Vytvorenie PP

Organisation: Slovenská spoločnosť infektológov pri SLS

Created at: 31.03.2025

Processed at: 07.04.2026

Question

Coadministration of ATM with CAZ/AVI is recommended by the IDSA 2023 (US) and ESCMID 2022 (European) guidelines, as well as other country-level guidelines that emphasize the need for treatment of infections caused by MBL-producing Enterobactrales, highlighting the unmet medical need for effective therapy for these types of infections. At the same time, however, in this way and in the current absence of an ATM/AVI combination, there is unnecessary use of CAZ and suboptimal dosing regimens.1-4 Emblaveo (aztreonam-avibactam [ATM/AVI]) is the first combination of aztreonam (ATM), a monocyclic β-lactam (also called monobactam), and avibactam (AVI), a β-lactamase inhibitor (BLI), in a fixed ratio of 3:1, including the treatment of suspected serious infections or ATM/AVI infections was developed for the treatment of serious Gram-negative infections, including those producing MBL, for which there are limited or no treatment options.5 ATM/AVI hereby covers an unmet medical need by optimizing the dosing regimen and eliminating unnecessary CAZ administration. The availability of ATM/AVI also addresses the need for safe and effective antibiotics to treat infections caused by MBL-producing Enterobacterales and S. maltophilia, which can also produce other problematic β-lactamases such as ESBLs, OXA-48, and KPCs. The global increase in antimicrobial resistance (AMR) requires new, effective treatment options to reduce mortality and limit costly resources for healthcare facilities worldwide. Based on the current available evidence from Phase 1, 2a, and 3 studies, ATM/AVI demonstrates a positive benefit-risk profile for the treatment of life-threatening infections caused by Enterobacterales (including those producing MBL) and S. maltophilia, which represent a serious problem with substantial unmet medical need. Emlaveo (aztreonam/avibactam) is indicated for the treatment of severe intra-abdominal infections, severe pneumonias (including ventilator-associated pneumonias) and severe uroinfections (including pyeonephritis). Based on the principal diagnosis as the reason for hospitalisation, hospital cases are assigned to different DRG groups The cost of routine standard antibiotic treatment is included in the cost of the relevant DRG group. Currently, three antibiotics from the cephalosporin group are separately reimbursed as add-on items to the hospital case (i.e. included in the Catalogue of Case Rates in Annex 1 Drugs and Medicines): ceftazidime/avibactam, ceftaroline foasamil and ceftolozane/tazobactam. Below are representative examples of hospitalisation cases: hospitalisation case with a principal diagnosis of N10 Acute tubulointerstitial nephritis, infectious interstitial nephritis, pyelitis, pyelonephritis and a secondary diagnosis of the causative agent with code U81! The causative agent with multidrug-resistance to antibiotics is assigned to DRG group L63F with a relative weight of 0.7284 (upper limit of treatment time of 14 days) or L63C with a relative weight of 1.3522 (upper limit of treatment time of 27 days). At the national reference base rate of €3 269, the reimbursement for this hospitalisation case is €2 3814.14 and €4 420.34 respectively. The cost of aztreonam/avibactam administered for only 7 days in the basic dosing schedule € 6,177.03. The hospitalisation case with principal diagnosis A41.53 Sepsis caused by multidrug-resistant Gram-negative bacteria is assigned to DRG group T60E with a relative weight of 1.3426 (upper limit of treatment time 22 days). At the national reference base rate of €3,269, the reimbursement for this hospitalisation case is €4,388.96. With aztreonam/avibactam administered for 14 days, the cost of this drug alone would be €11,118.60. The reimbursement for the hospital case, calculated as the product of the relative weight of the DRG group to which the hospital case is assigned and the basic rate, is not even sufficient to purchase the medicine alone, without taking into account the cost of other related treatment and the comprehensive provision of health care. The inclusion of a medicine in the List of Allowable Items will provide providers with certainty of financial stability, realistic reimbursement for the care provided and avoid the risk of the PHC falling into a negative economic balance. References: 1. Pintado V, Ruiz-Garbajosa P, Aguilera-Alonso D, et al. Executive summary of the consensus document of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) on the diagnosis and antimicrobial treatment of infections due to carbapenem-resistant Gram-negative bacteria. Enfermedades infecciosas y microbiologia clinica (English ed). 2023;41(6):360-370. 2 . Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious diseases society of America 2023 guidance on the treatment of antimicrobial resistant gram-negative infections. Clinical Infectious Diseases. 2023:428. 3. Paul M, Carrara E, Retamar P, et al. European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European society of intensive care medicine). Clinical Microbiology and Infection. 2022;28(4):521-547. 4. Zeng M, Xia J, Zong Z, et al. Guidelines for the diagnosis, treatment, prevention and control of infections caused by carbapenem-resistant Gram-negative bacilli. Journal of Microbiology, Immunology and Infection. 