Date:
Friday, July 21, 2017 - 12:00
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Παρασκευή 29 Σεπτεμβρίου 2017
What’s New in Autophagy
Erratum
An error appeared in the 15 June 2017 issue of the journal [Marks SM, Mase SR, Morris SB. Systematic Review, Meta-analysis, and Cost-effectiveness of Treatment of Latent Tuberculosis to Reduce Progression to Multidrug-Resistant Tuberculosis. Clin Infect Dis 2017; 64(12):1670–77. doi:10.1093/cid/cix208]. FQ/ETA was not cost-effective, was dominated by other regimens, in all scenarios examined. This results in the following changes:
Erratum
An error appeared in the 1 September 2016 issue of the journal [Kalil AC, Mertersky M, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016; 63(5):e61-e111]. In Table 4, the targeted level of vancomycin should be "15–20 µg/mL trough level" [not "15–20 mg/ml"].
Keeping Up With a World in Motion: Screening Strategies for Migrating Populations
tuberculosistuberculosis screeningmigrationasylum seekersmigrants
Systematic Tuberculosis Screening in Asylum Seekers in Italy
Abstract
The preliminary findings of a tuberculosis (TB) screening of asylum seekers performed in a reception center located in northern Italy reveal a post-entry screening prevalence rate of 535 per 100000 individuals screened. This result shows that systematic use of chest radiography is a useful tool for active TB screening among asylum seekers in Italy.Rapid Clearance and Frequent Reinfection With Enteric Pathogens Among Children With Acute Diarrhea in Zanzibar
Abstract
Background
Acute infectious gastroenteritis is an important cause of illness and death among children in low-income countries. In addition to rotavirus vaccination, actions to improve nutrition status, sanitation, and water quality are important to reduce enteric infections, which are frequent also among asymptomatic children. The aim of this study was to investigate if the high prevalence of these infections reflects that they often are not cleared properly by the immune response or rather is due to frequent pathogen exposure. Methods
Rectal swabs were collected at time of acute diarrhea and 14 days later from 127 children, aged 2–59 months and living in rural Zanzibar, and were analyzed by real-time polymerase chain reaction targeting multiple pathogens. Results
At baseline, detection rates >20% were found for each of enterotoxigenic Escherichia coli, Shigella, Campylobacter, Cryptosporidium, norovirus GII, and adenovirus. At follow-up, a large proportion of the infections had become cleared (34–100%), or the pathogen load reduced, and this was observed also for agents that were presumably unrelated to diarrhea. Still, the detection frequencies at follow-up were for most agents as high as at baseline, because new infections had been acquired. Neither clearance nor reinfection was associated with moderate malnutrition, which was present in 21% of the children. Conclusions
Children residing in poor socioeconomic conditions, as in Zanzibar, are heavily exposed to enteric pathogens, but capable of rapidly clearing causative and coinfecting pathogens.Erratum
A system error occurred in the 15 May 2017 and 1 June 2017 issues of the journal. A test script was triggered by the typesetter at press time, corrupting some parenthetical data within some articles. Single letters, numerals, or symbols were replaced with the issue's volume and number. The affected articles are listed below, in the order they appear within the issues.
