Disseminated Mycobacterium colombiense infection mimicking malignancy: A case report.

Mycobacterium colombiense, an infrequently reported non-tuberculous mycobacterium, is characterized by its slow-growing nature and capacity to simulate malignancies in clinical presentation. This report details a case of disseminated M. colombiense infection initially misidentified as cancer due to atypical symptoms, negative etiological tests, and imaging suggestive of a neoplastic disease. However, comprehensive diagnostic investigations, including a bone marrow biopsy and flow cytometry analysis, excluded malignancy as the diagnosis. The patient subsequently developed palpable masses, from which a definitive diagnosis was made using metagenomic Next-Generation Sequencing (mNGS) and culture of aspirate. A regimen of clarithromycin, ethambutol, rifampin, and amikacin was administered, leading to substantial improvement and resumption of activities at the eight-month follow-up. This case highlights the diagnostic challenges posed by the nonspecific clinical presentation of disseminated M. colombiense infection and the importance of rigorous investigation to avoid grave misdiagnosis and treatment delays.

A Rare Case Report of Disseminated Nocardia Farcinica Granulomatous Hepatitis and Clinical Management Experience.

Background: Nocardiosis is primarily an opportunistic infection affecting immunocompromised individuals, with a predilection for the lungs, brain, or skin in those with compromised immune function. Granulomatous hepatitis caused by Nocardia is a rare clinical manifestation. This study aims to provide a systematic overview of the clinical features of Nocardiosis caused by Nocardia farcinica, enhancing our understanding of this disease. Methods: We report a case of a 75-year-old male with no underlying diseases presenting with a history of "recurrent fever for more than 4 months", along with fatigue, poor appetite, and pleural and abdominal effusion. Despite treatment at multiple hospitals, the patient showed little improvement. Chest CT revealed chronic inflammation, small nodules, bilateral pleural effusion, and pleural thickening. Abdominal CT indicated multiple low-density lesions in the liver, multiple small calcifications, and abdominal effusion. Results: Liver biopsy suggested inflammatory changes, with focal granuloma formation. Metagenomic next-generation sequencing (mNGS) of liver tissue indicated Nocardia farcinica, leading to the final diagnosis of disseminated Nocardia farcinica granulomatous hepatitis. Conclusion: Nocardia infection is a rare disease primarily observed in immunocompromised patients but can also occur in those with normal immune function. The clinical and radiological features lack specificity; however, the utilization of mNGS technology enables rapid identification of the pathogenic microorganism. Nocardia farcinica is generally susceptible to sulfonamide drugs and amikacin, offering viable treatment options.

Whole-genome sequencing analysis of widely disseminated infection caused by ST2631 methicillin-sensitive Staphylococcusaureus.

Existing studies revealed high clonal diversity among Staphylococcus aureus bacteremia isolates, especially for methicillin-sensitive S. aureus (MSSA) strains. A 66-year-old male patient presenting with a widespread methicillin-sensitive Staphylococcus aureus (MSSA) infection, accompanied by concurrent carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection.To evaluate the evolution of the present isolate, whole genome sequencing and bioinformatics analysis were performed for all available MSSA isolates. This patient recovered eventually through drainage and antibiotics combination. Therefore, the virulence factors of MSSA, as the primary pathogenicity, led to widely disseminated infection. The appropriate initial treatment is a major concern after culture identification.

Oral USC-093, a novel homoserinamide analogue of the tyrosinamide (S)-HPMPA prodrug USC-087 has decreased nephrotoxicity while maintaining antiviral efficacy against human adenovirus infection of Syrian hamsters.

