Cryptococcus neoformans is a ubiquitous environmental fungus that can cause life-threatening meningitis and fungemia, often in the presence of acquired immunodeficiency syndrome (AIDS), liver ...cirrhosis, diabetes mellitus, or other medical conditions. To distinguish risk factors from comorbidities, we performed a hospital-based, density-sampled, matched case-control study.
All new-onset cryptococcal meningitis cases and cryptococcemia cases at a university hospital in Taiwan from 2002-2010 were retrospectively identified from the computerized inpatient registry and were included in this study. Controls were selected from those hospitalized patients not experiencing cryptococcal meningitis or cryptococcemia. Controls and cases were matched by admission date, age, and gender. Conditional logistic regression was used to analyze the risk factors.
A total of 101 patients with cryptococcal meningitis (266 controls) and 47 patients with cryptococcemia (188 controls), of whom 32 patients had both cryptococcal meningitis and cryptococcemia, were included in this study. Multivariate regression analysis showed that AIDS (adjusted odds ratio aOR = 181.4; p < 0.001), decompensated liver cirrhosis (aOR = 8.5; p = 0.008), and cell-mediated immunity (CMI)-suppressive regimens without calcineurin inhibitors (CAs) (aOR = 15.9; p < 0.001) were independent risk factors for cryptococcal meningitis. Moreover, AIDS (aOR = 216.3, p < 0.001), decompensated liver cirrhosis (aOR = 23.8; p < 0.001), CMI-suppressive regimens without CAs (aOR = 7.3; p = 0.034), and autoimmune diseases (aOR = 9.3; p = 0.038) were independent risk factors for developing cryptococcemia. On the other hand, diabetes mellitus and other medical conditions were not found to be risk factors for cryptococcal meningitis or cryptococcemia.
The findings confirm AIDS, decompensated liver cirrhosis, CMI-suppressive regimens without CAs, and autoimmune diseases are risk factors for invasive C. neoformans diseases.
A hypervirulent
(hvKp) pathotype is undergoing global dissemination. In contrast to the usual health care-associated epidemiology of classical
(cKp) infections, hvKp causes tissue-invasive infections ...in otherwise healthy individuals from the community, often involving multiple sites. An accurate test to identify hvKp strains is needed for improved patient care and epidemiologic studies. To fill this knowledge gap, clinical criteria or random blood isolates from North American and United Kingdom strain collections were used to assemble hvKp-rich (
= 85) and cKp-rich (
= 90) strain cohorts, respectively. The isolates were then assessed for multiple candidate biomarkers hypothesized to accurately differentiate the two cohorts. The genes
,
,
, plasmid-borne
gene (
), and
all demonstrated >0.95 diagnostic accuracy for identifying strains in the hvKp-rich cohort. Next, to validate this epidemiological analysis, all strains were assessed experimentally in a murine sepsis model.
,
,
,
, and
were all associated with a hazard ratio of >25 for severe illness or death, additionally supporting their utility for identifying hvKp strains. Quantitative siderophore production of ≥30 μg/ml also strongly predicted strains as members of the hvKp-rich cohort (accuracy, 0.96) and exhibited a hazard ratio of 31.7 for severe illness or death. The string test, a widely used marker for hvKp strains, performed less well, achieving an accuracy of only 0.90. Last, using the most accurate biomarkers to define hvKp, prevalence studies were performed on two Western strain collections. These data strongly support the utility of several laboratory markers for identifying hvKp strains with a high degree of accuracy.
The role of ventilation in preventing tuberculosis (TB) transmission has been widely proposed in infection control guidance. However, conclusive evidence is lacking. Modeling suggested the threshold ...of ventilation rate to reduce effective reproductive ratio (ratio between new secondary infectious cases and source cases) of TB to below 1 is corresponding to a carbon dioxide (CO2) level of 1000 parts per million (ppm). Here, we measured the effect of improving ventilation rate on a TB outbreak involving 27 TB cases and 1665 contacts in underventilated university buildings. Ventilation engineering decreased the maximum CO2 levels from 3204 ± 50 ppm to 591‐603 ppm. Thereafter, the secondary attack rate of new contacts in university dropped to zero (mean follow‐up duration: 5.9 years). Exposure to source TB cases under CO2 >1000 ppm indoor environment was a significant risk factor for contacts to become new infectious TB cases (P < .001). After adjusting for effects of contact investigation and latent TB infection treatment, improving ventilation rate to levels with CO2 <1000 ppm was independently associated with a 97% decrease (95% CI: 50%‐99.9%) in the incidence of TB among contacts. These results show that maintaining adequate indoor ventilation could be a highly effective strategy for controlling TB outbreaks.
