Preview

PULMONOLOGIYA

Advanced search

Therapy of gram-negative infection in the complex treatment of cystic fibrosis

https://doi.org/10.18093/0869-0189-2023-33-4-498-508

Abstract

Chronic lung infections are a consequence of the disturbance of mucociliary clearance process in cystic fibrosis. For most patients with cystic fibrosis, chronic lung infection is associated with a poor prognosis. The impact of chronic Pseudomonas aeruginosa infection on progressive deterioration of lung function and nutritional status has been established. Timely and effective antibiotic therapy aimed at eradication or control of gram-negative flora affects the duration and quality of life. The purpose of the study. To investigate the safety and efficacy of inhaled administration of sodium colistimethate (Colimistin®). Methods. The study enrolled 42 patients (27 patients aged 5 to 17 years and 15 patients over 18 years) with an established diagnosis of cystic fibrosis, 38 with monoculture of P. aeruginosa or various associations, 4 with Achromobacter spp. culture. Microbial status, external respiratory function, nutritional status, assessment of well-being, adverse reactions, exacerbations, and use of antibiotic therapy during colimistin inhalations were recorded in all patients at baseline and at 3 months. Results. A significant improvement in nutritional status in terms of weight (p < 0.007) and height (p < 0.001) was shown in the general patient group and the children’s group. In the group of children, there was a significant increase in weight (p < 0.034) and height (p < 0.0001). In the group of patients older than 18 years, there was a significant increase in weight (p < 0.045) and BMI three months after therapy (p < 0.013). There were no significant improvements in FVC and FEV1. The treatment efficacy was shown by the assessment of well-being in the general patient group (p < 0.001) and in the children’s group (p < 0.002). No significant difference was found in the adult patient group (p < 0.067). Two patients dropped out of the study due to ADR at the start of therapy. Conclusion. Sodium colistimethate showed efficacy and safety in bronchopulmonary infections caused by P. aeruginosa in monoculture and in association with Achromobacter spp. and may be recommended for use in children and adults with cystic fibrosis.

About the Authors

A. Yu. Voronkova
Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics”, Ministry of Science and Higher Education of the Russian Federation; Moscow Region State Budgetary Healthcare Institution “Research Clinical Institute of Childhood, Ministry of Health of the Moscow Region”
Russian Federation

Anna Yu. Voronkova - Candidate of Medicine, Leading Researcher, Scientific and Clinical Department of Cystic Fibrosis, Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics”, Ministry of Science and Higher Education of the Russian Federation; Pediatrician, Department of Cystic Fibrosis, Moscow Region State Budgetary Healthcare Institution “Research Clinical Institute of Childhood, Ministry of Health of the Moscow Region”.

Moskvorechye ul. 1, Moscow, 115522; Bolshaya Serpukhovskaya ul. 62, Moscow, 115093

tel.: (495) 111-03-03


Competing Interests:

None



E. K. Zhekaite
Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics”, Ministry of Science and Higher Education of the Russian Federation; Moscow Region State Budgetary Healthcare Institution “Research Clinical Institute of Childhood, Ministry of Health of the Moscow Region”
Russian Federation

Elena K. Zhekaite - Candidate of Medicine, Senior Researcher, Department of Cystic Fibrosis, Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics”, Ministry of Science and Higher Education of the Russian Federation; Pediatrician, Department of Cystic Fibrosis, Moscow Region State Budgetary Healthcare Institution “Research Clinical Institute of Childhood, Ministry of Health of the Moscow Region”.

Moskvorechye ul. 1, Moscow, 115522; Bolshaya Serpukhovskaya ul. 62, Moscow, 115093

tel.: (499) 324-15-01


Competing Interests:

None



V. D. Sherman
Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics”, Ministry of Science and Higher Education of the Russian Federation
Russian Federation

Viktoriya D. Sherman - Candidate of Medicine, Leading Researcher, Research and Clinical Division of Cystic Fibrosis, Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics”, Ministry of Science and Higher Education of the Russian Federation.

Moskvorechye ul. 1, Moscow, 115522

tel.: (916) 188-24-76


Competing Interests:

None



E. L. Amelina
Federal State Budgetary Institution “Pulmonology Scientific Research Institute” under Federal Medical and Biological Agency of Russian Federation
Russian Federation

Elena L. Amelina - Candidate of Medicine, Head of the Laboratory of Cystic Fibrosis, Federal State Budgetary Institution “Pulmonology Scientific Research Institute” under Federal Medical and Biological Agency of Russian Federation.

