Ceftolozane And Tazobactam
Ceftolozane And Tazobactam Uses, Dosage, Side Effects, Food Interaction and all others data.
Ceftolozane is a semi-synthetic broad-spectrum fifth generation cephalosporin. It was approved by the FDA in 2014 for use in combination with Tazobactam for the treatment of serious infections, such as intra-abdominal infections and complicated urinary tract infections. The manufacturer of this drug is Cubist Pharmaceuticals. Most recently, in June 2019, ceftolozane-tazobactam was approved for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia.
Hospital-acquired pneumonia and ventilator-associated pneumonia are major causes of morbidity and mortality in hospitalized patients and the use of ceftolozane-tazobactam offers effective activity against various organisms causing these infections, such as Pseudomonas aeruginosa.
Ceftolozane exerts bactericidal activities against susceptible gram-negative and gram-positive infections by interfering with bacterial cell wall synthesis. When it is combined with tazobactam, it exerts further activity against beta-lactamase enzyme producing bacteria, which are normally resistant to beta-lactam antibiotics and interfere with infection treatment. The addition of tazobactam strengthens the therapeutic response to ceftolozane, giving it the ability to treat a broader range of bacterial infections and resistant organisms.
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 | Ceftolozane And Tazobactam |
| Generic | Ceftolozane + Tazobactam |
| Weight | 1g + 0.5g, |
| Type | Intravenous Powder For Injection, Intravenous |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Ceftolozane is a cephalosporin antibiotic used to treat complicated intra-abdominal infections in combination with metronidazole, complicated urinary tract infections, and hospital-acquired pneumonia.
This drug is administered in combination with tazobactam for the treatment of complicated intra-abdominal infections (in combination with metronidazole) and complicated urinary tract infections, which may include pyelonephritis. Ceftolozane-tazobactam is also indicated in the treatment of bacterial ventilator-associated pneumonia and bacterial hospital-acquired pneumonia.
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.
Ceftolozane And Tazobactam is also used to associated treatment for these conditions: Hospital Acquired Bacterial Pneumonia, Ventilator Associated Bacterial Pneumonia, Complicated Bacterial Urinary Tract Infections, Complicated Pyelonephritis, Complicated intra-abdominal bacterial infectionsAnimal 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 Ceftolozane And Tazobactam works
Ceftolozane belongs to the cephalosporin class of antibacterial drugs. Ceftolozane exerts antibacterial effects, preventing the formation of cell walls that protect bacteria from injury and confer resistance to some antibiotics. Its antibacterial activity is also mediated through ceftolozane binding to penicillin-binding proteins (PBPs), which are required for peptidoglycan cross-linking for bacterial cell wall synthesis. As a result of cell wall synthesis inhibition, bacterial cells are killed, treating various infections. Ceftolozane has a particularly high affinity to the penicillin-binding proteins for Pseudomonas aeruginosa and Escherichia coli as well as Klebsiella pneumoniae and other enteric bacteria. In particular, a high affinity has been seen in vitro for penicillin-binding proteins 1b, 1c, 2, and 3 when compared to other antibiotics, ceftazidime and imipenem.
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.
Toxicity
A note on nephrotoxicity
This drug is mainly excreted by the kidneys, and if administered to a patient with a creatinine clearance of less than 50 mL/min, may cause renal damage. Consult official product labeling for dosing adjustments in patients with renal impairment.
Overdose information
If an overdose occurs, discontinue the drug and follow this with supportive treatment. Dialysis may be used.
Use in pregnancy
Ceftolozane-tazobactam is a pregnancy category B drug, but human studies have not been performed to validate this in humans. At doses equivalent to 4-7 the standard dose administered in humans, no developmental abnormalities were seen. Since animal studies are not always predictive of drug response in humans, it is advisable to exercise caution if this drug is prescribed during pregnancy. The mother's clinical need should be assessed as well as possible risks to the fetus.
Use in lactation
Whether this drug is excreted in human breast milk is unknown. Caution is advised if this drug is administered during lactation, as many other drugs are known to be secreted into breast milk.
Carcinogenesis/mutagenesis
Formal studies have not been conducted in humans to assess mutagenicity or carcinogenicity. Studies in mice and rats did not reveal any mutagenic or carcinogenic potential, however, the potential risks resulting from long-term use have not been studied.
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.
Volume of Distribution
13.5 L Tissue distribution of ceftalozone-tazobactam is rapid and shows good penetration into the lung, rendering it an ideal treatment for bacterial pneumonia.
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
The area under the curve (AUC) of ceftolozane-tazobactam after an injected dose of 1 g/0.5 g every 8 hours for 1 day was 172 mcg•h/mL. The Cmax (peak concentration) and AUC are dose-dependent. The Cmax on day one of the above dose of ceftolozane-tazobactam was 69.1 mcg/mL.
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
2.77 hours on day 1 of treatment on a dose of 1 g/0.5 g every 8 hours. 3.12 hours on day 10 of treatment on a dose of 1 g/0.5 g every 8 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 renal clearance of was measured to be 3.41 – 6.69 L/h after a single dose of ceftolozane-tazobactam. Dose adjustments of this drug are required in patients with impaired renal function with a creatinine clearance of 50 mL/min or below. Consult official labeling for dosing adjustment guidelines.
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
Ceftolozane is mainly excreted in the urine.
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.
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