VABOMERE® has 32-fold more in vitro activity than meropenem alone against KPC-producing Enterobacterales1*

Adding vaborbactam significantly reduces the MIC of meropenem alone against KPC-producing Enterobacterales1

  • Meropenem alone and in combination with vaborbactam was evaluated against KPC-producing strains of Enterobacterales involving >1900 isolates1

MIC90 FOR MEROPENEM VS VABOMERE® (MEROPENEM AND VABORBACTAM)1†

*In vitro activity does not necessarily correlate with clinical efficacy.

†Study description

The activity of meropenem in combination with vaborbactam against >1900 KPC-producing clinical isolates of Enterobacterales was evaluated in both prospective and retrospective in vitro studies. Vaborbactam potentiated the activity of meropenem in these studies; lowest concentrations of the antibiotic at which 90% of the isolates were inhibited (MIC90s) were >32 μg/mL for meropenem alone and were reduced to 0.5-1 μg/mL in the presence of vaborbactam. This activity was consistent across different studies.1

VABOMERE restored activity of meropenem against select KPC-producing isolates2

Over 90% of the 135 KPC-producing isolates had an MIC <1 μg/mL2*

MICs OF VABOMERE AND MEROPENEM2,3*

*In vitro activity does not necessarily correlate with clinical efficacy.

  • 135 KPC-producing Enterobacterales clinical isolates were evaluated, in a study of >14,000 gram-negative clinical isolates, from 82 hospitals worldwide in 20142
  • A total of 135 (50.9% of the CRE isolates; 1.3% of the overall population) isolates carried blaKPC genes, including 60 blaKPC-2, 74 blaKPC-3, and 1 blaKPC-4 gene2
  • In this study, 133 of the 135 organisms of the KPC-producing isolates were inhibited by meropenem-vaborbactam at ≤2 μg/mL, and all isolates were inhibited by this combination at ≤8μg/mL2

Study description

A total of 14,304 gram-negative bacterial clinical isolates were consecutively collected in 82 worldwide hospitals. All isolates were tested for susceptibility against meropenem-vaborbactam and comparators using the reference broth microdilution method as described by the Clinical and Laboratory Standards Institute (CLSI). Meropenem was combined with vaborbactam at a fixed concentration of 8μg/mL.2

VABOMERE addresses a broad spectrum of resistant gram-negative pathogens4,5

Vaborbactam inhibits a number of β-lactamases and ESBLs4

  • VABOMERE demonstrated in vitro activity against Enterobacterales in the single or multiple β-lactamases from various classes (KPC, SME, TEM, SHV, CTX-M, CMY, and ACT groups)4*

VABOMERE RESTORES THE POTENCY OF MEROPENEM1†

table

*In vitro activity does not necessarily correlate with clinical efficacy.

†39 KPC-producing isolates of Enterobacteriaceae were obtained from JMI Laboratories (SENTRY surveillance program). Strains presented above are representative of the broad distribution of meropenem MIC values in the presence of vaborbactam 8 μg/mL.1

VABOMERE inhibited2*:

97percent
100percent
99percent

*Percentages derived from an evaluation of VABOMERE against 315 clinical isolates of serine carbapenemase-producing Enterobacterales collected over a period of 13 (2000-2013) years from multiple countries. The majority of the isolates evaluated were K pneumoniae (66%), and the most common resistance genes detected among the Enterobacterales were blaKPC-2 (46%) and blaKPC-3 (37%).2,6

VABOMERE demonstrated in vitro activity against additional gram-negative bacteria including4:

  • Citrobacter freundii
  • Citrobacter koseri
  • Enterobacter aerogenes
  • Klebsiella oxytoca
  • Morganella morganii
  • Proteus mirabilis
  • Providencia spp.
  • Pseudomonas aeruginosa
  • Serratia marcescens

The efficacy of VABOMERE in treating clinical infections due to these bacteria has not been established in adequate and well-controlled clinical trials, and in vitro data does not necessarily correlate to clinical efficacy.

