Infections In HIV-negative Patients Research Articles

Th1 cell immune response in Talaromyces marneffei infection with anti-interferon-γ autoantibody syndrome.

Anti-interferon-γ autoantibody (AIGA) syndrome may be the basis of disseminated Talaromyces marneffei infection in human immunodeficiency virus (HIV)-negative adults. However, the pathogenesis of Th1 cell immunity in T. marneffei infection with AIGA syndrome is unknown. A multicenter study of HIV-negative individuals with T. marneffei infection was conducted between September 2018 and September 2020 in Guangdong and Guangxi, China. Patients were divided into AIGA-positive (AP) and AIGA-negative (AN) groups according to the AIGA titer and neutralizing activity. The relationship between AIGA syndrome and Th1 immune deficiency was investigated by using AP patient serum and purification of AIGA. Fifty-five HIV-negative adults with disseminated T. marneffei infection who were otherwise healthy were included. The prevalence of AIGA positivity was 83.6%. Based on their AIGA status, 46 and 9 patients were assigned to the AP and AN groups, respectively. The levels of Th1 cells, IFN-γ, and T-bet were higher in T. marneffei-infected patients than in healthy controls. However, the levels of CD4+ T-cell STAT-1 phosphorylation (pSTAT1) and Th1 cells were lower in the AP group than in the AN group. Both the serum of patients with AIGA syndrome and the AIGA purified from the serum of patients with AIGA syndrome could reduce CD4+ T-cell pSTAT1, Th1 cell differentiation and T-bet mRNA, and protein expression. The Th1 cell immune response plays a pivotal role in defense against T. marneffei infection in HIV-negative patients. Inhibition of the Th1 cell immune response may be an important pathological effect of AIGA syndrome.IMPORTANCEThe pathogenesis of Th1 cell immunity in Talaromyces marneffei infection with anti-interferon-γ autoantibody (AIGA) syndrome is unknown. This is an interesting study addressing an important knowledge gap regarding the pathogenesis of T. marneffei in non-HIV positive patients; in particular patients with AIGA. The finding of the Th1 cell immune response plays a pivotal role in defense against T. marneffei infection in HIV-negative patients, and inhibition of the Th1 cell immune response may be an important pathological effect of AIGA syndrome, which presented in this research could help bridge the current knowledge gap.

P403 Metagenomic sequencing as an effective diagnostic tool for Talaromycosis in HIV-negative patients: A retrospective study

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMObjectiveThe diagnosis of Talaromyces marneffei (T. marneffei) infection in HIV-negative patients is still challenging. The aim of this study was to evaluate the effectiveness and efficiency of metagenomic next-generation sequencing (mNGS) for T. marneffei infection in non-HIV-infected patients by comparing the diagnostic value of mNGS and traditional microbiological culture on different specimens.MethodsA total of 57 HIV-negative patients with suspected infectious diseases were enrolled in the study from July 2018 to November 2021. mNGS and culture were performed on all enrolled samples. Data were collected on demographic characteristics, clinical symptoms, laboratory findings, and antifungal results. The diagnostic value of mNGS and conventional microbiological culture was compared.ResultsA total of 66 samples from 57 patients were analyzed, 29 were diagnosed with T. marneffei infection and 28 were of non-T. marneffei infected patients. Compared with the final diagnosis, mNGS showed a sensitivity of 97.22%, which was higher than that of conventional culture (61.11%). In addition, mNGS provides greater diversity in sample selection compared to culture.ConclusionOur study demonstrated that mNGS can be considered a promising tool for rapid and accurate pathogenic diagnosis in HIV-negative patients with suspected T. marneffei.

