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Can Prolonged Incubation of Negative Blood Cultures Show Fungal Positivity?

Year 2023, Volume: 12 Issue: 3, 543 - 547, 28.09.2023
https://doi.org/10.53424/balikesirsbd.1205875

Abstract

Objective: Standard duration of one set blood culture (BC) is a maximum of 5-7 days. The aim of this study was to evaluate “culture-negative” vials with a prolonged incubation (max 30 days) time and to observe any mycological growth. Materials and Methods: Routine BCs obtained from adult patients of Balıkesir Atatürk City Hospital for a year period were included. Render BC System BC128 (Render Biotech Co. Ltd., Shenzhen, China) were used. Randomly selected vials were re-incubated for additional three weeks by conventional methods. In case of any growth, identifications were done by PhoenixTM 100 system (Becton Dickinson, MA, USA) with cornmeal tween 80 agar (RTA Laboratories, Kocaeli, Türkiye). Antifungal susceptibility testing was applied with CLSI disk diffusion method. Results: A total of 6047 BC sets were obtained and randomly chosen 1040+122 negative sets (A and B groups, respectively) were included. In group A, none of them had fungal growth. In B (ongoing empiric antifungal ≤48h), only 2 sets showed significant fungal growth, which were observed in 7±2 days, and all strains were identified as Candida glabrata complex and these patients were on empiric fluconazole (200 mg/day). One isolate was susceptible dose dependent; the other one was resistant for fluconazole. Latter sets of these fungemia patients showed positive signals in routine incubation period. Conclusion: Invasive fungal infections are increasingly encountered and isolation capacity and optimization of BCs are crucial. In this study, it was obviously observed that standard incubation period is satisfactory in order to detect almost all fungemia.

Thanks

The authors wish to declare special thanks to Muradiye YARAR, M.D., İlkay BOZDAĞ, M.D., Onur IRMAK, M.D., and Osman KILINÇ, M.D. (Atatürk City Hospital, Department of Medical Microbiology, Balıkesir, Turkey) for their precious support.