Reply to Dobler
To the Editor—We thank Dr Dobler for her comments regarding the methods of how we calculated and compared cumulative incidence of tuberculosis (TB) in cancer patients and country-specific TB incidence in our study [1]. We estimated the cumulative incidence (proportion) of developing TB during a specific study period in cancer cohorts divided by the mean annual TB incidence in the general US population over the same study period. We were not able to estimate the incidence of TB per year or by unit of time of follow-up in cancer patients because neither time to TB diagnosis of all cases nor the amount of time cancer cohorts were followed was reported in the included studies. Although we adjusted for the change in TB incidence in the general population over the study period, we assumed that the majority of TB cases would have occurred early after the cancer diagnosis. We did not account for the fact that the denominator estimated the annual TB incidence in the United States (also a proportion) and thus all new cases occurring in the US population per year. On reexamination of the data, 2 of the included studies provide insight into the timing of onset of active TB after a cancer diagnosis and support our assumption [2, 3]. In the study by Kaplan et al, 41% of TB cases occurred concurrently with the cancer diagnosis and 90% of all cases occurred within 18 months of cancer therapy [2]. Similarly, in the study by Libshitz et al, 30% of TB cases were diagnosed concurrently with the cancer and 79% of all cases occurred within 18 months of completion of cancer therapy, which for most cancers is approximately 2 years after cancer diagnosis [3]. Extrapolating from studies in which follow-up time of cancer cohorts was reported (Table 1 of our manuscript), this was usually relatively short (2–5 years) whereas study periods were generally longer (up to 13 years) [1]. Thus, cancer patients in the Kamboj study were likely not followed for the entire 25-year study period and, if the timing of TB after cancer diagnosis followed the same pattern as the Kaplan and Libshitz studies, the majority of TB cases also would have occurred within 2 years of cancer diagnosis [2–4].
Cumulative Incidence and Incidence Rate Ratio for Estimation of Risk of Tuberculosis in Patients With Cancer
To the Editor—In their systematic review and meta-analysis of the risk of active tuberculosis (TB) in patients with cancer, Cheng et al evaluated the cumulative incidence of TB among patients with cancer and used this information together with annual country-specific TB incidence rates from the World Health Organization to estimate the incidence rate ratio of TB in patients with cancer compared to the general population [1]. The analysis raises some methodological concerns that have implications for the interpretation of the results. The authors use the term "cumulative incidence rate," when indeed cumulative incidence is a proportion, not a rate (events expressed per unit time) [2, 3]. For included studies that only contained information on cumulative incidence, but not an actual incidence rate, the authors used cumulative incidence (over the study period) divided by the incidence rate per year in the general population to calculate an incidence rate ratio. This calculation is methodologically incorrect [3] and will result in overestimation of the incidence rate ratio. The included study by Kamboj and Sepkowitz that evaluated the risk of TB among patients with cancer at the Memorial Sloan-Kettering Cancer Center in New York City between 1980 and 2004 illustrates the problem [4]. In this study, there were 103 cases of TB among 186843 patients with cancer during the study period, resulting in a cumulative incidence of 55 cases of TB per 100000 patients (over 25 years). In Table 1 of their article, Cheng et al presented the cumulative incidence of 55 and divided this number by the TB incidence per 100000 persons/year in the general population during the study period (8.6/100000/year), resulting in an incidence rate ratio (calculated by the authors) of 6.3 (55/8.6). The problem is that the cumulative incidence among cancer patients accumulated over 25 years whereas the incidence in the general population represented events occurring within 1 year. Assuming a regular distribution of these TB cases over time, the TB incidence rate would have been 2.2/100000 per year (55 cases of TB per 100000 patients over 25 years), but of course this estimate is not correct either, because it wrongly assumes that every patient survived and was followed up for 25 years. Thus, the available study data do not allow calculation of an incidence rate ratio, and the analysis should have been limited to studies that provided a true incidence rate of TB.
