Ceftolozane sulfate with tazobactam sodium
- Aust Prescr 2016;39:106-7
- 1 June 2016
- DOI: 10.18773/austprescr.2016.044
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Approved indication: specified infections
Zerbaxa (Merck, Sharp and Dohme)
vials containing 1000 mg/500 mg powder for reconstitution
Australian Medicines Handbook section 5.1.3
Antibiotic resistance is a growing problem. This combination of ceftolozane (a cephalosporin) with tazobactam (a beta-lactamase inhibitor) is an attempt to address multidrug resistant Gram-negative bacteria. These organisms can cause severe intra abdominal infections and complicated urinary tract infections.
Ceftolozane has a bactericidal action. Its spectrum of activity is extended by combining with tazobactam to inhibit the beta-lactamase enzymes produced by organisms such as Escherichia coli and Klebsiella species. The combination also has efficacy against bacteria such as Pseudomonas aeruginosa, Enterobacter and Proteus mirabilis. It is not effective for infections caused by Staphylococcus aureus or enterococci.
The combination has to be given by intravenous infusion. The reconstituted solution is diluted and infused over an hour every eight hours. Most of the dose is renally excreted, so lower doses are needed in patients with a creatinine clearance below 50 mL/minute. As there is a potential for hypersensitivity reactions, the infusion should be given where there are facilities for managing anaphylaxis.
A multicentre study enrolled patients with pyelonephritis or complicated lower urinary tract infections. One group of 543 was randomised to receive infusions of ceftolozane with tazobactam, while 540 received infusions of levofloxacin (a quinolone). Approximately 74% of the patients had a positive urine culture. Most of them were infected with E. coli. Treatment for seven days with the combination eradicated the organisms in 80.4% of patients compared with 72.1% with levofloxacin. There was a clinical cure in 92% of these patients treated with the combination and 88.6% of those given levofloxacin.1
Another trial studied patients with complicated intra-abdominal infections such as appendiceal abscess or perforation. A group of 487 patients was randomised to receive ceftolozane/tazobactam and metronidazole, while 506 were randomised to intravenous meropenem. E. coli was frequently found, but most of the infections were polymicrobial. Treatment was for 4–10 days, but could continue for 14 days. At the end of therapy there was a clinical cure in 89.2% of the patients treated with the combination and 92.3% of those given meropenem. When the patients were assessed a median of 27 days after the start of therapy, the clinical cure rates were 83% with the combination and 87.3% with meropenem.2
In the clinical trials the most frequent adverse events in patients taking the combination of ceftolozane with tazobactam were nausea, headache and diarrhoea. In some cases the diarrhoea was associated with Clostridium difficile. Although 12 patients treated with the combination died, none of these deaths were considered to be related to treatment.
There are no studies of the combination in pregnancy. It is also unknown if the drugs are excreted in breast milk.
While the clinical trials show that ceftolozane with tazobactam is effective, the combination should probably be reserved for severe cases where a multidrug resistant organism is suspected. In Australia cephalosporins are not usually first-line drugs. Therapeutic Guidelines3 recommends that an empirical therapy for severe pyelonephritis is gentamicin with ampicillin or amoxycillin.
The Transparency Score () is explained in New drugs: transparency, Vol 37 No 1, Aust Prescr 2014;37:27.
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