I invite you to read and soak up new insights along with me. Every infectious disease case starts with a moment of uncertainty—a symptom that doesn't quite fit, a lab result that raises more questions than answers. This collection focuses on those moments through short, easy-to-search case stories inspired by real patients and classic clinical reports. As we read each article together, complex cases are broken down into clear, focused narratives that walk through the diagnostic thinking, call out key microbiologic clues as they appear, and pause to share practical teaching pearls—ideas meant to stick with you long after you finish reading, whether you're at the bench, at the bedside, or getting ready for exams.
A patient with multidrug-resistant tuberculosis (MDR-TB) developed resistance to bedaquiline (BDQ) and clofazimine (CFZ) during treatment. The clinical presentation involved persistent Mycobacterium tuberculosis infection despite standard therapy. Diagnostic methods included whole-genome sequencing, which identified a novel loss-of-function mutation in the pepQ gene. This genetic change was directly associated with the acquired resistance to both BDQ and CFZ, highlighting a critical mechanism of treatment failure. The case underscores the importance of genomic surveillance in guiding effective MDR-TB management and understanding emerging resistance patterns. This finding offers new insights into the molecular basis of drug resistance in M. tuberculosis.
Key note: Novel mutations in genes like pepQ can lead to simultaneous resistance to multiple critical anti-TB drugs.
A severely immunocompromised patient with acute myeloid leukemia developed multisystem Lomentospora prolificans infection, presenting with skin lesions, pulmonary nodules, and eye involvement. Despite initial in vitro susceptibility to fosmanogepix and its administration, the infection progressed, leading to the patient's death. Diagnosis was confirmed through biopsy and culture from multiple sites. This case highlights the critical challenge of treating highly resistant fungal infections like L. prolificans, even with novel antifungals showing in vitro activity. The discrepancy between in vitro susceptibility and clinical outcome underscores the urgent need for expanded clinical research into new antifungal agents and their real-world efficacy.
Key note: In vitro susceptibility to novel antifungals does not always predict successful clinical outcomes in severely immunocompromised patients with highly resistant infections.
An immunocompromised patient presented with a severe brain abscess caused by Cladophialophora bantiana, a rare dematiaceous mold with high CNS tropism. The diagnosis was confirmed through advanced microbiological techniques, revealing the fungal etiology of the intracranial lesion. Despite the challenging nature and high mortality associated with this infection in immunocompromised individuals, the patient achieved a remarkable recovery following aggressive antifungal therapy and surgical intervention. This case highlights the critical importance of early and accurate pathogen identification, alongside a multidisciplinary approach, to improve outcomes in rare and severe fungal CNS infections.
Key note: Early diagnosis and aggressive, multidisciplinary treatment are crucial for successful outcomes in severe fungal brain abscesses in immunocompromised patients.
A patient presented with a refractory, extensively drug-resistant (XDR) Pseudomonas osteomyelitis and hardware infection, likely following a traumatic injury and subsequent surgical intervention. The infection was caused by a hypermutator strain of Pseudomonas aeruginosa, identified through culture and genomic sequencing. Standard antibiotic therapies were ineffective due to the pathogen's resistance profile. Adjunctive bacteriophage therapy was administered, leading to successful clearance of the infection and preservation of the hardware. This case highlights the potential of phage therapy for complex, multidrug-resistant bacterial infections where conventional treatments fail.
Key note: Bacteriophage therapy can be a crucial adjunctive treatment for otherwise untreatable XDR bacterial infections, especially those involving hardware.
A 54-year-old male with Crohn’s disease, undergoing ustekinumab therapy, presented with fever, cough, and dyspnea. Initial chest X-ray showed infiltrates, and he was admitted for community-acquired pneumonia. Despite broad-spectrum antibiotics, his condition worsened. Bronchoalveolar lavage and sputum analysis, including PCR, ultimately identified Chlamydia psittaci as the causative agent. The patient improved significantly after treatment with doxycycline. This case highlights the importance of considering atypical pathogens like C. psittaci in immunocompromised patients, even those on biologics like ustekinumab, and the utility of specific diagnostic methods when empiric therapy fails.
