Tirdad T. Zangeneh

Background: Mucormycosis, an invasive fungal infection with high morbidity and mortality rates, requires prompt surgical and antifungal therapies; however, the role of antifungal susceptibility testing (AFST) in clinical management of mucormycosis remains underexplored. We aimed to describe the experience of using AFST in the clinical management of mucormycosis. Methods: We conducted a retrospective study from 1 October 2017 to 8 February 2023. We included non-pregnant patients aged ≥ 18 years old with a positive culture for Mucorales and with proven or probable mucormycosis. We collected clinical and microbiological data using a chart review. Results: Over the study period, a total of 119 patients were included, with 36 (30%) undergoing AFST. Of all patients, the median age was 54 years, with 80 (67%) being White and not Hispanic and 73 (61%) being male. Fifty-three (45%) patients had DM, 27 (23%) had hematological malignancy, 15 (13%) had SOT, and 23 (19%) had COVID-19. Half of the cases met the criteria of proven invasive mucormycosis, with pulmonary involvement being the most common presentation (46, 39%), followed by rhino-cerebral-orbital involvement (35, 29%). The majority of Mucorales isolates were Rhizopus species (79, 66%). Among the 36 who underwent AFST, posaconazole minimal inhibitory concentrations (MICs) were lower than isavuconazole (range 0.03 to 2 µg/mL versus 0.1 to 16 µg/mL, respectively). AFST resulted in a change in antifungal therapy from isavuconazole to posaconazole in 3/36 (8%) cases. There was no statistically significant difference in the mortality between the patients whose isolates received AFST versus those who did not have AFST performed. Conclusions: AFST led to a change in antifungal therapy in a minority of mucormycosis cases. Further studies to understand the epidemiological range of antifungal MICs and the effect of AFST-informed antifungal therapy are needed.

Coccidioidomycosis is associated with an increased risk of mortality and morbidity among immunosuppressed patients. The sensitivity of current commercial Coccidioides serologic tests is not well evaluated in patients with hematological malignancy. We conducted a retrospective study, including patients with culture-proven coccidioidomycosis, from October 1, 2017, to December 12, 2023. Cases with hematological malignancy and hematopoietic stem cell transplant (HM) were matched with an immunocompetent cohort (1:2) to compare the sensitivity of serology (enzyme immunoassay IgG/IgM or complement fixation) tests—matched by age, gender, and race. We matched 43 HM patients with 86 controls. The median age of the HM/hematopoietic stem cell transplant cohort was 67 (Interquartile Range [IQR], 52–75), 65% male, and 86% White. Most HM had lymphoma (37%), followed by leukemia (35%). Most cases had pulmonary infection (74%) versus controls (84%), P-value = .2, and 12% had a prior history of coccidioidomycosis compared to controls (17%), P-value = .4. Positive Coccidioides serology test results among HM were statistically significantly lower than controls (37% versus 72%), P-value ≤ .001. Multivariate conditional logistic regression identified HM and a history of coccidioidomycosis as statistically significantly associated with positive serologic testing, with Odds Ratio (OR) 0.27 (95% Confidence Interval [CI] 0.12–0.62, P-value = .002) and OR 6.07 (95% CI 1.25–29.4, P-value = .025), respectively.Coccidioides serology tests in HM patients with culture-proven coccidioidomycosis had low sensitivity. Given the increased risk of complications in this group, future studies are needed to evaluate more sensitive diagnostic tests.

A recent report in Open Forum Infectious Diseases linked hypoalbuminemia with the occurrence of subtherapeutic posaconazole concentrations. Specifically, 22.7% failed to achieve the trough concentrations desired for prophylaxis, and 50% failed to achieve concentrations of at least 1.25 µg/mL for therapy. Using logistic regression, albumin concentrations 98%), mostly to albumin. Many patients at risk for fungal infections have hypoalbuminemia. There is no doubt that the extent of protein binding can affect pharmacokinetics, but the implications of these changes are not simple [ 2]. There has been 1 report in which total and unbound concentrations were measured. Low serum albumin was associated with reduced probability of attaining target total, but not unbound posaconazole concentrations. The authors recommended TDM of unbound concentrations where available [ 3]; however, availability is likely limited to research. Measurement of unbound concentrations for drugs that are highly bound is difficult due to sample separation variables and sensitivity requirements.