See the clinical data of VABOMERE

References: 1. Data on file: Melinta Therapeutics, LLC. 2. Castanheira M, Rhomberg PR, Flamm RK, Jones RN. Effect of the β-lactamase inhibitor vaborbactam combined with meropenem against serine carbapenemase-producing Enterobacteriaceae. Antimicrob Agents Chemother. 2016;60(9):5454-5458. 3. Hecker SJ, Reddy KR, Totrov M, et al. Discovery of a cyclic boronic acid β-lactamase inhibitor (RPX7009) with utility vs class A serine carbapenemases. J Med Chem. 2015;58(9):3682-3692.
4. VABOMERE [package insert]: Melinta Therapeutics, LLC. 5. Baldwin CM, Lyseng-Williamson KA, Keam SJ. Meropenem: a review of its use in the treatment of serious bacterial infections. Drugs. 2008;68(6):803-838. 6. Bhowmick T, Weinstein MP. Microbiology of meropenem-vaborbactam: a novel carbapenem beta-lactamase inhibitor combination for carbapenem-resistant Enterobacterales infections. Infect Dis Ther. 2020;9(4):757-767.

INDICATION AND USAGE

VABOMERE® (meropenem and vaborbactam) is indicated for the treatment of patients 18 years of age and older with complicated urinary tract infections (cUTI) including pyelonephritis caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae species complex.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of VABOMERE® and other antibacterial drugs, VABOMERE® should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

IMPORTANT SAFETY INFORMATION

Contraindications

VABOMERE® is contraindicated in patients with known hypersensitivity to any components of VABOMERE® (meropenem and vaborbactam), or to other drugs in the same class or in patients who have demonstrated anaphylactic reactions to beta-lactam antibacterial drugs.

Warnings and Precautions

  • Hypersensitivity reactions were reported in patients treated with VABOMERE® in the clinical trials. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported in patients receiving therapy with beta-lactam antibacterial drugs. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe hypersensitivity reactions when treated with another beta-lactam antibacterial drug. If an allergic reaction to VABOMERE® occurs, discontinue the drug immediately.
  • Seizures and other adverse Central Nervous System (CNS) experiences have been reported during treatment with meropenem, which is a component of VABOMERE®. Close adherence to the recommended dosage regimens is urged, especially in patients with known factors that predispose to convulsive activity.
  • Rhabdomyolysis has been reported with the use of meropenem, a component of VABOMERE® If signs or symptoms of rhabdomyolysis such as muscle pain, tenderness or weakness, dark urine, or elevated creatine phosphokinase are observed, discontinue VABOMERE and initiate appropriate therapy.
  • Clostridioides difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including VABOMERE®, and may range in severity from mild diarrhea to fatal colitis. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued.
  • The concomitant use of VABOMERE® and valproic acid or divalproex sodium is generally not recommended. Case reports in the literature have shown that co-administration of carbapenems, including meropenem, to patients receiving valproic acid or divalproex sodium results in a reduction in valproic acid concentrations. The valproic acid concentrations may drop below the therapeutic range as a result of this interaction, therefore increasing the risk of breakthrough seizures. If administration of VABOMERE® is necessary, consider supplemental anticonvulsant therapy.
  • In patients with renal impairment, thrombocytopenia has been observed in patients treated with meropenem, but no clinical bleeding has been reported.
  • Alert patients receiving VABOMERE® on an outpatient basis regarding adverse reactions such as seizures, delirium, headaches and/or paresthesias that could interfere with mental alertness and/or cause motor impairment.
  • Prescribing VABOMERE® in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of drug-resistant bacteria.
  • As with other antibacterial drugs, prolonged use of VABOMERE® may result in overgrowth of nonsusceptible organisms.

Adverse Reactions

The most frequently reported adverse reactions occurring in ≥3% of patients treated with VABOMERE® were headache, phlebitis/infusion site reactions, and diarrhea.

Please see full Prescribing Information.
Important Safety Information

INDICATION AND USAGE

VABOMERE® (meropenem and vaborbactam) is indicated for the treatment of patients 18 years of age and older with complicated urinary tract infections (cUTI) including pyelonephritis caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae species complex.


Contraindications

VABOMERE® is contraindicated in patients with known hypersensitivity to any components of VABOMERE® (meropenem and vaborbactam), or to other drugs in the same class or in patients who have demonstrated anaphylactic reactions to beta-lactam antibacterial drugs.