搜索结果：ASM case reports

The Enterobacter cloacae complex (ECC) includes opportunistic pathogens that can be carbapenem resistant, thus complicating treatment regimens. Here, we characterized a carbapenem- and colistin-resistant ECC O89H7 isolate expressing KPC carbapenemase. ECC O89H7 was isolated in January 2021 from an axillary swab performed during routine screening for multidrug-resistant (MDR) bacteria from a patient after 39 days of hospitalization in the intensive care unit (ICU) for severe COVID-19 pneumonia at Nini hospital (Tripoli, Lebanon). The ECC O89H7 was identified as E. roggenkampii (Er) belonging to sequence type (ST)422 and contained eight different plasmids as revealed by whole-genome sequencing (WGS). Er O89H7 was predicted to be a human pathogen (96.3%), harboring 51 virulence factors as well as genes conferring resistance to heavy metals and quaternary ammonium compounds. Er O89H7 was highly drug resistant, including resistance to carbapenems and colistin. The resistome revealed six β-lactamase genes: the chromosome-encoded bla MIR-3 cephalosporinase, bla LAP-2 and bla SHV-12 encoded on a 115-kb IncM-1 plasmid, and bla OXA-10 , bla TEM-40, and bla KPC-2 on a mobilizable IncP-6 plasmid of 51 kb, as revealed by mating-out assays. Here, we have characterized a human pathogenic Er ST422 harboring bla KPC-2 carbapenemase on an IncP-6 plasmid from Lebanon. Er O89H7 represents a major health threat due to limited therapeutic options, especially because novel β-lactam/inhibitor combinations are not available in Lebanon. Our results highlight an urgent need for improved carbapenemase screening and detection capacity in clinical laboratories and for enhanced genomic surveillance of MDR bacteria to implement intervention strategies to control their spread in Lebanon and beyond.

Hypervirulent Klebsiella pneumoniae (hvKp) is a globally emerging pathotype known for causing severe and disseminated infections across multiple organ systems. Diabetes is a risk factor for hvKp infection; however, otherwise healthy individuals from the community are also at risk. Two patients from Nebraska presented with complex abscesses of unknown origin. Both cases required interventional procedures and prolonged hospitalization. PCR-based testing, animal studies, and whole-genome sequencing analysis confirmed that hvKp was the offending pathotype. This report describes the first confirmed cases of hvKp infection in Nebraska, USA. These cases demonstrated the utility of using molecular methods to identify hvKp. The microbiology lab can be operationalized to provide valuable insights into the genetic makeup of pathogens, inform the institutional clinical decision-making processes, and epidemiological surveillance. This study highlights the collaborative relationships between the Infectious Diseases staff and the Clinical Microbiology Laboratory to work up complex cases.

Niemann-Pick disease type B (NPD-B) is a rare lysosomal storage disorder characterized by residual activity of acid sphingomyelinase (ASM). While functional inhibitors of ASM (FIASMAs) are widely prescribed as psychotropic medications, they may pose a particular risk to patients with NPD-B by further reducing the already impaired enzymatic function. Here, we report the case of a 20-year-old male with genetically confirmed NPD-B who experienced rapid clinical deterioration following the administration of zuclopenthixol, a drug not previously associated with FIASMA activity. Within 48 hours of treatment initiation, the patient developed profound lethargy and markedly elevated creatine kinase (CK) levels of up to 22,000 U/L, consistent with rhabdomyolysis. Symptoms resolved quickly after discontinuation of zuclopenthixol. In vitro experiments using a radioactive [1 4 C]-sphingomyelin assay in Jurkat cells demonstrated that zuclopenthixol dose-dependently inhibited ASM activity by up to 71.5%. Zuclopenthixol had not previously been recognized as a FIASMA and might therefore have been considered a rational choice for treating patients with NPD-B. Our findings challenge this assumption by identifying zuclopenthixol as a potent inhibitor of ASM activity. This novel insight is of high clinical relevance, given the frequent use of antipsychotics in the management of neuropsychiatric symptoms in lysosomal storage disorders. We propose that zuclopenthixol and other potential FIASMAs be carefully re-evaluated for use in this vulnerable patient population.