Fluoroquinolone Resistance Mutation Detection Is Equivalent to Culture-Based Drug Sensitivity Testing for Predicting Multidrug-Resistant Tuberculosis Treatment Outcome: A Retrospective Cohort Study
Abstract
Background
Molecular diagnostics that rapidly and accurately predict fluoroquinolone (FQ) resistance promise to improve treatment outcomes for individuals with multidrug-resistant (MDR) tuberculosis (TB). Mutations in the gyr genes, though, can cause variable levels of in vitro FQ resistance, and some in vitro resistance remains unexplained by gyr mutations alone, but the implications of these discrepancies for treatment outcome are unknown. Methods
We performed a retrospective cohort study of 172 subjects with MDR/extensively drug-resistant TB subjects and sequenced the full gyrA and gyrB open reading frames in their respective sputum TB isolates. The gyr mutations were classified into 2 categories: a set of mutations that encode high-level FQ resistance and a second set that encodes intermediate resistance levels. We constructed a Cox proportional model to assess the effect of the gyr mutation type on the time to death or treatment failure and compared this with in vitro FQ resistance, controlling for host and treatment factors. Results
Controlling for other host and treatment factors and compared with patients with isolates without gyr resistance mutations, "high-level" gyr mutations significantly predict poor treatment outcomes with a hazard ratio of 2.6 (1.2–5.6). We observed a hazard of death and treatment failure with "intermediate-level" gyr mutations of 1.3 (0.6–3.1), which did not reach statistical significance. The gyr mutations were not different than culture-based FQ drug susceptibility testing in predicting the hazard of death or treatment failure and may be superior. Conclusions
FQ molecular-based diagnostic tests may better predict treatment response than traditional drug susceptibility testing and open avenues for personalizing TB therapy.Characterization of Aerosols Generated During Patient Care Activities
Abstract
Background
Questions remain about the degree to which aerosols are generated during routine patient care activities and whether such aerosols could transmit viable pathogens to healthcare personnel (HCP). The objective of this study was to measure aerosol production during multiple patient care activities and to examine the samples for bacterial pathogens. Methods
Five aerosol characterization instruments were used to measure aerosols during 7 patient care activities: patient bathing, changing bed linens, pouring and flushing liquid waste, bronchoscopy, noninvasive ventilation, and nebulized medication administration (NMA). Each procedure was sampled 5 times. An SKC BioSampler was used for pathogen recovery. Bacterial cultures were performed on the sampling solution. Patients on contact precautions for drug-resistant organisms were selected for most activity sampling. Any patient undergoing bronchoscopy was eligible. Results
Of 35 sampling episodes, only 2 procedures showed a significant increase in particle concentrations over baseline: NMA and bronchoscopy with NMA. Bronchoscopy without NMA and noninvasive ventilation did not generate significant aerosols. Of 78 cultures from the impinger samples, 6 of 28 baseline samples (21.4%) and 14 of 50 procedure samples (28.0%) were positive. Conclusions
In this study, significant aerosol generation was only observed during NMA, both alone and during bronchoscopy. Minimal viable bacteria were recovered, mostly common environmental organisms. Although more research is needed, these data suggest that some of the procedures considered to be aerosol-generating may pose little infection risk to HCP.A 17-Year Nationwide Study of Burkholderia cepacia Complex Bloodstream Infections Among Patients in the United States Veterans Health Administration
Abstract
Background
Burkholderia cepacia complex (Bcc) are a group of multidrug-resistant gram-negative bacteria rarely reported in patients without cystic fibrosis (CF) or immunocompromising conditions. We investigated Bcc bloodstream infections (BSIs) in a cohort of non-CF patients from the US Veterans Health Administration (VHA). Methods
Using VHA databases, we identified patients with Bcc BSI at facilities nationwide from 1999 through 2015. We ascertained clinical characteristics, treatments, and outcomes and identified factors associated with 30-day mortality in logistic regression analysis. Results
We identified 248 patients with Bcc BSI, who were of advanced age (mean, 68 years), chronically ill, and had severe disease. The most common sources were central venous catheters (41%) and pneumonia (20%). Most cases were hospital-acquired (155 [62%]) or healthcare-associated (70 [28%]). Mortality at 14, 30, and 90 days was 16%, 25%, and 36%, respectively. Trimethoprim-sulfamethoxazole (TMP-SMX) and fluoroquinolones were active against 94% and 88% of isolates, respectively. Susceptibility to ceftazidime and meropenem occurred in approximately 70% of the isolates. The most prescribed antibiotics were fluoroquinolones (35%), followed by carbapenems (20%), TMP-SMX (18.5%), and ceftazidime (11%). In regression analysis, age (OR, 1.06 [95% confidence interval {CI}, 1.02–1.10], per added year) and the Pitt bacteremia score (OR, 1.65 [95% CI, 1.44–1.94], per unit increase) were associated with higher 30-day mortality. Conclusions