P253 Features of Cryptococcosis in human immunodeficiency virus-negative patients, France 1985-2020

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectivesHIV-negative individuals make up an increasing proportion of cases of cryptococcosis in France, but the features of disease and outcomes in this population have yet to be characterized. We describe the presentations and outcomes according to host factors underlying cryptococcosis in HIV-negative individuals in France.MethodsThe French National Reference Centre for Invasive Mycoses and Antifungals has implemented nationwide surveillance of cryptococcosis since 1985 with the determination of the infecting serotype. We analyzed the characteristics of infection in HIV-negative patients diagnosed up to 2020. We also compared the demographic characteristics, presenting features, treatment regimen, and outcomes according to host factor and infecting serotype in patients diagnosed since 2005.ResultsThe mean age of patients was 56.2 years, 60.8% were male, and 60.1% were born in Europe. Only 26 cases were due to Cryptococcus gattii, all others were caused by C. neoformans. Of the 1051 cases, 349 occurred in patients with malignancy (33.2%, including 268 patients with hematological malignancy, 69% of whom had lymphoid neoplasms), 205 occurred in solid-organ transplant (SOT) recipients (19.5%, including 147 kidney and 27 liver), and 298 occurred in patients with ‘other’ underlying factors (28.4%, including auto-immune disease (n = 86), end-stage liver or kidney disease (n = 47), sarcoidosis (n = 42), chronic pulmonary disease (n = 25), and diabetes mellitus (n = 16). A total of 19% of patients (n = 199) had no apparent underlying risk factor.Among 632 patients diagnosed since 2005, there were significant differences according to the four major categories of risk factors (malignancy, SOT, others, and none) in terms of age, diagnostic methods, proportion of patients with positive cryptococcal antigen (CrAg), antigen titers, disease localization, treatment regimens, and 90-day mortality. In the diagnostic workup, a lumbar puncture and blood culture were performed for 96% and 64.2% of patients, respectively, more frequently for immunocompromised patients than those with no underlying host factor (P = .09 and P <.001, respectively). SOT patients had more frequent central nervous system involvement (P <.001), and positive serum CrAg detection with antigen titers >1:512 (P <.001). Patients with malignancy were significantly older (P = .0001) with more frequent fungemia (P = .007). Isolated lung infections (P = .002) and isolated skin lesions (P <.001) were more frequent in patients with ‘other’ conditions and in those with no underlying factor, respectively. Immunocompromised patients were more likely to receive combination antifungals including flucytosine (66.7%, 45.4%, and 42.7% for SOT, malignancies, and ‘other’ conditions, respectively) compared with patients with no underlying factor (33.3%, P <.001). Overall, all cause 90-day mortality was 27.0% (95% CI: 23, 3-31.0%). Patients with malignancy had the highest 90-day mortality (37.3%, <0.001), compared with SOT recipients (23.7%), those with ‘other' conditions (24.7%), and those without underlying conditions (13.9%). Compared with patients with serotype D infections, those infected with serotype A were significantly younger (P = .004), more likely to be born in Africa (P <.001), to have isolated pulmonary disease (P <.005), and less likely to have isolated skin infections (P <.001).ConclusionHIV-seronegative patients with cryptococcosis are a heterogeneous group of patients encompassing different disease characteristics and outcomes. Management of cryptococcosis in HIV-negative patients should be tailored to underlying host factors, disease localization, and infecting serotype.

Clinical features and risk factors of surgical site infections in HIV-negative patients with cryptococcal meningitis underwent ventriculoperitoneal shunt operations: a retrospective study