References

  • Arikan-Akdagli, S., Gülmez, D., Doğan, Ö., Çerikçioğlu, N., Dereli, M. D., Birinci, A., & et al. (2019). First multicentre report of in vitro resistance rates in candidaemia isolates in Turkey. Journal of Global Antimicrobial Resistance, 18, 230-234. https://doi.org/10.1016/j.jgar.2019.04.003.
  • Baron, E. J., Scott, J. D., & Tompkins, L. S. (2005). Prolonged incubation and extensive subculturing do not increase recovery of clinically significant microorganisms from standard automated blood cultures. Clinical Infectious Diseases, 41(11), 1677-1680. https://doi.org/10.1086/497595.
  • Bourassa, L., Kates, O., & Liu, C. (2019). Limited diagnostic utility of extended aerobic blood culture incubation for fungal pathogen detection. Open Forum Infectious Diseases, 6(Suppl 2): S140.
  • Burduniuc, P. O., Bunescu, I., Sofronie, O., Bivol, M., Craciun, O., Burduniuc, A., & Balan, G. (2019). The importance of blood cultures in the effective management of bloodstream infections. Moldovan Medical Journal, 62(3), 28-37. https://doi.org/10.5281/zenodo.3404096 .
  • Butta, H., Sardana, R., Mendiratta, L., Sibal, A., Gupta, V., Chawla, R., & Jafri, A. A. (2019). Time to detection of yeast isolates in pediatric and adult patients with fungemia and its relevance to clinical profile and outcome. Indian Journal of Critical Care Medicine, 23(1): 27-30. https://doi.org/10.5005/jp-journals-10071-23108. Carreté, L., Ksiezopolska, E., Gómez-Molero, E., Angoulvant, A., Bader, O., Fairhead, C., & Gabaldón, T. (2019). Genome comparisons of Candida glabrata serial clinical isolates reveal patterns of genetic variation in infecting clonal populations. Frontiers in Microbiology, 10, 112. https://doi.org/10.3389/fmicb.2019.00112.
  • Clinical and Laboratory Standards Institute (CLSI). Method for antifungal disk diffusion susceptibility testing of yeasts, 3rd edition. CLSI Document M44. Wayne, Pennsylvania, USA, 2018.
  • Clinical and Laboratory Standards Institute (CLSI). Performance standards for antifungal susceptibility testing of yeasts, 1st edition. CLSI Supplement M60. Wayne, Pennsylvania, USA, 2017.
  • Cornely, O. A., Bassetti, M., Calandra, T., Garbino, J., Kullberg, B. J., Lortholary, O., & et al. (2012). ESCMID guideline for the diagnosis and management of Candida diseases 2012: non‐neutropenic adult patients. Clinical Microbiology and Infection, 18, 19-37. https://doi.org/10.1111/1469-0691.12039. Cuenca‐Estrella, M., Verweij, P. E., Arendrup, M. C., Arikan‐Akdagli, S., Bille, J., Donnelly, J. P., & et al. (2012). ESCMID guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures. Clinical Microbiology and Infection, 18, 9-18. https://doi.org/10.1111/1469-0691.12038 .
  • De Plato, F., Fontana, C., Gherardi, G., Privitera, G. P., Puro, V., Rigoli, R., & et al. (2019). Collection, transport and storage procedures for blood culture specimens in adult patients: recommendations from a board of Italian experts. Clinical Chemistry and Laboratory Medicine (CCLM), 57(11), 1680-1689. https://doi.org/10.1515/cclm-2018-1146 .
  • Dudakova, A., Blei, C., Groß, U., & Schulze, M. H. (2022). Impact of routine bedside infectious diseases service on clinical management and prognosis of patients with Candida fungemia–an example for Antifungal Stewardship at university level in Germany. International Journal of Infectious Diseases, 119, 150-159. https://doi.org/10.1016/j.ijid.2022.03.054.
  • Gülmez, D., Sığ, A. K., Akar, N., & Duyan, S. (2021). Changing trends in isolation frequencies and species of clinical fungal strains: what do the 12-years (2008-2019) mycology laboratory data tell about?. Mikrobiyoloji Bulteni, 55(1), 53-66. https://doi.org/10.5578/mb.20156.
  • Gülmez, D., Alp, S., Gursoy, G., Ayaz, C. M., Dogan, O., Arikan-Akdagli, S., & Akova, M. (2020). Mixed fungaemia: an 18-year report from a tertiary-care university hospital and a systematic review. Clinical Microbiology and Infection, 26(7), 833-841. https://doi.org/10.1016/j.cmi.2020.03.030.
  • Hassan, Y., Chew, S. Y., & Than, L. T. L. (2021). Candida glabrata: pathogenicity and resistance mechanisms for adaptation and survival. Journal of Fungi, 7(8), 667. https://doi.org/10.3390/jof7080667.
  • Hope, W. W., Castagnola, E., Groll, A. H., Roilides, E., Akova, M., Arendrup, M. C., & et al. (2012). ESCMID* guideline for the diagnosis and management of Candida diseases 2012: prevention and management of invasive infections in neonates and children caused by Candida spp. Clinical Microbiology and Infection, 18, 38-52. https://doi.org/10.1111/1469-0691.12040.
  • Kämmer, P., McNamara, S., Wolf, T., Conrad, T., Allert, S., Gerwien, F., & et al. (2020). Survival strategies of pathogenic Candida species in human blood show independent and specific adaptations. Mbio, 11(5), e02435-20. https://doi.org/10.1128/mBio.02435-20.
  • Kotey, F. C., Dayie, N. T., Tetteh-Uarcoo, P. B., & Donkor, E. S. (2021). Candida bloodstream infections: changes in epidemiology and increase in drug resistance. Infectious Diseases: Research and Treatment, 14, 11786337211026927. https://doi.org/10.1177/11786337211026927.
  • Lamy, B., Dargère, S., Arendrup, M. C., Parienti, J. J., & Tattevin, P. (2016). How to optimize the use of blood cultures for the diagnosis of bloodstream infections? A state-of-the art. Frontiers in microbiology, 7, 697. https://doi.org/10.3389/fmicb.2016.00697.
  • La Rocco M. Processing specimens for fungal culture. In: Garcia LS (editor), Clinical Microbiology Procedures Handbook, 3th Edition. ASM press, USA, 2010.
  • Lin, S. Y., Lu, P. L., Tan, B. H., Chakrabarti, A., Wu, U. I., Yang, J. H., & et al. (2019). The epidemiology of non‐Candida yeast isolated from blood: the asia surveillance study. Mycoses, 62(2), 112-120. https://doi.org/10.1111/myc.12852.
  • Marginson, M. J., Daveson, K. L., & Kennedy, K. J. (2014). Clinical impact of reducing routine blood culture incubation time from 7 to 5 days. Pathology, 46(7), 636-639. https://doi.org/10.1097/PAT.0000000000000167.
  • Morio, F., Jensen, R. H., Le Pape, P., & Arendrup, M. C. (2017). Molecular basis of antifungal drug resistance in yeasts. International journal of antimicrobial agents, 50(5), 599-606. https://doi.org/10.1016/j.ijantimicag.2017.05.012.
  • Ransom, E. M., Alipour, Z., Wallace, M. A., & Burnham, C. A. D. (2021). Evaluation of optimal blood culture incubation time to maximize clinically relevant results from a contemporary blood culture instrument and media system. Journal of Clinical Microbiology, 59(3), e02459-20. https://doi.org/10.1128/JCM.02459-20.
  • Rex, J. H., & Pfaller, M. A. (2002). Has antifungal susceptibility testing come of age?. Clinical Infectious Diseases, 35(8), 982-989. https://doi.org/10.1086/342384.
  • Seagle, E. E., Williams, S. L., & Chiller, T. M. (2021). Recent trends in the epidemiology of fungal infections. Infectious Disease Clinics, 35(2), 237-260. https://doi.org/10.1016/j.idc.2021.03.001.
  • Ullmann, A. J., Akova, M., Herbrecht, R., Viscoli, C., Arendrup, M. C., Arikan‐Akdagli, S., & et al. (2012). ESCMID guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT). Clinical Microbiology and Infection, 18, 53-67. https://doi.org/10.1111/1469-0691.12041.

