Laboratory networks were established to provide accurate and timely laboratory confirmation of infections, an essential component of disease surveillance systems. The World Health Organization (WHO) coordinates global laboratory surveillance of vaccine-preventable diseases (VPDs), including polio, measles and rubella, yellow fever, Japanese encephalitis, rotavirus, and invasive bacterial diseases. In addition to providing high-quality laboratory surveillance data to help guide disease control, elimination, and eradication programs, these global networks provide capacity-building and an infrastructure for public health laboratories. There are major challenges with sustaining and expanding the global laboratory surveillance capacity: limited resources and the need for expansion to meet programmatic goals. Here, we describe the WHO-coordinated laboratory networks supporting VPD surveillance and present a plan for the further development of these networks.
Vaccines (3) Measles (4), Rubella (4), Poliomyelitis (4), more mentions
In April 2016, an outbreak of gastrointestinal illness (4,136 cases) occurred in Catalonia, Spain. We detected high levels of norovirus genotypes I and II in office water coolers associated with the outbreak. Infectious viral titer estimates were 33-49 genome copies/L for genotype I and 327-660 genome copies/L for genotype II.
The first Spanish multi-centre study on the microbiology of cystic fibrosis (CF) was conducted from 2013 to 2014. The study involved 24 CF units from 17 hospitals, and recruited 341 patients. The aim of this study was to characterise Pseudomonas aeruginosa isolates, 79 of which were recovered from 75 (22%) patients. The study determined the population structure, antibiotic susceptibility profile and genetic background of the strains. Fifty-five percent of the isolates were multi-drug-resistant, and 16% were extensively-drug-resistant. Defective mutS and mutL genes were observed in mutator isolates (15.2%). Considerable genetic diversity was observed by pulsed-field gel electrophoresis (70 patterns) and multi-locus sequence typing (72 sequence types). International epidemic clones were not detected. Fifty-one new and 14 previously described array tube (AT) genotypes were detected by AT technology. This study found a genetically unrelated and highly diverse CF P. aeruginosa population in Spain, not represented by the epidemic clones widely distributed across Europe, with multiple combinations of virulence factors and high antimicrobial resistance rates (except for colistin).
Clindamycin has high bioavailability together with good diffusion in bone tissue and could represent an alternative antibiotic compound for the treatment of bone and joint infections (BJIs). However, data regarding the efficacy and safety of clindamycin for BJIs are limited. A monocentric cohort study based on our medical dashboard, which prospectively recorded 28 characteristics for all hospitalized patients since July 2005, was performed. BJIs were selected, and then, all mono-microbial BJI managed with clindamycin-based therapy were included. Remission was defined as the absence of clinical and/or microbiological relapse after treatment. The duration of follow-up without relapse was determined retrospectively using computerized medical records. For 10 years, 196 BJIs, of which 80 (41%) were device-associated infections, were treated with clindamycin-based therapy. The bacterial causative agent was Staphylococcus aureus in 130 cases (66%), coagulase-negative staphylococci in 29 cases (15%), streptococci in 31 cases (16%) and other bacteria in 6 cases (3%). When used in combination therapy, clindamycin was mainly paired with fluoroquinolones (31%) or rifampin (27%). The mean duration of clindamycin treatment was 7.4 ± 3.2 weeks (range, 1-24). An AE was recorded for 9 (4.5%) patients. Remission was recorded for 111 (57%) patients, with a mean duration of clinical follow-up of 28 ± 24 months. Treatment failure occurred in 22 (11%) patients, 50 patients (25%) were lost to follow-up, and 8 (4%) required long-term suppressive therapy. Among the assessable patients, clindamycin-based therapy was efficient in 111/133 cases (83%) and thus represents a reliable and safe alternative treatment option.
BACKGROUND: An improved understanding of Clostridium difficile is important as it is used as a measure of hospital quality and is associated with substantial morbidity. This study utilizes the National Surgical Quality Improvement Program to determine the incidence, timing, risk factors, and clinical implications of C difficile colitis in patients undergoing primary total hip or knee arthroplasty (THA or TKA).
