Escalante, Patricio

Introduction. The diagnostic standard forPneumocystis jiroveciipneumonia (PCP) is direct microscopic identification; however, in recent years, polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL) samples to detectPneumocystisnucleic acids has proven to be more sensitive and specific. Sputum samples have been presumed inferior to bronchoscopic samples secondary to variability and adequacy of sample collection. We observed several cases of positive sputum PCP-PCR results with negative PCP-PCR BAL results. The aim of the current study was to further characterize the clinical setting and outcomes in patients with positive sputum PCP-PCR samples and negative BAL PCP-PCR samples.Methods. We identified all patients who underwentP. jirovecii-PCR testing at Mayo Clinic between 2011 and 2016. Patients with a positive sputum and negative BAL sample collected within a 14-day time frame were identified and underwent further chart review for demographics, immunocompromised state, and clinical outcome.Results. From 2011 to 2016, 4431 respiratory samples from 3021 unique patients were tested for the presence ofP. jiroveciiby PCR. Fifty-five samples (1.2% of all samples collected) belonging to 24 unique patients (0.79% of patients tested) were identified as having a positive and negative sample collected within 14 days. Of these 24 patients, 10 (46%) patients had a positive sputum or tracheal secretion sample with negative BAL or bronchial washings. Out of these 10 patients, 8 were immunocompromised and 9 underwent treatment for PCP with 6 patients improving.Conclusion. Our results suggest that discordantP. jirovecii-PCR testing results from sputum and bronchoscopic specimens are an infrequent occurrence. Patients with positiveP. jirovecii-PCR sputum/tracheal secretion samples and negative bronchoscopic samples appear to be clinically infected and respond to PCP treatment. SputumP. jirovecii-PCR testing may be a viable alternative to invasive testing.

Tumor necrosis factor α antagonists are increasingly used to treat inflammatory and autoimmune disorders and are associated with increased risk of active tuberculosis. Diagnosis of active tuberculosis in patients taking tumor necrosis factor α antagonists can be challenging owing to increased incidence of extrapulmonary manifestations and false-negative results on current available diagnostic tests. We present a case of a young woman on infliximab for ulcerative colitis who presented with disseminated tuberculosis. As part of a research study, we performed flow cytometric immune profiling, which has previously not been reported in patients with active tuberculosis taking tumor necrosis α antagonists. The flow cytometry results were within the positive thresholds for tuberculosis infection. Flow cytometric immune profiling may be a valid diagnostic tool for patients taking tumor necrosis factor α antagonists.

Citrobacter koseri is a motile, gram-negative rod traditionally known to cause infection in individuals with significant comorbidities and immunocompromised status. While most cases represent nosocomial infections, rarely community-acquired infections have been reported. We present a previously healthy man in his 60s with C. koseri pneumonia who was subsequently found to have underlying pulmonary adenocarcinoma, illustrating the need for further investigation for immunodeficiency and/or intrapulmonary pathology.

Drug resistance has emerged as a major obstacle to global control of tuberculosis (TB). Treatment with currently available medications requires prolonged courses of numerous drugs, many of which are associated with significant adverse effects. New drugs are urgently needed to meet the challenge posed by drug-resistant TB, in order to relieve the burden that drug resistance has placed on individual patients and health systems. Fortunately, many new drugs have been developed for the treatment of drug-resistant TB in recent years. The new antimycobacterial agents are derived from various medication classes, work by means of an assortment of mechanisms of action, and are at differing phases of development. This review provides a survey of the most promising new agents, in order to promote familiarity with these emerging drugs and compounds.

Abstract Rationale Most immunocompetent patients diagnosed with latent tuberculosis infection (LTBI) will not progress to tuberculosis (TB) reactivation. However, current diagnostic tools cannot reliably distinguish nonprogressing from progressing patients a priori, and thus LTBI therapy must be prescribed with suboptimal patient specificity. We hypothesized that LTBI diagnostics could be improved by generating immunomarker profiles capable of categorizing distinct patient subsets by a combinatorial immunoassay approach. Objectives A combinatorial immunoassay analysis was applied to identify potential immunomarker combinations that distinguish among unexposed subjects, untreated patients with LTBI, and treated patients with LTBI and to differentiate risk of reactivation. Methods IFN-γ release assay (IGRA) was combined with a flow cytometric assay that detects induction of CD25+CD134+ coexpression on TB antigen–stimulated T cells from peripheral blood. The combinatorial immunoassay analysis was based on receiver operating characteristic curves, technical cut-offs, 95% bivariate normal density ellipse prediction, and statistical analysis. Risk of reactivation was estimated with a prediction formula. Measurements and Main Results Sixty-five out of 150 subjects were included. The combinatorial immunoassay approach identified at least four different T-cell subsets. The representation of these immune phenotypes was more heterogeneous in untreated patients with LTBI than in treated patients with LTBI or unexposed groups. Patients with IGRA(+) CD4+CD25+CD134+ T-cell phenotypes had the highest estimated reactivation risk (4.11 ± 2.11%). Conclusions These findings suggest that immune phenotypes defined by combinatorial assays may potentially have a role in identifying those at risk of developing TB; this potential role is supported by risk of reactivation modeling. Prospective studies will be needed to test this novel approach.