Tazimide

Tazimide Uses, Dosage, Side Effects, Food Interaction and all others data.

Ceftazidime is a semisynthetic, broad-spectrum, beta-lactam antibiotic for parenteral administration. Ceftazidime is bactericidal in action exerting its effect by inhibition of enzymes responsible for cell-wall synthesis. A wide range of gram-negative organisms is susceptible to ceftazidime in vitro, including strains resistant to gentamicin and other aminoglycosides. In addition, ceftazidime has been shown to be active against gram-positive organisms. It is highly stable to most clinically important beta-lactamases, plasmid or chromosomal, which are produced by both gram-negative and gram-positive organisms and, consequently, is active against many strains resistant to ampicillin and other cephalosporins.

Ceftazidime is a semisynthetic, broad-spectrum, third-generation cephalosporin antibiotic that is bactericidal through inhibition of enzymes responsible for cell-wall synthesis, primarily penicillin-binding protein 3 (PBP3). Among cephalosporins, ceftazidime is notable for its resistance to numerous β-lactamases and its broad spectrum of activity against Gram-negative bacteria, including Pseudomonas aeruginosa. However, it is less active than first- and second-generation cephalosporins against Staphylococcus aureus and other Gram-positive bacteria and also has low activity against anaerobes. Ceftazidime has confirmed activity against clinically relevant Gram-negative bacteria including Citrobacter spp., Enterobacter spp., Klebsiella spp., Proteus spp., Serratia spp., _Escherichia coli, Haemophilus influenzae, Neisseria meningitidis, Pseudomonas aeruginosa, and some Gram-positive bacteria including Staphylococcus spp. and Streptococcus spp. There are also in vitro data for ceftazidime efficacy against a wide variety of other bacteria, such as Acinetobacter baumannii and Neisseria gonorrhoeae, but no clear clinical studies to support the use of ceftazidime for infections caused by these bacteria.

Although β-lactam antibiotics like ceftazidime are generally well tolerated, there remains a risk of serious acute hypersensitivity reactions, which is higher in patients with a known allergy to ceftazidime or any other β-lactam antibiotic. As with all antibiotics, ceftazidime may result in the overgrowth of non-susceptible organisms and potentially serious effects including Clostridium difficile-associated diarrhea (CDAD); CDAD should be considered in patients who develop diarrhea and, in confirmed cases, supportive care initiated immediately. Ceftazidime is primarily renally excreted such that high and prolonged serum concentrations can occur in patients with renal insufficiency, leading to seizures, nonconvulsive status epilepticus (NCSE), encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia. Treatment may lead to the development or induction of resistance with a risk of treatment failure. Periodic susceptibility testing should be considered, and monotherapy failure may necessitate the addition of another antibiotic such as an aminoglycoside. Cephalosporin use may decrease prothrombin activity, which may be improved by exogenous vitamin K. Inadvertent intra-arterial administration of ceftazidime may result in distal necrosis.

Tazobactam is an antibiotic of the beta-lactamase inhibitor class that prevents the breakdown of other antibiotics by beta-lactamase enzyme producing organisms. It is combined with Piperacillin and Ceftolozane for the treatment of a variety of bacterial infections.

Piperacillin-tazobactam was initially approved by the FDA in 1994, and ceftolozane-tazobactam was approved by the FDA in 2014, providing wider antibacterial coverage for gram-negative infections. In June 2019, ceftolozane-tazobactam was approved by the FDA for treating hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia, which are significant causes of morbidity and mortality in hospitalized patients.

Tazobactam inhibits the action of bacterial beta-lactamase producing organisms, which are normally resistant to beta-lactam antibiotics. This augments the effects of antibiotics which would otherwise not be effective in treating certain infections. These antibiotics contain a beta-lactam ring in their chemical structure, which is destroyed by beta-lactam resistant organisms. When combined with other antibiotics, a variety of infections, including serious and life-threatening infections may be treated.

Trade Name Tazimide
Generic Ceftazidime + Tazobactam
Weight 1g
Type Injection
Therapeutic Class
Manufacturer
Available Country India
Last Updated: September 19, 2023 at 7:00 am
Tazimide
Tazimide

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.

Tazobactam is a beta lactamase inhibitor administered with antibiotics such as piperacillin and ceftolozane to prevent their degradation, resulting in increased efficacy.

Tazobactam is used in combination with piperacillin or ceftolozane to broaden the spectrum of piperacillin antibacterial action, treating susceptible infections. As with any other antibiotic, tazobactam should only be used for infections that are either proven or strongly suspected to be susceptible to the tazobactam containing drug.

Tazobactam-piperacillin

When combined with piperacillin, it is used to treat a variety of infections, including those caused by aerobic and facultative gram-positive and gram-negative bacteria, in addition to gram-positive and gram-negative anaerobes. Some examples of infections treated with piperacillin-tazobactam include cellulitis, diabetic foot infections, appendicitis, and postpartum endometritis infections. Certain gram-negative bacilli infections with beta-lactamase producing organisms cannot be treated with piperacillin-tazobactam, due to a gene mutation conferring antibiotic resistance.

