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Enterocytozoon bieneusi and Cryptosporidium spp. are prevalent zoonotic parasites associated with a high burden among children. To date only limited molecular epidemiological data on E. bieneusi and Cryptosporidium spp. in humans living in Thailand has been published.
PCR-based tools were used to detect and characterize E. bieneusi and Cryptosporidium spp. The internal transcribed spacer (ITS) region of the rRNA gene was used to investigate E. bieneusi, and the small subunit (SSU) rRNA gene was used to investigate Cryptosporidium spp., and 697 fecal samples from villagers and school children in rural areas in Thailand were analyzed.
The infection rates were 2.15% (15/697) for E. bieneusi and 0.14% (1/697) for Cryptosporidium spp. The prevalence of E. bieneusi was significantly high in Loei province. Sequence analysis indicated that the Cryptosporidium isolate was C. parvum. Nine E. bieneusi genotypes were identified, EbpC, Peru12, TMH6, TMH3, TMH7, H, D, and two novel genotypes TMLH1 and TMLH2. E. bieneusi prevalence was significantly higher in male participants than in female participants, and in children aged 3–15 years than in participants aged > 15 years.
The prevalence, genotypes, and zoonotic potential of E. bieneusi were found to vary significantly high even in one country. Transmission routes and key animal carriers of E. bieneusi may be associated with differences in hygiene, sanitation, and cultural behaviors. Further molecular studies including longitudinal studies will be required to unveil epidemiological characteristics of these opportunistic intestinal protozoa in all over the countries.
Helen Alexandra Shaw, Mark D. Preston, Karuna E.W. Vendrik, Michelle D. Cairns, Hilary P. Browne, Richard A. Stabler, Monique J.T. Crobach, Jeroen Corver, Hanna Pituch, Andre Ingebretsen, Munir Primohammed, Alexandra Faulds-Pain, Esmeralda Valiente, Trevor D. Lawley, Neil F. Fairweather, Ed J. Kuijper, Brendan W. Wren
Clostridium difficile is a major global human pathogen divided into five clades, of which clade 3 is the least characterised and consists predominantly of PCR ribotype (RT) 023 strains. Our aim was to analyse and characterise this clade.
The number of new rickettsial species are rapidly increasing, and increasing numbers of Rickettsia raoultii (R. raoultii) infection cases have been detected in humans. However, neurological abnormalities caused by R. raoultii are rarely reported, especially in northwestern China.
A 36-year-old Kazakh shepherd with an attached tick on part temporalis, presented with right eyelid droop, lethargy, fever, headache, fever (38.0–41.0 °C) and erythematous rash. The examination of cerebrospinal fluid (CSF) showed cerebrospinal pressure of 200 mm H2O, leukocyte count of 300.0 × 106/L, adenosine deaminase of 2.15 U/L, and total protein concentration of 0.93 g/L. The diagnosis of R. raoultii infection was confirmed by six genetic markers, and semi-quantified by enzyme-linked immunosorbent assay for rickettsial antigen. The patient gradually recovered after treatment with doxycycline and ceftriaxone. R. raoultii DNA was found both in a tick detached from this patient and in 0.18% (2/1107) of blood samples collected from local shepherds.
This is the first reported case with neurological abnormalities caused by R. raoultii in northwestern China. It is vital to detect rickettsial agents both in blood and CSF for tick bite patients with neurological abnormalities. Public health workers and physicians should pay attention to neurological abnormalities caused by Rickettsia.
Non-typhoidal salmonellae (NTS) have been associated with invasive disease, notably meningitis, in immunocompromised individuals. Infections of this nature carry high rates of morbidity and mortality. Colistin resistance in salmonellae is a rare finding, more so in an invasive isolate such as cerebrospinal fluid (CSF). Colistin resistance has important infection control implications and failure to manage this phenomenon may lead to the loss of our last line of defence against multi-drug resistant Gram-negative organisms. To our knowledge, this is the first reported clinical case of colistin-resistant Salmonella Enteritidis meningitis in South Africa.
We report a case of a young male patient with advanced human immunodeficiency virus (HIV) infection who presented to hospital with symptoms of meningitis. Cerebrospinal fluid (CSF) cultured a Salmonella Enteritidis strain. Antimicrobial susceptibility testing (AST) of the isolate, revealed the strain to be colistin resistant. Despite early and aggressive antimicrobial therapy, the patient succumbed to the illness after a short stay in hospital. Subsequent genomic analysis of the isolate showed no presence of the mcr genes or resistance-conferring mutations in phoPQ, pmrAB, pmrHFIJKLME/arnBCADTEF, mgrB, and acrAB genes, suggesting the presence of a novel colistin resistance mechanism.
Invasive non-typhoidal salmonellae infection should be suspected in patients with advanced immunosuppression who present with clinical features of meningitis. Despite early and appropriate empiric therapy, these infections are commonly associated with adverse outcomes to the patient. Combination therapy with two active anti-Salmonella agents may be a consideration in the future to overcome the high mortality associated with NTS meningitis. Colistin resistance in clinical Salmonella isolates, although a rare finding at present, has significant public health and infection control implications. The causative mechanism of resistance should be sought in all cases.
Yadav, R., Saini, A., Agarwal, P., Kapoor, P., Aggarwal, A. N., Sethi, S.
We read the study by Seifert et al on Mycobacterium tuberculosis single nucleotide polymorphisms to predict treatment outcome published in May 2019 with interest1....
C. Ginevra, J. Chastang, S. David, M. Mentasti, E. Yakunin, V.J. Chalker, V. Chalifa-Caspi, L. Valinsky, S. Jarraud, J. Moran-Gilad, ESCMID Study Group for Legionella Infections (ESGLI)
Legionella pneumophila serogroup 1 (Lp1) Sequence Type (ST) 1 is globally widespread in the environment and accounts for a significant proportion of Legionella infections, including nosocomial Legionnaires’ disease (LD). This study aimed to design a sensitive and specific detection method for Lp ST1 that will underpin epidemiological investigations and risk assessment.
