Vabomere, a combination of meropenem and vaborbactam, is a new antibiotic indicated for the treatment of adults with complicated urinary tract infections (cUTI), including pyelonephritis. A cUTI is a UTI in which urinary tract comorbidities increase the risk of treatment failure. Vabomere is effective against most isolates of Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae species complex. In general, Enterobacter organisms do not infect healthy people. However, Enterobacter-related hospital-acquired infections are increasing, especially in ICUs where patients are often intubated, have had recent surgery, and have comorbidities.
Enterobacter species organisms are often resistant to multiple drug therapies, making Enterobacter-related infections difficult to treat. These bacteria can also spread mobile drug resistance elements to other bacteria, increasing the prevalence of multidrug-resistant organisms. Carbapenem-resistant Enterobacteriaceae are common organisms in the gastrointestinal tract. According to the Centers for Disease Control and Prevention, infections caused by these organisms are associated with high mortality rates-up to 50%. Major risk factors for these infections include hospitalization and receiving antibiotic therapy. Outbreaks have been noted in long-term care facilities (for more information, see http://www.cdc.gov/hai/organisms/cre/cre-clinicianfaq.html).
The two components of Vabomere-meropenem and vaborbactam-work to eradicate cUTIs in different ways. Meropenem is a member of the drug class known as carbapenem antibiotics. It kills susceptible bacteria by inhibiting the synthesis of the bacteria's cell wall. Meropenem is stable to hydrolysis by first-generation [beta]-lactamases (penicillinases and cephalosporinases, for example). However, the evolution in some gram-negative organisms to produce newer types of [beta]-lactamases has presented a challenge to antibiotic therapy. The drug's other component, vaborbactam, is not an antibiotic. It is a [beta]-lactamase inhibitor that protects meropenem from being degraded by the newer [beta]-lactamases that can break down carbapenem antibiotics.
A double-blind, double-dummy, multicenter clinical trial compared treatment with Vabomere to treatment with piperacillin/tazobactam in 545 adults with cUTIs. Both therapies were given intravenously every eight hours. Patients could be switched to oral antibiotics after receiving a minimum of 15 doses of the iv course of treatment. The mean duration of iv treatment was eight days for both groups and the mean duration of total treatment (iv and oral) was 10 days. At the end of the iv treatment regimen, 98.4% of patients receiving Vabomere, compared with 94.3% of those receiving piperacillin/tazobactam, demonstrated "clinical cure or improvement" and a negative urine culture. Approximately a week after the completion of all treatment, clinical cure and a negative urine culture were observed in 76.5% of those receiving Vabomere compared with 73.2% of those receiving piperacillin/tazobactam. No cross-resistance with other antibiotic classes was identified in clinical trials.
The recommended dose of Vabomere is 4 g (2 g each of meropenem and vaborbactam) given intravenously every 8 hours. Each infusion should be administered over three hours. Because the drug is primarily excreted via the kidneys mostly unchanged, lower doses are recommended in patients with renal impairment. Vabomere requires reconstitution and then further dilution before administration. When reconstituting the drug, nurses must be careful to mix the correct dose. The drug comes in 2-g vials, so two vials are needed to achieve the recommended 4-g dose. Nurses should also be careful to infuse the reconstituted and diluted drug over three hours; this is true even if the patient is receiving less than 4 g of the drug because of renal disease. The infusion of the reconstituted and diluted solution must be completed within four hours if it is stored at room temperature or within 22 hours if it is refrigerated.
The most common adverse effects of Vabomere, occurring in at least 3% of patients, are headache, phlebitis/infusion site reactions, and diarrhea. Serious, though uncommon, adverse effects include hypersensitivity reactions and seizures. Nurses should assess patients carefully for any known hypersensitivity or anaphylactic reactions to [beta]-lactam antibiotics, as Vabomere is contraindicated in patients with a history of these reactions. Patients should also be assessed for any new hypersensitivity reactions that occur during Vabomere therapy. The risk of seizures appears to be greatest in patients who already have a seizure disorder or brain lesions, bacterial meningitis, and/or compromised renal function. These patients should initially be kept in a safe environment in case a seizure develops. Coadministration of carbapenems, such as meropenem, and valproic acid or divalproex sodium, which are used to treat seizures, have been noted to cause decreased concentrations of the anticonvulsant drug. If valproic acid concentrations fall below the therapeutic range, an increased risk of seizures can result. For these patients, nurses should discuss with the prescriber the likely need for a higher dose of the anticonvulsant drug in order to maintain its therapeutic level.
Like most antibacterial therapies, Vabomere may induce Clostridium difficile-associated diarrhea. Nurses should tell patients to report diarrhea that is watery, frequent, and accompanied by abdominal pain, or that contains blood or pus. As these bacterial infections are common in the hospital, prevention of transmission is paramount. The chances of transmission are minimized by adhering closely to medical asepsis. Nurses should be sure to wash their hands frequently and to remind other health care team members to do the same. Adherence to handwashing practice has been noted to be poorest in the ICU, during high-risk procedures, when intensity of care is highest, on weekends, and when nurse-to-patient staffing ratios are high. Patients taking Vabomere will need contact isolation precautions to prevent the spread of carbapenem-resistant Enterobacteriaceae infections.
For complete prescribing information for Vabomere, see http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209776lbl.pdf.