Background <p>In resource-limited settings, febrile neutropenia (FN) is one of the leading causes of morbidity and mortality among immunocompromised individuals particularly those undergoing chemotherapy for malignancies. The clinical diagnosis and management of disease is challenging, due to the diverse range of causative pathogens and overreliance on the traditional diagnostic techniques. TaqMan array card (TAC), a microfluidics-based technique that allows simultaneous and rapid detection of multiple pathogens, addressing these diagnostic needs.</p> Objective <p>The aim of this study was to determine the role of TAC in improving pathogen identification in hospitalized patients with FN.</p> Methods <p>This cross-sectional study enrolled 155 FN patients admitted to Aga Khan University and Hospital, Karachi, Pakistan. 9 samples were excluded due to failed post-extraction quality control, yielding 146 samples for final TAC analysis. Both blood cultures and TAC assays were performed on the collected broths. Enrichment strategies were employed to reduce the impact of PCR inhibitors and increase microbial biomass, thereby enhancing the diagnostic sensitivity of TAC.</p> Results <p>TAC identified a diverse range of pathogens compared with traditional blood culture. Of 155 study participants, 61 (39.1%) were culture positive. At the Ct ≤ 35, at least one pathogen was identified in 37 TAC positive samples. The most frequently detected bacteria were <i>E. coli</i> (13/146, 8.90%), <i>K. pneumoniae</i> (11/146, 7.53%), <i>A. baumannii</i> (4/146, 2.74%), and <i>P. aeruginosa</i> (4/146, 2.74%). TAC showed diagnostic sensitivity of 23.5% for <i>E. coli</i> and 19.6% for <i>K. pneumoniae</i> at the primary Ct ≤ 35 threshold, with specificity above 98% for both. In multivariable penalized logistic regression, <i>K. pneumoniae</i>, <i>E. coli</i>, <i>P. aeruginosa</i>, and <i>A. baumannii</i> were independently associated with higher mortality. Antimicrobial resistance profiling demonstrated carbapenem and cephalosporin resistance across all three blood culture types.</p> Conclusion <p>The findings of this study suggest that TAC identifies a wider range of pathogen compared with traditional blood culture in FN patients. Only blood culture was able to detect Candida tropicalis in this experiment; TAC was unable to identify any fungal infection, highlighting the panel’s current flaw. Multicenter studies are needed to validate these results and assess the effectiveness of TAC in broader clinical settings.</p>

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Enhanced detection of sepsis pathogens in hospitalized febrile neutropenia patients using blood culture broths with TaqMan array card

  • Furqan Kabir,
  • Hammad Afzal Kayani,
  • Dur e Shahwar,
  • Rufei Ma,
  • Sara Iqbal,
  • Akram Hussain,
  • Jawaid Hussain,
  • Adil Kalam,
  • Fatima Aziz,
  • Sehrish Munir,
  • Farrukh Qazi,
  • Jie Liu,
  • Eric Houpt,
  • Erum Khan,
  • Junaid Iqbal,
  • Asad Ali

摘要

Background

In resource-limited settings, febrile neutropenia (FN) is one of the leading causes of morbidity and mortality among immunocompromised individuals particularly those undergoing chemotherapy for malignancies. The clinical diagnosis and management of disease is challenging, due to the diverse range of causative pathogens and overreliance on the traditional diagnostic techniques. TaqMan array card (TAC), a microfluidics-based technique that allows simultaneous and rapid detection of multiple pathogens, addressing these diagnostic needs.

Objective

The aim of this study was to determine the role of TAC in improving pathogen identification in hospitalized patients with FN.

Methods

This cross-sectional study enrolled 155 FN patients admitted to Aga Khan University and Hospital, Karachi, Pakistan. 9 samples were excluded due to failed post-extraction quality control, yielding 146 samples for final TAC analysis. Both blood cultures and TAC assays were performed on the collected broths. Enrichment strategies were employed to reduce the impact of PCR inhibitors and increase microbial biomass, thereby enhancing the diagnostic sensitivity of TAC.

Results

TAC identified a diverse range of pathogens compared with traditional blood culture. Of 155 study participants, 61 (39.1%) were culture positive. At the Ct ≤ 35, at least one pathogen was identified in 37 TAC positive samples. The most frequently detected bacteria were E. coli (13/146, 8.90%), K. pneumoniae (11/146, 7.53%), A. baumannii (4/146, 2.74%), and P. aeruginosa (4/146, 2.74%). TAC showed diagnostic sensitivity of 23.5% for E. coli and 19.6% for K. pneumoniae at the primary Ct ≤ 35 threshold, with specificity above 98% for both. In multivariable penalized logistic regression, K. pneumoniae, E. coli, P. aeruginosa, and A. baumannii were independently associated with higher mortality. Antimicrobial resistance profiling demonstrated carbapenem and cephalosporin resistance across all three blood culture types.

Conclusion

The findings of this study suggest that TAC identifies a wider range of pathogen compared with traditional blood culture in FN patients. Only blood culture was able to detect Candida tropicalis in this experiment; TAC was unable to identify any fungal infection, highlighting the panel’s current flaw. Multicenter studies are needed to validate these results and assess the effectiveness of TAC in broader clinical settings.