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Журнал микробиологии, эпидемиологии и иммунобиологии. 2020; 97: 418-423

Колонизационная активность клинических изолятов дрожжевых грибов рода Candida и их антибиотикочувствительность

Ахапкина Ирина Гавриловна, Глушакова Анна Марковна, Родионова Евгения Николаевна, Качалкин Алексей Владимирович

https://doi.org/10.36233/0372-9311-2020-97-5-4

Аннотация

Введение. Развитие микозов связывают с иммунокомпрометацией макроорганизма. Задачей исследования было изучение колонизационной активности и резистентности дрожжевых грибов рода Candida, выделенных из клинического материала в 2014 и 2019 гг. в Москве.

Материалы и методы. Диско-диффузным методом определяли антибиотикочувствительность 75 штаммов дрожжевых грибов следующих видов: C. albicans, C. parapsilosis, C. glabrata, C. krusei (Pichia kudriavzevii), C. intermedia, C. tropicalis, C. lusitaniae (Clavispora lusitaniae), C. guilliermondii (Meyerozyma guilliermondii). В 2014 г. выделены 34 штамма у людей с гиперчувствительностью в анамнезе (27 — с кожных покровов, 7 — со слизистой ротовой полости), в 2019 г выделили 41 штамм со слизистой влагалища людей с онкологическими заболеваниями. Использовали диски с флуконазолом (40 мкг), нистатином (80 мкг), клотримазолом (10 мкг), итраконазолом (10 мкг), амфотерицином В (40 мкг).

Результаты. В 2014 г. колонизационная активность убывала в ряду: C. albicans (23,53%), C. tropicalis (20,59%), C. guilliermondii (20,59%), C. parapsilosis (17,65%), C. glabrata (17,65%); в 2019 г. — C. parapsilosis (21,95%), C. albicans (17,07%), C. tropicalis (12,19%), C. guilliermondii (12,19%), C. krusei (9,76%), C. glabrata (9,76%), C. lusitaniae (9,76%), C. intermedia (7,32%). Выделенные в 2014 г. грибы обладали чувствительностью ко всем антимикотикам, за исключением 16,67% штаммов C. glabrata (флуконазол) и 14,28% штаммов C. tropicalis (нистатин). Выделенные в 2019 г. 11,11% C. parapsilosis и 40% C. tropicalis были резистентны ко всем антимикотикам; 71,43% C. albicans, 50% C. glabrata, 20% C. guilliermondii — к флуконазолу; 28,57% C. albicans — к нистатину, клотримазолу, итраконазолу, амфотерицину В; 25% C. glabrata — к амфотерицину В; C. krusei — к клотримазолу (100%), флуконазолу и нистатину (50%), итраконазолу и амфотерицину В (25%); C. lusitaniae — к флуконазолу и нистатину (100%), клотримазолу и амфотерицину В (75%), итраконазолу (50%).

Заключение. В течение 5 лет в Московском регионе расширился спектр выявляемых видов грибов за счет C. krusei, C. lusitaniae и C. intermedia (26,86% кандидозов в 2019 г). При этом дрожжевые грибы, выделенные в 2019 г, отличаются высоким количеством резистентных штаммов по сравнению с грибами, выделенными в 2014 г.

Список литературы

1. Krcmery V, Barnes AJ. Non-albicans Candida spp. causing fungaemia: pathogenicity and antifungal resistance. J. Hosp. Infect. 2002; 50(4): 243-60. https://doi.org/10.1053/jhin.2001.1151

2. Aquino V.R., Lunardi L.W., Goldani L.Z., Barth A.L. Prevalence, susceptibility profile for fluconazole and risk factors for candidemia in a tertiary care hospital in southern Brazil. Braz. J. Infect. Dis. 2005; 9(5): 411-8. https://doi.org/10.1590/s1413-86702005000500009

3. Di Mambro T., Guerriero I., Aurisicchio L., Magnani M., Marra E. The yin and yang of current antifungal therapeutic strategies: how can we harness our natural defenses? Front. Pharmacol. 2019; 10: 80. https://doi.org/10.3389/fphar.2019.00080

