Eileen M. Burd

Background: Fascioliasis is a zoonotic trematode infection caused by members of the genus Fasciola ( F. hepatica and F. gigantica ) that localize to the hepatic biliary ducts in humans. Parasites are acquired after ingestion of freshwater plants, and fascioliasis has been reported on every inhabited continent. Typically, fascioliasis is diagnosed by serology or stool examination. This case reports the unusual finding of adult Fasciola organisms during an endoscopic retrograde cholangiopancreatography (ERCP). Case Summary: A 65-year-old woman who returned to the United States after traveling in Vietnam presented with abdominal pain, eosinophilia, and cholangitis. Filling defects/debris were detected in the common bile duct (CBD) upon imaging studies, so an ERCP was performed to investigate further. During the procedure, between three and four adult flukes were recovered from the biliary ducts and were later identified as Fasciola at a reference laboratory. Conclusion: The recovery of intact Fasciola during a surgical procedure is a highly unusual finding. It is crucial to accurately identify these organisms as there are numerous different species of liver flukes. Some flukes may resemble Fasciola at the egg or adult stage, such as Fasciolopsis buski . The treatment of Fasciola differs from that of all other liver flukes, as it is resistant to praziquantel and must be treated with triclabendazole, and improper treatment can lead to chronic complications.

Background: Pluralibacter gergoviae is a rare, opportunistic, urease-producing gram-negative organism infrequently implicated in invasive infections. Reports in organ transplant or extracorporeal membrane oxygenation (ECMO) settings are exceedingly uncommon. This case is distinctive for describing P. gergoviae bacteremia potentially associated with severe hyperammonemia and encephalopathy in a lung transplant recipient on prolonged ECMO support, expanding the clinical spectrum of infection-related hyperammonemia beyond the traditionally recognized Ureaplasma and Mycoplasma species. Case Summary: A 32-year-old woman with cystic fibrosis underwent bilateral lung transplantation while on ECMO for refractory hypoxemic respiratory failure. Her post-operative course was complicated by multiorgan failure, Candida parapsilosis fungemia, and later, surgical site infection. During the fourth month of hospitalization, P. gergoviae was isolated from surgical wound and blood cultures. Around the time of bacteremia, she developed acute encephalopathy with markedly elevated plasma ammonia (262 µmol/L) in the absence of hepatic dysfunction. The P. gergoviae isolate was confirmed to be urease positive. Management included targeted antimicrobial therapy with ceftriaxone and meropenem, along with lactulose, rifaximin, and zinc for hyperammonemia. Ammonia levels and mental status gradually normalized following treatment, and blood cultures cleared. Conclusion: This case illustrates P. gergoviae as an emerging opportunistic pathogen capable of causing invasive infection and possibly metabolic complications in profoundly immunocompromised hosts.

Metagenomic next-generation sequencing (mNGS) in plasma, cerebrospinal fluid (CSF), and bronchoalveolar lavage fluid is a relatively new technology that offers a means to potentially provide a diagnosis in cases where infection is suspected, but conventional diagnostic testing has not revealed a pathogen. There have been many publications of individual cases and overall appraisals of its utility in detecting bacteria, fungi, and DNA viruses associated with otherwise undiagnosed systemic infections. A recent article by Phillips et al. published in ASM Case Reports (2:e00053-25, 2025, https://doi.org/10.1128/asmcr.00053-25 ) presents a case of meningitis in an immunosuppressed child that was ultimately determined to be caused by Trichosporon inkin using mNGS. Elevated ß−1,3-D-glucan (BDG) levels in CSF and serum projected a diagnosis of fungal meningitis. Bacterial, fungal, and mycobacterial cultures were negative. Positive lateral flow cryptococcal antigen titers in serum and CSF complicated the anticipated diagnosis since Cryptococcus spp. are thought to not have sufficient cell wall BDG to produce positive test results. Given the ultimate diagnosis of T. inkin meningitis and the known cross-reactivity with Trichosporon asahii per package insert, the unexpected cryptococcal antigen results raised the possibility of additional cross-reactivity. The authors uncovered this possibility by testing three known clinical isolates of T. inkin which generated positive results. This case adds to the growing literature that highlights the utility of mNGS in providing a diagnosis in otherwise unresolved cases and shows that mNGS can be further instructive in elucidating limitations in commonly used diagnostic tests.

