Brand Name: Xacduro

Drug Name: Sulbactam + Durlobactam

FDA Approval Date: 23rd May 2023 [Ref]

Primary Indication: Treatment of HAP/ VAP caused by resistant Acinetobacter baumanii

Xacduro (Sulbactam, Durlobactam) is a new fast-track approved drug to treat HAP (hospital-acquired pneumonia) and VAP (ventilator-associated pneumonia caused by Acinetobacter baumanni.

Acinetobacter baumanni is a serious infection and often resistant to all the commonly used antibiotics including carbapenems. Patients develop HAI or HAP (hospital-acquired infections or hospital-acquired pneumonia) or VAP (ventilator-associated pneumonia) while being admitted for more than 48 hours in the hospital or on a ventilator in the ICU.

Most patients who developed HAP or VAP have positive cultures of Acinetobacter baumanni. Most of these cases are multi-drug resistant and there are very few choices out there to treat them.

Colistin (Colomycin) or Polymyxins are used to treat Acinetobacter baumanni infections when culture results show sensitivity to these antibiotics, however, these antibiotics are very toxic, and finding safer alternatives is the need of the time to save the lives of our patients.

Xacduro is a medication composed of two components: sulbactam, a drug structurally similar to penicillin, and durlobactam. Sulbactam is effective in killing A. baumannii bacteria, while durlobactam serves to protect sulbactam from degradation by enzymes that may be produced by A. baumannii. This combination is administered to patients through intravenous infusion.

Xacduro for HAP and VAP caused by Acinetobacter baumanni:

The efficacy of Xacduro was established in a multicenter, active-controlled, open-label clinical trial involving 177 hospitalized adults diagnosed with pneumonia caused by carbapenem-resistant A. baumannii. In this trial, patients were randomly assigned to receive either Xacduro or colistin (a comparator antibiotic) for a maximum of 14 days.

Additionally, both treatment groups received another antibiotic, imipenem/cilastatin, as background therapy to target potential pathogens other than Acinetobacter baumannii-calcoaceticus complex that may cause hospital-acquired or ventilator-associated bacterial pneumonia.

The primary measure of efficacy in this trial was the mortality rate due to any cause within 28 days of treatment among patients with confirmed infections caused by carbapenem-resistant A. baumannii. The study results revealed that 19% (12 out of 63 patients) who received Xacduro died, while 32% (20 out of 62 patients) who received colistin died. These findings indicate that Xacduro was noninferior to colistin in terms of efficacy.

The most frequently reported adverse reaction associated with Xacduro usage was abnormalities in liver function test results. It is important to note that Xacduro carries specific warnings and precautions, including the risk of hypersensitivity reactions and the possibility of developing Clostridioides difficile-associated diarrhea.

Patients with a known history of severe hypersensitivity to components of Xacduro, sulbactam, or other beta-lactam antibacterial drugs should not receive Xacduro.

Below is a table summarizing the key information:

Summary:

In summary, Xacduro, a combination of sulbactam and durlobactam, is an effective treatment for pneumonia caused by carbapenem-resistant A. baumannii. It has been proven non-inferior to colistin in reducing mortality rates.

While liver function test abnormalities are the most common adverse reaction, caution is advised for hypersensitivity reactions and Clostridioides difficile-associated diarrhea. Patients with a history of severe hypersensitivity to Xacduro or beta-lactam antibacterial drugs should avoid its use.

Overall, Xacduro provides a promising treatment option with efficacy and manageable side effects for this type of pneumonia.