Bacteria of the Achromobacter genus, more particularly xylosoxidans species, are responsible for various healthcare associated infections (HAI) which are increasingly described since the last decade. Cystic fibrosis (CF) patients are considered as potential reservoirs in hospitals. We performed a retrospective study to estimate the frequencies of Achromobacter spp. HAI among patients from French West Indies, to determine characteristics of infected patients and establish a possible link between CF and infections.
All adults with at least one Achromobacter spp. positive sample and infection criteria in accordance with European official definitions of HAI, hospitalized in University Hospital of Martinique from 2006 to 2016 for more than 48 h, were included. Patient clinical features, immune status and underlying diseases were obtained from medical files. A list of CF patients was given by clinicians.
Antibiotic-susceptibility profiles of the strains were determined using an automated method.
Mean incidence density was 0.038/1000 days of hospitalization. Achromobacter spp. HAI evolved as an endemic situation with a low but pretty much stable incidence rate over the 11-year observation period. An epidemic peak was noticed in 2013. Among the 66 included patients, 56.1% were immunocompetent and no one had CF. Pneumonia and bacteraemia were the two main HAI. Among the 79 isolated strains, 92.4% were resistant to at least 1 major antibiotic and 16.4% met the definition of multidrug-resistant bacteria.
This microorganism, little known in our country because of the scarcity of CF patients, represents a threat for both immunosuppressed and immunocompetent patients and a therapeutic challenge because of its high resistance.
Richards, J. P., Cai, W., Zill, N. A., Zhang, W., Ojha, A. K.
Mycobacterium tuberculosis (Mtb) spontaneously grows at the air-medium interface forming pellicle biofilms, which harbor more drug tolerant persisters than planktonic cultures. The underlying basis for increased persisters in Mtb biofilms is unknown. Using a Tn-seq approach, we show here that multiple genes that are necessary for fitness of Mtb cells within biofilms, but not in planktonic cultures, are also implicated in tolerance of bacilli to a diverse set of stressors and antibiotics. Thus, development of Mtb biofilms appears to be associated with an enrichment of population, in which challenging growth conditions within biofilm architecture select for cells that maintain intrinsic tolerance to exogenous stresses including antibiotic exposure. We further observed that the intrinsic drug tolerance of constituent cells of a biofilm determines the frequency of persisters. These findings together allow us to propose that the selection of elite cells during biofilm development promotes the frequency of persisters. Furthermore, probing the possibility that the population enrichment is an outcome of unique environment within biofilms, we demonstrate biofilm-specific induction in the synthesis of isonitrile lipopeptides (INLP). Mutation analysis indicates that INLP is necessary for the architecture development of Mtb biofilms. In summary, the study offers an insight into persistence of Mtb biofilms under antibiotic exposure, while identifying INLP as a potential biomarker for further investigation of this phenomenon.
American Journal of Respiratory and Critical Care Medicine, Volume 200, Issue 6, Page 651-652, September 15, 2019.
Alan H. Jobe, Steven H. Abman
American Journal of Respiratory and Critical Care Medicine, Volume 200, Issue 6, Page 659-660, September 15, 2019.
In Nepal, cases of Cholera occur annually either as sporadic or as outbreaks claiming the lives of many in rural areas. The present study is a laboratory based surveillance which aims to analyze the changing epidemiology and antimicrobial susceptibility trend of V. cholerae strains isolated or referred to National Public Health Laboratory (NPHL) over a period of 11 years (2006–2016).
Specimens of fresh stool /rectal swab either received at sentinel sites or NPHL were processed following standard microbiological techniques. Suspected colonies on selective medium were identified using routine biochemical tests and confirmed by serotyping. Antimicrobial susceptibility testing was performed following Kirby Baeur disc diffusion method.
Of the 836 confirmed isolates, 87% (728/836) were V.cholerae O1 Ogawa,12% (103/836) were V.cholerae O1 Inaba and only 6 isolates were V.cholerae O1 Hikojima. In 2006 all the Vibrio isolates were of Inaba serotype, followed by all 3 serotypes during 2007.During 2008–2014 only Ogawa serotype was isolated while few cases of Inaba again surfaced in 2015. Resistance to ampicillin decreased from 93% in 2006 to 18% by 2010 and again raised to 100% by 2016.Cotrimoxazole resistance remained at constant range (77–100%).Nalidixic acid resistance was 100% since 2006.Ciprofloxacin and tetracycline resistance emerged in 2007, reached a peak during 2010–2012 and declined to 0 by 2016.Susceptibility to Furazolidone has re-emerged.63.6% of the isolates were Multi drug resistant.
With changing epidemiology and antibiogram of V.cholerae in Nepal, the present study reflects the importance of continuous monitoring, which could be used by policy makers and health professionals for better management of outbreaks. Decline in tetracycline and ciprofloxacin resistance along with emerging sensitivity to furazolidone shows that these drugs could make an effective comeback in future.
With one in every 20 Pakistanis already infected, Pakistan has the second largest number of hepatitis C virus (HCV) infections globally. The aim of this study was to present a quantitative and analytical characterization of the HCV epidemic in Pakistan.
A standardized database of HCV antibody incidence and prevalence and HCV genotypes in all subpopulations was systematically assembled. Random-effects meta-analyses and random-effects meta-regressions were performed. Shannon Diversity Index was calculated to determine genotype diversity.