Adenovirus infections of immunocompromised humans are a significant source of morbidity and mortality. Presently, there is no drug specifically approved for the treatment of adenovirus infections by the FDA. The state-of-the-art treatment of such infections is the off-label use of cidofovir, an acyclic nucleotide phosphonate. While cidofovir inhibits adenovirus replication, it has dose-limiting kidney toxicity. There is an apparent need for a better compound to treat adenovirus infections. To this end, we have been developing acyclic nucleotide phosphonate prodrugs that utilize an amino acid scaffold equipped with a lipophilic modifier. Here, we compare the antiviral potential of two prodrugs of HPMPA that differ only in the amino acid-based promoiety: USC-087, based on an N-hexadecyl tyrosinamide, and USC-093, based on an N-hexadecyl serinamide. Oral administration of both compounds was very efficacious against disseminated HAdV-C6 infection in immunosuppressed Syrian hamsters, suppressing virus replication and mitigating pathology even when treatment was withheld until 4 days after challenge. We saw only marginal efficacy after respiratory infection of hamsters, which may reflect suboptimal distribution to the lung. Importantly, neither compound induced intestinal toxicity, which was observed as the major adverse effect in clinical trials of brincidofovir, a prodrug of cidofovir which also contains a C-16 modifier. Notably, we found that there was a significant difference in the nephrotoxicity of the two compounds: USC-087 caused significant kidney toxicity while USC-093 did not, at effective doses. These findings will be valuable guidepoints in the future evolution of this new class of potential prodrugs to treat adenovirus infections.

Massive Airway Bleeding Caused by Pulmonary Strongyloidiasis in a Patient with a Transplanted Kidney.

Introduction: We report a fatal case of massive airway bleeding caused by pulmonary strongyloidiasis in a patient with a transplanted kidney. Case Presentation: A 47-year-old male, regularly taking immunosuppressants post-kidney transplant, visited our hospital with symptoms of abdominal bloating, nausea, and emesis persisting for three days. After hospitalization, he developed a cough, hemoptysis, and respiratory failure. Sputum analysis confirmed an infestation with Strongyloides stercoralis. Despite receiving albendazole therapy and bronchoscopic management for bronchial hemorrhage, the patient ultimately died due to acute respiratory and circulatory collapse triggered by severe airway bleeding. Conclusion: Patients undergoing immunosuppressive therapy following kidney transplantation are at increased risk for disseminated strongyloidiasis. Consequently, infectious disease screening prior to transplantation, along with essential preventive pharmacotherapy, is of paramount importance.

Case Report: Disseminated Edwardsiella tarda infection in an immunocompromised patient.

Human infection caused by bacteria of the Edwardsiella genus is rare and most often presents with gastroenteritis that rarely requires antibiotics. Our case report describes a medically complex patient with chronic steroid use contributing to an immunocompromised state, who presented with fever and abdominal pain. The patient was later found to have Edwardsiella tarda (E. tarda) bacteremia and underwent paracentesis confirming E. tarda bacterial peritonitis requiring a prolonged antibiotic course. This case report aims to illustrate the presentation, diagnosis, and management of an uncommon infection that can have severe complications especially among immunocompromised patients.

Strongyloides stercoralis Infection in Humans: A Narrative Review of the Most Neglected Parasitic Disease.

Strongyloidiasis is a helminth infection affecting 613.9 million people annually, mainly in the tropics and subtropics. The reported seroprevalence in the United States is 4% with most of the cases reported in immigrants. Human T-lympho-tropic virus 1 (HTLV-1) infections, hypogammaglobulinemia, immunosuppressant use - particularly steroid use, alcoholism, and malnutrition have been associated with an increased risk of strongyloidiasis. Recently, cases of strongyloidiasis hyperinfection syndrome have been described in coronavirus disease 2019 (COVID-19) patients treated with steroids as well. This brief review discusses the epidemiology, clinical features, management, and prevention of strongyloidiasis including some facts about the infection in pregnancy, transplant recipients, and COVID-19 patients. We conducted an online search using the PubMed, Scopus, and Google Scholar databases. Strongyloidiasis can be asymptomatic or present with mild symptoms. Strongyloides stercoralis is known to cause autoinfection. In immunocompromised individuals, it can present with severe symptoms, hyperinfection, or disseminated disease. Reported mortality in cases of disseminated Strongyloidiasis is 87.1%. Serology and detection of larvae in stool by direct microscopy are the most commonly used methods to diagnose strongyloidiasis. The drug of choice for the treatment is ivermectin. However, the use of ivermectin in human pregnancy is not well studied, and its teratogenic risks are unknown. Proactive screening of strongyloidiasis is necessary in immunocompromised individuals to prevent severe disease.

Disseminated Mycobacterium abscessus infection with osteoarticular manifestations as an important differential diagnosis of inflammatory arthritis: A case report and literature review.

