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BackgroundThe Xpert MTB/RIF (Xpert) assay is a rapid nucleic acid amplification test widely used in settings of high tuberculosis prevalence to detect tuberculosis as well asrpoBmutations associated with rifampin resistance. Data are needed on the diagnostic performance of Xpert in lower-prevalence settings to inform appropriate use for both tuberculosis detection and the need for respiratory isolation.MethodsXpert was compared to 2 sputum samples, each evaluated with acid-fast bacilli (AFB) smear and mycobacterial culture using liquid and solid culture media, from participants with suspected pulmonary tuberculosis from the United States, Brazil, and South Africa.ResultsOf 992 participants enrolled with evaluable results, 22% had culture-confirmed tuberculosis. In 638 (64%) US participants, 1 Xpert result demonstrated sensitivity of 85.2% (96.7% in participants with AFB smear-positive [AFB(+)] sputum, 59.3% with AFB smear-negative [AFB(-)] sputum), specificity of 99.2%, negative predictive value (NPV) of 97.6%, and positive predictive value of 94.9%. Results did not differ between higher- and low-prevalence settings. A second Xpert assay increased overall sensitivity to 91.1% (100% if AFB(+), 71.4% if AFB(-)), with specificity of 98.9%. In US participants, a single negative Xpert result predicted the absence of AFB(+)/culture-positive tuberculosis with an NPV of 99.7%; NPV of 2 Xpert assays was 100%, suggesting a role in removing patients from airborne infection isolation. Xpert detected tuberculosis DNA and mutations associated with rifampin resistance in 5 of 7 participants with rifampin-resistant, culture-positive tuberculosis. Specificity for rifampin resistance was 99.5% and NPV was 98.9%.ConclusionsIn the United States, Xpert testing performed comparably to 2 higher-tuberculosis-prevalence settings. These data support the use of Xpert in the initial evaluation of tuberculosis suspects and in algorithms assessing need for respiratory isolation.

Objectives Nosocomial pathogens such as Acinetobacter baumannii are a growing public health threat, due in part to their increasing resistance to antibiotics. Since some strains are resistant to all available antibiotics, novel therapies are urgently needed. Plasmablasts are short-lived B cells found in the blood that can be collected and harnessed to produce therapeutic antibodies. We set out to determine whether plasmablasts are induced during infection with A. baumannii and other nosocomial pathogens. Methods We obtained blood samples from patients infected with antibiotic-resistant nosocomial pathogens, and analysed their plasmablast response by flow cytometry. Results We observed a strong induction of plasmablasts in patients with antibiotic-resistant A. baumannii infection. Furthermore, plasmablasts were also induced in response to other drug-resistant nosocomial pathogens. Conclusions These data suggest that plasmablasts may be broadly harnessed to develop therapeutic antibodies to combat otherwise untreatable antibiotic-resistant infections. [ABSTRACT FROM PUBLISHER]

BACKGROUND: Children with sickle cell disease (SCD) are at increased risk for bloodstream infections (BSIs), mainly because of functional asplenia. Immunizations and antibiotic prophylaxis have reduced the prevalence of invasive bacterial infections, but contemporary analysis of BSI in children with SCD is limited. METHODS: We conducted a retrospective cohort study of children aged <18 years with SCD who had blood cultures collected at our institution from 2010 to 2019 to identify BSI. Probable contaminant organisms were identified and not included as BSI. We calculated the annual incidence of BSI at our institution with 95% confidence intervals (CIs) and used multivariate logistic regression to evaluate associations. RESULTS: There were 2694 eligible patients with 19 902 blood cultures. Excluding repeated cultures and contaminant cultures, there were 156 BSI episodes in 144 patients. The median age at BSI was 7.5 years. The average incidence rate of BSI was 0.89 per 100 person-years (95% CI 0.45--1.32). The most common pathogens were Streptococcus pneumoniae (16.0%), Streptococcus viridans group (9.0%), Escherichia coli (9.0%), Staphylococcus aureus (7.7%), Bordetella holmesii (7.7%), Haemophilus influenzae (7.1%), and Salmonella species (6.4%). Odds of BSI were higher with sickle cell anemia genotypes (odds ratio [OR] 1.88; 95% CI 1.20--2.94) and chronic transfusions (OR 2.66; 95% CI 1.51--4.69) and lower with hydroxyurea (OR 0.57; 95% CI 0.39--0.84). CONCLUSIONS: BSI remains a risk for children with SCD. Overall incidence, risk factors, and spectrum of pathogens are important considerations to guide prevention and empirical treatment of suspected infection in SCD. [ABSTRACT FROM AUTHOR]