Antiseizure medications (ASMs) are the cornerstone of epilepsy treatment, but their potential reproductive toxicity may impact male fertility. Globally, approximately 15% of couples are affected by infertility, with male factors accounting for 50%. This study aimed to analyze the association between ASMs and male infertility using the FDA Adverse Event Reporting System (FAERS). Data from January 1, 2004, to September 30, 2024, were extracted from FAERS. A hybrid signal detection framework combining non-Bayesian (Reporting Odds Ratio, ROR) and Bayesian (Bayesian Confidence Propagation Neural Network, BCPNN) methods was employed to evaluate the reporting frequency and risk of male infertility adverse events for different ASMs. Among 81,618 deduplicated case reports involving specified ASMs, 60 were related to male infertility. Disproportionality analysis revealed that carbamazepine (ROR = 8.73; IC = 3.10) and valproic acid (ROR = 6.82; IC = 2.74) posed the highest risks. Oxcarbazepine, lamotrigine, and levetiracetam also showed positive signals. Phenytoin sodium, topiramate, and clonazepam showed no significant risk. Regarding overall ASM-related reports, the majority originated from the United States and involved patients aged 18-65. Despite the limitations of the FAERS database, these findings emphasize the importance of monitoring reproductive health in male patients, particularly those of childbearing age, and highlight the need to balance ASM efficacy with potential reproductive toxicity in clinical practice. Further research is needed to validate these findings and explore underlying mechanisms.

Cladophialophora bantiana is a globally distributed dematiaceous mold which acts as an uncommon source of human infection. With a predilection for the central nervous system (CNS), this organism accounts for nearly half of all cerebral phaeohyphomycosis, with a mortality rate over 60%. Due to the rarity of this disease, treatment regimens are primarily based on retrospective reviews of case reports. The best clinical response occurred with a dual approach of surgical resection and antifungal therapy, though mortality rates remain high. A 68-year-old immunocompromised woman presented with imaging findings concerning for a neoplastic process, such as a glial neoplasm or CNS lymphoma. With microbiology, flow cytometry, and cytology of the cerebrospinal fluid negative and frozen section of the lesion favoring glial neoplasm, the scarce pigmented fungal hyphae on permanent sections were unexpected. Broad-range fungal DNA testing identified the organism as C. bantiana. Without further surgical resection, dual antifungal therapy was utilized to achieve clinical stability and return to pre-infection baselines. This is a rare case of a C. bantiana fungal brain abscess in an immunocompromised patient. Complete surgical resection was not possible; however, this case provides additional data to show the benefits of a dual antifungal treatment approach without additional surgical intervention, and the dosages used to achieve stability at 18 months post-presentation. This case highlights the importance of prompt efforts in determining causative organisms in unexpected fungal brain abscesses, which allows for targeted and improved success in the treatment of this highly fatal disease.

Niemann-Pick disease (NPD) is a rare autosomal recessive lysosomal storage disorder caused by acid sphingomyelinase (ASM) deficiency, resulting in progressive lipid accumulation in multiple cell types and organs. To describe a rare case of suspected NPD type B with secondary sea-blue histiocytosis and to explore its diagnostic implications. Comprehensive clinical and laboratory evaluations were conducted to assess the patient's condition. We report a rare case of Niemann-Pick disease type B accompanied with secondary sea-blue histiocytosis in a 32-year-old woman who had previously undergone splenectomy for congenital splenomegaly. She presented with abdominal distension, poor appetite and abdominal pain. Clinical evaluations revealed decompensated cirrhosis with no neurologic abnormalities. Transjugular liver biopsy demonstrated foamy cells infiltration, while bone marrow examination identified sea-blue histiocytes (approximately 4.5% of nucleated cells) and Niemann-Pick cells (approximately 2.5%). Although ASM activity testing and SMPD1 sequencing were recommended, the patient declined further evaluation for financial reasons. This case highlights the significance of considering ASM deficiency in patients with cryptogenic cirrhosis and underscores the diagnostic value of histopathology when definitive gene or enzyme testing is unavailable. It also raises the possibility that prior splenectomy may influence the clinical presentation of the disease.

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. 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. This case illustrates P. gergoviae as an emerging opportunistic pathogen capable of causing invasive infection and possibly metabolic complications in profoundly immunocompromised hosts.