The database included two incidence, 309 prevalence, and 48 genotype measures. Pooled mean HCV prevalence ranged between 7.0% (95% confidence interval (CI): 5.8–8.3%) in Sindh and 0.9% (95% CI: 0.1–2.4%) in Federally Administered Tribal Areas (F.A.T.A). Estimated number of chronically-infected persons ranged between 4.2 million in Punjab and 0.03 million in F.A.T.A. HCV prevalence was stable over time [adjusted odds ratio (AOR) of 1.0 (95% CI: 1.0–1.0)]. Population classification was the strongest predictor of HCV prevalence, explaining 51.8% of prevalence variation. Relative to the general population, HCV prevalence was higher in people who inject drugs [AOR of 23.8 (95% CI: 13.0–43.6)], populations with liver-related conditions [AOR of 22.3 (95% CI: 15.7–31.6)], and high-risk clinical populations [AOR of 7.8 (95% CI: 4.8–12.7)]. Low genotype diversity was observed (Shannon diversity index of 0.67 out of 1.95; 34.5%). There were only minor differences in genotype diversity by province, with genotype 3 being most common in all provinces.
Pakistan’s HCV epidemic shows homogeneity across the provinces, and over time. HCV prevalence is strikingly persistent at high level, with no evidence for a decline over the last three decades. Scale up of HCV treatment and prevention is urgently needed.
Ana Helena A. Figueiredo, Matthijs C. Brouwer, Merijn W. Bijlsma, Arie van der Ende, Diederik van de Beek
Pneumonia is considered a focus of infection in patients presenting with community-acquired bacterial meningitis but the impact on disease course is unclear. The aim was to study presenting characteristics, clinical course and outcome of meningitis patients with co-existing pneumonia on admission.
Ison, M. G., Hirsch, H. H.
Patients undergoing solid-organ transplantation (SOT) or allogeneic hematopoietic cell transplantation (HCT) are at increased risk for infectious complications. Community-acquired respiratory viruses (CARVs) pose a particular challenge due to the frequent exposure pre-, peri-, and posttransplantation. Although influenza A and B viruses have a top priority regarding prevention and treatment, recent molecular diagnostic tests detecting an array of other CARVs in real time have dramatically expanded our knowledge about the epidemiology, diversity, and impact of CARV infections in the general population and in allogeneic HCT and SOT patients. These data have demonstrated that non-influenza CARVs independently contribute to morbidity and mortality of transplant patients. However, effective vaccination and antiviral treatment is only emerging for non-influenza CARVs, placing emphasis on infection control and supportive measures. Here, we review the current knowledge about CARVs in SOT and allogeneic HCT patients to better define the magnitude of this unmet clinical need and to discuss some of the lessons learned from human influenza virus, respiratory syncytial virus, parainfluenzavirus, rhinovirus, coronavirus, adenovirus, and bocavirus regarding diagnosis, prevention, and treatment.
Alveolar echinococcosis (AE) is caused by the larval stage of Echinococcus multilocularis (E. multilocularis), and considered as public health issue. Parasite-host immune interaction is pivotal during infection. As a subset of innate lymphoid cells, NK cells are known to play an important role during virus, bacteria, intra/extracellular parasitic infections and tumor progression. However, the possible role of NK cells in E. multilocularis infection in both human and murine is little known. Herein, the functional alteration of hepatic NK cells and their related molecules in E. multilocularis infected mice were studied.
2000 protoscoleces (PSCs) were injected to C57BL/6 mice via the portal vein to establish secondary E. multilocularis infection. NK cells population and their related molecules (CD69, Ly49D, Ly49G2, Ly49H, Ly49I, NKG2A, NKG2D, granzyme B, IFN-γ, TNF-α) were assessed by using fluorescence-activated cell sorter (FACS) techniques and qRT-PCR. NK cell depletion was performed for further understanding the possible function of NK cells during infection.
The total frequencies of NK cells and NK-derived IFN-γ production were significantly reduced at designated time points (2, 4, 12 weeks). The liver resident (CD49a+DX5−) NK cells are decreased at 4 weeks after inoculation and which is significantly lower than in control mice. Moreover, in vivo antibody-mediated NK cell depletion increased parasitic load and decreased peri-parasitic fibrosis. Expression of the inhibitory receptor NKG2A was negatively related to NK- derived IFN-γ secretion.
Our study showed down regulates of NK cells and upper regulates of NKG2A expression on NK cells during E. multilocularis infection. Reduction of NK cell frequencies and increased NKG2A might result in low cytotoxic activity through decreased IFN-γ secretion in E. multilocularis infection. This result might be helpful to restore NK cell related immunity against E. multilocularis infection to treat alveolar echinococcosis.
Globally, diarrhea is the leading cause of morbidity and mortality among less than 5 years old children and it contributes to the deaths of approximately one million children every year. In Ethiopia, diarrhea is the second cause of under-five mortality and morbidity. However, in the study area, studies were limited. Therefore, this study has assessed the prevalence of diarrhea and associated factors among
Rappo, U., Dunne, M. W., Puttagunta, S., Baldassarre, J. S., Su, S., Desai-Krieger, D., Inoue, M.
Dalbavancin is a lipoglycopeptide antibiotic with a prolonged half-life. A Phase 1 study assessed dalbavancin levels in epithelial lining fluid (ELF) in 35 healthy adults using ELF bronchial microsampling up to 168 hrs after 1500 mg dalbavancin. The penetration of dalbavancin into ELF was 36%. ELF levels of dalbavancin exceeded the MIC90 of S. pneumoniae and S. aureus for ≥ 7 days.
Theilacker C, Vyse A, Jodar L, et al.
Yui Eto, K., Firth, N., Davis, A. M., Kwong, S. M., Krysiak, M., Lee, Y. T., O'Brien, F. G., Grubb, W. B., Coombs, G. W., Bond, C. S., Ramsay, J. P.