METHODS: Patients who underwent primary THA or TKA as part of the 2015 National Surgical Quality Improvement Program were identified. The primary outcome was a diagnosis of C difficile colitis within the 30-day postoperative period. Risk factors for the development of C difficile colitis were identified using Poisson multivariate regression.
RESULTS: A total of 39,172 patients who underwent primary THA or TKA were identified. The incidence of C difficile colitis was 0.10% (95% confidence interval [CI] 0.07-0.13). Of the cases that developed C difficile colitis, 79% were diagnosed after discharge and 84% had not had a preceding infection diagnosed. Independent preoperative and procedural risk factors for the development of C difficile colitis were greater age (most notably ≥80 years old, relative risk [RR] 5.28, 95% CI 1.65-16.92, P = .008), dependent functional status (RR 4.05, 95% CI 1.44-11.36, P = .008), preoperative anemia (RR 2.52, 95% CI 1.28-4.97, P = .007), hypertension (RR 2.51, 95% CI 1.06-5.98, P = .037), and THA (vs TKA; RR 2.25, 95% CI 1.16-4.36, P = .017). Postoperative infectious risk factors were urinary tract infection (RR 10.66, 95% CI 3.77-30.12, P < .001), sepsis (RR 17.80, 95% CI 3.77-84.00, P < .001), and "any infection" (RR 6.60, 95% CI 2.66-16.34, P < .001).
CONCLUSION: High-risk patients identified in this study should be targeted with preventative interventions and have perioperative antibiotics judiciously managed.
Urology (1), Cardiovascular Diseases (1), Blood Disorders and Hematology (1) Colitis (8), Infections (2), Anemia (1), more mentions
INTRODUCTION: The efficacy of currently recommended third-line therapies for Helicobacter pylori is suboptimal, even that of culture-guided treatments. Resistance to multiple antibiotics is the major factor related to treatment failure. The aim of this study was to evaluate the effectiveness and safety of a 14-day therapy using high-dose of amoxicillin, metronidazole and esomeprazole.
MATERIAL AND METHODS: Multicenter open-label study as a register in routine clinical practice in patients with two previous failures of eradication therapy. A triple therapy with esomeprazole 40 mg b.d., amoxicillin 1 g t.d.s and metronidazole 500 mg t.d.s for 2 weeks was administered as a third-line therapy after a first treatment including clarithromycin and a second treatment including a quinolone. Helicobacter pylori status was determined by either histology or (13) C-UBT both before and after treatment.
RESULTS: A total of 68 patients were included in this study. An interim analysis showed that only three out of eight patients who had received metronidazole in previous eradication regimens were cured (37%, 95% CI 8-75); as a result, after this interim analysis only metronidazole-naïve patients were included. The ITT eradication rate in metronidazole-naive patients was 64% (95% CI 51-76). Adverse events occurred in 58% of patients, all of them mild-to-moderate. Two patients (3%) did not complete >90% of the treatment because of side effects. No severe adverse events occurred.
CONCLUSION: Cure rates of this 14-day schedule using high-dose esomeprazole, amoxicillin and metronidazole as a third-line eradication regimen were suboptimal, especially in patients who had received metronidazole in previous failed eradication regimens.
Pseudomonas aeruginosa is a major pathogen in the lungs of cystic fibrosis (CF) patients. However, it is now recognised that a diverse microbial community exists in the airways comprising aerobic and anaerobic bacteria as well as fungi and viruses. This rich soup of microorganisms provides ample opportunity for interspecies interactions, particularly when considering secreted compounds. Here, we discuss how P. aeruginosa-secreted products can have community-wide effects, with the potential to ultimately shape microbial community dynamics within the lung. We focus on three well-studied traits associated with worsening clinical outcome in CF: phenazines, siderophores and biofilm formation, and discuss how secretions can shape interactions between P. aeruginosa and other commonly encountered members of the lung microbiome: Staphylococcus aureus, the Burkholderia cepacia complex, Candida albicans and Aspergillus fumigatus. These interactions may shape the evolutionary trajectory of P. aeruginosa while providing new opportunities for therapeutic exploitation of the CF lung microbiome.