Trichophyton indotineae is an emerging Trichophyton species associated with extensive dermatophytosis frequently demonstrating terbinafine resistance. While early cases were reported in South Asia, T. indotineae has since spread globally, with several cases reported in the United States since 2023. To our knowledge, we describe the first cases reported in Virginia. Patients A and B each presented to the dermatology clinic with a diffuse, pruritic rash unresponsive to previous courses of topical and antifungal therapy. Both presentations raised concern for T. indotineae infection, which was confirmed with internal transcribed spacer (ITS) genome sequencing of isolates from the lesions. Both patients were initially prescribed an 8-week course of itraconazole 200 mg daily. Patient A required an additional month of treatment, but both patients had improved at follow-up. The present cases highlight several key points regarding the epidemiology, diagnosis, and management of T. indotineae infections, including continued expansion within the US, the need for ITS sequencing to distinguish T. indotineae from Trichophyton mentagrophytes and Trichophyton interdigitale, and the growing role of oral itraconazole as first-line therapy.

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. We investigated a role of nonconvulsive status epilepticus (NCSE) in cognitive dysfunction in pathologically confirmed NIID. We also analyzed distinctive factors to differentiate NIID from Alzheimer's disease (AD). A 63-year-old man presented with transient consciousness disturbance (Day 1). For previous 6 years he had been suffering from similar episodes and gradually progressive cognitive decline. Clinical characteristics and response to antiseizure medications (ASM) were analyzed with a narrative literature review. Neurological examination showed disorientation, memory disturbance, aphasia, agraphia, and impaired visuospatial ability. On Day 27, his MMSE scored 10. Diffusion-weighted MRI showed high intensity signal in the corticomedullary junction of the frontal lobe, which could not explain his neurological manifestations. EEG showed seizure patterns arising from the bilateral occipital areas. ASM improved MMSE score to 23. Skin biopsy confirmed his diagnosis as dementia-dominant sporadic NIID. He died on Day 77. Cognitive dysfunction in visuospatial execution, manifested by impaired pentagon drawing and agraphia of both kanji (Japanese morphograms) and kana (Japanese syllabograms), its fluctuating course, and reactivity to ASM were clear distinction from AD. NCSE can accelerate cognitive decline and ASM can improve cognitive function in NIID. Cognitive evaluation using pentagon drawing and handwriting of both morphograms and syllabograms can be useful to differentiate NIID from AD.

The expanding use of B-cell-depleting anti-CD20 monoclonal antibodies has introduced diagnostic challenges for infections that are traditionally confirmed through serologic testing. Seronegative secondary syphilis is exceptionally rare and has historically been described only in profoundly immunocompromised patients with advanced HIV/AIDS. This case represents a novel clinical scenario in the era of targeted immunologic therapy. We report the case of a 44-year-old man with marginal zone lymphoma receiving maintenance obinutuzumab, who presented with a symmetric, pruritic, palmoplantar predominant papulosquamous eruption accompanied by fatigue and elevated inflammatory markers. Extensive serologic testing for syphilis, including repeated treponemal (TP-PA, treponemal IgG) and nontreponemal (RPR) assays, remained completely nonreactive on multiple occasions. However, a skin punch biopsy demonstrated epidermal hyperplasia with a dense plasma cell-rich lymphohistiocytic infiltrate. Immunohistochemical staining for Treponema pallidum revealed numerous spirochetes in the epidermis and superficial dermis, confirming the diagnosis of secondary syphilis. The patient received three weekly intramuscular doses of benzathine penicillin G (2.4 million units per dose) with complete clinical resolution and no adverse effects. Serologic tests remained nonreactive on follow-up evaluation. This case is the first documented report of persistent seronegative secondary syphilis in a patient receiving obinutuzumab therapy. It underscores the critical importance of maintaining a high index of clinical suspicion and pursuing tissue-based diagnostics when serologic tests fail to explain compelling clinical findings in patients with profound B-cell depletion. Clinicians managing patients on anti-CD20 therapies must recognize the limitations of serologic diagnosis for infections that typically depend on antibody detection.

Epilepsy surgery remains underutilized despite strong evidence supporting its efficacy for appropriately selected patients with drug-resistant epilepsy (DRE). We describe the case of a 23-year-old woman with a 4-year history of refractory focal impaired awareness seizures, experiencing up to four episodes per week despite multiple trialed antiseizure medications at tolerated doses. Initial investigations including magnetic resonance imaging (MRI), EEG, and paraneoplastic screening were unremarkable, and she was managed as having non-lesional left temporal lobe epilepsy. As part of an artificial intelligence driven research initiative, a natural language processing based random forest algorithm reviewing neurology clinic documentation identified her as a potential surgical candidate. Complementary large language model analysis supported extraction of relevant seizure and imaging information. This prompted re-evaluation of the case, with PET demonstrating left temporal hypometabolism and repeat MRI revealing a previously unrecognized encephalocele. She subsequently underwent left temporal lobe polectomy with encephalocele disconnection. The procedure was successful, and she has remained seizure-free for 1 year postoperatively, allowing initiation of ASM weaning and the possibility of long-term cure. This case illustrates the transformative potential of epilepsy surgery for individuals with DRE and the promising role of artificial intelligence augmented triage systems in reducing delays to surgical referral. Given the morbidity, mortality, and economic burden associated with DRE, timely surgical evaluation should be considered the standard of care for eligible patients. Integrating artificial intelligence tools into clinical workflows may help overcome longstanding barriers to access and ensure that life-changing interventions are offered earlier in the disease course.