Negatif Kan Kültürlerinin Uzatılmış İnkübasyonu Fungal Pozitiflik Verebilir Mi?

Year 2023, Volume: 12 Issue: 3, 543 - 547, 28.09.2023
https://doi.org/10.53424/balikesirsbd.1205875

Abstract

Amaç: Standart kan kültürü azami 5-7 günde sonuçlanmaktadır. Çalışmanın amacı, kültür negatif şişelerin uzatılmış inkübasyonu ile mikolojik üreme olup olmayacağının araştırılmasıdır. Gereç ve Yöntem: Atatürk Şehir Hastanesi’nde bir yıl boyunca erişkin hastaların kan kültürleri Render BC Sistemi (Render Biotech Co. Ltd., Çin) ile çalışmaya dahil edildi. Kan kültürlerinden randomize seçilmiş şişelerin (A grubu) inkübasyonu haftalık geleneksel ekimlerle 30 güne tamamlandı. Muhtemel/Olası invazif fungal enfeksiyonu (IFI) olan, ampirik/preemptif antifungal alanların negatif şişeleri ayrıca değerlendirilmiştir (B grubu). Üremelere PhoenixTM 100 sistemi (Becton Dickinson, ABD) ve mısırunu tween 80 agarla (RTA Laboratories, Türkiye) tanımlama, CLSI disk difüzyonla antifungal duyarlılık yapılmıştır. Bulgular: Toplam 6047 kan kültürü seti (%23.06 pozitif) işlendi. Randomize seçilmiş 1040+122 negatif set (sırasıyla A ve B grupları) çalışmaya alındı. A grubunda fungal üreme olmazken, B grubunda (flukonazol-200 mg/gün≤48 saat) 2 sette anlamlı fungal üreme oldu (7-9. günler)(Candida glabrata kompleks). Flukonazol için, bir izolat doza bağımlı duyarlıyken, diğeri dirençliydi. Takip eden ikinci setleri normal sürede pozitif verdi. Sonuç: Kan kültürlerinin izolasyon kapasitesi ile optimizasyonu IFI tanısında kritik önemdedir. Mikroorganizmaların %99’unun tespiti için uygun hacimde en az iki set kan kültürü alınması gerektiğinden, takip eden setlerin normal süreçte pozitif vermesi sebebiyle, üremeler “uzamış pozitif” olarak değerlendirilmedi. Standart inkübasyon süreci tatmin edici olarak kabul edildi.

