This retrospective study analyzed the results of two types of blood culture bottles utilized for the detection of BSIs in HIV-positive patients. The study revealed that the predominant pathogens causing BSIs in patients with HIV were primarily fungi, particularly T. marneffei. Additionally, Myco/F culture bottles exhibited higher positive rate regardless of the type of BSIs. Furthermore, our study revealed that Myco/F culture bottles offered significant advantages in the detection of mycobacteria and fungi.
Currently, blood culture is considered the gold standard for BSI. When there is suspicion of BSI, the guidelines recommend using both aerobic and anaerobic blood culture bottles during a single session in order to enhance the detection rate of pathogens [9]. Guidelines from the Infectious Diseases Society of America and the American Society for Microbiology recommend that 20–30 mL of blood per culture set (one aerobic bottle and on anaerobic bottle) is collected and may require 2–3 sets [10]. Generally, within 1 h after identifying sepsis, two sets of blood samples (aerobic and anaerobic culture) before antibiotic use are collected for culture [11]. We observed a significantly low positivity rate (8 of 246, contain contaminants) in the anaerobic culture bottles, with the same pathogens as the aerobic culture bottles. Hence, they were excluded from the analysis in our study. Although blood culture is the gold standard for the diagnosis of BSI, its limitations affect its clinical application. The sensitivity of conventional blood cultures for the diagnosis of BSIs is suboptimal [12], and its consistency with clinical results is also lower than that of metagenomic next-generation sequencing (mNGS) [13]. According to our research data, the positive rate of the aerobic culture bottles was found to be 69.05%. Low positive rate leads to missed clinical diagnoses, which are associated with high mortality rates in hospitalized patients with HIV-associated BSIs.
BSI is a leading cause of hospitalization among individuals living with HIV. The selection of suitable detection methods can enhance the pathogen detection rate and minimize the risk of missed diagnoses. The Myco/F culture bottles are primarily designed for culturing fungi and mycobacteria[14]. The components in this culture bottle differ from those in the aerobic culture bottles. Certain nutrients, such as hemolysin, can induce cell lysis, thereby facilitating the liberation of intracellular parasitic pathogenic bacteria such as mycobacteria and fungi from the host cells. When comparing the aerobic and Myco/F culture bottles, we observed that the positive rate of the latter was markedly greater than that of the former (89.29% versus 69.05%; P = 0.001). The former culture bottles also demonstrated a significant advantage in diagnosing fungemia, with a higher accuracy rate of 88.57% compared with 72.86% (P = 0.018). However, the time to positive report was significantly shorter for aerobic culture bottles compared with Myco/F culture bottles (12.43 ± 6.89 days and 5.47 ± 2.14 days, respectively; P < 0.001), which was inconsistent with previous studies [15, 16]. This is related to the higher prevalence of T. marneffei infections, as well as infections caused by Candida spp. [15]. mNGS is a molecular biology-based method for pathogen detection. It offers rapid detection, high sensitivity, and specificity, and has been utilized in the diagnosis of BSIs[17, 18]. Although mNGS has the aforementioned advantages, it remains challenging to implement in most hospitals due to its high cost and the technological demands associated with detection. Hence, the utilization of Myco/F culture bottles serves as a valuable adjunct to aerobic culture bottles in diagnosing BSI in patients with HIV.
A low CD4+ T cell count is considered to be a risk factor for opportunistic infections. Patients with HIV/AIDS and CD4+ T cell counts lower than 200 cells/μl are at a heightened risk of opportunistic infections caused by pathogens such as T. marneffei, MTB, and Cryptococcus neoformans [19,20,21]. The incidence of BSIs, the epidemiological distribution of the involved pathogen species, and mortality rates can vary depending on geographical location [2, 6]. Whether HIV infection also affects the type of pathogens that cause BSIs, a study in eastern China [22] found that the pathogens of community-associated bloodstream infections are mainly bacteria. Wenzhou is situated on the southeastern coast of China and is known for its humid climate during the Mei-yu season, which provides favorable conditions for the growth and transmission of T. marneffei. Our study demonstrated that T. marneffei was responsible for 75% of patients with BSIs, which was significantly higher compared with other pathogens. This finding aligns with the study conducted by Lai et al. [23]. Mycobacterial infection should not be overlooked in individuals with advanced HIV/AIDS. In our study population, seven episodes of mycobacterial BSIs would have been missed if only the aerobic culture bottles had been used. Due to the relatively slow growth of mycobacteria, the automated blood culture system failed to detect pathogen growth before the aerobic culture bottles were discarded. Furthermore, no statistically significant difference was observed in the detection rate of bacteria between the two groups (87.5% versus 75%). Hence, the Myco/F culture bottles are better suited for the detection of fungal and mycobacterial BSIs compared with the conventional culture bottles.
Mixed infections are frequently observed in patients who have advanced HIV/AIDS [1, 17]. Regrettably, our study revealed that only two patients had different pathogens detected in their blood samples, and these pathogens were found in separate culture bottles. We hypothesized the presence of competition among different pathogens in the culture medium, with the identified pathogen exhibiting inhibitory effects on the growth of other pathogens [24]. Another possible reason is that pathogens with relatively slow growth rates may have the potential to go unnoticed.
There are some limitations to our study. First, this is a single-center retrospective analysis. Second, this study utilized blood culture results and clinical diagnosis as the criteria for judgment; clinical diagnosis is mainly based on clinical symptoms and other laboratory results, such as 1,3-beta-d-glucan test, galactomannan test, interferon gamma release assay, and sputum culture, but some patients may have misdiagnosis due to lack of etiological evidence. Third, mixed infections are very common in advanced HIV/AIDS patients, blood cultures often cannot report multiple pathogens simultaneously, and higher bacterial loads are often easily detected, potentially introducing detection bias. In addition, the guideline does not require the number of fungal culture bottles, and this study only used one fungal culture bottle, which may lead to false negatives. Furthermore, this study did not analyze the influence of culture-based anti-infective therapy on patient outcomes, thereby providing additional evidence for the benefits of culture bottles. In future clinical practice, increased attention should be given to BSIs in patients with HIV. Furthermore, it is imperative to include individuals from the non-HIV population to more comprehensively assess the diagnostic efficacy of these two culture bottles in the context of BSIs. It is also necessary to conduct multicenter prospective studies.
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