Background: The purpose of this study was to understand how transplant infectious disease (TID) physicians assess a potential donor with known or suspected infection and describe posttransplant management. Methods: We designed a survey of 10 organ offer scenarios and asked questions pertaining to organ acceptability for transplantation and management posttransplant. The survey was distributed to TID clinicians via transplant society listservs and email. Responses were recorded in REDCap, and descriptive statistics were employed. Results: One hundred thirteen infectious disease physicians responded to the survey, of whom 85 completed all cases. Respondents were generally in agreement regarding organ acceptability, although some divergence was seen when evaluating lungs from donors with influenza, tuberculosis, or multidrug‐resistant Acinetobacter infection. Posttransplant management showed more variation. Areas of optimization were identified: (1) Further understanding of where risk‐mitigation strategies within the donor offer process may improve donor acceptability and therefore organ utilization; (2) importance of recipient considerations in assessing degree of infectious risk; and (3) gaps in evidenced‐based data regarding optimal posttransplant management of recipients. Conclusion: Evaluation of donor offers by TID clinicians is a complex process. Although the survey does not itself serve to make recommendations regarding best practices, it highlights areas where generation of data to inform acceptance and management practices may allow for improved organ utilization and recipient management. image

The colonic microbiome plays a critical role in resisting the ingrowth of pathogenic microbes like Clostridioides difficile (C. difficile). Disruption of the microbiome by antibiotics is known to cause antibiotic-associated diarrhea (AAD) and C. difficile infection (CDI). Outpatient parenteral antimicrobial therapy (OPAT) reduces hospital length of stay and exposure to healthcare-associated pathogens which may decrease the incidence of CDI. Previous studies that compared patients who received metronidazole for non-CDI indications with those who did not found a reduction in CDI among patients who received metronidazole. The aim was to study the incidence of AAD and CDI in the OPAT patient population and compare the incidence rate between patients who received oral metronidazole for non-CDI indications with those who did not. We retrospectively reviewed a cohort from our facility's OPAT program. We included adult patients (18 years or older) discharged to home or skilled nursing facility (SNF) on OPAT over a 2-year time span, regardless of diagnosis. Pregnant patients, patients with active CDI before starting OPAT, and those who were receiving an associated CDI treatment were excluded. Antibiotic-associated diarrhea was defined as 3 or more loose or watery stools per day with negative CDI testing or spontaneous improvement after stopping antibiotics. Community-onset and healthcare facility–associated CDI (CO-HCFA CDI) was defined as 3 or more watery stools per day with a positive stool C. difficile diagnostic test in the community or within the first 3 days of readmission, provided the diagnosis was made less than 4 weeks since discharge from a healthcare facility. Patients selected between June 1, 2018 and June 2020, grouped by whether or not they developed Clostridioides difficile infection (CDI). SD= standard deviation; Q1= 1st quartile; Q3= 3rd quartile. Of the 617 charts that met inclusion criteria, 31 had AAD and 3 had CO-HCFA CDI. Incidence of CO-HCFA CDI was < 1%; < 1 per 1000 person-day and incidence of AAD was 5.02%. The protective role of metronidazole could not be studied due to the rarity of CDI in this study. Although our study was not able to answer our initial question when comparing the effect of metronidazole within OPAT groups and rates of CDI, our data is promising for showing low rates of CDI in patients receiving OPAT. This study demonstrates the putative benefits of OPAT with reduced CDI incidence regardless of use of anti-CDI drugs. Tirdad Zangeneh, DO, AiCuris: Grant/Research Support

Coccidioidomycosis is a fungal infection endemic in the southwestern United States, Mexico, and parts of Central and South America. While coccidioidomycosis is associated with mostly mild infections in the general population, it can lead to devastating infections in immunocompromised patients, including solid organ transplant (SOT) recipients. Early and accurate diagnosis is important in achieving better clinical outcomes in immunocompromised patients. However, the diagnosis of coccidioidomycosis in SOT recipients can be challenging due to the limitations of diagnostic methods including cultures, serology, and other tests in providing a timely and accurate diagnosis. In this review, we will discuss the available diagnostic modalities and approaches when evaluating SOT recipients with coccidioidomycosis, from the use of conventional culture methods to serologic and molecular testing. Additionally, we will discuss the role of early diagnosis in assisting with the administration of effective antifungal therapy to reduce infectious complications. Finally, we will discuss ways to improve the performance of coccidioidomycosis diagnostic methods in SOT recipients with an option for a combined testing approach.

Coccidioidomycosis is a fungal infection endemic to the Southwestern United States which is associated with high morbidity and mortality in immunocompromised hosts. Serology is the main diagnostic tool, although less sensitive among immunocompromised hosts. (1→3)-β-D-glucan (BDG) is a non-specific fungal diagnostic test that may identify suspected coccidioidomycosis and other invasive fungal infections. We retrospectively investigated the utility of BDG between 2017 and 2021 in immunocompromised hosts with positive Coccidioides spp. cultures at our institutions. During the study period, there were 368 patients with positive cultures for Coccidioides spp.; among those, 28 patients were immunocompromised hosts, had both Coccidioides serology and BDG results available, and met other inclusion and exclusion criteria. Half of the patients had positive Coccidioides serology, and 57% had a positive BDG ≥ 80 pg/mL. Twenty-three (82%) had at least one positive test during their hospitalization. Among immunocompromised hosts with suspicion for coccidioidomycosis, the combination of Coccidioides serology and BDG can be useful in the initial work up and the timely administration of appropriate antifungal therapy. However, both tests failed to diagnose many cases, underscoring the need for better diagnostic techniques for identifying coccidioidomycosis in this population.