic suppurative Otitis media, Hospital-acquired bacterial pneumonia caused by susceptible Gram-negative microorganisms, Malignant Otitis Externa, Skin and skin-structure infections, Susceptible Intra-Abdominal Infection caused by susceptible Gram-negative microorganism

How Ceftazidime works

The bacterial cell wall, which is located at the periphery of Gram-positive bacteria and within the periplasm of Gram-negative bacteria, comprises a glycopeptide polymer synthesized through cross-linking of glycans to peptide stems on alternating saccharides, which is known commonly as peptidoglycan. Cell wall formation, recycling, and remodelling require numerous enzymes, including a family of enzymes with similar active site character despite distinct and sometimes overlapping roles as carboxypeptidases, endopeptidases, transpeptidases, and transglycosylases, known as "penicillin-binding proteins" (PBPs). The number of PBPs differs between bacteria, in which some are considered essential and others redundant. In general, inhibition of one or more essential PBPs results in impaired cell wall homeostasis, loss of cell integrity, and is ultimately bactericidal.

Ceftazidime is a semisynthetic third-generation cephalosporin with broad activity against numerous Gram-negative and some Gram-positive bacteria. Like other β-lactam antibiotics, ceftazidime exhibits its bactericidal effect primarily through direct inhibition of specific PBPs in susceptible bacteria. In vitro experiments in Gram-negative bacteria such as Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae suggest that ceftazidime primarily binds to PBP3, with weaker binding to PBP1a/1b and PBP2 as well; although binding to other PBPs, such as PBP4, is detectable, the concentrations required are much greater than those achieved clinically. Similarly, ceftazidime showed binding to Staphylococcus aureus PBP 1, 2, and 3 with a much lower affinity for PBP4. Recent data for Mycobacterium abcessus suggest that ceftazidime can inhibit PonA1, PonA2, and PbpA at intermediate concentrations.

Dosage

Ceftazidime dosage

Dosage: The usual adult dosage is 1 gram administered intravenously or intramuscularly every 8 to 12 hours. The dosage and route should be determined by the susceptibility of the causative organisms, the severity of infection and the condition, and renal function of the patient.

Recommended Dosage Schedule

Uncomplicated urinary tract infections: 250 mg IV or IM Q 12h

Bone and joint infections: 2 grams IV Q 12h

Complicated urinary tract infections: 500 mg IV or IM Q 8-12h

Uncomplicated pneumonia; mild skin and skin structure infections: 500 mg -1 gram IV or IM Q 8h

Serious gynecologic and intra-abdominal infections: 2 grams IV Q 8h

Meningitis: 2 grams IV Q 8h

Very Severe life threatening infections, especially in immunocompromised patients: 2 grams IV Q 8h

Lung infections caused by Pseudomonas spp. In patients with cystic fibrosis with normal renal function: 30-50 mg/kg IV to a maximum of 6 grams per day Q 8h

Neonates (0 - 2 months): 25-60 mg/kg/day IV Q 12h

Infants & Children (2 months - 12 years): 30-100 mg/kg/day IV to a maximum of 6 grams per day Q 8-12h.

Impaired Hepatic Function: No adjustment in dosage is required for patients with hepatic dysfunction.

Impaired Renal Function: In patients with impaired renal function (glomerular filtration rate [GFR]<50 mL/min) it is recommended that the dosage of Ceftazidime be reduced to compensate for its slower excretion. In patients with suspected renal insufficiency, an initial loading dose of 1 gram of Ceftazidime may be given.

Recommended Maintenance Dosages of Ceftazidime in renal insufficiency:

Creatinine clearance 50-31 mL/min: 1 gram Q12h

Creatinine clearance 30-16 mL/min: 1 gram Q24h

Creatinine clearance 15-6 mL/min: 500 mg Q24h

Creatinine clearance <5 mL/min: 500 mg Q48h

Administration: Sidobac may be given intravenously or by deep IM injection into a large muscle mass such as the upper outer quadrant of the gluteus maximus or lateral proof of the thigh. Intra-arterial administration should be avoided. For IV/IM administration, Sidobac should be constituted with the supplied Sterile Water for Injection.

Single-dose vial Administration Amount of WFI to be added: 

• 250 mg IM in 1.5 ml
• 250 mg IV in 5 ml
• 500 mg IM in 1.5 ml
• 500 mg IV in 5 ml
• 1 gm IM in 3 ml
• 1 gm IV in 10 ml

Step 1: Add recommended volume of solvent slowly. Remove the syringe needle.

Step 2: Gently shake the vial to dissolve the powder. Carbon dioxide is released & a clear solution will be obtained.

