Burkholderia semiarida as Cause of Recurrent Pulmonary Infection in Immunocompetent Patient, China.

Burkholderia semiarida was previously identified solely as a plant pathogen within the Burkholderia cepacia complex. We present a case in China involving recurrent pneumonia attributed to B. semiarida infection. Of note, the infection manifested in an immunocompetent patient with no associated primary diseases and endured for >3 years.

Host immunity involvement in the outcome of phage therapy against hypervirulent Klebsiella pneumoniae infections.

Highly encapsulated hypervirulent Klebsiella pneumoniae (hvKp) causes severe infections. Bacteriophage therapy, an antibiotic alternative, effectively treats bacterial infections. Phage φFK1979 encoding polysaccharide depolymerases can target and disarm the capsule of hvKp FK1979, showing promise against FK1979 infection. Resistant strains induced by φFK1979 are possibly eliminated by host immunity and new phage phiR3 targeting them. We constructed varied immunocompromised FK1979 infection mouse models to assess the therapy efficacy of φFK1979 alone or in combination with phiR3. Survival rates, bacterial loads, histopathology, inflammation, and immune cell distribution of mice were studied. Prompt and adequate administration of φFK1979, rather than phiR3, significantly improved survival rates in mice with different immune statuses. However, immunocompromised mice showed lower efficacy due to reduced tolerance to low-virulence φFK1979-resistant bacteria compared to immunocompetent mice. Adding phiR3 sequentially greatly enhanced therapy efficacy for them, leading to increased survival rates and notable improvements in pathology and inflammation. Immunocompetent mice exhibited the most favorable response to φFK1979 monotherapy, as their immune system cleared φFK1979-resistant bacteria while avoiding a robust response to phiR3 combating φFK1979-resistant bacteria. This study revealed host immunity involvement in the outcome of phage therapy against infections and introduced, for the first time, personalized phage therapy strategies for hvKp-infected mice with varying immune statuses.IMPORTANCEHypervirulent Klebsiella pneumoniae (hvKp), with high capsular polysaccharide production, can cause severe invasive infections. Capsule-targeting phage poses the potential to fight against hvKp. We previously elucidated that the capsule-targeting phage induces resistance in hvKp, while phage-resistant strains exhibit sensitivity to host innate immunity and new phages targeting them. This indicated that phage-resistant strains can be eliminated by the immune system in immunocompetent patients, whereas they may require treatment with phages targeting resistant bacteria in immunocompromised patients. HvKp can infect individuals with varying immune statuses, including both immunocompetent and immunocompromised/deficient patients. This study, for the first time, developed personalized phage therapy strategies for hvKp-infected mice with different immune statuses, optimizing phage therapy against hvKp infections. This research is expected to provide a theoretical foundation and novel insights for clinical phage therapy against hvKp infections, offering significant societal benefits and clinical value.

Prognostic significance of plasma cytomegalovirus (CMV) DNA load in immunocompetent patients with CMV pneumonia: A retrospective cohort study.

Cytomegalovirus (CMV) pneumonia, often presented as pneumonitis, is characterized by respiratory failure and large interstitial infiltrates visible on chest radiographs. This retrospective cohort study investigates the predictive significance of plasma CMV DNA load on the short- and long-term mortality among immunocompetent patients diagnosed with CMV pneumonia. The study included 61 immunocompetent patients suspected of having CMV pneumonia, treated with intravenous ganciclovir after positive CMV DNA results from bronchoalveolar lavage or plasma. Our multivariate Cox regression analysis identified several independent predictors of mortality. Having idiopathic pulmonary fibrosis (IPF) significantly increased the risk of in-hospital mortality (HR: 7.27, 95% CI: 1.62-32.52, p = 0.009), as did shorter durations of antiviral therapy (HR: 0.90, 95% CI: 0.84-0.97, p = 0.005) and higher CMV DNA levels (>3870 IU/mL; HR: 9.63, 95% CI: 2.32-39.98, p = 0.002). High CMV DNA levels (>5154 IU/mL) were also predictors of 30-day mortality (HR: 9.39, 95% CI: 2.20-40.01, p = 0.002). For 1-year mortality, the presence of IPF (HR: 2.96, 95% CI: 1.08-8.06, p = 0.034), hypersensitivity pneumonia (HP) (HR: 4.30, 95% CI: 1.57-11.78, p = 0.005), shorter duration of total antiviral therapy (HR: 0.95, 95% CI: 0.93-0.99, p = 0.010), and higher CMV DNA levels (>327 IU/mL) (HR: 3.36, 95% CI: 1.33-8.47, p = 0.010) were identified as independent determinants. The study reveals that IPF increases short and long-term mortality risks, while HP increases long-term mortality. Extended antiviral treatment duration results in a 10% reduction in in-hospital mortality for each additional day of treatment. Furthermore, elevated viral loads are associated with higher mortality rates, highlighting the necessity for careful monitoring.