Horizontal transfer of plasmids encoding antimicrobial-resistance and virulence determinants has been instrumental in Staphylococcus aureus evolution, including the emergence of community-associated methicillin-resistant S. aureus (CA-MRSA). In the early 1990s the first CA-MRSA isolated in Western Australia (WA), WA-5, encoded cadmium, tetracycline and penicillin-resistance genes on plasmid pWBG753 (~30 kb). WA-5 and pWBG753 appeared only briefly in WA, however, fusidic-acid-resistance plasmids related to pWBG753 were also present in the first European CA-MRSA at the time. Here we characterized a 72-kb conjugative plasmid pWBG731 present in multiresistant WA-5-like clones from the same period. pWBG731 was a cointegrant formed from pWBG753 and a pWBG749-family conjugative plasmid. pWBG731 carried mupirocin, trimethoprim, cadmium and penicillin-resistance genes. The stepwise evolution of pWBG731 likely occurred through the combined actions of IS257, IS257-dependent miniature inverted-repeat transposable elements (MITEs) and the BinL resolution system of the β-lactamase transposon Tn552. An evolutionary intermediate ~42-kb non-conjugative plasmid pWBG715, possessed the same resistance genes as pWBG731 but retained an integrated copy of the small tetracycline-resistance plasmid pT181. IS257 likely facilitated replacement of pT181 with conjugation genes on pWBG731, thus enabling autonomous transfer. Like conjugative plasmid pWBG749, pWBG731 also mobilized non-conjugative plasmids carrying oriT mimics. It seems likely that pWBG731 represents the product of multiple recombination events between the WA-5 pWBG753 plasmid and other mobile genetic elements present in indigenous CA-MSSA. The molecular evolution of pWBG731 saliently illustrates how diverse mobile genetic elements can together facilitate rapid accrual and horizontal dissemination of multiresistance in S. aureus CA-MRSA.
Margaret F. Ragland, Christopher J. Benway, Sharon M. Lutz, Russell P. Bowler, Julian Hecker, John E. Hokanson, James D. Crapo, Peter J. Castaldi, Dawn L. DeMeo, Craig P. Hersh, Brian D. Hobbs, Christoph Lange, Terri H. Beaty, Michael H. Cho, Edwin K. Silverman
American Journal of Respiratory and Critical Care Medicine, Volume 200, Issue 6, Page 677-690, September 15, 2019.
Peter M. A. Calverley, Paul P. Walker
American Journal of Respiratory and Critical Care Medicine, Volume 200, Issue 6, Page 654-655, September 15, 2019.
The accuracy of different laboratory tests for diagnosis of diabetes mellitus (DM) and prediabetes (preDM) in populations exposed to tuberculosis (TB) remains poorly understood. Here, we examined the prevalence of DM and preDM in TB affected people in Lima, Peru.
A prospective cohort study of patients affected TB and their household contacts (HHC), was conducted between February and November 2017 in Lima, Peru. Fasting plasma glucose (FPG), HbA1c and oral glucose tolerance test (OGTT) were used to detect DM and preDM in a prospective cohort of TB patients (n = 136) and household contacts (n = 138). Diagnostic performance of the laboratory tests was analyzed. Potential effects of sociodemographic and clinical factors on detection of dysglycemia were analyzed.
In TB patients, prevalence of DM and preDM was 13.97 and 30.88% respectively. Lower prevalence of both DM (6.52%) and preDM (28.99%) were observed in contacts. FPG, HbA1c and OGTT had poor agreement in detection of preDM in either TB cases or contacts. TB-DM patients had substantially lower hemoglobin levels, which resulted in low accuracy of HbA1c-based diagnosis. Classic sociodemographic and clinical characteristics were not different between TB patients with or without dysglycemia.
High prevalence of DM and preDM was found in both TB patients and contacts in Lima. Anemia was strongly associated with TB-DM, which directly affected the diagnostic performance of HbA1c in such population.
The global burden of sexually transmitted infections (STIs) is high and there have been reports of increasing chlamydial and gonorrheal infections. High-volume screening programs for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are an important component of STI control. This study evaluated the high-volume workflow and performance of the cobas® CT/NG assay for use on the automated Roche cobas® 6800 system, with the cobas p 480 instrument for pre-analytics, compared with the Aptima Combo 2 assay on the Hologic Panther system.
High-volume workflow and performance were evaluated using paired female urine specimens. Workflow analysis (n = 376) included hands-on time (HoT), number of manual interventions, and time to first and last results. For performance assessment, paired results from the cobas CT/NG and Aptima Combo 2 assays, for both CT and NG, were compared and two-sided 95% confidence intervals calculated to provide estimates of positive percent agreement (PPA), negative percent agreement (NPA), and overall percent agreement (OPA) between the tests. McNemar’s test was used for significance testing.
Pre-analytical preparations and system start-up on the cobas 6800 system required 00:27:38 (hr:min:sec) HoT whilst the Panther system required 00:30:43. The cobas 6800 system required eight interactions and 00:43:59 HoT to process 376 samples. The Panther system required six interactions and 00:39:10 HoT. Time to first results was 02:53:00 on the cobas c6800 system for 96 samples and 03:28:29 on the Panther system for five samples. The cobas 6800 system delivered all 376 results 3 h faster than the Panther system (07:45:26 and 10:47:30, respectively). The performance correlation between both assays was high (PPA, NPA and OPA > 99% for both CT and NG). McNemar’s test revealed no statistically significant difference between the assays.
For high-volume automated CT/NG testing, both the cobas 6800 system and Panther system provided accurate results. Although less manual intervention steps were needed for the Panther system, improved turnaround time was obtained with the cobas 6800 system with less risk for contamination. The additional testing capacity on the cobas 6800 system would allow a growing service to deliver more results in a single shift.
Michael J. Abramson, Yuming Guo
American Journal of Respiratory and Critical Care Medicine, Volume 200, Issue 6, Page 652-654, September 15, 2019.
Chronic infection with hepatitis B virus (HBV) is a serious global health problem. Persistence of the virus occurs as a result of stability of the replication intermediate comprising covalently closed circular DNA (cccDNA). Development of drugs that are capable of disabling this cccDNA is vital.
To investigate an epigenetic approach to inactivating viral DNA, we engineered transcriptional repressors that comprise an HBV DNA-binding domain of transcription activator like effectors (TALEs) and a fused Krüppel Associated Box (KRAB). These repressor TALEs (rTALEs) targeted the viral surface open reading frame and were placed under transcription control of constitutively active or liver-specific promoters.