Step 3: Now insert the needle in the free space of the reconstituted vial & withdraw the pressurized air from the free space.

Step 4: Finally withdraw the solution from the vial by syringe

Side Effects

The most common side-effects are local reactions following IV injection and allergic and gastrointestinal reactions. Hypersensitivity reactions are pruritus, rash, and fever. Angioedema and anaphylaxis have been reported very rarely. Gastrointestinal symptoms are diarrhea, nausea, vomiting, and abdominal pain. Central nervous system reactions included headache, dizziness, and paresthesia.

Toxicity

Ceftazidime overdosage has occurred in patients with renal failure. Reactions included seizure activity, encephalopathy, asterixis, neuromuscular excitability, and coma. Patients who receive an acute overdosage should be carefully observed and given supportive treatment. In the presence of renal insufficiency, hemodialysis or peritoneal dialysis may aid in the removal of ceftazidime from the body.

Precaution

The total daily dosage should be reduced when Ceftazidime is administered to patients with renal insufficiency. Ceftazidine should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.

Interaction

Increased nephrotoxicity has been reported following concomitant administration of Cephalosporins and aminoglycoside antibiotics.

Food Interaction

Ceftazidime Hypertension interaction

[Moderate] Fortaz, Tazicef, and Tazidime (brands of parenteral ceftazidime pentahydrate) are formulated with sodium carbonate and contain approximately 53 mg (2.3 mEq) of sodium per each gram of ceftazidime activity.

The sodium content should be considered in patients with conditions that may require sodium restriction, such as congestive heart failure, hypertension, and fluid retention.

Ceptaz, another brand of ceftazidime, is formulated with l-arginine and contains no sodium.

Ceftazidime Drug Interaction

Moderate: sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprim, ciprofloxacin, ciprofloxacinUnknown: aspirin, aspirin, epinephrine, epinephrine, amoxicillin / clavulanate, amoxicillin / clavulanate, albuterol / ipratropium, albuterol / ipratropium, lvp solution, lvp solution, acetaminophen, acetaminophen, valproic acid, valproic acid, phytonadione, phytonadione

Ceftazidime Disease Interaction

Major: colitisModerate: renal dysfunction, renal impairment, sodium, dialysis, liver disease, seizure disorders

Volume of Distribution

Ceftazidime has a volume of distribution of 15-20 L.

Elimination Route

Ceftazidime administered intravenously in healthy males produced mean C_max values of between 42 and 170 μg/mL for doses between 500 mg and 2 g, and are reached immediately following the end of the infusion period. The C_max for 1 g of ceftazidime administered intramuscularly is attained approximately one hour following injection and is between 37 and 43 mg/L. Following intramuscular administration of 500 mg and 1 g of ceftazidime, the serum concentration remained above 4 μg/mL for six and eight hours, respectively.

Ceftazidime C_max and AUC show linear proportionality to the dose over the therapeutic range. In individuals with normal renal function, ceftazidime given intravenously every eight hours for 10 days as either 1 or 2 g doses showed no accumulation.

Half Life

Ceftazidime has an elimination half-life of 1.5-2.8 hours in healthy subjects. As ceftazidime is primarily renally excreted, its half-life is significantly prolonged in patients with renal impairment. In patients with creatinine clearance < 12 mL/min, the half-life is prolonged to between 14 and 30 hours.

Clearance

The mean renal clearance of ceftazidime in healthy subjects ranges from 72 to 141 mL/min while the calculated plasma clearance is approximately 115 mL/min.

Elimination Route

Approximately 80% to 90% of an intramuscular or intravenous dose of ceftazidime is excreted unchanged by the kidneys over a 24-hour period. When administered intravenously, 50% of the dose appears in the urine within two hours, with another 32% of the dose appearing by eight hours post-administration.

Pregnancy & Breastfeeding use

Pregnancy: No adequate and well controlled studies in pregnant women have been conducted with Ceftazidime. Because animal reproduction studies are not always predictive of human response this drug should be used during pregnancy only if clearly needed.

Lactation: Ceftazidime is excreted in human milk in low concentrations. Because many drugs are excreted in human milk and because safety of the component of the injections in nursing infants has not been established, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Contraindication

Ceftazidime is contraindicated in patients with known hypersensitivity to cephalosporin antibiotics.

Acute Overdose

Ceftazidime overdosage has occurred in patients with renal failure. Reactions have included seizure activity, encephalopathy, asterixis, neuromuscular excitability, and coma. Patients who receive an acute overdosage should be carefully observed and given supportive treatment.

Storage Condition

Store below 25° C, protected from light and moisture. Reconstituted solutions are stable for up to 24 h if stored between 2°-8° C

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