Prevalence and progression of pneumonia in immunocompetent adults with varicella.

Pneumonia is the most common complication of varicella infections. Although previous studies have tended to focus mainly on immunocompromised patients, varicella pneumonia can also occur in healthy adults. Therefore, in this study, we aimed to assess the progression of varicella pneumonia in immunocompetent hosts. This retrospective study involved immunocompetent adult outpatients with varicella who attended the adult Fever Emergency facility of Peking University Third Hospital from April 1, 2020, to October 31, 2022. Varicella pneumonia was defined as a classic chickenpox-type rash in patients with infiltrates on chest computed tomography. The study included 186 patients, 57 of whom had a contact history of chickenpox exposure. Antiviral pneumonia therapy was administered to 175 patients by treating physicians. Computed tomography identified pneumonia in 132 patients, although no deaths from respiratory failure occurred. Seventy of the discharged patients were subsequently contacted, all of whom reported being well. Follow-up information, including computed tomography findings, was available for 37 patients with pneumonia, among whom 24 reported complete resolution whereas the remaining 13 developed persistent calcifications. Notably, we established that the true incidence of varicella pneumonia is higher than that previously reported, although the prognosis for immunocompetent hosts is generally good.

Histoplasmosis in non-immunosuppressed patients from an endemic area in Northeastern Brazil.

Differently from immunocompromised patients, very little information is available in the literature regarding the clinical presentation, epidemiology, and outcomes of histoplasmosis in non-immunosuppressed individuals living in endemic areas. This retrospective case series study was carried out by reviewing the medical records of non-immunocompromised patients with histoplasmosis, residents in a hyperendemic area in northeastern Brazil, between 2011 and 2022. Thirty HIV-negative patients were identified with histoplasmosis, and 19 cases met the inclusion criteria: three had acute, five subacute and one chronic pulmonary forms; two with mediastinal picture and eight had disseminated disease (two with severe symptoms). The median age of our sample was 32.7 years old [interquartile range: 24-45]. Most of the patients were male (male-to-female ratio = 15:4) and resided in the state capital (n = 9). The majority had a previous history of exposure to well-known risk factors for Histoplasma infection. Pulmonary nodules were observed in all subacute form, two patients (acute and subacute forms) were initially treated empirically for pulmonary tuberculosis; one death was registered in the subacute form. The chronic pulmonary form of histoplasmosis was diagnosed in one patient only after the symptoms persisted despite specific treatment. The primary clinical manifestations of the moderate form of DH were enlarged lymph nodes, with histopathology being the main diagnostic method. The cases were detected as isolated occurrences and not as an outbreak, suggesting that exposure to Histoplasma can be more widespread than presumed. Despite the self-limiting nature of the disease, death can occur even in previously heathy patients.

This study aimed to describe the presentation of histoplasmosis outside the context of immunosuppression, including the diagnostic methods, epidemiology, and main radiological and clinical features. A better understanding of the various forms of this disease will help improve case management.

Rhinocerebral mucormycosis in immunocompetent patients: a case report and review of literature.

