Impact of next-generation sequencing on antimicrobial treatment in immunocompromised adults with suspected infections

BACKGROUND:Prompt pathogen identification can have a substantial impact on the optimization of antimicrobial treatment.The objective of the study was to assess the diagnostic value of next-generation sequencing(NGS)for identifying pathogen and its clinical impact on antimicrobial intervention in immunocompromised patients with suspected infections.METHODS:This was a retrospective study.Between January and August 2020,47 adult immunocompromised patients underwent NGS testing under the following clinical conditions:1)prolonged fever and negative conventional cultures;2)new-onset fever despite empiric antimicrobial treatment;and 3)afebrile with suspected infections on imaging.Clinical data,including conventional microbial test results and antimicrobial treatment before and after NGS,were collected.Data were analyzed according to documented changes in antimicrobial treatment(escalated,no change,or deescalated)after the NGS results.RESULTS:The median time from hospitalization to NGS sampling was 19 d.Clinically relevant pathogens were detected via NGS in 61.7% of patients(29/47),more than half of whom suffered from fungemia(n=17),resulting in an antimicrobial escalation in 53.2% of patients(25/47)and antimicrobial de-escalation in 0.2% of patients(1/47).Antimicrobial changes were mostly due to the identification of fastidious organisms such as Legionella,Pneumocystis jirovecii,and Candida.In the remaining three cases,NGS detected clinically relevant pathogens also detected by conventional cultures a few days later.The antimicrobial treatment was subsequently adjusted according to the susceptibility test results.Overall,NGS changed antimicrobial management in 55.3%(26/47)of patients,and conventional culture detected clinically relevant pathogens in 14.9% of the patients(7/47).CONCLUSION:With its rapid identification and high sensitivity,NGS could be a promising tool for identifying relevant pathogens and enabling rapid appropriate treatment in immunocompromised patients with suspected infections.

Critical considerations for the management of acute abdomen in transplant patients

The number of solid organ transplantations performed annually is increasing and are increasing in the following order:Kidney,liver,heart,lung,pancreas,small bowel,and uterine transplants.However,the outcomes of transplants are impro-ving(organ survival>90%after the 1st year).Therefore,there is a high probability that a general surgeon will be faced with the management of a transplant patient with acute abdomen.Surgical problems in immunocompromised patients may not only include graft-related problems but also nongraft-related problems.The perioperative regulation of immunosuppression,the treatment of accompanying problems of immunosuppression,the administration of cortisol and,above all,the realization of a rapidly deteriorating situation and the accurate evaluation and interpretation of clinical manifestations are particularly important in these patients.The perioperative assessment and preparation includes evaluation of the patient’s cardiovascular system and determining if the patient has hypertension or suppression of the hypothalamic-pituitary-adrenal axis,or if the patient has had any coagulation mechanism abnormalities or thromboembolic episodes.Immunosuppression in transplant patients is associated with the use of calci-neurin inhibitors,corticosteroids,and antiproliferation agents.Many times,the clinical picture is atypical,resulting in delays in diagnosis and treatment and leading to increased morbidity and mortality.Multidetector computed tomo-graphy is of utmost importance for early diagnosis and management.Transplant recipients are prone to infections,especially specific infections caused by cytomegalovirus and Clostridium difficile,and they are predisposed to intraop-erative or postoperative complications that require great care and vigilance.It is necessary to follow evidence-based therapeutic protocols.Thus,it is required that the clinician choose the correct therapeutic plan for the patient(conservative,emergency open surgery or minimally invasive surgery,including laparoscopic or even robotic surgery).