4. Леонов В.В., Миронов А.Ю., Леонова Л.В., Никитина Л.Ю. Этиологическая структура и биологические свойства возбудителей инфекций кровотока. Клиническая лаборатор¬ная диагностика. 2016; 61(11): 790-3. https://doi.org/10.18821/0869-2084-2016-11-790-793

5. Gale C., Finkel D., Tao N., Meinke M., McClellan M., Olson J., et al. Cloning and expression of a gene encoding an integrin-like protein in Candida albicans. Proc. Natl. Acad. Sci. USA. 1996; 93(1): 357-61. https://doi.org/10.1073/pnas.93.1.357

6. Jensen R.H. Resistance in human pathogenic yeasts and fila-mentous fungi: prevalence, underlying molecular mechanisms and link to the use of antifungals in humans and the environ-ment. Dan. Med. J. 2016; 63(10): B5288.

7. Yao D., Chen J., Chen W., Li Z., Hu X. Mechanisms of azole resistance in clinical isolates of Candida glabrata from two hos-pitals in China. Infect. Drug Resist. 2019; 12: 771-81. https://doi.org/10.2147/IDR.S202058

8. Arastehfar A., Daneshnia F., Zomorodian K., Najafzadeh M.J., Khodavaisy S., Zarrinfar H., et al. Low level of antifungal re-sistance in iranian isolates of Candida glabrata recovered from blood samples in a Multicenter Study from 2015 to 2018 and potential prognostic values of genotyping and sequencing of PDR1. Antimicrob. Agents Chemother. 2019; 63(7): e02503-18. https://doi.org/10.1128/aac.02503-18

9. Jacobsen I.D., Wilson D., Wachtler B., Brunke S., Naglik J.R., Hube B. Candida albicans dimorphism as a therapeutic target. Expert. Rev. Anti Infect. Ther. 2012; 10(1): 85-93. https://doi.org/10.1586/eri.11.152

10. Munoz P., Sanchez-Somolinos M., Alcala L., et al. Candida krusei fungaemia: antifungal susceptibility and clinical presen-tation of an uncommon entity during 15 years in a single general hospital. J. Antimicrob. Chemother. 2005; 55(2): 188-93. https://doi.org/10.1093/jac/dkh532

11. Tan T.Y., Tan A.L., Tee N.W., Ng L.S. A retrospective analysis of antifungal susceptibilities of Candida bloodstream isolates from Singapore hospitals. Ann. Acad. Med. Singap. 2008; 37(10): 835-40.

12. Pfaller M.A., Diekema D.J. Twelve years of fluconazole in clinical practice: global trends in species distribution and fluco-nazole susceptibility of bloodstream isolates of Candida. Clin. Microbiol. Infect. 2004; 10(Suppl. 1): 11-23. https://doi.org/10.1111/j.1470-9465.2004.t01-1-00844.x

13. Karabijak N., Alem N. Antifungal susceptibility profiles of Candida species to triazole: application of new CLSI species-specific clinical breakpoints and epidemiological cutoff values for characterization of antifungal resistance. Mikrobiyol. Bul. 2016; 50(1): 122-32. (in Turkish)

14. Кулько А.Б. Активность in vitro анидулафунгина в отношении дрожжевых грибов возбудителей системных и диссеминированных микозов. Онкогематология. 2015; 10(3): 51-55. https://doi.org/10.17650/1818-8346-2015-103-53-57

15. Кулько А.Б., Митрохин С.Д., Мороз А.М. Микотическая инфекция дыхательных путей во фтизиатрической практике: видовой состав и чувствительность клинических штаммов грибов рода Candida к антифунгальным препаратам. Антибиотики и химиотерапия. 2005; 50(4): 14-7.