Tazobactam-ceftolozane

Tazobactam-ceftolozane combined with metronidazole is used to treat complicated urinary tract infections (UTI) and complicated intra-abdominal infections, as well as ventilator-associated bacterial pneumonia and hospital-acquired bacterial pneumonia.. This combination increases efficacy against infections with gram-negative bacilli.

Tazimide 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 microorganismAnimal bite, Cellulitis, Complicated Appendicitis, Cutaneous Abscess, Diabetic Foot Ulcers (DFU), Pelvic Inflammatory Disease (PID), Peritonitis, Pneumonia, Hospital-Acquired, Postpartum Endometritis, Surgical Site Infections, Ventilator-Associated Pneumonia (VAP), Complicated Bacterial Urinary Tract Infections, Complicated Pyelonephritis, Complicated intra-abdominal bacterial infections, Moderate Bacterial Infections, Moderate Community acquired pneumonia, Moderate Nosocomial pneumonia, Severe Bacterial Infections, Severe Nosocomial pneumonia, Uncomplicated skin and subcutaneous tissue bacterial infections

How Tazimide 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.

Tazobactam broadens the spectrum of piperacillin and ceftolozane by making them effective against organisms that express beta-lactamase and would normally degrade them. This occurs through the irreversible inhibition of beta-lactamase enzymes. In addition, tazobactam may bind covalently to plasmid-mediated and chromosome-mediated beta-lactamase enzymes. Tazobactam is predominantly effective against the OHIO-1, SHV-1, and TEM groups of beta-lactamases, but may also inhibit other beta-lactamases.

Tazobactam shows little antibacterial activity by itself, and for this reason, is generally not administered alone.

Dosage

Tazimide 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.

Overdose

Post-marketing reports have been made of overdose cases with piperacillin/tazobactam. Nausea, vomiting, and diarrhea are frequent manifestations of an overdose. Neuromuscular excitability or seizures may also occur with high intravenous doses or renal failure. There is no specific antidote. Provide supportive measures in case of an overdose. Anticonvulsive agents may be indicated when neuromuscular excitability or seizures occur. If anaphylaxis occurs, traditional measures should be taken to manage hypersensitivity (for example, adrenaline, antihistamines, corticosteroids, and oxygen/airway maintenance). Similar measures should be taken after a ceftolozane-tazobactam overdose. Hemodialysis can be used to remove the drug from the circulation .

A note on nephrotoxicity

Cases of life-threatening nephrotoxicity have been seen in critically ill patients receiving piperacillin-tazobactam. Alternative therapy and/or renal monitoring should be considered in critically ill patients.

Carcinogenesis/Mutagenesis

Tazobactam tested negative for genotoxic effects in the Ames assay, an after in vitro chromosomal aberration and point mutation assay in the Chinese hamster, an various other assays.

Use in pregnancy

Tazobactam has been found cross the placenta in rats. No data on human studies are available, however, rat studies have shown no teratogenetic effects at doses 6-14 times the equivalent maximum recommended human dose.

Use in lactation

There are no data on the presence of tazobactam in human breastmilk. No data are currently available on the effects of tazobactam on the infant, or how it affects milk production. Use clinical judgement and consider the maternal need for the drug and the benefits of breastfeeding the infant before administration during lactation. Small concentrations of piperacillin-tazobactam have been found in the breastmilk and can lead to hypersensitivity in a breastfeeding infant. In some cases, breastfeeding may have to be discontinued temporarily.

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.

Volume of Distribution

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

18.2 L when given with piperacillin

13.5-18.2 L when given with ceftolozane

Piperacillin-tazobactam is widely distributed in body tissues and fluids. These may include but are not limited to the intestine, gallbladder, lung, female reproductive organs, and the bile. Meningeal distribution of piperacillin-tazobactam increases with inflammation, but is otherwise low.

Elimination Route

Ceftazidime administered intravenously in healthy males produced mean Cmax 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 Cmax 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 Cmax 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.

Tazobactam is coadministered with piperacillin or ceftolozane, pharmacokinetic information will be provided for these combinations.

Piperacillin-tazobactam

Peak plasma concentrations occur immediately after the completion of intravenous infusion. Following several doses of piperacillin-tazobactam infusions every 6 hours, peak concentrations were similar to those that were measured after the initial dose.

Ceftolozane-piperacillin

AUC: 24.4-25 mcg•h/mL

Peak concentrations are reached on day 1 after the first dose and range from 18 to 18.4 mcg/mL.

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.

Piperacillin-tazobactam

After a single dose in healthy volunteers, the plasma half-life of piperacillin and tazobactam was in the range of 0.7 to 1.2 hours.

Ceftolozane-tazobactam

0.91-1.03 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.

Because tazobactam is cleared by the kidneys and is a substrate of the transporters OAT1 and OAT3, inhibitors of these transporters should be avoided to ensure efficacy. Dosage adjustments of piperacillin-tazobactam and ceftolozane-tazobactam must be made for patients with impaired renal clearance.

The mean clearance rate of tazobactam was found to be 48.3-83.6 mL/min in patients admitted to the intensive care unit who were given renal replacement therapy and receiving intravenous piperacillin-tazobactam.

The clearance of tazobactam is dependent on renal function, as determined by renal clearance.

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.

Tazobactam and its metabolite are mainly eliminated by the kidneys with about 80% of the administered dose eliminated as unchanged drug. The remaining drug is excreted as a single metabolite.

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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