BackgroundTo investigate the clinical features and risk factors of ventriculoperitoneal shunt (VPS) associated surgical site infections (SSIs) in HIV-negative patients with cryptococcal meningitis (CM).MethodsWe retrospectively reviewed the medical records of HIV-negative patients with CM underwent VPS operation admitted to The Third Affiliated Hospital of Sun Yat-sen University in Southwest China over the past 7 years.Results193 patients were included, of whom 25 (12.95%) had SSIs in 6 (median duration, 1–48 days) days after operation. Compared with patients without SSIs, patient with SSIs tended to be shorter preoperative stay. 52% patients in SSIs group and 25% patients in no-SSIs group underwent VPS operations within 3 days after admission (p = 0.017). Although body temperature and infectious indicators slightly elevated postoperative in both groups. The patients with SSIs experienced more fever; more central nervous system symptoms; higher PCT value and lower cerebrospinal fluid (CSF) glucose in contrast to the no-SSIs group. Multivariate regression analysis found a 2.653 fold increase in the risk of infection for every 1 °C increase in postoperative body temperature. Among the 25 patients, 9 patients had positive culture results, three samples reported to be oxacillin resistant coagulase-negative Staphylococci.ConclusionsSSIs was one of the serious surgical complications after VPS operation. High body temperature, the occurrence of dizziness and headache, low postoperative hemoglobin are risk factors. Postoperative patients with high fever, high PCT and low CSF glucose should be paid more attention to.

Anti-interferon-γ autoantibody-associated immunodeficiency.

Anticytokine autoantibodies are an emerging disease etiology, through the disturbance of physiological functions of cognate cytokines. Anti-interferon (IFN)-γ autoantibodies (AIGAs) were first identified in patients with severe mycobacterial infections, and were considered to be an autoimmune phenocopy of inborn genetic errors of the IL-12/IFN-γ axis. More than 600 reported cases, most originating from Southeast Asia, have been diagnosed over the last decade. Specific HLA class II molecules are associated with these autoantibodies, which provide a genetic basis for the high prevalence of this immunodeficiency syndrome in certain ethnic groups. Salmonellosis and herpes zoster reactivation are observed in more than half the patients with AIGAs. Moreover, AIGAs have been shown to underlie severe Taralomyce marneffei infection in HIV-negative patients. AIGAs may, thus, be considered a new form of late-onset immunodeficiency conferring a predisposition not only to severe mycobacterial, but also to some bacterial and fungal infections.

Serum Sphingolipids Aiding the Diagnosis of Adult HIV-Negative Patients with Talaromyces marneffei Infection.

Increasing attention has been directed to Talaromyces marneffei (T. marneffei) infection in HIV-negative patients due to its high mortality rate. However, nonspecific symptoms and biological characteristics similar to those of other common pathogenic fungi complicate the rapid and accurate diagnosis of T. marneffei infection. Sphingolipids (SPLs) are bioactive lipids involved in the regulation of various physiological and pathological processes and have been identified as serum biomarkers for several diseases. This study employed a sphingolipidomic approach established in our previous work to explore the use of serum SPLs in the diagnosis of HIV-negative patients with T. marneffei infection. Additional clinical cohorts of patients infected with other microorganisms were also recruited. We found that sphinganine (Sa) (d16:0) exhibited obvious depletion after infection; moreover, its level in patients with T. marneffei infection was significantly lower than that in patients infected with other microorganisms. Therefore, Sa (d16:0) was considered a specific diagnostic biomarker for T. marneffei infection, and 302.71 nM was selected as the optimal cutoff value with a diagnostic sensitivity of 87.5% and specificity of 100%. These results suggested that determination of serum Sa (d16:0) levels can be used as a new alternative tool for the rapid diagnosis of T. marneffei infection in HIV-negative patients.

X-RAY-morphological features of the current COVID-19 and HIV infection

Infection of HIV-infected with a new coronavirus infection, due to its high contagiousness, is inevitably growing all over the world. According to estimates of Chinese scientists, their number is currently more than 500 thousand people. Considering that COVID-19 leads to suppression of immunity and the emergence of opportunistic infections in HIV-negative patients, the activation of secondary diseases in patients with HIV is natural. In view of this, the study of the features of the X-ray morphological picture of inflammatory changes in the lungs according to MSCT data in patients with COVID-19/HIV became the goal of this study. 13 patients who underwent treatment at the Surgut Regional Clinical Hospital during the period from March to July 2020 underwent MSCT of the chest organs upon admission, before discharge, as well as in case of deterioration or lack of effect from the therapy — every 3 days. The detection of pathognomonic CT signs of COVID-19 in the lungs in patients with HIV (the nature of the lesion, the stage of the disease, the severity of the inflammatory process) was carried out in parallel with the diagnosis of opportunistic infections. During the examination, atypical clinical and X-ray morphological signs of the course of COVID-19/HIV coinfection were identified. In HIV-infected people, COVID-19 proceeds more easily and in disguise, while opportunistic infections both in clinical and radiological manifestations have priority signs. They are the reasons for the aggravation of the course of the disease, as well as the development of complications in these patients.