INTRODUCTION: Mucormycosis of the head and neck region is a rare but aggressive fungal infection that usually involves immunocompromised patients. More infrequently, this infection can also occur in people with no otherwise known underlying immunological deficit. This rarity usually causes a delay in diagnosis and may severely decrease the chance of survival in these patients. In this study, we present an extreme case of mucormycosis in an immunocompetent patient. By conducting a thorough review of the literature, we aim to increase our knowledge on this matter. Our goal is to improve diagnosis and start treatment at an earlier stage. CASE PRESENTATION AND METHODS: Our patient was a 31-year-old man who presented with bilateral face numbness, neck pain, headache, and a necrotic palatal lesion 45 days after a dental root canal procedure. There was extensive involvement of facial and skull base bony and soft tissues. Through two debridement sessions and intravenous antifungal treatment, the patient was discharged with near-complete disease resolution. We identified 48 cases in the literature that matched our study criteria. We searched the current literature for proven cases of mucormycosis in the head and neck region who didn't have any underlying disease. We extracted their data and added the data of our patient. Then, we re-analyzed them using descriptive analysis, chi-square, and binary logistic regression to better understand the different factors for survival and disease burden in these patients. RESULTS: 49 patients were analyzed in this study. The mean age was 46.93 ± 15.75 (min 16 and max78 years old). The most prevalent subsite to be involved was the sino-nasal mucosa, followed by the surrounding soft tissues and the orbit. While both orbit and intracranial tissue involvement differed significantly between surviving and deceased patients, only intracranial tissue involvement could be used to predict survival. The overall survival rate was 91.8%. CONCLUSION: Although very rare, mucormycosis can occur in immunocompetent patients. Physicians should consider mucormycosis when faced with refractory conditions and unusual symptoms such as exposed bones, facial numbness, headaches, and intractable pain. Complementary imaging (CT scan with or without MRI) and histopathological examination are critical for timely diagnosis or exclusion of this potentially fatal yet treatable disease.

Brain abscesses: the first report of disseminated Nocardia beijingensis infection in an immunocompetent individual in China.

Nocardia is widely distributed in the natural environment and typically cause opportunistic infections. However, it is important to note that the pathogenicity of different Nocardia species may vary significantly. Here we reported the first case of brain abscess caused by Nocardia beijingensis (N. beijingensis) infection in China. A 70-year-old male immunocompetent individual came to our hospital for treatment due to headache. After examination, it was found that he had a brain abscess caused by N. beijingensis. By utilizing a combination of surgical intervention and antibiotic therapy, the patient ultimately achieved full recovery. In addition, we isolated this strain and displayed its ultrastructure through scanning electron microscopy. The phylogenetic tree was analyzed by 16 S rRNA sequence. A literature review of N. beijingensis infections in all immunocompetent and immunocompromised patients was presented. It highlighted that abscess formation appears to be a common manifestation of N. beijingensis infection, and N. beijingensis has become an emerging pathogen in immunocompetent individuals.

Disseminated Cryptococcus neoformans infection involving multiple bones and lung in an immunocompetent patient: a case report.

BACKGROUND: Cryptococcal osteomyelitis is a rare and potentially serious condition, typically encountered in individuals with compromised immune systems. This case underscores the unusual occurrence of disseminated Cryptococcosis in an immunocompetent person, involving multiple bones and lungs, with Cryptococcus neoformans identified as the causative agent. CASE PRESENTATION: An Indonesian man, previously in good health, presented with a chief complaint of successive multiple bone pain lasting for more one month, without any prior history of trauma. Additionally, he reported a recent onset of fever. On physical examination, tenderness was observed in the left lateral chest wall and right iliac crest. Laboratory findings indicated mildly elevated inflammatory markers. A computed tomography (CT) scan of the chest revealed an ovoid solid nodule in the right lower lung and multifocal osteolytic lesions in the sternum, ribs, and humeral head. A magnetic resonance imaging (MRI) study of the sacrum showed multiple lesions in the bilateral iliac bone and the lower L4 vertebral body. Confirmation of Cryptococcal osteomyelitis involved a fine-needle biopsy and culture, identifying Cryptococcus neoformans in the aspirate. The patient responded positively to targeted antifungal treatments, leading to a gradual improvement in his condition. CONCLUSIONS: This case emphasizes the need to consider Cryptococcus neoformans osteomyelitis in immunocompetent patients with bone pain. A definitive diagnosis involves a fine-needle biopsy for pathology and culture, and prompt initiation of appropriate antifungal treatment has proven effective in preventing mortality.

Histoplasmosis peritonitis in an immunocompetent patient: case report.