Bloodstream infections (BSIs) have become increasingly challenging to treat due to emerging antimicrobial resistance (AMR). As rapid administration of appropriate antimicrobials is crucial to positive patient outcomes, clinical alternatives to slow phenotypic antimicrobial susceptibility testing (AST) must be developed. We developed an automated real-time, colorimetric assay (ChroMIC) that phenotypically determines minimum inhibitory concentrations (MICs) directly from positive blood culture. Gram-negative bacteria within positive blood cultures from 83 patients were directly analyzed with ChroMIC. Both ChroMIC MICs and the much slower VITEK 2 MICs for each of seven antibiotics were compared to broth microdilution (BMD). Direct-from-blood-culture ChroMIC MICs were obtained without the ~18-hour growth and isolation steps needed to obtain both VITEK 2 and BMD MICs. ChroMIC assays yielded >90% categorical and essential agreement within 7 h from the start of the experiment and within 4 h of initial growth detection. ChroMIC minor, major, and very major errors were all comparable to, or in the case of VMEs, better than, those from VITEK 2 ASTs—the latter being performed only after an additional ~18-hour subculturing delay. As these patient blood samples were run in parallel with VITEK 2 MICs, a retrospective impact analysis on patient care suggests that ChroMIC could have facilitated faster therapeutic decision-making in nearly all cases, saving an average of >35 and >43 h for antimicrobial escalation and de-escalation, respectively, compared to VITEK 2. IMPORTANCE: The often sluggish pace of phenotypic antimicrobial susceptibility testing (AST), relative to sepsis progression, limits flexibility in altering patient treatment. We report a new direct-from-blood culture phenotypic AST that delivers excellent results within ~7 h of blood culture positivity. This rapid and accurate determination of optimal bloodstream infection treatment was compared in a retrospective study on patient blood cultures that flagged positive for Gram-negative pathogens. Although standard clinical methods were used to guide treatment, our testing was performed in parallel and could have enabled correction of the treatment course ~40 h earlier than was actually performed. Once clinically implementable, such innovative, low-labor, automated, and accurate susceptibility determinations hold great potential for improving patient outcomes and lowering overall healthcare costs.

Background: Development of rapid bacterial identification from blood cultures has been an area of intense study in diagnostic microbiology. Shortened turnaround time coupled with antimicrobial stewardship interventions have been shown to improve patient outcomes and decrease healthcare-associated costs. Objectives: We report the validation of a short incubation method for Gram-positive and Gram-negative bacterial identification utilizing MALDI-TOF MS without additional instrumentation, processing or cost compared with current practice. Methods: Prospective, observational, single-centre study in a quaternary care academic hospital encompassing 376 blood cultures subjected to bacterial identification after short incubation periods of 3–4 and 6–8 h. Results: There was 97.5% species-level identification agreement with tests undertaken after 3–4 h incubation with 83.6% isolates identified, and 99.7% species-level identification agreement after 6–8 h incubation with 96.7% isolates identified. Conclusions: The short incubation method provides a rapid MALDI-TOF MS bacterial identification method, reducing turnaround time by 10–18 h compared with standard practice without additional cost, processing or instrumentation.