Disseminated Histoplasmosis Infection in HIV-Negative Patients: Series Case and Literature Review

Histoplasmosis is a deep mycosis distributed worldwide and caused by Histoplasma capsulatum. Development countries and underdeveloped countries already considered an endemic disease, and its etiology comes from fungi located in soil contaminated with bird and bat droppings. Habits such as tobacco and alcohol consumption can be factors that can help to the development of disseminated histoplasmosis mainly in immunocompetent patients. Clinical manifestations can include fever, weakness, weight loss, hepatosplenomegaly, mucocutaneous lesions, and ulcer oral lesions. Oral lesions represents a commonly manifestation in the disseminated form of the disease, and it is more frequently observed in immunocompromised patients, mainly on HIV-positive patients. In this study, we presented five cases of disseminated histoplasmosis on HIVnegative patients diagnosed with lesions located in oral cavity and we performed a literature review about cases of disseminated histoplasmosis lesions in head and neck region on HIV-negative patients associating possible factors that may contribute to lesions formatting.

Evaluation of a cryptococcal antigen lateral flow assay test for rapid detection of cryptococcal infection in HIV-negative patients in Ibadan, Nigeria

Background: A number of studies have been conducted in Nigeria on the prevalence of cryptococcal infections mostly on HIV-infected patients using culture, India ink and/or latex agglutination tests. These tests are either laborious, time-consuming and expensive or have low sensitivity, thus limiting their use. Cryptococcal antigen lateral flow assays (LFA) were introduced in the last decade as rapid user-friendly tests for diagnosis. In this study, we sought to determine the diagnostic accuracy of an LFA kit for the detection of cryptococcal antigen in the serum of HIV-negative patients with or without cerebrovascular accident (CVA) or stroke in University College Hospital, Ibadan, Nigeria.Methodology: The diagnostic accuracy of Dynamiker CrAg LFA was tested against BiosynexR CryptoPS on serum samples of 100 HIV-negative patients with and without stroke. Samples were tested and results interpreted in accordance with the manufacturer’s instructions. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios of the Dynamiker CrAg LFA were calculated by comparing with the BiosynexR CryptoPS as ‘gold standard’.Results: Overall, a total of 98 valid patient sample results were analysed; 17 samples (17.3%) were positive with Dynamiker CrAg LFA cryptococcal antigen and 16 samples (16.3%) were positive with BiosynexR CryptoPS. The sensitivity, specificity, PPV and NPV of Dynamiker CrAg LFA compared to the BiosynexR CryptoPS were 100%, 98.8%, 94.1% and 100% respectively, while the positive and negative likelihood ratios were 82 and 0 respectively.Conclusion: In comparison to the BiosynexR CryptoPS, the Dynamiker CrAg LFA is a highly sensitive and specific test for the detection of cryptococcal antigen in serum. The test kit should be considered as a screening device for cryptococcal infection both in outreach and clinical settings, especially in antiretroviral therapy (ART) centres.&#x0D; Keywords: Cryptococcus; evaluation; lateral flow assay; HIV-negative; stroke

AAIT: A novel prognostic model for HIV-negative patients with cryptococcal meningoencephalitis New Scoring Model for Non-HIV Patients with CM.