Histoplasmosis is a fungal infection most frequently seen in immunocompromised patients. It is endemic in Central and South America and in Africa. The infection is usually asymptomatic in a healthy individual. Extrapulmonary dissemination can be seen in immunocompromised hosts. Gastrointestinal manifestations frequently involve the terminal ileum and cecum, mimicking Crohn's disease or malignancy. We describe the case of a 36-year-old healthy man from Cameroon, living in Switzerland for 13 years and without any medical nor surgical history, who presented peritonitis not responding to antibiotics. CT-scan showed bowel obstruction and signs of peritonitis. We opted for an explorative laparoscopy, which was converted to laparotomy with extensive adhesiolysis. Diagnostic of histoplasmosis was confirmed by histology and PCR analysis on biopsy. To our knowledge, this is the first described case of peritonitis as main outcome of a disseminated histoplasmosis involving the peritoneum in an immunocompetent patient.

Cryptococcosis with pulmonary cavitation in an immunocompetent child: a case report and literature review.

BACKGROUND: Pulmonary cryptococcosis (PC) rarely occurs in immunocompetent children. CASE PRESENTATION: A 13-year-old boy was admitted to the First Affiliated Hospital of Ningbo University in February 2023 with complaints of cough and chest pain. Physical examination showed slightly moist rales in the right lung. Chest computed tomography (CT) suggested a lung lesion and cavitation. Blood routine test, lymphocyte subsets, immunoglobulin, and complement tests indicated that the immune system was normal. However, the serum cryptococcal antigen test was positive. Next-generation sequencing revealed Cryptococcus infection. The child was diagnosed with PC and was discharged after treating with fluconazole 400 mg. Four months later, chest CT showed that the lung lesion diminished, and reexamination of serum cryptococcal antigen test turned positive. CONCLUSION: PC should be considered in an immunocompetent child with pulmonary cavities with nonspecific symptoms.

Progressive multifocal leukoencephalopathy in patients with chronic kidney disease.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic central nervous system infection caused by the human polyomavirus 2, leading to demyelination from oligodendrocyte death and rapid neurologic decline. Most commonly, PML affects patients in immunocompromised states. However, rare reports of PML in an immunocompetent host exist. Here, we report two cases of PML in older individuals with chronic kidney disease (CKD). CKD can ultimately lead to immune system dysfunction and place patients in a relatively immunosuppressed state. Testing for JC virus should remain a consideration for rapid, unexplained neurologic decline even without known immunocompromised status in the appropriate clinical setting.

Kodamaea ohmeri Leg Skin Ulcer Infection in an Immunocompetent Patient: A Case Report.

INTRODUCTION: Kodamaea ohmeri is an emerging fungus recognised as an important pathogen in immunocompromised hosts, responsible for life-threatening infections. CASE PRESENTATION: We describe a case of a 69-year-old immunocompetent man with a long history of leg skin ulcers infected by K. ohmeri. This is the first case of leg wounds infected by K. ohmeri in an immunocompetent patient. The infection was successfully treated with voriconazole 200 mg daily. CONCLUSION: Though rare, K. ohmeri should be considered in patients with skin ulcers that are poorly responsive to medical treatment, even if not immunocompromised.

A retrospective observational study on disseminated herpes zoster in immunocompetent patients.

INTRODUCTION: Disseminated herpes zoster (DHZ) is a severe infection associated with high incidences and mortality rates in immunocompromised patients. Although studies have shown its occurrence in immunocompetent patients, its epidemiology, clinical presentation, and treatment outcomes in this cohort remain unknown. Thus, this study aimed to examine the clinical presentation, treatment, complications, and outcomes of DHZ in immunocompetent patients and compare these findings with previous studies. METHODS: We included 20 immunocompetent patients of DHZ at our institution and reviewed 42 previously published cases. We then investigated the clinical features, predisposing factors, laboratory findings, treatment, and outcomes of all cases including in-hospital mortality, neurological dysfunction at discharge, and postherpetic neuralgia. We compared DHZ-immunocompetent patients to DHZ-immunocompromised patients. RESULTS: Patients had a median age of 71.5 years and were predominantly male. The trigeminal area was the most common site of initial rash, with a mean dissemination time of 6.5 days. Pain was the most common symptom, followed by fever (approximately 40 % of cases); acyclovir was the most used treatment. Additionally, the in-hospital mortality was 0 %, neuropathy at discharge was observed in approximately 10 % of patients, and postherpetic neuralgia was present in approximately 40 % of patients. In the immunocompromised cases, the mortality rate was 12 %, which was higher than in our cases; however, the rates of neuropathy and postherpetic neuralgia were lower. CONCLUSIONS: This study provides new insights into the clinical presentation, treatment, and outcomes of DHZ cases in immunocompetent patients, highlighting its tendency for residual neurological damage despite having low mortality rates.

