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Utility of incorporation of beta-D-glucan and T2Candida testing for diagnosis and treatment of candidemia

Zacharioudakis, Ioannis M; Zervou, Fainareti N; Marsh, Kassandra; Siegfried, Justin; Yang, Jenny; Decano, Arnold; Dubrovskaya, Yanina; Mazo, Dana; Aguero-Rosenfeld, Maria
The additive role of non-culture-based methods for the diagnosis of candidemia remains unknown. We evaluated 2 clinical practices followed in our hospitals for the diagnosis of candidemia, namely practice#1 including a combination of blood cultures and T2Candida, and practice#2 that also included Beta-D-glucan (BDG). Three out of 96 patients testing positive with practice#1 received a complete antifungal course. Of the 120 patients evaluated with practice#2, 29 were positive. Only 55.2% of those received a complete course. We observed significant differences in antifungal utilization, with 268.5 antifungal days/1000 patient-days for practice#1, as opposed to 371.9 days for practice#2, a nearly 40% difference. However, we found similar rates of antifungal discontinuation among negative patients at 3 days of testing (36.8% and 37.0% respectively). No differences were detected in death and/or subsequent diagnosis of candidemia. In summary, addition of BDG was interpreted variably by clinicians, was associated with an increase in antifungal utilization, and did not correlate with measurable clinical benefits for patients.
PMID: 38071859
ISSN: 1879-0070
CID: 5589412

Extra-urogenital infection by Mycoplasma hominis in transplant patients: two case reports and literature review [Case Report]

Ahamad, Afrinash; Zervou, Fainareti N; Aguero-Rosenfeld, Maria E
BACKGROUND:Mycoplasma hominis is a facultative anaerobic bacterium commonly present in the urogenital tract. In recent years, M. hominis has increasingly been associated with extra-urogenital tract infections, particularly in immunosuppressed patients. Detecting M. hominis in a diagnostic laboratory can be challenging due to its slow growth rate, absence of a cell wall, and the requirements of specialized media and conditions for optimal growth. Consequently, it is necessary to establish guidelines for the detection of this microorganism and to request the appropriate microbiological work-up of immunosuppressed patients. CASE PRESENTATION/METHODS:We hereby present two cases of solid organ transplant patients who developed M. hominis infection. Microscopic examination of the bronchial lavage and pleural fluid showed no microorganisms. However, upon inoculating the specimens onto routine microbiology media, the organism was successfully identified and confirmation was performed using 16S rDNA sequencing. Both patients received appropriate treatment resulting in the resolution of M. hominis infection. CONCLUSIONS:The prompt detection of M. hominis in a clinical specimen can have a significant impact on patient care by allowing for early intervention and ultimately resulting in more favorable clinical outcomes, especially in transplant patients.
PMCID:10503128
PMID: 37710154
ISSN: 1471-2334
CID: 5593512

Evaluation of BioFire® FilmArray® Pneumonia Panel in Bronchoalveolar Lavage Samples From Immunocompromised Patients With Suspected Pneumonia