AAIT (age, albumin, combined bacterial infection, and total triiodothyronine) is a straightforward and clear prognostic score that can add value to predict the outcomes HIV-negative patients with CM.

Anti-IFN-γ autoantibodies underlie disseminated Talaromyces marneffei infections.

Talaromyces marneffei causes life-threatening opportunistic infections, mainly in Southeast Asia and South China. T. marneffei mainly infects patients with human immunodeficiency virus (HIV) but also infects individuals without known immunosuppression. Here we investigated the involvement of anti-IFN-γ autoantibodies in severe T. marneffei infections in HIV-negative patients. We enrolled 58 HIV-negative adults with severe T. marneffei infections who were otherwise healthy. We found a high prevalence of neutralizing anti-IFN-γ autoantibodies (94.8%) in this cohort. The presence of anti-IFN-γ autoantibodies was strongly associated with HLA-DRB1*16:02 and -DQB1*05:02 alleles in these patients. We demonstrated that adult-onset acquired immunodeficiency due to autoantibodies against IFN-γ is the major cause of severe T. marneffei infections in HIV-negative patients in regions where this fungus is endemic. The high prevalence of anti-IFN-γ autoantibody-associated HLA class II DRB1*16:02 and DQB1*05:02 alleles may account for severe T. marneffei infections in Southeast Asia. Our findings clarify the pathogenesis of T. marneffei infection and pave the way for developing novel treatments.

The decreased number and function of lymphocytes is associated with Penicillium marneffei infection in HIV-negative patients.

Penicillium marneffei (P. marneffei) infection, which has been traditionally considered as an indicator of immunosuppression, is one of the most common systemic opportunistic infections in patients with AIDS. Recently, more and more P. marneffei infections have been documented in HIV-negative patients without underlying diseases, which challenges the traditional view that P. marneffei infection is an indicator of immunosuppression. We aimed to evaluate the number and function of lymphocytes in HIV-negative patients with P. marneffei infection. 15 HIV-negative P. marneffei-infected patients and 18 healthy controls were recruited and investigated. The number and function of lymphocytes were analyzed by flow cytometry. Most laboratory tests were within the reference ranges, except for a significant increase in total IgE in P. marneffei-infected patients. Lymphocyte subset analysis showed that the number of CD4+ T cells and NK cells was significantly decreased in HIV-negative marneffei-infected patients compared with healthy controls. However, almost half of the marneffei-infected patients still had normal levels of lymphocytes. A further analysis of cell function showed that the activation and proliferation of CD4+ T cells, the cytotoxicity of CD8+ T cells and NK cells, and the cytokine secretion potential of CD4+ T cells and NK cells were all impaired, in comparison with healthy controls. P. marneffei infection has to be regarded as an indicator of immunosuppression. A further investigation of cell function is required in patients with opportunistic infection, as the cell function may be impaired in this condition.

P.103 When a neurosurgeon should care about pneumonia: the case for Pneumocystis jirovecii pneumonia prophylaxis in neurosurgical patients

Background: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic interstitial fungal pneumonia. The incidence of PJP in HIV-positive populations is decreasing, while it is increasing in HIV-negative immunocompromised populations, such as neurosurgical patients treated with high-dose corticosteroids. Morbidity and mortality can be severe owing to acute respiratory failure. Methods: Two cases are described and a literature review performed to determine the incidence of PJP in the neurosurgery population. A standardized care pathway is proposed to reduce preventable harm. Results: Long-term, high-dose corticosteroid regimens (≥4 mg dexamethasone daily for ≥4 weeks) with taper are associated with increased risk of PJP infection. Additional risk factors for infection in HIV-negative patients include CNS malignancy and concurrent radiation therapy. TMP-SMX is the first-line agent for PJP prophylaxis. Conclusions: Clinicians should maintain a high index of suspicion of PJP and adopt a standardized protocol for prophylaxis in neurosurgical patients treated with high-dose corticosteroids.