Use of real-time polymerase chain reaction for the diagnosis of Pneumocystis pneumonia in immunocompromised patients： a meta-analysis

Background The diagnosis of Pneumocystis pneumonia （PCP） in immunocompromised patients is still challenging today due to the absence of an in vitro culture system and the low diagnostic accuracy of microscopic examinations. Herein, we performed a meta-analysis to evaluate the accuracy of real-time polymerase chain reaction （PCR） in the diagnosis of PCP. Methods We searched Web of Knowledge and Medline from 1990 to May 2010 for studies reporting diagnostic accuracy data regarding the use of real-time PCR in the diagnosis of PCP in immunocompromised patients. Results Ten individual studies were included. Overall, the sensitivity of real-time PCR was 97% （95% CI： 93%-99%）; the specificity was 94% （95% CI： 90%-96%）. The area under the HSROC curve （95% CO for real-time PCR was 0.99 （0.97-0.99）. In a subgroup analysis regarding studies involving HIV patients among the study population, the sensitivity and specificity were 97% （95% CI： 93%-99%） and 93% （95% CI： 89%-96%）, respectively. Regarding studies using Bronchoalveolar lavage （BAL） samples only： sensitivity =98% （95% CI： 94%-99%）; specificity =93% （95% CI： 89%- 96%）, respectively. Regarding studies using microscopy as a reference standard： sensitivity =97% （95% CI： 92%-99%）; specificity =93% （95% CI： 88%-96%）. However, high between-study statistical heterogeneity was observed in all analyses. Conclusions Real-time PCR has a good diagnostic accuracy and may provide a useful adjunctive tool for the diagnosis of PCP in immunocompromised patients. Further studies are needed in order to identify any differences in the diagnostic performance of real-time PCR in HIV and non-HIV immunocompromised patients.

Altered CD8＋ T-cell counts as an early predictor of prognosis in critically ill immunocompromised patients with invasive pulmonary aspergillosis

Background The number of critically ill immunocompromised （CIIC） patients has increased dramatically in recent years,and they represent a high risk population for invasive pulmonary aspergillosis （IPA） infection.Host immunity should play a major role in determining the outcome and recovery of these patients.The purpose of this study was to evaluate the dynamic changes in host immune status and its potential influence on prognosis in CIIC patients with IPA.Methods We monitored the evolution of a number of key cellular and humoral parameters on days 1,3,and 10 （D1,D3 and D10） following ICU admission in sixty-two CIIC patients with microbiological evidence of IPA.We included immunoglobulins IgG,IgA and IgM,complement factors C3 and C4,and lymphocyte subgroups CD3＋,CD4＋,CD8＋,CD28＋CD4＋,and CD28＋CD8＋ T cells,CD19＋B cells,and CD3-CD16＋CD56＋ natural killer cells （NK）.Results The primary outcome was 28-day mortality.Thirty-eight （61.3％） patients died within the 28 days following ICU admission.Compared to patients who died,CD3＋,CD8＋,CD28＋CD8＋ T-cell counts on D1,D3,and D10,CD28＋CD4＋ T-cell counts on D3 and D10,and NK counts on D3 and D10 were significantly higher in survivors.Receiver operating characteristic （ROC） analysis of immune parameters predicting 28-day mortality revealed area under the curve （AUC） values of 0.82 （95％ CI 0.71-0.92）,0.94 （95％ CI 0.87-0.99）,and 0.94 （95％ CI 0.85-0.99） for CD8＋ T-cell counts for D1,D3,and D10 respectively,and 0.84 （95％ CI 0.75-0.94）,0.92 （95％ CI 0.85-0.99）,and 0.90 （95％ CI 0.79-0.99） for CD28＋CD8＋ T-cell counts for D1,D3,and D10 respectively.Kaplan-Meier survival analysis showed that CD8＋ T-cell counts ＜149.5×106 cells/L and CD28＋CD8＋ T-cell counts ＜75×106 cells/L at ICU admission were associated with lower survival probabilities in CIIC patients with IPA （both Log rank：P＜0.001）.Conclusions Low CD8＋ and CD28＋CD8＋ T-cell counts were associated with high mortality in CIIC patients with IPA.Early counts of CD8＋ and CD28＋CD8＋ T cells in CIIC patients with IPA may be valuable for predicting outcome.