Orekhovyy bul’var 28, Moscow, 115682

tel.: (495) 410-67-00


Competing Interests:

None



A. V. Orlov
St. Petersburg State Budgetary Institution of Health Care “Children’s City Hospital of St. Olga”; North-Western State Medical University named after I.I. Mechnikov, Ministry of Health of the Russian Federation
Russian Federation

Aleksander V. Orlov - Candidate of Medicine, Head of the Infectious-Boxing Department, St. Petersburg State Budgetary Institution of Health Care “Children's City Hospital of St. Olga”; Associate Professor, Department of Pediatrics and Neonatology, North-Western State Medical University named after I.I. Mechnikov, Ministry of Health of the Russian Federation.

Zemledel’cheskaya ul. 2, Saint-Petersburg, 194156; Kirochnaya ul. 41, Saint-Petersburg, 191015

tel.: (812) 246-09-41


Competing Interests:

None



O. V. Usacheva
State Budgetary Clinical Health Institution of the Yaroslavl Region “Central City Hospital”, Department of Health and Pharmacy
Russian Federation

Olga V. Usacheva - Pulmonologist - Children's Polyclinic No.1, State Budgetary Clinical Health Institution of the Yaroslavl Region “Central City Hospital”, Department of Health and Pharmacy, Yaroslavl Region.

Oktyabrya pr. 52, 150040, Yaroslavl

tel.: (4852) 72-89-52


Competing Interests:

None



V. V. Tarakanova
State Budgetary Clinical Health Institution of the Yaroslavl Region “Central City Hospital”, Department of Health and Pharmacy
Russian Federation

Valentina V. Tarakanova - Pulmonologist, Pulmonology Department, State Budgetary Clinical Health Institution of the Yaroslavl Region “Central City Hospital”, Department of Health and Pharmacy, Yaroslavl Region.

Oktyabrya pr. 52, 150040, Yaroslavl

tel.: (4852) 72-89-52


Competing Interests:

None



L. V. Smirnova
State Budgetary Clinical Health Institution of the Yaroslavl Region “Central City Hospital”, Department of Health and Pharmacy
Russian Federation

Larisa V. Smirnova - Candidate of Medicine, Pulmonologist, Pediatric Pulmonology Department, State Budgetary Clinical Health Institution of the Yaroslavl Region “Central City Hospital”, Department of Health and Pharmacy, Yaroslavl Region.

Oktyabrya pr. 52, 150040, Yaroslavl

tel.: (4852) 72-89-52


Competing Interests:

None



E. V. Pasnova
Moscow Region State Budgetary Healthcare Institution “Research Clinical Institute of Childhood, Ministry of Health of the Moscow Region”
Russian Federation

Ekaterina V. Pasnova - Head of the Department of Cystic Fibrosis, Moscow Region State Budgetary Healthcare Institution “Research Clinical Institute of Childhood, Ministry of Health of the Moscow Region”.

Bolshaya Serpukhovskaya ul. 62, Moscow, 115093

tel.: (499) 237-02-23


Competing Interests:

None



N. D. Odinaeva
Moscow Region State Budgetary Healthcare Institution “Research Clinical Institute of Childhood, Ministry of Health of the Moscow Region”
Russian Federation

Nuriniso D. Odinaeva - Doctor of Medicine, Professor, Director, Moscow Region State Budgetary Healthcare Institution “Research Clinical Institute of Childhood, Ministry of Health of the Moscow Region”.

Bolshaya Serpukhovskaya ul. 62, Moscow, 115093

tel.: (499) 237-02-23


Competing Interests:

None



E. I. Kondratyeva
Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics”, Ministry of Science and Higher Education of the Russian Federation; Moscow Region State Budgetary Healthcare Institution “Research Clinical Institute of Childhood, Ministry of Health of the Moscow Region”
Russian Federation

Elena I. Kondratyeva - Doctor of Medicine, Professor, Head of the Scientific and Clinical Department of cystic fibrosis, Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics”, Ministry of Science and Higher Education of the Russian Federation; Deputy Director for Science, Moscow Region State Budgetary Healthcare Institution “Research Clinical Institute of Childhood, Ministry of Health of the Moscow Region”.

Moskvorechye ul. 1, Moscow, 115522; Bolshaya Serpukhovskaya ul. 62, Moscow, 115093

tel.: (495) 111-03-03


Competing Interests:

None



References

1. Kapranov N.I., Kashirskaya N.Yu., Kondratyeva E.I., eds. [Cystic fibrosis]. 2nd Edn. Moscow: Medpraktika; 2021 (in Russian).

2. Emerson J., Rosenfeld M., McNamara S. et al. Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis. Pediatr. Pulmonol. 2002; 34 (2): 91–100. DOI: 10.1002/ppul.10127.