References

  • Arikan-Akdagli, S., Gülmez, D., Doğan, Ö., Çerikçioğlu, N., Dereli, M. D., Birinci, A., & et al. (2019). First multicentre report of in vitro resistance rates in candidaemia isolates in Turkey. Journal of Global Antimicrobial Resistance, 18, 230-234. https://doi.org/10.1016/j.jgar.2019.04.003.
  • Baron, E. J., Scott, J. D., & Tompkins, L. S. (2005). Prolonged incubation and extensive subculturing do not increase recovery of clinically significant microorganisms from standard automated blood cultures. Clinical Infectious Diseases, 41(11), 1677-1680. https://doi.org/10.1086/497595.
  • Bourassa, L., Kates, O., & Liu, C. (2019). Limited diagnostic utility of extended aerobic blood culture incubation for fungal pathogen detection. Open Forum Infectious Diseases, 6(Suppl 2): S140.
  • Burduniuc, P. O., Bunescu, I., Sofronie, O., Bivol, M., Craciun, O., Burduniuc, A., & Balan, G. (2019). The importance of blood cultures in the effective management of bloodstream infections. Moldovan Medical Journal, 62(3), 28-37. https://doi.org/10.5281/zenodo.3404096 .
  • Butta, H., Sardana, R., Mendiratta, L., Sibal, A., Gupta, V., Chawla, R., & Jafri, A. A. (2019). Time to detection of yeast isolates in pediatric and adult patients with fungemia and its relevance to clinical profile and outcome. Indian Journal of Critical Care Medicine, 23(1): 27-30. https://doi.org/10.5005/jp-journals-10071-23108. Carreté, L., Ksiezopolska, E., Gómez-Molero, E., Angoulvant, A., Bader, O., Fairhead, C., & Gabaldón, T. (2019). Genome comparisons of Candida glabrata serial clinical isolates reveal patterns of genetic variation in infecting clonal populations. Frontiers in Microbiology, 10, 112. https://doi.org/10.3389/fmicb.2019.00112.
  • Clinical and Laboratory Standards Institute (CLSI). Method for antifungal disk diffusion susceptibility testing of yeasts, 3rd edition. CLSI Document M44. Wayne, Pennsylvania, USA, 2018.
  • Clinical and Laboratory Standards Institute (CLSI). Performance standards for antifungal susceptibility testing of yeasts, 1st edition. CLSI Supplement M60. Wayne, Pennsylvania, USA, 2017.
  • Cornely, O. A., Bassetti, M., Calandra, T., Garbino, J., Kullberg, B. J., Lortholary, O., & et al. (2012). ESCMID guideline for the diagnosis and management of Candida diseases 2012: non‐neutropenic adult patients. Clinical Microbiology and Infection, 18, 19-37. https://doi.org/10.1111/1469-0691.12039. Cuenca‐Estrella, M., Verweij, P. E., Arendrup, M. C., Arikan‐Akdagli, S., Bille, J., Donnelly, J. P., & et al. (2012). ESCMID guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures. Clinical Microbiology and Infection, 18, 9-18. https://doi.org/10.1111/1469-0691.12038 .
  • De Plato, F., Fontana, C., Gherardi, G., Privitera, G. P., Puro, V., Rigoli, R., & et al. (2019). Collection, transport and storage procedures for blood culture specimens in adult patients: recommendations from a board of Italian experts. Clinical Chemistry and Laboratory Medicine (CCLM), 57(11), 1680-1689. https://doi.org/10.1515/cclm-2018-1146 .
  • Dudakova, A., Blei, C., Groß, U., & Schulze, M. H. (2022). Impact of routine bedside infectious diseases service on clinical management and prognosis of patients with Candida fungemia–an example for Antifungal Stewardship at university level in Germany. International Journal of Infectious Diseases, 119, 150-159. https://doi.org/10.1016/j.ijid.2022.03.054.
  • Gülmez, D., Sığ, A. K., Akar, N., & Duyan, S. (2021). Changing trends in isolation frequencies and species of clinical fungal strains: what do the 12-years (2008-2019) mycology laboratory data tell about?. Mikrobiyoloji Bulteni, 55(1), 53-66. https://doi.org/10.5578/mb.20156.
  • Gülmez, D., Alp, S., Gursoy, G., Ayaz, C. M., Dogan, O., Arikan-Akdagli, S., & Akova, M. (2020). Mixed fungaemia: an 18-year report from a tertiary-care university hospital and a systematic review. Clinical Microbiology and Infection, 26(7), 833-841. https://doi.org/10.1016/j.cmi.2020.03.030.