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.

Granulicatella adiacens is a fastidious Gram-positive coccus and is a rare but recognized cause of infective endocarditis. Infective endocarditis during pregnancy is uncommon but carries substantial maternal and fetal risk. Plasma metagenomic analysis of microbial cell-free DNA has emerged as a complementary diagnostic tool in culture-negative infections. We describe a 35-year-old pregnant woman with known mitral valve prolapse who presented at 21 weeks of gestation with an acute ischemic stroke. Initial etiological work-up, including transesophageal echocardiography, was unremarkable. Ten days later, she re-presented with left-arm pain and neurologic symptoms. Repeat echocardiography revealed multiple mitral vegetations compatible with infective endocarditis. Despite multiple sets of prolonged-incubation blood cultures and extensive serological testing, all microbiological investigations remained negative. Empirical intravenous ceftriaxone was initiated based on the working diagnosis of HACEK endocarditis. A plasma metagenomic cell-free DNA test ultimately identified G. adiacens, which was suspected to have entered the body through dental treatment received a few weeks earlier. Ceftriaxone was continued given the favorable clinical response, with vegetation resolution, troponin decline, and uncomplicated term delivery of a healthy infant. This case illustrates the diagnostic challenges of culture-negative infective endocarditis in pregnancy and underscores the value of plasma microbial cell-free DNA sequencing as a complementary tool when conventional methods fail. It also emphasizes the need to repeat echocardiography when clinical suspicion remains high and raises the question of antibiotic prophylaxis for high-risk dental procedures in pregnant women with underlying valvular heart disease.

Tuberculosis (TB) remains a major opportunistic infection in solid organ transplant recipients, with an incidence significantly higher than in the general population. Immunosuppression often leads to atypical and disseminated forms of TB, complicating timely diagnosis. Extrapulmonary TB can manifest in various genitourinary sites, but penile involvement is exceedingly rare, comprising less than 1% of urogenital TB cases. We report a confirmed case of penile TB in a 56-year-old abattoir worker with a history of renal transplant, who presented with a penile ulcer with cellulitis and systemic symptoms. Imaging revealed miliary pulmonary TB, confirmed on molecular testing from both respiratory and skin tissue samples. The patient was commenced on a four-drug anti-tuberculous regimen with dose modifications due to drug interactions with immunosuppressive medications. Clinical improvement with resolution of the penile lesion and systemic symptoms was noted. This case highlights the need for increased clinical suspicion for TB in immunosuppressed patients presenting with atypical genitourinary symptoms. Early recognition and prompt initiation of treatment, alongside careful adjustment of immunosuppression, are critical to achieving favorable outcomes. Given the rarity of penile TB and the complexity of its management in transplant recipients, this case contributes to the limited literature and underscores the importance of a multidisciplinary approach.

Rapidly growing non-tuberculous mycobacteria (NTM) are increasingly recognized as causative agents in healthcare-associated infections. Mycobacterium wolinskyi, first described in 1999, has been associated with post-traumatic and post-operative wound infections. We report a case of M. wolinskyi pacemaker pocket infection and lead endocarditis in a 73-year-old man, 3 weeks after implantable cardioverter-defibrillator (ICD) implantation. Initial culture from a superficial pocket swab yielded slow-growing, white colonies on chocolate agar, and the strain was identified by MALDI-TOF as M. wolinskyi. However, the 16S rRNA, hsp65, rpoB, and recA sequences were identical to those of the unofficially described M. jacuzzi species but different from the corresponding sequences of the M. wolinskyi ATCC 700010 reference strain, which showed an average nucleotide identity (ANI) of 97.49% upon whole genome comparison. Therapy consisted of ICD removal, surgical debridement of the pocket, and prolonged combination therapy with oral moxifloxacin and co-trimoxazole, with favorable clinical outcome. This case demonstrates that our strain of M. wolinskyi could be an emerging pathogen in device-associated infections. The case highlights the diagnostic limitations of routine methods and emphasizes the role of 16S sequencing and whole genome sequencing in accurate taxonomic classification of NTM species. Broader genomic surveillance is warranted to understand the epidemiology and taxonomy of this rapidly growing NTM.