Evaluation in cultured cells and following hydrodynamic injection of mice revealed that the rTALEs significantly inhibited production of markers of HBV replication without evidence of hepatotoxicity. Increased methylation of HBV DNA at CpG island II showed that the rTALEs caused intended epigenetic modification.
Epigenetic modification of HBV DNA is a new and effective means of inactivating the virus in vivo. The approach has therapeutic potential and avoids potentially problematic unintended mutagenesis of gene editing.
Catherine R. Sears, Tobias Peikert, Jennifer D. Possick, Jarushka Naidoo, Mizuki Nishino, Sandip P. Patel, Philippe Camus, Mina Gaga, Edward B. Garon, Michael K. Gould, Andrew H. Limper, Philippe R. Montgrain, William D. Travis, M. Patricia Rivera
American Journal of Respiratory and Critical Care Medicine, Volume 200, Issue 6, Page e31-e43, September 15, 2019.
Michael G. Surette, Dawn M. E. Bowdish
American Journal of Respiratory and Critical Care Medicine, Volume 200, Issue 6, Page 660-662, September 15, 2019.
Brink, M., Glimaker, M., Sjölin, J., Naucler, P.
Objectives Cefotaxime, alone or with ampicillin, is frequently used as empirical treatment of acute bacterial meningitis (ABM). Meropenem is a less investigated alternative. The aim of the study was to investigate the effects of empirical treatment with meropenem compared to cefotaxime plus ampicillin on outcome in ABM.Methods The study was based on data from the Swedish quality register for ABM between January 2008 and December 2016. A propensity score matching was performed to adjust for baseline differences between the groups. Mortality within 30-days was the primary outcome.Results The treatment regimens of interest were administered to 623 patients; 328 were given cefotaxime plus ampicillin whereas 295 received meropenem. After propensity score matching the 30-day mortality was 3.2% in the cefotaxime plus ampicillin group and 3.6% in the meropenem group. For matched cases the OR for 30-day mortality for meropenem vs. cefotaxime plus ampicillin was 1.15 (CI: 0.41–3.22; p=0.79). The OR for 90-day mortality was 1.47 (CI: 0.62–3.52; p=0.38), and for unfavorable outcome 1.10 (CI: 0.75–1.63; p=0.62).Conclusions The findings of our study indicate that meropenem is an effective empirical treatment option for adults with community-acquired ABM. However, to spare carbapenems, guidelines should continue to recommend third-generation cephalosporins as empirical treatment for the majority of patients with ABM.
Infections by Streptococcus gallolyticus subsp. pasteurianus (SGSP) is often underestimated. Herein, the epidemiological features and resistant characteristics of SGSP in mainland China are characterized to enable a better understanding of its role in clinical infections.
In the present work, 45 SGSP isolates were collected from the samples of bloodstream, urine, aseptic body fluid, and fetal membrane/placenta from patients in 8 tertiary general hospitals of 6 cities/provinces in China from 2011 to 2017. The identification of all isolates was performed using traditional biochemical methods, 16S rRNA and gyrB sequencing, followed by the characterization of their antibiotic resistance profiling and involved genes.
Among 34 non-pregnancy-related patients, 4 (4/34,11.8%) patients had gastrointestinal cancer, 10 (10/34, 29.4%) patients had diabetes, and one patient had infective endocarditis. Moreover, 11 cases of pregnant women were associated with intrauterine infection (9/11, 81.2%) and urinary tract infection (1/11, 9.1%), respectively. Except one, all other SGSP isolates were correctly identified by the BD Phoenix automated system. We found that all SGSP isolates were phenotypically susceptible to penicillin, ampicillin, cefotaxime, meropenem, and vancomycin. Forty strains (40/45, 88.9%) were both erythromycin and clindamycin-resistant, belonging to the cMLSB phenotype, and the majority of them carried erm(B) gene (39/40, 97.5%). Although the cMLSB/erm(B) constituted the most frequently identified phenotype/genotype combination (25/40, 62.5%) among all erythromycin-resistant cMLSB isolates, erm(B)/erm(A), erm(B)/mef(A/E), and erm(B)/erm(T) was detected in 7, 4, and 3 isolates, respectively. Furthermore, 43 strains (43/45, 95.6%) were tetracycline-resistant, and out of these, 39 strains (39/45, 86.7%) carried tet(L), 27(27/45, 60.0%) strains carried tet(O), and 7 (7/45, 15.6%) strains carried tet(M), alone or combined, respectively. All erythromycin-resistant isolates were also resistant to tetracycline.
It is important to study and draw attention on SGSP, an underreported opportunistic pathogen targeting immunodeficient populations, notably elderly subjects, pregnant women and neonates.
Bradley A. Edwards, Susan Redline, Scott A. Sands, Robert L. Owens
American Journal of Respiratory and Critical Care Medicine, Volume 200, Issue 6, Page 691-703, September 15, 2019.
Catherine E. Simpson, Paul M. Hassoun
American Journal of Respiratory and Critical Care Medicine, Volume 200, Issue 6, Page 662-663, September 15, 2019.
Laborda, P., Alcalde-Rico, M., Blanco, P., Martinez, J. L., Hernando-Amado, S.