This case report describes a 52-year-old immunocompromised man diagnosed with disseminated Mycobacterium abscessus complex (MABC) infection. The patient had a history of malignant lymphoma and presented with fever and polyarthritis that lasted 3 weeks. Upon initial evaluation, blood and synovial fluid cultures from the swollen joints were negative. Reactive arthritis or rheumatoid arthritis was suspected as the cause of inflammatory synovitis in multiple joints. Administration of prednisolone followed by an interleukin-6 inhibitor improved the fever, but polyarthritis persisted, and destruction of the left hip joint was observed. Two months later, M. abscessus was detected in a blood culture and right shoulder joint synovium, leading to a final diagnosis of disseminated MABC infection. The joint symptoms resolved with combined antimicrobial therapy using amikacin, azithromycin, and imipenem/cilastatin. To date, 12 cases of disseminated MABC infection with osteoarticular manifestations have been reported. A total of 13 cases, including the present case, were reviewed. Seven patients had bone involvements, five had joint involvement, and the remaining one had bursa involvement. All the cases with joint involvement, except for our case, presented with monoarthritis. MABC infection is diagnosed based on the demonstration of MABC itself. Clinicians should keep disseminated MABC infection in mind as a possible cause of persistent arthritis. As demonstrated in our case, multiple replicate cultures of blood or specimens from the affected sites may be needed to detect it.

Successful long-term management for postoperative sternal infection with multiple disseminated lymphadenitis caused by Mycobacterium abscessus.

BACKGROUND: Postoperative sternal infection caused by Mycobacterium abscessus (M. abscessus) is rare, but associated with a high 2-year mortality rate of 40%. Decision-making around treatment strategy is challenging. Here, we present a successfully treated case of postoperative M. abscessus sternal infection with multiple disseminated lymphadenitis. CASE PRESENTATION: The patient, an 80-year-old woman with anterior mediastinal tumor and myasthenia gravis, underwent extended thymectomy under median sternotomy. Redness appeared around the scar two months after the operation. Sternal wires were removed, debridement was performed, and the wound was kept open. Mycobacterium abscessus was isolated from the wound culture. The disseminated lesions in the right axillary, parasternal, and bilateral supraclavicular lymph nodes, rendered surgical options for infection control difficult; therefore, she was treated conservatively with antibiotics and negative pressure wound therapy (NPWT). The wound diminished but infectious granulation tissue remained after NPWT. Two disseminated lesions were percutaneously punctured and drained of pus, which resulted in negative cultures. Additional debridement and wound closure were performed. She was discharged after switching to oral antibiotics. No recurrence was observed five months after the antibiotics were completed (total sensitive antibiotics use: 366 days). CONCLUSIONS: Repeated culture assessment of disseminated lesions is recommended to facilitate the development of appropriate therapeutic strategies. Localized procedures may be an option for patients with controlled disseminated lesions evidenced by negative cultures.

Disseminated non-tuberculous mycobacterial infection caused by Mycobacterium obuense in an immunocompromised patient: a case report.

BACKGROUND: Mycobacterium obuense (M. obuense) is a rapidly growing mycobacterium (RGM) which has been considered nonpathogenic. Here, we report a case of disseminated non-tuberculous mycobacterial (NTM) infection caused by M. obuense in an immunocompromised patient. CASE PRESENTATION: A 16-year-old boy was referred to our hospital due to acute myeloid leukemia. During the treatment of leukemia, the patient exhibited continuous fever, and diffuse miliary nodules with random distribution were found on chest computed tomography. Repeated examinations of bacterial culture tests revealed sputum and urine samples to be smear-positive for acid-fast bacillus, and blood culture from a peripherally inserted central catheter line showed the growth of NTM. The NTM species was identified as M. obuense by mass spectrometry and confirmed by genome sequencing. Combination therapy with amikacin, rifampicin, azithromycin, and moxifloxacin significantly improved the patient's symptoms and radiological findings. CONCLUSION: We report a case of disseminated NTM infection caused by M. obuense for which combination anti-microbial therapy was effective. An immunocompromised host indwelling catheter is at risk of RGM bloodstream infections. Although relatively rare, M. obuense may be considered as a potential pathogen causing infectious diseases, especially in high-risk patients.

Mortality After Nocardiosis: Risk Factors and Evaluation of Disseminated Infection.