Myobacterium kansasii as the Primary Etiology of Pulmonary Infections due to Non-Tuberculous Mycobacterium (NTM) in Patients WIthout Human Immunodeficiency Virus (HIV): Experience from a Center in Buenos Aires, Argentina

Introduction: Pulmonary diseases due to non-tuberculous mycobacterium (NTM) lung infection in HIV-negative patients are rarely described in the literature. Currently, NTM consist of more than 150 species, and they are globally ubiquitous in both natural and man-made environments.The objective of this study was to define the most frequent species of NTM causing pulmonary disease in HIV-negative patients in the city of Buenos Aires, Argentina. The prevalence of pulmonary diseases caused by NTM is difficult to determine since the isolation of NTM does not necessarily indicate disease.

Factors which influence treatment initiation for pulmonary non-tuberculous mycobacterium infection in HIV negative patients; a multicentre observational study

BackgroundClinical, radiological and microbiological criteria inform diagnosis of pulmonary Non-Tuberculous Mycobacteria (NTM) disease and treatment decisions. This multicentre, review aims to characterise NTM disease meeting ATS/IDSA criteria and define factors associated with initiation of treatment. MethodsSputum samples growing NTM from 5 London hospitals between 2010 and 2014 were identified. Data for HIV-negative individuals meeting ATS/IDSA guidelines for pulmonary NTM disease were extracted. Associations between clinical variables and treatment decision were investigated using Chi-squared, Fishers-exact or Mann Whitney tests. Factors associated with treatment in univariate analysis (p < 0.150) were included in a multivariate logistic regression model. ResultsNTM were identified from 817 individuals' sputum samples. 108 met ATS/IDSA criteria. 42/108 (39%) were initiated on treatment. Median age was 68 (56–78) in the cohort.On multivariate analysis, factors significantly associated with treatment of pulmonary NTM infection were: Cavitation on HRCT (OR: 6.49; 95% CI: 2.36–17.81), presenting with night sweats (OR 4.18; 95% CI: 1.08–16.13), and presenting with weight loss (OR 3.02; 95% CI: 1.15–7.93).Of those treated, 18(43%) have completed treatment, 9(21%) remain on treatment, 10(24%) stopped due to side effects, 5(12%) died during treatment. Mortality was 31% (n = 13) in treated versus 21% (n = 14) in the non-treated cohort. Subgroup analysis of individual NTM species did not observe any differences in treatment initiation or outcomes between groups. DiscussionDecision to treat pulmonary NTM infection requires clinical judgement when interpreting clinical guidelines. Factors independently associated with decision to treat in this HIV-negative cohort include cavitation on HRCT and presenting with night sweats or weight loss.

Cerebral Toxoplasmosis in an HIV-Negative Patient: A Case Report

Introduction: Toxoplasmosis is caused by infection with the obligate intracellular parasite Toxoplasma gondii. Toxoplasmosis is generally a late complication of HIV infection and usually occurs in patients with CD4+ T-cell counts below 200 cells/iL. Case Presentation: A case of cerebral toxoplasmosis is reported in a healthy 39-year-old woman who was admitted to hospital with the complaint of a headache. Gadolinium-enhanced brain magnetic resonance imaging (MRI) showed an irregular, ring enhancing, hyperintense lesion in the right temporoparietal lobe. Toxoplasma serology revealed raised IgG antibody levels. Based on the MRI features, biopsy, and serology, a diagnosis of cerebral toxoplasmosis was made. Conclusions: Cerebral toxoplasmosis can occur outside the setting of advanced HIV immunodeficiency or drug-induced immunosuppression. This highlights the fact that it should be considered in the differential diagnosis of opportunistic infections in HIV-negative patients.