3. Lazareva A.V., Chebotar' I.V., Kryzhanovskaya O.A. et al. [Pseudomonas aeruginosa: pathogenicity, pathogenesis and diseases]. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya. 2015; 17 (3): 170–186. Available at: https://cmac-journal.ru/publication/2015/3/cmac-2015-t17-n3-p170/cmac-2015-t17-n3-p170.pdf (in Russian).

4. Shaginyan I.A., Kapranov N.I., Chernukha M.Yu. et al. [Microbial landscape of developing developmental pathways in different age groups of children with cystic fibrosis]. Zhurnal mikrobiologii, epidemiologii i immunobiologii. 2010; 87 (1): 15–20. Available at: https://microbiol.crie.ru/jour/article/view/13395 (in Russian).

5. Kondratyeva E.I., Krasovskiy S.A., Starinova M.A., eds. [Register of patients with cystic fibrosis in the Russian Federation. 2020]. Moscow: Medpraktika-M; 2022. Available at: http://audit-orfan.clin-reg.ru/assets/files/site_Registre_2020.pdf (in Russian).

6. Kondratyeva E.I., Kashirskaya N.Yu., Kapranova N.I., eds. [National consensus. Cystic fibrosis: definition, diagnostic criteria, therapy. Moscow: Borges; 2019. Available at: https://mukoviscidoz.org/doc/konsensus/2019/konsensus-2019-bez-rentgenogramm.pdf (in Russian).

7. Sukhorukova M.V., Eidelshtein M.V., Skleenova E.Yu. et al. [Antimicrobial resistance of nosocomial Enterobacterales isolates in Russia: results of multicenter epidemiological study “MARATHON 2015–2016”]. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya. 2019; 21 (2): 147–159. DOI: 10.36488/cmac.2019.2.147-159 (in Russian).

8. Polikarpova S.V., Kondratyeva E.I., Shabalova L.A. et al. [Microflora of the respiratory tract in patients with cystic fibrosis and sensitivity to antibiotics in a 15-year follow-up (2000–2015)]. Meditsinskiy sovet. 2016; (15): 84–89. DOI: 10.21518/2079-701X-2016-15-84-89 (in Russian).

9. Avetisyan L.R., Shaginyan I.A., Chernukha M.Yu, Siyanova E.A. [Molecular mechanisms of formation of antibiotic resistance in Pseudomonas aeruginosa during chronic lung infection in patients with cystic fibrosis. Abstracts of the XX International IACMAC Congress on Antimicrobial Therapy and Clinical Microbiology]. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya. 2018; 20 (Suppl. 1): 8. Available at: https://www.ulsu.ru/media/uploads/artamonovamn2013%40yandex.ru/2018/12/13/XX_%D0%9C%D0%90%D0%9A%D0%9C%D0%90%D0%A5_%D1%82%D0%B5%D0%B7%D0%B8%D1%81%D1%8B.pdf (in Russian).

10. Voronkova A.Yu., Kondratyeva, Chernukha M.Yu. et al. [Analysis of the microbiological landscape of patients with cystic fibrosis in the Russian Federation in 2018-2019]. Rossiyskiy vestnik perinatologii i pediatrii. 2020; 65 (4): 298. Available at: https://cyberleninka.ru/article/n/analiz-mikrobiologicheskogo-peyzazha-patsientov-s-mukovistsidozom-v-rossiyskoy-federatsii-v-2018-2019g/viewer (in Russian).

11. Hengzhuang W., Green K., Pressler T. et al. Optimization of colistin dosing regimen for cystic fibrosis patients with chronic Pseudomonas aeruginosa biofilm lung infections. Pediatr. Pulmnol. 2019; 54 (5): 509–657. DOI: 10.1002/ppul.24269.

12. Shabalova L.A., Polikarpova S.V., Pivkina N.V. et al. [Experience of sodium colistimethate (colistin) use for pseudomonas aeruginosa infection in children with cystic fibrosis]. Pediatriya. Zhurnal im. G. N. Speranskogo. 2016; (6): 85–88 Available at: http://pediatriajournal.ru/files/upload/mags/355/2016_6_4772.pdf [Accessed: March 20, 2023] (in Russian).

13. Balalaeva M.A., Selivanova L.V., Dymova O.V. et al. [Clinical case of effective treatment of pneumonia caused by polyresistant strains with the use of inhalation colistimethate sodium]. Vestnik anesteziologii i reanimatologii. 2022; 19 (6): 72–77. DOI: 1021292/2078-5658-2022-19-6-72-77 (in Russian).

14. Castellani C., Duff A.J.A., Bell S.C. et al. ECFS best practice guidelines: the 2018 revision. J. Cyst. Fibros. 2018; 17 (2): 153–178. DOI: 10.1016/j.jcf.2018.02.006.