Key note: Immunocompromised patients on biologics require a high index of suspicion for atypical infections.
A 23-year-old male presented with fever, night sweats, weight loss, and hepatosplenomegaly, initially diagnosed with chronic active Epstein-Barr virus (CAEBV) infection. Despite various treatments, his condition progressed to hemophagocytic lymphohistiocytosis (HLH) and subsequently to NK/T-cell lymphoma, confirmed by bone marrow biopsy and EBV DNA detection. The patient's disease was refractory to multiple therapies, including chemotherapy and targeted agents, leading to a fatal outcome. This case highlights the aggressive and complex nature of CAEBV, which can rapidly evolve into life-threatening hematologic malignancies.
Key note: Chronic active Epstein-Barr virus infection can rapidly progress to fatal hemophagocytic lymphohistiocytosis and NK/T-cell lymphoma, requiring early aggressive management.
The highly divergent SARS-CoV-2 variant BA.3.2, first detected in a South African respiratory sample on November 22, 2024, has spread worldwide. By February 11, 2026, it was reported in 23 countries. In the U.S., initial detections included four international travelers via nasal swabs, three airplane wastewater samples, and clinical samples from five patients, including two hospitalized older adults and a young child, all of whom survived. Genomic surveillance identified BA.3.2 in 132 wastewater samples across 25 states. This variant exhibits approximately 70-75 spike protein substitutions relative to current vaccine antigens, indicating potential immune evasion.
Key note: Continued multimodal genomic surveillance is crucial to track SARS-CoV-2 evolution and assess the public health impact of new variants like BA.3.2.
This report details a significant increase in Kaposi Sarcoma–Associated Herpesvirus (KSHV) infections and complications among solid organ transplant recipients in the United States between January 2021 and September 2025. Forty-six deceased donors were suspected of transmitting KSHV, leading to 74 (48%) of 153 recipients developing post-transplantation KSHV infection. Clinical presentations included Kaposi sarcoma (61%), lymphoproliferative disorders (14%), and KSHV inflammatory cytokine syndrome (8%), with 25 (16%) recipient deaths. Most donors and recipients were HIV-negative, but two-thirds of donors had a history of nonmedical drug use, indicating a changing risk profile for KSHV transmission. Diagnosis relied on molecular, serologic, or immunohistochemical assays.
Key note: Clinicians must maintain a high index of suspicion for KSHV in transplant recipients, especially with donor risk factors like nonmedical drug use, to facilitate prompt diagnosis and management.
This article does not present a clinical case report involving a specific patient, symptoms, or pathogen identification. Instead, it is an ASM Laboratory Practices Subcommittee report focusing on the foundational role of the microbiology laboratory in diagnostic stewardship (DxS). It highlights DxS as a cross-disciplinary method to enhance patient care quality and manage healthcare resources effectively. The report emphasizes the critical contributions of clinical microbiology laboratorians in implementing and optimizing DxS initiatives.
Key note: This article is a review or report on diagnostic stewardship, not a clinical case report with a specific pathogen or infection type.
This article is a review summarizing the history, background, and initiatives for Clinical Lab 2.0, supported by the Project Santa Fe Foundation. It discusses the critical role of the clinical laboratory in diagnostic stewardship and population health management. The review highlights how laboratory services contribute significantly to effective patient care and public health strategies, emphasizing their evolving impact beyond traditional testing. It details the foundational aspects and future directions of Clinical Lab 2.0, advocating for enhanced integration and utilization of laboratory data for broader health outcomes. This is a review article, not a clinical case report, so no specific patient presentation or pathogen identification is available.
Key note: This article emphasizes the strategic importance of clinical laboratories in modern healthcare and population health.