Li-Geng, Tony; Zervou, Fainareti N; Aguero-Rosenfeld, Maria; Zacharioudakis, Ioannis M
Objectives Immunocompromised patients, specifically those with solid organ transplants or cancer on chemotherapy, are at particularly high risk of severe pneumonia and opportunistic infections. In select patients, bronchoalveolar lavage (BAL) is performed to provide high-quality samples for analysis. We compare BioFire® FilmArray® Pneumonia Panel (BioFire Diagnostics, Salt Lake City, Utah, United States), a multiplex polymerase chain reaction (PCR) assay, with standard of care diagnostics in BAL samples from immunocompromised patients to identify opportunities for this test to affect clinical decision making. Methods Patients hospitalized with pneumonia based on clinical and radiographic findings who underwent evaluation with bronchoscopy between May 2019 to January 2020 were reviewed. Among those patients undergoing bronchoscopy, those who were immunocompromised were selected for inclusion in the study. BAL specimens submitted to the microbiology laboratory were chosen based on as part of the internal validation of the panel in comparison with sputum culture at our hospitals. We compared the outcomes of the multiplex PCR assay with traditional culture methods and evaluated the role of PCR assay in de-escalating antimicrobial therapy. Results Twenty-four patients were identified for testing with the multiplex PCR assay. Of the 24 patients, 16 were immunocompromised, all with solid or hematological malignancy or a history of organ transplant. Seventeen individual BAL samples from the 16 patients were reviewed. BAL culture results and the multiplex PCR assay were in agreement in 13 samples (76.5%). In four cases, the multiplex PCR assay identified a possible causative pathogen not detected by standard workup. The median time to de-escalation of antimicrobials was three days (interquartile range (IQR) 2-4) from the day of collection of the BAL samples. Conclusions Studies have established the additive role of multiplex PCR testing in addition to traditional diagnostic tools like sputum culture in diagnosing the etiology of pneumonia. Limited data exist specifically looking at immunocompromised patients, in whom a timely and accurate diagnosis is particularly important. There is a potential benefit for performing multiplex PCR assays as an additive diagnostic tool in BAL samples for these patients.
PMCID:10205050
PMID: 37228561
ISSN: 2168-8184
CID: 5527182

Utility of Incorporation of Beta-D-glucan Testing in Algorithms for Diagnosis and Treatment of Candidemia [Meeting Abstract]

Zacharioudakis, I; Zervou, F; Marsh, K L; Siegfried, J; Yang, J; Decano, A; Dubrovskaya, Y; Mazo, D; Aguero-Rosenfeld, M E
Background. Candidemia is a common hospital acquired infection that is associated with significant morbidity and mortality. The optimal strategy for diagnosis remains unknown. Methods. We evaluated 2 distinct diagnostic strategies in hospitalized patients with suspicion of Candida bloodstream infection, namely strategy #1 that included simultaneous blood cultures and T2Candida and strategy #2 that included blood cultures, T2Candida testing and Beta-D-glucan (BDG). We examined the consistency with which each diagnostic algorithm led to changes in antifungal prescribing, the overall rate of antifungal utilization and patients' clinical outcomes. Flow Chart. Results. Among 96 patients tested with strategy #1, 3 had a positive result. Of those 100% completed a 14-day antifungal course for candidemia or were on antifungals until hospital discharge. Of the 29 out 120 patients that tested positive with strategy #2, 55.2% received a complete 14-day course or were on antifungals until hospital discharge. The percentage of completed treatment increased to 75.0% and 80.0% when the threshold for BDG positivity was increased at 200 pg/ml and 500 pg/ml respectively. We observed a significant difference in the overall antifungal utilization with 268.5 days of antifungals per 1,000 patient days for strategy #1, as opposed to 371.9 days of antifungals for strategy #2, a 38.5% increase. Negative tests at both diagnostic strategies led to a similar rate of antifungal discontinuation 3 days after testing (36.8% and 37.0% for strategy #1 and #2 respectively). We did not find significant benefits in death and/or subsequent diagnosis of candidemia between the 2 diagnostic strategies. Sensitivity analyses performed based on indication for testing and severity of illness did not significantly alter results. Conclusion. In summary, the addition of BDG in diagnostic algorithms for candidemia was interpreted variably by clinicians, was associated with a significant increase in antifungal utilization, and it did not appear to lead to measured clinical benefits for patients. Diagnostic strategies of common and serious infections that incorporate non-culture diagnostics need to be evaluated for added benefit. (Figure Presented)
EMBASE:640022141
ISSN: 2328-8957
CID: 5513402

Diagnostic stewardship in infectious diseases: steps towards intentional diagnostic testing

Zacharioudakis, Ioannis M; Zervou, Fainareti N
PMID: 35670110
ISSN: 1746-0921
CID: 5277712

The Utility of Scoring Systems in Determining the Need for Echocardiography in Patients with Staphylococcus aureus Bacteremia

Zervou, Fainareti N; Zacharioudakis, Ioannis M
PMID: 33972992
ISSN: 1537-6591
CID: 4867272