15. Morton R., Doe S., Banya W. et al. EPS7.10 Clinical benefit of continuous nebulised Aztreonam Lysine for Inhalation (AZLI) in adults with cystic fibrosis – a retrospective cohort study. J. Cyst. Fibros. 2017; 16 (Suppl. 1): 55. DOI: 10.1016/S1569-1993(17)30340-5.

16. Ratjen F., Munck A., Kho P. et al. Treatment of early Pseudomonas aeruginosa infection in patients with cystic fibrosis: the ELITE trial. Thorax. 2010; 65 (4): 286–291. DOI: 10.1136/thx.2009.121657.

17. Taccetti G., Bianchini E., Cariani L. Early antibiotic treatment for Pseudomonas aeruginosa eradication in patients with cystic fibrosis: a randomised multicentre study comparing two different protocols. Thorax. 2012; 67 (10): 853–859. DOI: 10.1136/thoraxjnl-2011-200832.

18. Proesmans M., Vermeulen F., Boulanger L. et al. Comparison of two treatment regimens for eradication of Pseudomonas aeruginosa infection in children with cystic fibrosis. J. Cyst. Fibros. 2013; 12 (1): 29–34. DOI: 10.1016/j.jcf.2012.06.001.

19. Döring G., Flume P., Heijerman H. et al. Treatment of lung infection in patients with cystic fibrosis: current and future strategies. J. Cyst. Fibros. 2012; 11 (6): 461–479. DOI: 10.1016/j.jcf.2012.10.004.

20. Smith S., Rowbotham N.J., Regan K.H. Inhaled anti-pseudomonal antibiotics for long-term therapy in cystic fibrosis. Cochrane Database Syst. Rev. 2018; 3 (3): CD001021. DOI: 10.1002/14651858.CD001021.pub3.

21. Vardakas K.Z., Voulgaris G.L., Samonis G., Falagas M.E. Inhaled colistin monotherapy for respiratory tract infections in adults without cystic fibrosis: a systematic review and meta-analysis. Int. J. Antimicrob. Agents. 2018; 51 (1): 1–9. DOI: 10.1016/j.ijantimicag.2017.05.016.

22. Langton Hewer S.C., Smyth A.R. Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis. Cochrane Database Syst. Rev. 2014; (11): CD004197. DOI: 10.1002/14651858.cd004197.pub4.

23. Taccetti G., Francalanci M., Pizzamiglio G. et al. Cystic fibrosis: recent Insights into inhaled antibiotic treatment and future perspectives. Antibiotics (Basel). 2021; 10 (3): 338. DOI: 10.3390/antibiotics10030338.

24. Graham B.L., Steenbruggen I., Miller M.R. et al. Standardization of spirometry 2019 update. An official American Thoracic Society and European Respiratory Society Technical Statement. Am. J. Respir. Crit. Care Med. 2019; 200 (8): e70–88. DOI: 10.1164/rccm.201908-1590st.

25. Polgar G.V. Promadhat pulmonary function testing in children: Techniques and standards. Philadelphia: W.B.Saunders Co; 1971.

26. Polikarpova S.V., Zhilina S.V., Kondratenko O.V. et al. [Guidelines for the microbiological diagnosis of respiratory tract infections in patients with cystic fibrosis]. Tverʹ; 2019 (in Russian).

27. Ministry of Health of the Russian Federation [Methods of bacteriological research of conditionally pathogenic microorganisms in clinicalmicrobiology: Guidelines]. Moscow; 1991. Available at: https://files.stroyinf.ru/Index2/1/4293727/4293727337.htm [Accessed: March 03, 2023] (in Russian).

28. [IACMAC recommendations. Determination of the sensitivity of microorganisms to antimicrobial drugs]. 2021. Available at: https://www.antibiotic.ru/minzdrav/category/clinical-recommendations/ [Accessed: March 17, 2023] (in Russian).

29. The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 12.0. 2022. Available at: https://www.eucast.org/clinical_breakpoints [Accessed: March 17, 2023].


Supplementary files

Review

For citations:


Voronkova A.Yu., Zhekaite E.K., Sherman V.D., Amelina E.L., Orlov A.V., Usacheva O.V., Tarakanova V.V., Smirnova L.V., Pasnova E.V., Odinaeva N.D., Kondratyeva E.I. Therapy of gram-negative infection in the complex treatment of cystic fibrosis. PULMONOLOGIYA. 2023;33(4):498-508. (In Russ.) https://doi.org/10.18093/0869-0189-2023-33-4-498-508

Views: 434


ISSN 0869-0189 (Print)
ISSN 2541-9617 (Online)