Pneumocystis Pneumonia in Inflammatory Bowel Disease: The Costs of Immunosuppression

Patients with inflammatory bowel disease (IBD) are subject to a spectrum of immunosuppressive agents including corticosteroids, immunomodulators, and biological therapies. Despite the benefits of these therapies and their ability to induce remission, they increase the risk of infectious complications with various organisms including Pneumocystis jiroveci pneumonia (PCP), which is associated with significant morbidity and mortality. Although PCP infection is typically associated with HIV-infected populations, the risk is increased in patients with IBD. Inflammatory autoimmune diseases like IBD account for as high as 20% of PCP infection in HIV-negative patients with greater than 50% mortality. Despite this, there are no clear guidelines for PCP prophylaxis in IBD. PCP should be considered in the differential when an IBD patient on immunosuppression presents with fever and respiratory symptoms. Here we review the existing literature regarding PCP risk in inflammatory bowel disease, the role of tumor necrosis alpha-inhibitors, and considerations for prophylaxis.

Disseminated Mycobacterium genavense with pulmonary nodules in a kidney transplant recipient: case report and review of the literature

We report a case of disseminated Mycobacterium genavense with pulmonary nodules in a kidney transplant recipient and review the associated literature. Disease caused by M. genavense has been recognized in acquired immunodeficiency syndrome (AIDS) patients since 1990, with subsequent case reports in other immunocompromised host populations. In AIDS patients, pulmonary lesions are an uncommon finding. This is the first report to our knowledge of a human immunodeficiency virus (HIV)-negative patient with pulmonary nodules as a feature of disseminated M. genavense. Diagnosis of M. genavense is often challenging and frequently requires nucleic acid-based identification techniques. Because of limitations in culture and drug susceptibility testing, treatment regimens rely on reported clinical experience. This case report and literature review illustrates a successful approach to the diagnosis and treatment of disseminated M. genavense and summarizes the reports of M. genavense infection in HIV-negative patients.

Large pulmonary cryptococcoma and cryptococcal meningitis in an immunocompetent patient: A case report

Pulmonary cryptococcoma is a life threatening mycosis and is an unusual disease for immunocompetent individuals. Herein we report a case of large pulmonary cryptococcoma associated with cryptococcal meningitis, presenting radiologically as a lung mass in right upper lobe, in a previously healthy, HIV negative, immunocompetent young individual. Since cryptococcosis continues to be an important infection in HIV negative patients and is associated with substantial overall and cause-specific mortality, the need for consideration of this entity in the differential diagnosis of a lung mass is emphasized.

Pulmonary nontuberculous mycobacterial infections: Antibiotic treatment and associated costs

Recent studies suggest an increasing prevalence of pulmonary nontuberculous mycobacteria (NTM) disease. In the absence of prevalence and cost data, the public health burden of pulmonary NTM disease is difficult to assess. The goal of this study was to assess costs associated with NTM disease treatment and to identify risk factors associated with increased costs. Records from subjects with pulmonary NTM disease enrolled in a natural history protocol were abstracted for presenting symptoms, comorbidities, microbiology, and treatment histories. Antibiotic frequency, duration, adverse reaction, and costs were noted, the total antibiotic burden and cost were calculated, and risk factors associated with high costs were analyzed. From Jan 2004 to Dec 2005, 33 subjects were enrolled; 27 met disease criteria and had sufficient data to assess antibiotic use. Mycobacterium avium complex was present in 89% and Mycobacterium abscessus was present in 21% of subjects. Subjects received a median of 5 (1-10) antibiotics. Adverse effects were common seen in up to 50% with common antibiotics and up to 100% with uncommonly used antibiotics. Median burden of treatment was 2638 (84-7689) drug-days and the median total cost per patient was $19,876 ($398-70,917). Subjects with high treatment costs had an adjusted 9.5 fold (95% CI 1.5-97.2) likelihood of having M. abscessus and a 4.2 fold (95% CI 0.6-59.3) increased likelihood of having more extensive disease. Pulmonary NTM represent an underappreciated disease burden in the US population, with an associated treatment cost comparable to that for other chronic diseases of infectious origin such as HIV/AIDS.