  • Hassan, Y., Chew, S. Y., & Than, L. T. L. (2021). Candida glabrata: pathogenicity and resistance mechanisms for adaptation and survival. Journal of Fungi, 7(8), 667. https://doi.org/10.3390/jof7080667.
  • Hope, W. W., Castagnola, E., Groll, A. H., Roilides, E., Akova, M., Arendrup, M. C., & et al. (2012). ESCMID* guideline for the diagnosis and management of Candida diseases 2012: prevention and management of invasive infections in neonates and children caused by Candida spp. Clinical Microbiology and Infection, 18, 38-52. https://doi.org/10.1111/1469-0691.12040.
  • Kämmer, P., McNamara, S., Wolf, T., Conrad, T., Allert, S., Gerwien, F., & et al. (2020). Survival strategies of pathogenic Candida species in human blood show independent and specific adaptations. Mbio, 11(5), e02435-20. https://doi.org/10.1128/mBio.02435-20.
  • Kotey, F. C., Dayie, N. T., Tetteh-Uarcoo, P. B., & Donkor, E. S. (2021). Candida bloodstream infections: changes in epidemiology and increase in drug resistance. Infectious Diseases: Research and Treatment, 14, 11786337211026927. https://doi.org/10.1177/11786337211026927.
  • Lamy, B., Dargère, S., Arendrup, M. C., Parienti, J. J., & Tattevin, P. (2016). How to optimize the use of blood cultures for the diagnosis of bloodstream infections? A state-of-the art. Frontiers in microbiology, 7, 697. https://doi.org/10.3389/fmicb.2016.00697.
  • La Rocco M. Processing specimens for fungal culture. In: Garcia LS (editor), Clinical Microbiology Procedures Handbook, 3th Edition. ASM press, USA, 2010.
  • Lin, S. Y., Lu, P. L., Tan, B. H., Chakrabarti, A., Wu, U. I., Yang, J. H., & et al. (2019). The epidemiology of non‐Candida yeast isolated from blood: the asia surveillance study. Mycoses, 62(2), 112-120. https://doi.org/10.1111/myc.12852.
  • Marginson, M. J., Daveson, K. L., & Kennedy, K. J. (2014). Clinical impact of reducing routine blood culture incubation time from 7 to 5 days. Pathology, 46(7), 636-639. https://doi.org/10.1097/PAT.0000000000000167.
  • Morio, F., Jensen, R. H., Le Pape, P., & Arendrup, M. C. (2017). Molecular basis of antifungal drug resistance in yeasts. International journal of antimicrobial agents, 50(5), 599-606. https://doi.org/10.1016/j.ijantimicag.2017.05.012.
  • Ransom, E. M., Alipour, Z., Wallace, M. A., & Burnham, C. A. D. (2021). Evaluation of optimal blood culture incubation time to maximize clinically relevant results from a contemporary blood culture instrument and media system. Journal of Clinical Microbiology, 59(3), e02459-20. https://doi.org/10.1128/JCM.02459-20.
  • Rex, J. H., & Pfaller, M. A. (2002). Has antifungal susceptibility testing come of age?. Clinical Infectious Diseases, 35(8), 982-989. https://doi.org/10.1086/342384.
  • Seagle, E. E., Williams, S. L., & Chiller, T. M. (2021). Recent trends in the epidemiology of fungal infections. Infectious Disease Clinics, 35(2), 237-260. https://doi.org/10.1016/j.idc.2021.03.001.
  • Ullmann, A. J., Akova, M., Herbrecht, R., Viscoli, C., Arendrup, M. C., Arikan‐Akdagli, S., & et al. (2012). ESCMID guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT). Clinical Microbiology and Infection, 18, 53-67. https://doi.org/10.1111/1469-0691.12041.
There are 25 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Articles
Authors

Ali Korhan Sığ 0000-0003-2907-257X

Diğdem Özer Yıldırım 0000-0002-6277-1615

Başak Göl Serin 0000-0003-4810-3239

Mustafa Güney 0000-0002-8478-1072

Publication Date September 28, 2023
Submission Date November 17, 2022
Published in Issue Year 2023 Volume: 12 Issue: 3

Cite

APA Sığ, A. K., Özer Yıldırım, D., Göl Serin, B., Güney, M. (2023). Can Prolonged Incubation of Negative Blood Cultures Show Fungal Positivity?. Balıkesir Sağlık Bilimleri Dergisi, 12(3), 543-547. https://doi.org/10.53424/balikesirsbd.1205875

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