16. Li R., Zhang L., Zhang H., Yi Y, Wang L., Chen L., et al. Protective effect of a novel antifungal peptide derived from human chromogranin a on the immunity of mice infected with Candida krusei. Exp. Ther. Med. 2017; 13(5): 2429-34. https://doi.org/10.3892/etm.2017.4290

Journal of microbiology, epidemiology and immunobiology. 2020; 97: 418-423

Colonization activity of Candida clinical isolates and their antibiotic sensitivity

Akhapkina Irina G., Glushakova Anna M., Rodionova Evgeniya N., Kachalkin Aleksey V.

https://doi.org/10.36233/0372-9311-2020-97-5-4

Abstract

Background. The development of fungal infections is associated with immunocompromising of a macroorganism.

Aim. To study the colonization activity and resistance of Candida yeast strains isolated from clinical specimens in 2014 and 2019 in Moscow.

Materials and methods. Antibiotic sensitivity of 75 strains of the following yeast species was determined by disc-diffuse method: C. albicans, C. parapsilosis, C. glabrata, C. krusei (Pichia kudriavzevii), C. intermedia, C. tropicalis, C. lusitaniae (Clavispora lusitaniae), C. guilliermondii (Meyerozyma guilliermondii). In 2014, 34 strains were isolated in people with hypersensitivity history (27 — from the skin, 7 — from the oral mucosa). In 2019, 41 strains were isolated from the vaginal mucosa in people with cancer. Discs with fluconazole (40 pg), nystatin (80 pg), clotrimazole (10 pg), itraconazole (10 pg), amphotericin B (40 pg) were used.

Results. Among strains isolated in 2014, colonization activity was detected, in descending order, in C. albicans (23.53%), C. tropicalis (20.59%), C. guilliermondii (20.59%); C. parapsilosis (17.65%), C. glabrata (17.65%); in 2019 — C. parapsilosis (21.95%), C. albicans (17.07%), C. tropicalis (12.19%), C. guilliermondii (12.19%), C. krusei (9.76%), C. glabrata (9.76%), C. lusitaniae (9.76%), C. intermedia (7.32%). The yeasts isolated in 2014 were resistant to all antimicotics except 16.67% strains of C. glabrata (fluconazole) and 14.28% strains of C. tropicalis (nystatin). 11.11% C. parapsilosis and 40% C. tropicalis isolated in 2019 were sensitive to all antimicotics; 71.43% C. albicans, 50% C. glabrata, 20% C. guilliermondii were resistant to fluconazole; 28.57% C. albicans were resistant to nystatin, clotrimazole, intraconazole, amphotericin B; 25% C. glabrata resistant to amphotericin В; C. krusei — were resistant to clotrimazole (100%), fluconazole and nystatin (50%), itraconazole и amphotericin B (25%); C. lusitaniae resistant to fluconazole and nystatin (100%), clotrimazole and amphotericin B (75%), itraconazole (50%).

Conclusion. The range of detected species has expanded over five years in the Moscow region due to C. krusei, C. lusitaniae and C. intermedia (26.86% of candidiasis in 2019). Moreover, yeast fungi isolated in 2019 have a high number of resistant strains, compared to fungi isolated in 2014.

References

1. Krcmery V, Barnes AJ. Non-albicans Candida spp. causing fungaemia: pathogenicity and antifungal resistance. J. Hosp. Infect. 2002; 50(4): 243-60. https://doi.org/10.1053/jhin.2001.1151

2. Aquino V.R., Lunardi L.W., Goldani L.Z., Barth A.L. Prevalence, susceptibility profile for fluconazole and risk factors for candidemia in a tertiary care hospital in southern Brazil. Braz. J. Infect. Dis. 2005; 9(5): 411-8. https://doi.org/10.1590/s1413-86702005000500009

3. Di Mambro T., Guerriero I., Aurisicchio L., Magnani M., Marra E. The yin and yang of current antifungal therapeutic strategies: how can we harness our natural defenses? Front. Pharmacol. 2019; 10: 80. https://doi.org/10.3389/fphar.2019.00080