Intestinal epithelial expression of the tight junction protein claudin-2, which forms paracellular cation and water channels, is precisely regulated during development and in disease. Here, we show that small intestinal epithelial claudin-2 expression is selectively upregulated in septic patients. Similar changes occurred in septic mice, where claudin-2 upregulation coincided with increased flux across the paracellular pore pathway. In order to define the significance of these changes, sepsis was induced in claudin-2 knockout (KO) and wild-type (WT) mice. Sepsis-induced increases in pore pathway permeability were prevented by claudin-2 KO. Moreover, claudin-2 deletion reduced interleukin-17 production and T cell activation and limited intestinal damage. These effects were associated with reduced numbers of neutrophils, macrophages, dendritic cells, and bacteria within the peritoneal fluid of septic claudin-2 KO mice. Most strikingly, claudin-2 deletion dramatically enhanced survival in sepsis. Finally, the microbial changes induced by sepsis were less pathogenic in claudin-2 KO mice as survival of healthy WT mice injected with cecal slurry collected from WT mice 24 h after sepsis was far worse than that of healthy WT mice injected with cecal slurry collected from claudin-2 KO mice 24 h after sepsis. Claudin-2 upregulation and increased pore pathway permeability are, therefore, key intermediates that contribute to development of dysbiosis, intestinal damage, inflammation, ineffective pathogen control, and increased mortality in sepsis. The striking impact of claudin-2 deletion on progression of the lethal cascade activated during sepsis suggests that claudin-2 may be an attractive therapeutic target in septic patients.

Initial specimen diversion devices (ISDDs) are a potential solution for reducing blood-culture contamination rates. We report the implementation of an ISDD associated with a sustained reduction in blood-culture contamination rates for >18 months after implementation. We did not observe a clinically significant reduction in inpatient vancomycin usage.

Summary: Mycobacterium tuberculosis ( Mtb ) causes 1.6 million deaths annually. Active tuberculosis correlates with a neutrophil-driven type I interferon (IFN) signature, but the cellular mechanisms underlying tuberculosis pathogenesis remain poorly understood. We found interstitial macrophages (IMs) and plasmacytoid dendritic cells (pDCs) are dominant producers of type I IFN during Mtb infection in mice and non-human primates, and pDCs localize near human Mtb granulomas. Depletion of pDCs reduces Mtb burdens, implicating pDCs in tuberculosis pathogenesis. During IFN-driven disease, we observe abundant DNA-containing neutrophil extracellular traps (NETs) known to activate pDCs. Cell type-specific disruption of the type I IFN receptor suggests IFNs act on IMs to inhibit Mtb control. Single cell RNA-seq indicates type I IFN-responsive cells are defective in their response to IFN γ , a cytokine critical for Mtb control. We propose pDC-derived type I IFNs act on IMs to drive bacterial replication, further neutrophil recruitment, and active tuberculosis disease.

Expression of the tight junction–associated protein junctional adhesion molecule-A (JAM-A) is increased in sepsis, although the significance of this is unknown. Here, we show that septic JAM-A ^–/– mice have increased gut permeability, yet paradoxically have decreased bacteremia and systemic TNF and IL-1β expression. Survival is improved in JAM-A ^–/– mice. However, intestine-specific JAM-A ^–/– deletion does not alter mortality, suggesting that the mortality benefit conferred in mice lacking JAM-A is independent of the intestine. Septic JAM-A ^–/– mice have increased numbers of splenic CD44 ^hi CD4 ⁺ T cells, decreased frequency of TNF ⁺ CD4 ⁺ cells, and elevated frequency of IL-2 ⁺ CD4 ⁺ cells. Septic JAM-A ^–/– mice have increased numbers of B cells in mesenteric lymph nodes with elevated serum IgA and intraepithelial lymphocyte IgA production. JAM-A ^–/– × RAG ^–/– mice have improved survival compared with RAG ^–/– mice and identical mortality as WT mice. Gut neutrophil infiltration and neutrophil phagocytosis are increased in JAM-A ^–/– mice, while septic JAM-A ^–/– mice depleted of neutrophils lose their survival advantage. Therefore, increased bacterial clearance via neutrophils and an altered systemic inflammatory response with increased opsonizing IgA produced through the adaptive immune system results in improved survival in septic JAM-A ^–/– mice. JAM-A may be a therapeutic target in sepsis via immune mechanisms not related to its role in permeability.