Spontaneous remission of Pneumocystisjiroveci pneumonia in 2 non-AIDS immunocompromised patients

Pneumocystis jiroveci （P. jiroveci） pneumonia （PCP） in non-AIDS immunocompromised patients ismuch more critical than that in AIDS patients,1 Without treatment, mortality of PCP in immunocompromised patients approaches 100 percent, and there were no reports of spontaneous remissions of PCP without anti-PCP therapy.2 Here we report 2 non-AIDS immunocompromised patients in whom PCP developed and remitted without treatment.

A comparative study of clinical manifestations caused by tuberculosis in immunocompromised and non-immunocompromised patients

Objective To characterize the differences between clinical manifestations in immunocompromised patients (ICPs) and non-immunocompromised patients (non-ICPs) with tuberculosis.Methods Underlying diseases, clinical presentations, misdiagnosis, treatment and prognosis, etc, were analyzed retrospectively in 115 tuberculosis patients, including 39 ICPs and 76 non-ICPs.Results Compared with non-ICPs, the individuals who were ICP had more expectoration (64.1 % vs 35. 5%), pulmonary moist rale (41. 0% vs 9. 2%), miliary pulmonary tuberculosis (30. 8% vs 2. 6%), pleural effusion (48. 7% vs 25. 0%) and lymphadenopathy (18. 0% vs 4. 0 %). ICPs had less lung cavity (15. 4% vs 22. 4%) and pleural thickening (15. 4% vs 23. 7%) compared to non-ICPs. Pulmonary tuberculosis in ICPs was prone to be misdiagnosed as pneumonia (23.1 % vs 6. 6%). Pulmonary tuberculosis was found in the apicoposterior segment (SⅠ+SⅡ) in more cases in non-ICPs (21.7%, 10/46) than ICPs (10.3%, 3/29). The diagnostic value of tuberculin skin test and adenosine deaminase in pleural effusions was limited in ICPs. ICPs had significantly poorer prognoses than non-ICPs.Conclusion The clinical manifestations of ICPs with tuberculosis are atypical, misdiagnosis often occurs, resulting in a worse prognosis.

Tacrolimus-induced posterior reversible encephalopathy syndrome following liver transplantation

In this editorial,we talk about a compelling case focusing on posterior reversible encephalopathy syndrome(PRES)as a complication in patients undergoing liver transplantation and treated with Tacrolimus.Tacrolimus(FK 506),derived from Streptomyces tsukubaensis,is a potent immunosuppressive macrolide.It inhibits Tcell transcription by binding to FK-binding protein,and is able to amplify glucocorticoid and progesterone effects.Tacrolimus effectively prevents allograft rejection in transplant patients but has adverse effects such as Tacrolimus-related PRES.PRES presents with various neurological symptoms alongside elevated blood pressure,and is primarily characterized by vasogenic edema on neuroimaging.While computed tomography detects initial lesions,magnetic resonance imaging,especially the Fluid-Attenuated Inversion Recovery sequence,is superior for diagnosing cortical and subcortical edema.Our discussion centers on the incidence of PRES in solid organ transplant recipients,which ranges between 0.5 to 5+ACU-,with varying presentations,from seizures to visual disturbances.The case of a 66-year-old male status post liver transplantation highlights the diagnostic and management challenges associated with Tacrolimus-related PRES.Radiographically evident in the parietal and occipital lobes,PRES underlines the need for heightened vigilance among healthcare providers.This editorial emphasizes the importance of early recognition,accurate diagnosis,and effective management of PRES to optimize outcomes in liver transplant patients.The case further explores the balance between the efficacy of immunosuppression with Tacrolimus and its potential neurological risks,underlining the necessity for careful monitoring and intervention strategies in this patient population.