The study of the acquisition of antibiotic resistance (AR) has mainly focused in inherited processes, namely mutations and acquisition of AR genes. However, inducible, non-inheritable AR has received less attention and most information in this field derives from the study of antibiotics as inducers of their associated resistance mechanisms. Less is known about non-antibiotic compounds or situations that can induce AR during infection. Multidrug resistance efflux pumps are a category of AR determinants characterized by the tight regulation of their expression. Their contribution to acquired AR relies in their overexpression. Herein we analyzed potential inducers of the expression of the chromosomally-encoded Pseudomonas aeruginosa clinically-relevant efflux pumps, MexCD-OprJ and MexAB-OprM. For this purpose, we developed a set of luxCDABE-based P. aeruginosa biosensor strains, which allows the high-throughput analysis of compounds able of modifying the expression of these efflux pumps. Using these strains, we analyzed a set of 240 compounds present in Biolog Phenotype Microarrays. Several inducers of the expression of the genes that encode these efflux pumps were found. The study focused in dequalinium chloride, procaine and atropine, compounds that can be found in clinical settings. Using real-time PCR, we confirmed that these compounds indeed induce the expression of mexCD-oprJ. In addition, P. aeruginosa presents lower susceptibility to ciprofloxacin (a MexCD-OprJ substrate) when dequalinium chloride, procaine or atropine are present. This work emphasizes the need of studying compounds that can trigger transient AR during antibiotic treatment, a phenotype difficult to discover using classical susceptibility tests.
Bekerman, E., Hesselgesser, J., Carr, B., Nagel, M., Hung, M., Wang, A., Stapleton, L., von Gegerfelt, A., Elyard, H. A., Lifson, J. D., Geleziunas, R.
Antiretroviral therapy (ART) limits HIV-1 replication, but does not eliminate the long-lived reservoir established shortly after viral acquisition. A successful HIV cure intervention necessitates either elimination or generation of long-term immune control of the persistent viral reservoir. Immune modulating strategies in conjunction with ART hold promise for achieving cure by inducing viral antigen expression and augmenting infected cell killing. PD-1 blockade is a potential means to both activate and eliminate the latent reservoir by restoring exhausted T cell function. We assessed the therapeutic efficacy of PD-1 blockade, TLR7 activation with the agonist vesatolimod, or a combination of the two agents in chronically SIV-infected macaques suppressed with ART for over two years. Despite achieving extended anti-PD-1 antibody plasma exposure and TLR7-dependent immune activation after multiple administrations, neither individual treatment nor the combination resulted in changes to viral rebound kinetics following ART interruption or reduction in the SIV reservoir size. Our data in the context of other reports demonstrating improved viral control upon PD-1 blockade, suggest that its therapeutic utility may be restricted to specific experimental conditions or treatment times during viral pathogenesis.
The present meta-analysis examined the diagnostic accuracy of T2 Candida for candidiasis.
The literature databases, such as PubMed, Embase, DVIO, Cochrane library, Web of Science, and CNKI, were searched on T2 Candida detection.
A total of 8 articles, comprising of 2717 research subjects, were included in the study. The pooled sensitivity and specificity were 0.91 (95% confidence interval (CI): 0.88–0.94) and 0.94 95% CI: 0.93–0.95), respectively. The pooled positive likelihood ratio and negative likelihood ratio was 10.16 (95% CI: 2.75–37.50) and 0.08 (95% CI: 0.02–0.35), respectively. The combined diagnostic odds ratio is 133.65 95% CI: 17.21–1037.73), and the AUC of SROC is 0.9702 [(SE = 0.0235), Q* = 0.9201(SE = 0.0381)].
The current evidence supported that T2 Candida has high accuracy and sensitivity and is of major clinical significance in the diagnosis of Candida infection.
Serota D, Rosenberg E, Sullivan P, et al.
AbstractBackgroundHIV pre-exposure prophylaxis (PrEP) has great potential to reduce HIV incidence among young black men who have sex with men (YBMSM) but initiation and persistence for this group remain low. We sought to understand the patterns and predictors of PrEP uptake and discontinuation among YBMSM in Atlanta, Georgia.MethodsPrEP was offered to all participants in a prospective cohort of HIV-negative YBMSM aged 18-29. For initiators, time on and off PrEP was recorded. Time to PrEP uptake, first discontinuation, and final discontinuation were assessed with the Kaplan-Meier method, with Cox proportional hazard models used to identify factors associated with uptake and discontinuation.ResultsAfter 440 person-years of follow-up, 44% of YBMSM initiated PrEP through the study after a median of 122 days (IQR 44-275). Of PrEP initiators, 69% had a first discontinuation and 40% had a final discontinuation during the study period. The median time to first PrEP discontinuation was 159 days (IQR 97-237). Factors associated with PrEP uptake included higher self-efficacy, sexually transmitted infection, and condomless anal intercourse. Factors associated with discontinuation included younger age, cannabis use, STI, and fewer sex partners. HIV incidence was 5.23/100 person-years (95% CI 3.40-7.23) with lower rate among those who started PrEP (incidence rate ratio 0.39 [95% CI 0.16-0.92]).ConclusionsPersistent PrEP coverage in this cohort of YBMSM was suboptimal and discontinuations common despite additional support services available through the study. Interventions to support PrEP uptake and persistence, especially for younger and substance-using YBMSM, will be necessary to achieve full PrEP effectiveness.
Spinelli M, Buchbinder S.
Scabies, a parasitic disease of the skin, is a major public health problem, largely affecting children. Scabies is often complicated by impetigo which can result in serious complications including invasive infections and immune mediated diseases. Scabies and impetigo are reported to have high prevalence in tropical settings including the Solomon Islands.
We conducted a cross-sectional prevalence survey at Gizo Primary School in the Western Province of the Solomon Islands in August 2018. The diagnosis of scabies was based on criteria developed by the International Alliance for the Control of Scabies in 2018. Population attributable risk was calculated to determine the effect of scabies on the prevalence of impetigo, and both adjusted and unadjusted risk ratios were calculated to identify differences between sexes and age groups.
A total of 324 students were assessed (47.5% of those enrolled at the school). The prevalence of scabies was 54.3% (95% confidence interval [CI] 48.7–59.8) and most disease was mild (68.8%). The prevalence was higher in males (63.5%; adjusted risk ratio [ARR] 1.4, 95% CI 1.1–1.7), and in those aged 10–12 years (61.4%; ARR 1.8, 95% CI 1.1–2.9 when compared to those aged 4–6 years). The prevalence of impetigo was 32.1%, with males more likely to be affected (41.7%, ARR 1.7, 95% CI 1.2–2.4) but with no significant differences between age groups. 63.5% of those with impetigo had scabies, corresponding to a population attributable risk of 11.8%.