4. Leonov V.V., Mironov A.Yu., Leonova L.V., Nikitina L.Yu. Etiologicheskaya struktura i biologicheskie svoistva vozbuditelei infektsii krovotoka. Klinicheskaya laborator¬naya diagnostika. 2016; 61(11): 790-3. https://doi.org/10.18821/0869-2084-2016-11-790-793

5. Gale C., Finkel D., Tao N., Meinke M., McClellan M., Olson J., et al. Cloning and expression of a gene encoding an integrin-like protein in Candida albicans. Proc. Natl. Acad. Sci. USA. 1996; 93(1): 357-61. https://doi.org/10.1073/pnas.93.1.357

6. Jensen R.H. Resistance in human pathogenic yeasts and fila-mentous fungi: prevalence, underlying molecular mechanisms and link to the use of antifungals in humans and the environ-ment. Dan. Med. J. 2016; 63(10): B5288.

7. Yao D., Chen J., Chen W., Li Z., Hu X. Mechanisms of azole resistance in clinical isolates of Candida glabrata from two hos-pitals in China. Infect. Drug Resist. 2019; 12: 771-81. https://doi.org/10.2147/IDR.S202058

8. Arastehfar A., Daneshnia F., Zomorodian K., Najafzadeh M.J., Khodavaisy S., Zarrinfar H., et al. Low level of antifungal re-sistance in iranian isolates of Candida glabrata recovered from blood samples in a Multicenter Study from 2015 to 2018 and potential prognostic values of genotyping and sequencing of PDR1. Antimicrob. Agents Chemother. 2019; 63(7): e02503-18. https://doi.org/10.1128/aac.02503-18

9. Jacobsen I.D., Wilson D., Wachtler B., Brunke S., Naglik J.R., Hube B. Candida albicans dimorphism as a therapeutic target. Expert. Rev. Anti Infect. Ther. 2012; 10(1): 85-93. https://doi.org/10.1586/eri.11.152

10. Munoz P., Sanchez-Somolinos M., Alcala L., et al. Candida krusei fungaemia: antifungal susceptibility and clinical presen-tation of an uncommon entity during 15 years in a single general hospital. J. Antimicrob. Chemother. 2005; 55(2): 188-93. https://doi.org/10.1093/jac/dkh532

11. Tan T.Y., Tan A.L., Tee N.W., Ng L.S. A retrospective analysis of antifungal susceptibilities of Candida bloodstream isolates from Singapore hospitals. Ann. Acad. Med. Singap. 2008; 37(10): 835-40.

12. Pfaller M.A., Diekema D.J. Twelve years of fluconazole in clinical practice: global trends in species distribution and fluco-nazole susceptibility of bloodstream isolates of Candida. Clin. Microbiol. Infect. 2004; 10(Suppl. 1): 11-23. https://doi.org/10.1111/j.1470-9465.2004.t01-1-00844.x

13. Karabijak N., Alem N. Antifungal susceptibility profiles of Candida species to triazole: application of new CLSI species-specific clinical breakpoints and epidemiological cutoff values for characterization of antifungal resistance. Mikrobiyol. Bul. 2016; 50(1): 122-32. (in Turkish)

14. Kul'ko A.B. Aktivnost' in vitro anidulafungina v otnoshenii drozhzhevykh gribov vozbuditelei sistemnykh i disseminirovannykh mikozov. Onkogematologiya. 2015; 10(3): 51-55. https://doi.org/10.17650/1818-8346-2015-103-53-57

15. Kul'ko A.B., Mitrokhin S.D., Moroz A.M. Mikoticheskaya infektsiya dykhatel'nykh putei vo ftiziatricheskoi praktike: vidovoi sostav i chuvstvitel'nost' klinicheskikh shtammov gribov roda Candida k antifungal'nym preparatam. Antibiotiki i khimioterapiya. 2005; 50(4): 14-7.

16. Li R., Zhang L., Zhang H., Yi Y, Wang L., Chen L., et al. Protective effect of a novel antifungal peptide derived from human chromogranin a on the immunity of mice infected with Candida krusei. Exp. Ther. Med. 2017; 13(5): 2429-34. https://doi.org/10.3892/etm.2017.4290