Successively bilateral cytomegalovirus retinitis in immunocompromised patient with Good's syndrome

Dear Editor,I am Dr. Feng Hu, from the Department of Ophthalmology of Beijing Tongren Hospital, Beijing, China. I write to present a case report of cytomegalovirus retinitis (CMVR) in Good’s syndrome (GS).GS is an extremely rare primary immune-deficiency syndrome,which consists of simultaneous occurrence of

Crohn’s disease in human immunodeficiency virus-infected patient:A case report

BACKGROUND Inflammatory bowel disease(IBD)is an autoimmune condition treated with immunosuppressive drugs.However,the need for immune system suppression becomes questionable when infection with the human immunodeficiency virus(HIV)occurs simultaneously and impacts the course of IBD.Our reported case represents the clinical course,prescribed treatment and its effect,as well as clinical challenges faced by physicians in a combination of such diseases.We also present a comprehensive literature review of similar cases.CASE SUMMARY A 49-year-old woman suffering from a newly diagnosed Crohn’s disease was hospitalized due to exacerbated symptoms(abdominal pain,fever,and weight loss).During her hospital stay,she tested positive for HIV.With conservative treatment,the patient improved and was discharged.In the outpatient clinic,her HIV infection was confirmed as stage C3,and antiretroviral treatment was initiated immediately.That notwithstanding,soon the patient was rehospitalized with pulmonary embolism and developed a series of complications because of the subsequent coexistence of IBD and HIV.After intensive and meticulous treatment,the patient’s condition has improved and she remains in remission.CONCLUSION The paucity of studies and data on the coexistence of HIV and IBD leaves clinicians doubting the optimal treatment options.

Relationship between Radiological Stages and Prognoses of Pneumocystis Pneumonia in Non-AIDS Immunocompromised Patients

Background： Although radiological features ofpneumocystis pneumonia （PCP） in non-Acquired Immune Deficiency Syndrome （AIDS） immunocompromised patients have been reported by other authors, there were no studies on the radiological stages of PCP previously. This study aimed to elucidate the radiological stages and prognoses of PCP in non-AIDS immunocompromised patients. Methods： Retrospective analysis ofradiological manifestations and prognoses of 105 non-AIDS PCP immunocompromised patients from August 2009 to April 2016 was conducted. Chest radiograph was divided into three stages： early stage （normal or nearly normal chest radiograph）, mid stage （bilateral pulmonary infiltrates）, and late stage （bilateral pulmonary consolidations）; chest high-resolution computed tomography （HRCT） was also divided into three stages： early stage （bilateral diffuse ground-glass opacity [GGO]）, mid stage （bilateral diffuse GGO and patchy consolidations）, and late stage （bilateral diffuse consolidations）. Results： The case fatality rate （CFR） of all patients was 34.3% （36/105）, all of them took routine chest X-ray （CXR）, and 84 underwent chest CT examinations. According to the CXR most near the beginning ofanti-PCP therapy, 18 cases were at early stage and CFR was 0 （0/18, P 〈 0.01）, 50 cases were at mid stage and CFR was 28.0% （14/50, P〉 0.05）, and 37 cases were at late stage and CFR was 59.5% （22/37, P 〈 0.01）. According to the chest HRCT most near the beginning ofanti-PCP therapy, 40 cases were at early stage and CFR was 20.0% （8/40, P 〉 0.05）, 34 cases were at mid stage and CFR was 47.1% （l 6/34, P 〉 0.05）, and 10 cases were at late stage and CFR was 80.0% （8/10, P 〈 0.05）; barotrauma, including pneumothorax, pneumomediastinum, and pneumohypoderma, was found in 18 cases and the CFR was 77.8% （14/18, P 〈 0.01）. Conclusions： Based on the radiological manifestations, the course of PCP in non-A1DS immunocompromised patients can be divided into three stages： early stage, mid stage, and late stage. The prognoses of patients treated at early stage are good, and those at late stage are poor. Furthermore, the CFR of patients with barotrauma is high.