There is a very high burden of scabies and impetigo among primary school students in Gizo. There is a critical need for the development and implementation of control programs in areas where scabies is endemic.
Kolditz M, Schmitt J, Pletz M, et al.
Hideo Watanabe, Charles A. Powell
American Journal of Respiratory and Critical Care Medicine, Volume 200, Issue 6, Page 657-659, September 15, 2019.
Angelico Mendy, Jesse Wilkerson, Pӓivi M. Salo, Charles H. Weir, Lydia Feinstein, Darryl C. Zeldin, Peter S. Thorne
American Journal of Respiratory and Critical Care Medicine, Volume 200, Issue 6, Page 712-720, September 15, 2019.
Larviciding is an effective supplementary tool for malaria vector control, but the identification and accessibility of aquatic habitats impedes application. Dissemination of the insect growth regulator, pyriproxyfen (PPF), by gravid Anopheles might constitute a novel application strategy. This study aimed to explore the feasibility of using an attractive bait-station to contaminate gravid Anopheles gambiae sensu stricto with PPF and subsequently transfer PPF to larval habitats.
A bait-station was developed comprising of an artificial pond containing water treated with 20 ppm cedrol, an oviposition attractant, and a netting-cover treated with PPF. Three identical semi-field cages were used to assess the potential of gravid Anopheles to transfer PPF from the bait-station to ponds. Gravid females were released in two semi-field cages, one with PPF on its bait-station (test) and one without PPF (control). No mosquitoes were released in the third cage with a PPF-treated station (control). Transfer of PPF to open ponds was assessed by monitoring emergence of late instar insectary-reared larvae introduced into the ponds. The amount of PPF carried by a mosquito and transferred to water was quantified using liquid chromatography-mass spectrometry.
In the controls, 86% (95% CI 81–89%) of larvae introduced into open ponds developed into adults, indicating that wind did not distribute PPF in absence of mosquitoes. Emergence inhibition was observed in the test cage but was dependent on the distance between pond and bait-station. Only 25% (95% CI 22–29%) of larvae emerged as adults from ponds 4 m from the bait-station, but 92% (95% CI 89–94%) emerged from ponds 10 m away. Each mosquito was contaminated on average with 112 μg (95% CI 93–123 μg) PPF resulting in the transfer of 230 ng/L (95% CI 180–290 ng/L) PPF to 100 ml volumes of water.
The bait-stations successfully attracted gravid females which were subsequently dusted with effective levels of PPF. However, in this study design, attraction and dissemination was limited to short distances. To make this approach feasible for malaria vector control, stronger attractants that lure gravid females from longer distances, in landscapes with many water bodies, and better PPF delivery systems are needed.
Samuel T. Kuna
American Journal of Respiratory and Critical Care Medicine, Volume 200, Issue 6, Page 663-664, September 15, 2019.
Vickram Tejwani, Franco R. D’Alessio
American Journal of Respiratory and Critical Care Medicine, Volume 200, Issue 6, Page 656-657, September 15, 2019.
Kim, D., Hong, J. S., Yoon, E.-J., Lee, H., Kim, Y. A., Shin, K. S., Shin, J. H., Uh, Y., Shin, J. H., Park, Y. S., Jeong, S. H.
Introduction: This study was performed to evaluate the clinical impacts of putative risk factors in patients with Staphylococcus aureus bloodstream infections (BSIs) through a prospective, multicenter, observational study.Methods: All 576 patients with S. aureus BSIs that occurred during a one-year period in six general hospitals were included in this study. Host- and pathogsen-related variables were investigated to determine risk factors for the early mortality of patients with S. aureus BSIs.Results: The all-cause mortality rate was 14.8% (85/576) during the four-week follow-up period from the initial blood culture, and 76.5% (65/85) of the mortality cases occurred within the first two weeks. One-quarter (26.8%, 152/567) of the S. aureus blood isolates carried the tst-1 gene, and most (86.2%, 131/152) of them were identified as clonal complex 5-agr type 2-methicillin-resistant S. aureus (MRSA) strains harboring staphylococcal cassette chromosome mec type II, belonging to the New York/Japan epidemic clone. A multivariable logistic regression showed that tst-1-positivity of causative S. aureus isolates was associated with an increased two-week mortality rate both in patients with S. aureus BSIs [adjusted odds ratio (aOR), 1.62; 95% confidence interval (CI), 0.90-2.88] and in patients with MRSA BSIs (aOR, 2.61; 95% CI, 1.19-6.03).Conclusions: Both host-related factors, increased Pitt bacteremia score and advanced age, as well as a pathogen-related factor, carriage of tst-1 by causative MRSA isolates, were risk factors for two-week mortality in patients with BSIs, and careful management of patients with BSIs caused by the New York/Japan epidemic clone is needed to improve clinical outcomes.
Monod, M., Feuermann, M., Salamin, K., Fratti, M., Makino, M., Alshahni, M. M., Makimura, K., Yamada, T.
Mechanisms of terbinafine resistance in a set of clinical isolates of Trichophyton rubrum have been studied recently. Of these isolates, TIMM20092 also showed reduced sensitivity to azoles. The azole resistance of TIMM20092 could be inhibited by milbemycin oxime, prompting us to examine the potential of T. rubrum to develop resistance through multidrug efflux transporters. The introduction of a T. rubrum cDNA library into Saccharomyces cerevisiae allowed the isolation of one transporter of the MFS family conferring resistance to azoles (TruMFS1). To identify more azole efflux pumps among 39 ABC and 170 MFS transporters present within the T. rubrum genome, we performed a BLASTp analysis of Aspergillus fumigatus, Candida albicans, and Candida glabrata on transporters that were previously shown to confer azole resistance. The identified candidates were further tested by heterologous gene expression in S. cerevisiae. Four ABC transporters (TruMDR1, TruMDR2, TruMDR3, and TruMDR5) and a second MFS transporter (TruMFS2) proved to be able to operate as azole efflux pumps. Milbemycin oxime only inhibited TruMDR3. Expression analysis showed that both TruMDR3 and TruMDR2 were significantly up-regulated in TIMM20092. MDR3 transports voriconazole (VRC) and itraconazole (ITC), while TruMDR2 transports only ITC. Disruption of TruMDR3 in TIMM20092 abolished its resistance to VRC and reduced its resistance to ITC. Our study highlights TruMDR3, a newly identified transporter of the ABC family in T. rubrum, which can confer azole resistance if overexpressed. Finally, inhibition of TruMDR3 by milbemycin suggests that milbemycin analogs could be interesting compounds to treat dermatophyte infections in cases of azole resistance.