Efficacy of cefmetazole in immunocompetent patients with uncomplicated colonic diverticulitis: A propensity score matching analysis.

INTRODUCTION: The incidence of colonic diverticulitis is increasing in Japan. Although antimicrobial chemotherapy is a treatment option, Japanese guidelines for diverticulosis do not recommend any antibiotic in particular and antibiotic selection is left to the discretion of the prescribing physician, who often selects antibiotics with anti-pseudomonal activity. Therefore, this study compared the efficacy of cefmetazole (CMZ) with that of tazobactam/piperacillin (TAZ/PIPC) in hospitalized Japanese immunocompetent patients with uncomplicated colonic diverticulitis. PATIENTS AND METHODS: This retrospective study included Japanese immunocompetent patients hospitalized for colonic diverticulitis between April 2019 and March 2022. Participants were divided into the CMZ and TAZ/PIPC groups. After propensity score matching, the intergroup differences in clinical outcomes, including adverse events, mortality, and re-admission rate, were ascertained. RESULTS: During the study period, 142 Japanese patients were hospitalized with community-onset colonic diverticulitis; 124 of these patients were immunocompetent. Of the 124 patients, 42 were excluded, and the CMZ and TAZ/PIPC groups comprised 62 and 20 patients, respectively. After propensity score matching, there were 16 patients in each group. There was no significant intergroup difference in the mortality and re-admission rates; however, the incidence of liver dysfunction was significantly higher (p = 0.018) in the TAZ/PIPC group. CONCLUSION: In patients with colonic diverticulitis, CMZ therapy should be selected because of the adequate clinical outcomes and lower incidence of adverse events, as this would reduce broad-spectrum antibiotic use and minimize antibiotic-resistant bacteria.

A rare case of disseminated pulmonary cryptococcosis in an immunocompetent patient.

Pulmonary cryptococcosis is an uncommon invasive fungal infection of the lungs seen in immunocompromised individuals but increasingly reported among the immunocompetent. We report a rare case of pulmonary cryptococcosis in an immunocompetent host highlighting its unique clinical and radiological presentation.Clinical trial number: Not applicable.

Atypical cutaneous manifestations of methicillin resistant Staphylococcus aureus infections in two immunocompetent pediatric patients: Case reports and review of the literature.

Although many clinical variants of Staphylococcus aureus infection are well-recognized, atypical presentations may mimic other conditions. We describe two cases of atypical S. aureus infections in pediatric patients: a S. aureus infection presenting with a vesicopustular rash mimicking varicella zoster virus and a case of multifocal panniculitis. Both of these cases were specifically caused by methicillin-resistant S. aureus (MRSA). Additional cases of atypical S. aureus infections and presenting features from the current literature are also discussed.

Neurobrucellosis presenting as an infected cerebellopontine cistern epidermoid cyst.

Neurobrucellosis is a rare complication of brucella infection which presents as meningitis, meningoencephalitis, subdural empyema, brain abscess, myelitis, and radiculo- neuritis. We report the first case of neurobrucellosis presenting as an infected cerebellopontine cistern epidermoid cyst in a young immunocompetent male who presented with fever and acute raised intracranial pressure. MRI brain showed an extra-axial mass in the right cerebellopontine angle cistern with peripheral rim enhancement and diffusion restriction. Emergency surgery unveiled a well-encapsulated lesion containing thick pus and keratinous material, confirming an infected epidermoid cyst. Intriguingly, the culture revealed Brucella infection, but the source of the infection remained unclear.

Rethinking the role of surgical resection in the management of primary pituitary lymphoma.