In this issue of The Journal of Infectious Diseases, Hofmeister and colleagues 6 investigated the multistate outbreaks of hepatitis A that have continued in the United States since 2016. Because the ...outbreaks spanned 33 states, the study was conducted using data from a random sample of hepatitis A outbreak-associated cases in 3 severely affected states. Through case investigations performed by public health staff and medical records requested from hospitals, the information from 817 incident cases provides a thorough evaluation of epidemiological features and clinical outcomes. Notably, the difficulty in reaching the most heavily affected populations during the outbreaks (eg, people with substance use and experiences of homelessness) precludes clear identification of potential sources and hinders timely public health responses. Nevertheless, risk behaviors for acquiring hepatitis A can still be clearly categorized into injection drug use, noninjection drug use, homelessness, MSM status, incarceration, international travel, and epidemiological linkage. In addition, the data on clinical outcomes, including hospitalization, fulminant hepatitis, liver transplantation, and death offer valuable insights into the associated burden to health care system.
Low-molecular-weight fucoidan (LMF) is widely used as a food supplement for cancer patients. However, all of the studies are in vitro or were conducted using mice. Therefore, powerful clinical ...evidence for LMF use is relatively weak. This study aimed to evaluate the efficacy of LMF as a supplemental therapy to chemo-target agents in metastatic colorectal cancer (mCRC) patients.
We conducted a prospective, randomized, double-blind, controlled trial to evaluate the efficacy of LMF as a supplemental therapy to chemotarget agents in patients with metastatic colorectal cancer (mCRC). Sixty eligible patients with mCRC were included. Finally, 54 patients were enrolled, of whom 28 were included in the study group and 26 in the control group. The primary endpoint was the disease control rate (DCR), and secondary endpoints included the overall response rate (ORR), progression-free survival (PFS), overall survival (OS), adverse effects (AEs), and quality of life (QOL).
The DCRs were 92.8% and 69.2% in the study and control groups, respectively (
= 0.026), in a median follow-up period of 11.5 months. The OS, PFS, ORR, AEs, and QOL did not significantly differ between the two groups.
This is the first clinical trial evaluating the efficacy of LMF as a supplemental therapy in the management of patients with mCRC. The results indicate that LMF combined with chemotarget agents significantly improved the DCR.
Background Carbapenem resistance is perceived as a clinical challenge in the management of debilitated and immunocompromised patients who eventually will die from underlying diseases. We aimed to ...examine whether carbapenem resistance per se, rather than the underlying diseases, negatively affect outcomes, by comparing the excess mortality and morbidity from healthcare-associated infections (HAIs) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-susceptible A. baumannii (CSAB). Methods This was a nationwide retrospective matched cohort study of hospitalized patients in 96 hospitals which participated in Taiwan Nosocomial Infection Surveillance (TNIS). A total of 2,213 patients with A. baumannii HAIs were individually matched to 4,426 patients without HAIs. Main outcomes were excess risks for one-year all-cause mortality and one-year new-onset chronic ventilator dependence or dialysis-dependent end-stage renal disease. Results Excess one-year mortality was 27.2% in CRAB patients, compared with their matched uninfected inpatients, as well as 15.4% in CSAB patients (also compared with their matched uninfected inpatients), resulting in an attributable mortality of 11.8% (P <0.001) associated with carbapenem resistance. The excess risk associated with carbapenem resistance for new-onset chronic ventilator dependence was 5.2% (P <0.001). Carbapenem resistance was also associated with an extra cost of $2,511 per case of A. baumannii HAIs (P <0.001). Conclusion Carbapenem resistance is associated with a significant disease burden in terms of excess mortality, long-term ventilator dependence, and medical cost. Further studies on effects of antimicrobial stewardship programs in decreasing this burden are warranted.
Coronavirus disease 2019 (COVID-19) has caused great impact on healthcare systems, including antibiotic usage and multi-drug resistant (MDR) bacterial infections at hospitals. We aim to investigate ...the trends of antimicrobial resistance among the major pathogens causing healthcare-associated infection (HAI) at intensive care units (ICU).
The demographic characteristics of hospitalization, usage of antimicrobial agents, counted by half-an-year DID (defined daily dose per 1000 patient-days), and HAI density of five major MDR bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumoniae (CRKP), and carbapenem-resistant Pseudomonas aeruginosa (CRPA), of ICU patients at a medical center in Taiwan during January 2017 to December 2021 were collected and analyzed.