Katherine N. Cahill, Jing Cui, Parul Kothari, Katherine Murphy, Benjamin A. Raby, Joseph Singer, Elliot Israel, Joshua A. Boyce, Tanya M. Laidlaw
American Journal of Respiratory and Critical Care Medicine, Volume 200, Issue 6, Page 704-711, September 15, 2019.
Early Childhood Education Centre (ECEC) staff are strongly recommended to receive several immunizations including influenza and pertussis. However, evidence regarding the uptake is either old or lacking across all Australian States/Territories. This study aimed to explore the attitudes and barriers around ECEC staff vaccination and the immunisation policy/practices employed at their workplaces.
An online cross-sectional survey was undertaken of staff members (administrators and childcare center staff) in early 2017. We compared the individual’s knowledge, attitude and practices as well as the centre’s policy and practice variables between the vaccinated and unvaccinated respondents. A logistic model was used to identify the factors associated with uptake of the different vaccines.
A total of 575 ECEC staff completed the survey. Sixty percent reported being aware of the recommendations about staff immunisation. While participants did acknowledge that they could spread diseases if unvaccinated (86%), 30% could not recall receiving a dTpa in the last 10 years. Private centres were less likely to provide free or onsite vaccination compared to other categories of centres. Less than half reported receiving any encouragement to get the influenza vaccine and only 33% reported that their centre provides onsite influenza vaccination. Regarding the introduction of mandatory policies, 69% stated that they would support a policy.
Employers should consider supporting methods to maximize vaccination of their employees including providing free onsite vaccination. Participants were open to idea of mandatory vaccination; however, this needs to be explored further to determine how vaccine costs and access issues could be resolved.
Dijkstra M, Lin T, de Bree G, et al.
AbstractThe San Diego Early Test (SDET) score is a simple risk-assessment tool for acute and early HIV-infection. Validation in a prospective cohort of Amsterdam men who have sex with men showed fair prediction of HIV seroconversion (AUC 0.701). Use of this score can help prioritise and target HIV prevention strategies.
HIV self-testing (HIVST) is a promising approach to expand HIV testing. HIVST is a process in which a person performs an HIV test and interprets the result. Negative HIVST results may encourage men who have sex with men (MSM) to use HIV prevention services. The objective of this study was to examine behaviors (e.g., facility-based HIV testing, condom use) after a negative HIVST test result among Chinese MSM.
We collected data from MSM in eight Chinese cities over a 12-month period. This is a secondary analysis of longitudinal cohort data collected as part of an intervention trial to increase HIV testing. Men completed a survey that described sociodemographic information, sexual behaviors, HIV self-testing, and facility-based HIV testing. Men who completed at least one follow-up survey were included in this analysis. Generalized linear mixed models were used to evaluate whether HIVST increased subsequent facility-based HIV testing and consistent condom use.
We included 1219 men. Most men (78.7%) were under 30 years old and had never been married (87.0%). 755 (61.9%) men tested for HIV and 593 (49.3%) men self-tested during the study period. At baseline, among men who had never been tested for HIV, 44.9% (314/699) initiated HIVST during the study period. HIVST was associated with subsequent facility-based testing (aOR of 1.87, 95% CI: 1.47–2.37). HIVST was also associated with subsequent consistent condom use (aOR = 1.53, 95% CI: 1.13–2.06).
HIVST was associated with subsequent facility-based HIV testing and consistent condom use. HIVST may enhance uptake of related HIV prevention services at facilities, suggesting the need for more implementation research.
Retningslinjer til sundhedsprofessionelle vedr. håndtering af infektion med zikavirus (2019)
Antiviral behandling af hiv smittede personer (2019)
Lumbalpunktur af patienter i blodfortyndende behandling (2019)
Reply to Barner and Bruno-Murtha
23.09.2019Clinical Infectious Diseases Advance Access
False-negative Results of Human Immunodeficiency Virus (HIV) Rapid Testing in HIV Controllers
21.09.2019Clinical Infectious Diseases Advance Access
Resistance of Influenza Virus to Antiviral Medications
20.09.2019Clinical Infectious Diseases Advance Access
Oseltamivir resistance in severe influenza A(H1N1)pdm09 pneumonia and acute respiratory distress syndrome: a French multicenter observational cohort study
20.09.2019Clinical Infectious Diseases Advance Access
Baloxavir marboxil in Japanese pediatric patients with influenza: safety and clinical and virologic outcomes
20.09.2019Clinical Infectious Diseases Advance Access
Hvad synes Professor Thomas Benfield om"Oral versus Intravenous Antibiotics for Bone and Joint Infection."?
Hvorfor anbefaler Professor Niels Obel artiklen"Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis."?
Hvad synes Professor Thomas Benfield om"Duration of Antibiotic Treatment in Community-Acquired Pneumonia: A Multicenter Randomized Clinical Trial."?
Hvad tænker Professor Morten Sodemann om"Evidence-based clinical guidelines for immigrants and refugees."?
Hvorfor synes Professor Niels Obel, at du bør læse"Use of statins and risk of AIDS-defining and non-AIDS-defining malignancies among HIV-1 infected patients on antiretroviral therapy."?
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