2023;56(4):653-671. 5. Yehuda Carmeli, José Miguel Cisneros, Mical Paul, et al. Efficacy and Safety of Aztreonam-Avibactam for the Treatment of Serious Infections Due to Gram-Negative Bacteria, Including Metallo-β-Lactamase-Producing Pathogens: Phase 3 REVISIT Study. presented at: IDWeek 2023; 2023; Boston, USA. - For which indication do you use the desired potential PP, please describe examples of diagnoses, patient conditions Aztreonam/avibactam is indicated in adult patients for the treatment of the following infections : - complicated intra-abdominal infection (cIAI; complicated intra-abdominal infection), - nosocomial pneumonia (HAP; hospital-acquired pneumonia) including ventilator-associated pneumonia (VAP; ventilator-associated pneumonia), - complicated urinary tract infection (cUTI; complicated urinary tract infection) including pyelonephritis. Aztreonam/avibactam is indicated for adult patients with limited treatment options also for the treatment of infections caused by aerobic Gram-negative organisms - for drugs and CAM, please describe how the use of the above materials differs from routine practice (PP should not be a routinely used drug/ CAM, which is reimbursed in a lump sum payment at correctly reported costs) The drug Emblaveo (aztreonam/avibactam) belongs to the group of reserve antibiotics and will be used exclusively in hospitals after approval by the antibiotic committee based on the results of microbiological testing in the approved indications. - According to your approximate estimate of how many patients are affected by the use of PP, either in your facility, if you can estimate the above also in the Slovak Republic According to epidemiological data and also consultations with clinical experts, the use of PP affects approximately 100-150 patients with MBL-producing pathogens per year - approximate cost of the required PP Officially determined price of Emblaveo 1.5 g/0.5 g powder for concentrate for infusion solution, plc ifc 10x1.5 g/0.5 g (drug.inj.glass) is 1923,51 EUR (List of officially established prices for medicinal products (source: https://www.health.gov.sk/Clanok?zuuc-202503-lieky) The final price in the institutional pharmacy is 2059,01 EUR for one pack containing 10 ampoules. Cost of a 7-day treatment: - saturation dose : 2 ampoules of the medicine, - maintenance dose : 1 ampoule of the medicine, - maintenance dose : 1 ampoule of the medicine. 6 hours - total cost (29 ampoules) = € 5 971,10 - whether the PP is to be linked to an existing medical procedure or whether you are proposing to create a new medical procedure, in case of a proposal for a new medical procedure, please indicate the wording of the medical procedure you are proposing Inclusion in the List of attributable items is proposed in the same breakdown as the administration of the medicinal product in the List of Medical Procedures: Administration of aztreonam/avibactam, parenteral from 2 g/0.67 g to less than 3.5 g/1.12 g Administration of aztreonam/avibactam, parenteral from 3.5 g/1.12 g to less than 5 g/1.62 g Administration of aztreonam/avibactam, parenteral from 5 g/1.62 g to less than 6.5 g/2.12 g Administration of aztreonam/avibactam, parenteral from 6.5 g/2.12 g to less than 8 g/2.62 g Administration of aztreonam/avibactam, parenteral from 8 g/2.62 g to less than 14 g/4.62 g Administration of aztreonam/avibactam, parenteral from 14 g/4.62 g to less than 20 g/6.62 g Administration of aztreonam/avibactam, parenteral from 20 g/6 g to less than 20 g/6.62 g Administration of aztreonam/avibactam, parenteral from 20 g/6 g to less than 20 g/6.62 g62 g to less than 26 g/8,62 g Aztreonam/avibactam administration, parenteral from 26 g/8,62 g to less than 32 g/10,62 g Aztreonam/avibactam administration, parenteral from 32 g/10,62 g to less than 38 g/12.62 g Administration of aztreonam/avibactam, parenteral from 38 g/12.62 g to less than 44 g/14.62 g Administration of aztreonam/avibactam, parenteral from 44 g/14,62 g to less than 50 g/16.62 g Aztreonam/avibactam administration, parenteral from 50 g/16.62 g to less than 56 g/18.62 g Aztreonam/avibactam administration, parenteral from 56 g/18.62 g to less than 62 g/20,62 g Administration of aztreonam/avibactam, parenteral from 62 g/20,62 g to less than 68 g/22,62 g Administration of aztreonam/avibactam, parenteral from 68 g/22,62 g to less than 74 g/24,62 g Aztreonam/avibactam administration, parenteral from 74 g/24,62 g to less than 80 g/26,62 g Aztreonam/avibactam administration, parenteral from 80 g/26,62 g to less than 86 g/28,62 g

Answer

That request has been reassessed in accordance with Chapter 8 of the Methodology for Updating Attributable Items for SK-DRG 2026, available here: https://www.cksdrg.sk/sk/dokumenty/568/Metodika%20aktualizácie%20pripočítateľných%20položiek%20pre%20SK-DRG%202026.pdf

Given that the criteria were met, the Medical Review Panel proceeded to a vote, which is recorded in the minutes available here: https://www.cksdrg.sk/sk/dokumenty/571/Zápisy%20z%20rokovaní%20medicínsko-analytickej%20pracovnej%20skupiny%20s%20hlasovaniami.pdf

The proposed PP was approved and incorporated into the CMP with a Type A reimbursement in accordance with the above methodology and by vote of the working group with the pricing resulting from the methodology as 90% of the UUC.