Protection of inactivated vaccine against SARS-CoV-2 infections in patients with comorbidities:a prospective cohort study

Protection against severe acute respiratory syndrome Coronavirus 2(SARS-CoV-2)infection of inactivated vaccines is not well characterized in people with comorbidities,who are at high risk of severe infection.We compared the risk of SARS-CoV-2 infection after complete vaccination with Sinopharm/BBIBP in people with comorbidities(e.g.,autoimmune diseases,cardiovascular disease,chronic lung disease,and diabetes)with healthy individuals using a Cox-proportional hazard model.In July-September 2021,a total of 10548 people(comorbidities,2143;healthy,8405)receiving the complete primary series of vaccination with Sinopharm/BBIBP in Bangkok,Thailand were prospectively followed for SARS-CoV-2 infection through text messaging and telephone interviewing for 6 months.A total of 295 infections from 284 participants were found.HRs(95%CI)of individuals with any comorbidities did not increase(unadjusted,1.02(0.77–1.36),P=0.89;adjusted,1.04(0.78–1.38),P=0.81).HRs significantly increased in the subgroup of autoimmune diseases(unadjusted,2.64(1.09–6.38),P=0.032;adjusted,4.45(1.83–10.83),P=0.001)but not in cardiovascular disease,chronic lung disease,or diabetes.The protection against SARS-CoV-2 infection of the Sinopharm vaccine was similar in participants with any comorbidities vs.healthy individuals.However,the protection appeared lower in the subgroup of autoimmune diseases,which may reflect suboptimal immune responses among these people.

Fungal infections in immunocompromised critically ill patients

Diverse pathogenic fungi can produce severe infections in immunocompromised patients, thereby justifying intensive care unit (ICU) admissions. In some cases, the infections can develop in immunocompromised patients who were previously admitted to the ICU. Aspergillus spp., Pneumocystis jirovecii, Candida spp., and Mucorales are the fungi that are most frequently involved in these infections. Diagnosis continues to be challenging because symptoms and signs are unspecific. Herein, we provide an in-depth review about the diagnosis, with emphasis on recent advances, and treatment of these invasive fungal infections in the ICU setting.

Vascular leiomyoma of the nasal cavity:case report

Vascular leiomyomas are extremely rare in the nasal cavity, accounting for less than 1% of all vascular leiomyomas. The association of Epstein-Barr virus （EBV） with smooth muscle tumors in immunocompromised patients is well established. The geographic distributions of EBV infection and nasopharyngeal carcinoma in China and the close proximity of the sinonasal area to the nasopharynx raise the possibility, that EBV may be involved in the pathogenesis of nasal smooth muscle tumors. Herein. we report a case of vascular leiomyonla of the nasal cavity in an 88-year-old man and discuss the rote of sex hormones in tumorigenesis and a possible relationship with EBV infection.

Two case reports of toxocariasis mimicking endophthalmitis in immunosuppresed adults

This a case of 2 immunocompromised patients with a surprising ocular toxocariasis infestation.The first is a 23-year-old girl who is a known case of systemic lupus erythematosus,presenting with both eyes progressive blurring of vision for the past 3 months.Examinations showed bilateral panuveitis with posterior pole granuloma.She was treated as endogenous endophthalmitis as per protocol,but with limited improvement.To our surprise and with high index of clinical suspicion,Toxocara serology was positive.She was then started on oral albendazole for 4 weeks.The second case is a 51-year-old lady with end stage renal failure undergoing regular dialysis and on immunosuppressive therapy.She was warded for long duration for sepsis secondary to candidal fungal infection.Examinations revealed right peripheral and posterior pole granulomas almost exactly similar to the first patient.She was treated for endogenous endophthalmitis and again in close succession a positive serology was confirmed.Both cases since then showed gradual clinical improvement.