Shedding of Salmonella is not unusual in captive exotic animals; however, few cases link Salmonella to chronic disease or death of exotic felids. We report a multidrug-resistant (MDR) Salmonella enterica serovar Newport, persisting strain REPJJP01, isolated from exotic felids from two separate regional zoos and potentially contributing to the death of a snow leopard (Panthera uncia) and a Pallas's cat (Otocolobus manul). REPJJP01 strains of S. Newport are a recurring cause of human enteric disease outbreaks associated with travel to Mexico and beef products. This case highlights the value of genotypic and phenotypic techniques to identify shared and potentially MDR strains of Salmonella from human and animal hosts. Importantly, these cases expand the host range of S. Newport persisting strain REPJJP01.

Current U.S. surveillance for highly pathogenic avian influenza A(H5N1) in humans prioritizes individuals with known animal exposures, potentially missing community-acquired infections. To address this gap, we implemented universal H5 subtyping of all influenza A-positive respiratory samples collected within our hospital system, regardless of patient exposure history. Between August 2024 and April 2025, we subtyped 4,488 influenza A-positive samples and identified two cases positive for H5 RNA in Alameda County, California, USA. The first case was a 14-month-old girl with mild respiratory symptoms and no H5N1 exposure risks; sequencing of the sample revealed an H5 gene closely related to clade 2.3.4.4b, genotype B3.13 viruses circulating in U.S. dairies. The second case was a 79-year-old male, also with no known exposures, whose sample reproducibly tested positive with a high cycle threshold value but could not be confirmed by public health laboratories. Both patients had evidence of co-infection with other common respiratory viruses. These findings, while requiring cautious interpretation due to low virus levels and the presence of potential confounding factors, highlight limitations in exposure-based testing and demonstrate the potential for cryptic H5N1 circulation. This report underscores that broader, geographically targeted surveillance may be a critical tool for early detection of potential community transmission of pandemic-capable pathogens.

Pasteurella multocida is a gram-negative coccobacillus that colonizes the oropharyngeal and digestive tract of animals, particularly cats and dogs. It is commonly associated with mucocutaneous and osteoarticular infections. We report the case of a 25-year-old man with a history of obstructive uropathy and end-stage renal disease awaiting transplantation, who presented to the emergency department twice, 8 months apart, with afebrile back pain. On each admission, urine cultures grew Pasteurella multocida. Whole-genome sequencing of both isolates revealed only two single-nucleotide polymorphisms, supporting a recurrence caused by the same strain. He was treated with injections of ceftriaxone followed by fluoroquinolones for a total of 14 days. Further history revealed frequent cat bites and scratches in the household. Previously published cases of urinary tract infections due to Pasteurella sp. involved most often patients with underlying urological abnormalities. Contact with a pet was not consistently reported. This case underscores that P. multocida can cause recurrent urinary tract infection in immunocompromised patients with pet contact.

Enterococcus thailandicus was initially isolated from food in Thailand, and a single clinical case involving an intra-abdominal abscess was reported. No reports on the bacteremia or whole-genome sequencing of clinically isolated E. thailandicus have been published. A 50-year-old woman with intestinal Crohn's disease was admitted because of bloody stools. She had been treated twice previously for a perianal abscess. She developed a fever on day 15 of hospitalization. Both blood and urine cultures were polymicrobial and included E. thailandicus, which was susceptible to penicillins. She was treated for the perianal abscess and pyelonephritis with intravenous penicillins combined with beta-lactamase inhibitors for 2 weeks, followed by oral amoxicillin-clavulanic acid for 4 weeks. The identities of the isolates in the blood and urine cultures were confirmed using whole-genome analysis. No antimicrobial resistance genes, virulence genes, or plasmid replicons were identified in these isolates. Phylogenetic analysis of the clinical isolates and 21 E. thailandicus isolates in public databases indicated a relatively close lineage to that obtained from pig stool samples in Japan. No antimicrobial resistance genes conferring resistance to penicillins were identified in any of the E. thailandicus genomes. Phylogenetic analysis suggested that infection with E. thailandicus in this patient may have originated in Japan. The prognosis after treatment with penicillins was favorable.