In this large cohort of BSIs caused by Bcc, cases were mostly hospital-acquired and we observed high mortality, significant resistance to ceftazidime, and limited use of TMP-SMX. These observations add to our understanding of Bcc infection in non-CF patients and highlight the need for interventions to improve their outcome.Viral Load and Cytokine Response Profile Does Not Support Antibody-Dependent Enhancement in Dengue-Primed Zika Virus–Infected Patients
Abstract
Background
The pathogenesis of severe dengue disease involves immune components as biomarkers. The mechanism by which some dengue virus (DENV)–infected individuals progress to severe disease is poorly understood. Most studies on the pathogenesis of severe dengue disease focus on the process of antibody-dependent enhancement (ADE) as a primary risk factor. With the circulation of Zika virus (ZIKV) in DENV-endemic areas, many people infected by ZIKV were likely exposed to DENV. The influence of such exposure on Zika disease outcomes remains unknown. Methods
We investigated whether patients previously exposed to DENV exhibited higher viremia when exposed to a subsequent, heterologous dengue or Zika infection than those patients not previously exposed to dengue. We measured viral loads and cytokine profile during patients' acute infections. Results
Neither dengue nor Zika viremia was higher in patients with prior DENV infection, although the power to detect such a difference was only adequate in the ZIKV analysis. Of the 10 cytokines measured, only 1 significant difference was detected: Levels of interleukin 1β (IL-1β) were lower in dengue-infected patients who had experienced a previous dengue infection than patients infected with dengue for the first time. However, power to detect differences between groups was low. In Zika-infected patients, levels of IL-1β showed a significant, positive correlation with viral load. Conclusions
No signs of ADE were observed in vivo in patients with acute ZIKV infection who had prior exposure to DENV.Plasma Indoleamine 2, 3-Dioxygenase, a Biomarker for Tuberculosis in Human Immunodeficiency Virus-Infected Patients
Abstract
Background
There is no biomarker for diagnosing active tuberculosis in patients with human immunodeficiency virus (HIV) infection. Indoleamine 2, 3-dioxygenase (IDO) is an immunoregulatory enzyme that breaks down tryptophan (Trp) to metabolites known as kynurenines (Kyns). We investigated whether IDO activity, as measured by the ratio of Kyn to Trp, could be used to diagnose or predict active tuberculosis disease in HIV-infected adults. Methods
Kyn and Trp concentrations were measured using ultraperformance liquid chromatography mass spectrometry in plasma samples from 32 HIV-infected patients in whom active tuberculosis developed and who were followed up prospectively. We compared to 70 HIV-infected control subjects from the same cohort in whom tuberculosis did not develop, matched by age, sex, and CD4 cell count, and 37 unmatched HIV-infected patients with a diagnosis of pneumonia. Clinical parameters, including body mass index, CD4 cell count, HIV load, and C-reactive protein levels were analyzed. Results
At the time of tuberculosis diagnosis, IDO activity was significantly higher in patients with tuberculosis than in controls (P < .001). Six months before tuberculosis diagnosis, IDO activity was significantly higher in all patients who later developed tuberculosis (P < .001) than controls. After 6 months of tuberculosis treatment, IDO activity in patients with tuberculosis declined to levels similar to those in controls. IDO activity was 4-fold higher in patients with tuberculosis than in those with pneumonia, and could be used to distinguish them. With a receiver operating characteristic curve, IDO activity had a sensitivity of 97%, a specificity of 99%, and positive and negative predictive values of 89% and 100% for detecting active tuberculosis disease. Conclusion
Plasma IDO activity is suitable as a biomarker of active tuberculosis in HIV-positive patients.Importance of Carbapenemase Production Detection in Carbapenem-Resistant Enterobacteriaceae: Looking Beyond Epidemiological Purposes
To the Editor—We read with great interest the recent article by Tamma et al [1], who reported that patients with carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) have 2.6 and 4.9 higher odds for bacteremia recurrence at 30 days and mortality at 14 days, respectively, compared with patients with non-CP CRE.
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