BACKGROUND: Primary pituitary lymphoma (PPL) is a rare finding in immunocompetent patients, with only 54 patients reported to date (including ours). It presents most often with headache and hypopituitarism, with MRI findings comparable to more common pituitary tumours, making the diagnosis challenging. There is no consensus on the ideal management for these lesions with the role of surgical resection not clearly established. CASE REPORT: We present here a 49-year-old female who presented with acute vision loss and was found to have PPL of diffuse large B-cell lymphoma, non-germinal centre type. The radiologic findings were distinct from prior cases with haemorrhagic components and perilesional edoema in the bilobed sellar mass. Surgical resection was halted when a diagnosis of lymphoma was suspected. This decision was based on the guidelines for the treatment of primary CNS lymphoma (PCNSL) and the lack of evidence to support surgical resection of PPL specifically. Our patient lacked mutations commonly associated with a poor prognosis in DLBCL, such as TP53 and BCL6. She remains in remission with normal vision nearly two years after treatment with minimal resection, MR-CHOP, and consolidation radiotherapy. CONCLUSION: We highlight here the clinical and diagnostic features of PPL to guide clinicians to early recognition and diagnosis. Surgical resection should be limited to what is necessary to obtain a diagnosis and critical decompression; otherwise, these lesions respond excellently to steroids and typical chemoradiation regimens.

Trained Immunity and Trained Tolerance: The Case of Helicobacter pylori Infection.

Trained immunity is a concept in immunology in which innate immune cells, such as monocytes and macrophages, exhibit enhanced responsiveness and memory-like characteristics following initial contact with a pathogenic stimulus that may promote a more effective immune defense following subsequent contact with the same pathogen. Helicobacter pylori, a bacterium that colonizes the stomach lining, is etiologically associated with various gastrointestinal diseases, including gastritis, peptic ulcer, gastric adenocarcinoma, MALT lymphoma, and extra gastric disorders. It has been demonstrated that repeated exposure to H. pylori can induce trained immunity in the innate immune cells of the gastric mucosa, which become more responsive and better able to respond to subsequent H. pylori infections. However, interactions between H. pylori and trained immunity are intricate and produce both beneficial and detrimental effects. H. pylori infection is characterized histologically as the presence of both an acute and chronic inflammatory response called acute-on-chronic inflammation, or gastritis. The clinical outcomes of ongoing inflammation include intestinal metaplasia, gastric atrophy, and dysplasia. These same mechanisms may also reduce immunotolerance and trigger autoimmune pathologies in the host. This review focuses on the relationship between trained immunity and H. pylori and underscores the dynamic interplay between the immune system and the pathogen in the context of gastric colonization and inflammation.

Cost-effective In Vivo and In Vitro Mouse Models for Evaluating Anticryptosporidial Drug Efficacy: Assessing Vorinostat, Docetaxel, and Baicalein.

BACKGROUND: Cryptosporidiosis is a significant diarrheal disease in humans and animals. Immunodeficient mice are the primary small animal models, but their high costs and specialized breeding/housing requirements limit in vivo drug testing. Numerous anticryptosporidial lead compounds identified in vitro remain untested in vivo. METHODS: Cryptosporidium tyzzeri, a natural mouse parasite closely related to Cryptosporidium parvum and Cryptosporidium hominis, was isolated to establish an infection model in immunocompetent mice. The model was validated using classic anticryptosporidial drugs (paromomycin and nitazoxanide) and then employed to assess the efficacy of 3 new leads (vorinostat, docetaxel, and baicalein). An in vitro culture of C. tyzzeri was also developed to complement the animal model. RESULTS: Chronic C. tyzzeri infection was established in chemically immunosuppressed wild-type mice. Paromomycin (1000 mg/kg/d) and nitazoxanide (100 mg/kg/d) demonstrated efficacy against C. tyzzeri. Vorinostat (30 mg/kg/d), docetaxel (25 mg/kg/d), and baicalein (50 mg/kg/d) were highly effective against C. tyzzeri infection. In vitro, nitazoxanide, vorinostat, docetaxel, and baicalein exhibited low to submicromolar efficacy against C. tyzzeri. CONCLUSIONS: Novel in vivo and in vitro models have been developed for cost-effective anticryptosporidial drug testing. Vorinostat, docetaxel, and baicalein show potential for repurposing and/or optimization for developing new anticryptosporidial drugs.