Background: Nocardia primarily infects patients who are immunocompromised or those with chronic lung disease. Although disseminated infection is widely recognized as an important prognostic factor, studies have been mixed on its impact on outcomes of nocardiosis. Methods: We performed a retrospective cohort study of adults with culture-confirmed nocardiosis. Advanced infection was defined as disseminated infection, cavitary pulmonary infection, or pleural infection. The primary outcome was 1-year mortality, as analyzed by multivariable Cox regression. Results: Of 511 patients with culture growth of Nocardia, 374 (73.2%) who had clinical infection were included. The most common infection sites were pulmonary (82.6%), skin (17.9%), and central nervous system (14.2%). In total, 117 (31.3%) patients had advanced infection, including 74 (19.8%) with disseminated infection, 50 (13.4%) with cavitary infection, and 18 (4.8%) with pleural infection. Fifty-nine (15.8%) patients died within 1 year. In multivariable models, disseminated infection was not associated with mortality (hazard ratio, 1.16; 95% CI, .62-2.16; P = .650) while advanced infection was (hazard ratio, 2.48; 95% CI, 1.37-4.49; P = .003). N. farcinica, higher Charlson Comorbidity Index, and culture-confirmed pleural infection were also associated with mortality. Immunocompromised status and combination therapy were not associated with mortality. Conclusions: Advanced infection, rather than dissemination alone, predicted worse 1-year mortality after nocardiosis. N. farcinica was associated with mortality, even after adjusting for extent of infection. While patients who were immunocompromised had high rates of disseminated and advanced infection, immunocompromised status did not predict mortality after adjustment. Future studies should account for high-risk characteristics and specific infection sites rather than dissemination alone.

Single-cell multi-omics sequencing reveals the immunological disturbance underlying STAT3-V637M Hyper-IgE syndrome.

Hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by, among others, the excessive production of IgE and repetitive bacterial/fungal infections. Mutations in STAT3, a transcription factor that orchestrates immune responses, may cause HIES, but the underlying mechanisms are not fully understood. Here, we used multi-omic approaches to comprehensively decipher the immune disturbance in a male HIES patient harboring STAT3-V637M. In his peripheral blood mononuclear cell (PBMC) we found significant clonal expansion of CD8 T cells (with increased CD8 subunits expression, potentially enhancing responsiveness to MHC I molecules), but not in his CD4 T cells and B cells. Although his B cells exhibited a higher potential in producing immunoglobulin, elevated SPIC binding might bias the products toward IgE isotype. Immune checkpoint inhibitors, including CTLA4, LAG3, were overexpressed in his PBMC-CD4 T cells, accompanied by reduced CD28 and IL6ST (gp130) expression. In his CD4 T cells, integrative analyses predicted upstream transcription factors (including ETV6, KLF13, and RORA) for LAG3, IL6ST, and CD28, respectively. The down-regulation of phagocytosis and nitric oxide synthesis-related genes in his PBMC-monocytes seem to be the culprit of his disseminated bacterial/fungal infection. Counterintuitively, in his PBMC we predicted increased STAT3 binding in both naïve and mature CD4 compartments, although this was not observed in most of his PBMC. In his bronchoalveolar lavage fluid (BALF), we found two macrophage subtypes with anti-bacterial properties, which were identified by CXCL8/S100A8/S100A9, or SOD2, respectively. Together, we described how the immune cell landscape was disturbed in STAT3-V637M HIES, providing a resource for further studies.

Disseminated Nocardia farcinica infection associated with bacteraemia and osteomyelitis pubis in an elderly patient.

OBJECTIVE: We describe a rare case of a disseminated Nocardia farcinica infection associated with hip osteomyelitis. METHODS: A 91-year-old female patient was admitted with oedema of her right leg, fever of 38 °C and data consistent with ruptured Baker's cyst. A disseminated Nocardia farcinica infection including bloodstream infection, pneumonia and multiple abscesses along both lower limbs was observed. RESULTS: After a four-week course of 320 mg/1600 mg/12 h of intravenous trimethoprim/sulfamethoxazole and multiple chirurgic drainages the patient was discharged with oral trimethoprim/sulfamethoxazole. Nevertheless, the patient expired done month after being discharged from the hospital. CONCLUSIONS: The implementation of a combination of intravenous antibiotics and drainages resulted in an initial improvement in the patient's condition. However, despite these interventions, the patient ultimately passed away probably due to natural causes.