The total antibiotic usage, counted by DID, had a significant increasing trend, before COVID-19 occurrence in 2017–2019, but no further increase during the pandemic period in 2020–2021. However, comparing the two time periods, antibiotics consumption was significantly increased during pandemic period. There was no significant change of HAI density in MRSA, VRE, CRAB, CRKP, and CRPA, comparing the pandemic to the pre-pandemic period. Although, CRKP and CRPA infection rates were increasing during the pre-pandemic period, there was no further increase of CRKP and CRPA HAI rates during the pandemic period.
During COVID-19 pandemic, there was no significant increase in HAI density of five major MDR bacteria at ICU in Taiwan, despite increased antibiotic usage. Strict infection prevention measures for COVID-19 precautions and sustained antimicrobial stewardship probably bring these effects.
Researchers of person–job (P‐J) misfit have suggested that newcomers who “misfit” with their job often perform poorly and eventually leave the organization. However, no known studies have examined ...ways to alleviate the negative impacts of newcomers’ P‐J misfit. Based on the theory of work adjustment and the spillover model of person–environment fit, we explore whether newcomers’ fit with the social context (i.e. person–group P‐G and person–organization P‐O fit) and interpersonal relationships (i.e. person–mentor P‐M and person–supervisor P‐S fit) can buffer the detrimental outcomes of newcomers’ P‐J misfit. Using data from two field studies with time‐lag and multi‐source research designs, the results consistently show that: (1) newcomers’ P‐G fit buffered the positive relationship between their initial N–S misfit and subsequent actual turnover, (2) newcomers’ P‐M fit buffered the negative relationship between their initial D‐A misfit and subsequent task performance. Theoretical and practical implications are also discussed.
Standard inactivated influenza vaccines are poorly immunogenic in immunologically naive healthy young children, who are particularly vulnerable to complications from influenza. For them, there is an ...unmet need for better influenza vaccines. Oil-in-water emulsion-adjuvanted influenza vaccines are promising candidates, but clinical trials yielded inconsistent results. Here, we meta-analyze randomized controlled trials with efficacy data (3 trials, n = 15,310) and immunogenicity data (17 trials, n = 9062). Compared with non-adjuvanted counterparts, adjuvanted influenza vaccines provide a significantly better protection (weighted estimate for risk ratio of RT-PCR-confirmed influenza: 0.26) and are significantly more immunogenic (weighted estimates for seroprotection rate ratio: 4.6 to 7.9) in healthy immunologically naive young children. Nevertheless, in immunologically non-naive children, adjuvanted and non-adjuvanted vaccines provide similar protection and are similarly immunogenic. These results indicate that oil-in-water emulsion adjuvant improves the efficacy of inactivated influenza vaccines in healthy young children at the first-time seasonal influenza vaccination.
•In early 2020, the first large COVID-19 outbreak outside China occurred in Daegu•The SARS-CoV-2 strain involved in Daegu outbreak has an R0 of 3.6 (range: 2.3 to 5.6)•The Daegu outbreak was ...successfully controlled without restricting movement.•A combination of social distancing and testing-contact tracing is highly effective.•Both interventions must be enacted for successful control of an COVID-19 outbreak
In Spring 2020, South Korea applied non-lockdown social distancing (avoiding mass gathering and non-essential social engagement, without restricting the movement of people who were not patients or contacts), testing-and-isolation (testing), and tracing-and-quarantine the contacts (contact tracing) to successfully control the first large-scale COVID-19 outbreak outside China. However, the relative contributions of these two interventions remain uncertain.
We constructed an SEIR model of SARS-CoV-2 transmission (disproportionately through superspreading events) and fit the model to outbreak data in Daegu, South Korea, from February to April 2020. We assessed the effect of non-lockdown social distancing (population-wide control measures) and/or testing-contact tracing (individual-specific control measures), alone or combined, in terms of the basic reproductive number (R0) and the trajectory of the epidemic.
The point estimate for baseline R0 is 3.6 (sensitivity analyses range: 2.3 to 5.6). Combined interventions of non-lockdown social distancing and testing-contact tracing can suppress R0 to less than one and rapidly contain the epidemic, even under the worst scenario with a high baseline R0 of 5.6. In contrast, either intervention alone will fail to suppress R0. Non-lockdown social distancing alone just postpones the peak of the epidemic, while testing-contact tracing alone only flattens the curve but does not contain the outbreak.
To successfully control a large-scale COVID-19 outbreak, both non-lockdown social distancing and testing-contact tracing must be implemented. The two interventions are synergistic.
PDF