Leveraging Rapid Diagnostics and Electronic Health Records to Decrease Antimicrobial Utilization: a Step in the Right Direction

Zacharioudakis, Ioannis M; Zervou, Fainareti N; Decano, Arnold; Ahmed, Nabeela
PMID: 33319227
ISSN: 1537-6591
CID: 4717742

SARS-CoV-2 antibody responses in solid organ transplant recipients

Zervou, Fainareti N; Ali, Nicole M; Neumann, Henry J; Madan, Rebecca Pellett; Mehta, Sapna A
Antibody responses among immunocompromised solid organ transplant recipients (SOT) infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) may be diminished compared to the general population and have not been fully characterized. We conducted a cohort study at our transplant center to investigate the rate of seroconversion for SARS-CoV-2 IgG antibodies among SOT recipients who were diagnosed with Coronavirus disease 2019 (COVID-19) and underwent serum SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) testing. The 61 patients who were included in the final analysis underwent initial SARS-CoV-2 IgG testing at a median of 62 days (Interquartile range 55.0-75.0) from symptom onset. Note that, 51 of 61 patients (83.6%) had positive SARS-CoV-2 IgG results, whereas 10 (16.4%) had negative IgG results. Six (60%) out of 10 seronegative patients underwent serial IgG testing and remained seronegative up to 17 weeks post-diagnosis. Use of belatacept in maintenance immunosuppression was significantly associated with negative IgG antibodies to SARS-CoV-2 both in univariate and multivariate analyses (Odds ratio 0.04, p = .01). In conclusion, the majority of organ transplant recipients with COVID-19 in our study developed SARS-CoV-2 antibodies. Further longitudinal studies of the durability and immunologic role of these IgG responses and the factors associated with lack of seroconversion are needed.
PMID: 34505324
ISSN: 1399-3062
CID: 5012082

SARS-CoV-2 antibodies: IgA correlates with severity of disease in early COVID-19 infection

Zervou, Fainareti N; Louie, Ping; Stachel, Anna; Zacharioudakis, Ioannis M; Ortiz-Mendez, Yadira; Thomas, Kristen; Aguero-Rosenfeld, Maria E
Timing of detection of immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and their use to support the diagnosis are of increasing interest. We used the Gold Standard Diagnostics ELISA to evaluate the kinetics of SARS-CoV-2 IgG, IgA, and IgM antibodies in sera of 82 hospitalized patients with polymerase chain reaction (PCR)-confirmed coronavirus disease 2019 (COVID-19). Serum samples were collected 1-59 days post-onset of symptoms (PoS) and we examined the association of age, sex, disease severity, and symptoms' duration with antibody levels. We also tested sera of 100 ambulatory hospital employees with PCR-confirmed COVID-19 and samples collected during convalescence, 35-57 days PoS. All but four of the admitted patients (95.1%) developed antibodies to SARS-CoV-2. Antibodies were detected within 7 days PoS; IgA in 60.0%, IgM in 53.3%, and IgG in 46.7% of samples. IgG positivity increased to 100% on Day 21. We did not observe significant differences in the rate of antibody development in regard to age and sex. IgA levels were highest in patients with a severe and critical illness. In multiple regression analyses, only IgA levels were statistically significantly correlated with critical disease (p = .05) regardless of age, sex, and duration of symptoms. Among 100 ambulatory hospital employees who had antibody testing after 4 weeks PoS only 10% had positive IgA antibodies. The most frequently isolated isotype in sera of employees after 30 days PoS was IgG (88%). IgA was the predominant immunoglobulin in early disease and correlated independently with a critical illness. IgG antibodies remained detectable in almost 90% of samples collected up to two months after infection.
PMID: 33932299
ISSN: 1096-9071
CID: 4865782

Association of SARS-CoV-2 Genomic Load with COVID-19 Patient Outcomes

Zacharioudakis, Ioannis M; Prasad, Prithiv J; Zervou, Fainareti N; Basu, Atreyee; Inglima, Kenneth; Weisenberg, Scott A; Aguero-Rosenfeld, Maria E
PMID: 33119425
ISSN: 2325-6621
CID: 4646792