A case report: Severe disseminated infection caused by Strongyloides stercoralis in an immunocompromised patient by metagenomic next-generation sequencing.

Background: Strongyloides stercoralis (S. stercoralis) is a nematode that is widely distributed in the tropical and subtropical regions of the world and which can cause severe disseminated infection in immunocompromised individuals. However, strongyloidiasis, the disease caused by S. stercoralis, is difficult to diagnose because of its non-specific clinical presentation and the inadequate performance of conventional diagnostic methods. Case description: We report the case of a 75-year-old male patient with severe disseminated infection caused by S. stercoralis. The patient had a medical history of seasonal bronchitis and, as a consequence, had taken prednisone for many years. Initial clinical tests failed to detect any pathogens, but metagenomic next-generation sequencing (mNGS) resulted in the identification of S. stercoralis in the patient's bronchoalveolar lavage fluid (BALF) and blood. Subsequently, routine testing repeatedly detected nematode larvae in the patient's stool and sputum. Through a combination of mNGS results and clinical symptoms, the patient was finally diagnosed with severe disseminated infection caused by S. stercoralis. Conclusion: The clinical manifestations of disease caused by infection with S. stercoralis are not specific; therefore, early and accurate diagnosis is very important. mNGS can detect S. stercoralis even when it is present at only a low level. This case report supports the notion that mNGS is a valuable tool in the diagnosis of severe disseminated infections caused by S. stercoralis in immunocompromised patients.

Super acute-onset disseminated BCG infection: A case report.

Intravesical Bacillus Calmette-Guérin (BCG) instillation is an established immunotherapy for superficial bladder cancer. Herein, we describe a case of disseminated BCG infection that developed immediately after the first BCG injection. A 76-year-old man diagnosed with non-invasive bladder cancer underwent intravesical BCG instillation; he developed high fever and systemic arthralgia later that night. General examination did not reveal any infectious sources, and a combination therapy of isoniazid, rifabutin, and ethambutol was initiated after collecting his blood, urine, bone marrow, and liver biopsy samples for mycobacterial cultures. Three weeks later, Mycobacterium bovis was detected in the urine and bone marrow samples, and pathological investigation of liver biopsy revealed multiple small epithelial granulomas with focal multinucleated giant cells, leading to a diagnosis of disseminated BCG infection. The patient recovered after long-term antimycobacterial therapy without remarkable sequelae. Most cases of disseminated BCG infection occur after several doses of BCG injections, and its onset reportedly varies among cases, ranging from a few days to several months. The present case was notable as disease onset was observed only a few hours after the first BCG injection. Although rare, development of disseminated BCG infection should be considered as a differential diagnosis in patients at any time after intravesical BCG instillation therapy.

Risk factors and prophylaxis for nocardiosis in solid organ transplant recipients: A nested case-control study.

BACKGROUND: Nocardia is an opportunistic pathogen that primarily affects immunocompromised individuals, including solid organ transplant (SOT) recipients. Up to 2.65% of SOT recipients develop nocardiosis; however, few studies have examined risk factors and prophylaxis for nocardiosis. METHODS: We performed a multicenter, matched nested case-control study of adult SOT recipients with culture-confirmed nocardiosis from 2000 through 2020. Controls were matched up to 2:1 by sex, first transplanted organ, year of transplant, transplant center, and adequate post-transplant follow-up. Multivariable conditional logistic regression was performed to analyze associations with nocardiosis. Cox proportional hazards regression compared 12-month mortality between infection and uninfected patients. RESULTS: One hundred and twenty-three SOT recipients were matched to 245 uninfected controls. Elevated calcineurin inhibitor level, acute rejection, cytomegalovirus infection, lymphopenia, higher prednisone dose, and older age were significantly associated with nocardiosis while trimethoprim-sulfamethoxazole prophylaxis was protective (odds ratio [OR] .34; 95% confidence interval [CI] .13-.84). The effect of prophylaxis was similar, though not always statistically significant, in sensitivity analyses that only included prophylaxis dosed more than twice-per-week (OR .30; 95% CI .11-.80) or restricted to years 2015-2020 (OR .33, 95% CI .09-1.21). Nocardiosis was associated with increased 12-month mortality (hazard ratio 5.47; 95% confidence interval 2.42-12.35). CONCLUSIONS: Multiple measures of immunosuppression and lack of trimethoprim-sulfamethoxazole prophylaxis were associated with nocardiosis in SOT recipients. Effectiveness of prophylaxis may be related to trimethoprim-sulfamethoxazole dose or frequency. Trimethoprim-sulfamethoxazole should be preferentially utilized over alternative agents in SOT recipients with augmented immunosuppression or signs of heightened immunocompromise.

Engineered Superinfective Pf Phage Prevents Dissemination of Pseudomonas aeruginosa in a Mouse Burn Model.

Pf is a filamentous bacteriophage integrated in the chromosome of most clinical isolates of Pseudomonas aeruginosa. Under stress conditions, mutations occurring in the Pf genome result in the emergence of superinfective variants of Pf (SI-Pf) that are capable of circumventing phage immunity; therefore, SI-Pf can even infect Pf-lysogenized P. aeruginosa. Here, we identified specific mutations located between the repressor and the excisionase genes of Pf4 phage in the P. aeruginosa PAO1 strain that resulted in the emergence of SI-Pf. Based on these findings, we genetically engineered an SI-Pf (eSI-Pf) and tested it as a phage therapy tool for the treatment of life-threatening burn wound infections caused by PAO1. In validation experiments, eSI-Pf was able to infect PAO1 grown in a lawn as well as biofilms formed in vitro on polystyrene. eSI-Pf also infected PAO1 present in burned skin wounds on mice but was not capable of maintaining a sustained reduction in bacterial burden beyond 24 h. Despite not lowering bacterial burden in burned skin tissue, eSI-Pf treatment completely abolished the capability of P. aeruginosa to disseminate from the burn site to internal organs. Over the course of 10 days, this resulted in bacterial clearance and survival of all treated mice. We subsequently determined that eSI-Pf induced a small-colony variant of P. aeruginosa that was unable to disseminate systemically. This attenuated phenotype was due to profound changes in virulence determinant production and altered physiology. Our results suggest that eSI-Pf has potential as a phage therapy against highly recalcitrant antimicrobial-resistant P. aeruginosa infections of burn wounds. IMPORTANCE Pseudomonas aeruginosa is a major cause of burn-related infections. It is also the most likely bacterial infection to advance to sepsis and result in burn-linked death. Frequently, P. aeruginosa strains isolated from burn patients display a multidrug-resistant phenotype necessitating the development of new therapeutic strategies and prophylactic treatments. In this context, phage therapy using lytic phages has demonstrated exciting potential in the control P. aeruginosa infection. However, lytic phages can present a set of drawbacks during phage therapy, including the induction of bacterial resistance and limited bacteria-phage interactions in vivo. Here, we propose an alternative approach to interfere with P. aeruginosa pathogenesis in a burn infection model, i.e., by using an engineered superinfective filamentous phage. Our study demonstrates that treatment with the engineered Pf phage can prevent sepsis and death in a burn mouse model.

Vector Competence for Zika Virus Changes Depending on the Aedes aegypti's Region of Origin in Manaus: A Study of an Endemic Brazilian Amazonian City.

Zika virus (ZIKV) is transmitted to humans by the infectious bite of mosquitoes such as Aedes aegypti. In a city, the population control of mosquitoes is carried out according to alerts generated by different districts via the analysis of the mosquito index. However, we do not know whether, besides mosquito abundance, the susceptibility of mosquitoes could also diverge among districts and thus impact the dissemination and transmission of arboviruses. After a viremic blood meal, the virus must infect the midgut, disseminate to tissues, and reach the salivary gland to be transmitted to a vertebrate host. This study evaluated the patterns of ZIKV infection in the Ae. aegypti field populations of a city. The disseminated infection rate, viral transmission rate, and transmission efficiency were measured using quantitative PCR at 14 days post-infection. The results showed that all Ae. aegypti populations had individuals susceptible to ZIKV infection and able to transmit the virus. The infection parameters showed that the geographical area of origin of the Ae. aegypti influences its vector competence for ZIKV transmission.