Advances in sequencing technologies have enabled direct quantification of genome-wide errors that occur during RNA transcription. These errors occur at rates that are orders of magnitude higher than rates during DNA replication, but due to technical difficulties such measurements have been limited to single-base substitutions and have not yet quantified the scope of transcription insertions and deletions. Previous reporter gene assay findings suggested that transcription indels are produced exclusively by elongation complex slippage at homopolymeric runs, so we enumerated indels across the protein-coding transcriptomes of Escherichia coli and Buchnera aphidicola, which differ widely in their genomic base compositions and incidence of repeat regions. As anticipated from prior assays, transcription insertions prevailed in homopolymeric runs of A and T; however, transcription deletions arose in much more complex sequences and were rarely associated with homopolymeric runs. By reconstructing the relocated positions of the elongation complex as inferred from the sequences inserted or deleted during transcription, we show that continuation of transcription after slippage hinges on the degree of nucleotide complementarity within the RNA:DNA hybrid at the new DNA template location.IMPORTANCE The high level of mistakes generated during transcription can result in the accumulation of malfunctioning and misfolded proteins which can alter global gene regulation and in the expenditure of energy to degrade these nonfunctional proteins. The transcriptome-wide occurrence of base substitutions has been elucidated in bacteria, but information on transcription insertions and deletions-errors that potentially have more dire effects on protein function-is limited to reporter gene constructs. Here, we capture the transcriptome-wide spectrum of insertions and deletions in Escherichia coli and Buchnera aphidicola and show that they occur at rates approaching those of base substitutions. Knowledge of the full extent of sequences subject to transcription indels supports a new model of bacterial transcription slippage, one that relies on the number of complementary bases between the transcript and the DNA template to which it slipped.
OBJECTIVE(S): The purpose of the study was to review patients' characteristics and the location of extrapelvic endometriosis.
STUDY DESIGN: Out of 1000 women with endometriosis during a 20year period, we found 200 cases with extra pelvic endometriosis. Medical reports were evaluated and the diagnosis was confirmed on the pathological specimen. This study involved cases from two different geographical areas, New Haven and Crete. The age, parity, symptoms, previous surgeries, diagnostic modalities, histopathological evaluation and location of endometriotic implants found in other areas were recorded and analyzed from the patient's charts.
MAIN OUTCOME MEASURE(S): Statistical methods included x(2) and Mann-Whitney U test s measuring incidence of right-VS left sided endometriosis.
RESULTS: 200 patients with extrapelvic endometriosis and 800 patients with pelvic endometriosis were included in the study. The gastrointestinal tract represents the most common location of extrapelvic endometriosis with 104/200(52%) cases (p<0, 01), followed by the urinary system with70/200(35%) cases. We observed the Left-sided ureter being involved in 49/200(24, 5%) cases, significantly higher compare with the right-sided ureter 21/100(10, 5%) (p <0, 01). All women had similar characteristics involving age, weight, main complaints, age of menarche, endometriosis stages, gravid and family history of endometriosis.
CONCLUSION(S): The gastrointestinal tract and the urinary system are the most common sites of the extrapelvic endometriosis, which was obvious in both countries. Moreover, we observed that there are no significant differences in demographic variants, menstrual and reproductive characteristics in women with extrapelvic and pelvic endometriosis.
The human intestinal microbiota is essential for microbial homeostasis, regulation of metabolism, and intestinal immune tolerance. Rapidly evolving understanding of the importance of the microbiota implicates changes in the composition and function of intestinal microbial communities in an assortment of systemic conditions. Complications following allogeneic stem cell transplant now join the ever-expanding list of pathologic states regulated by intestinal microbiota. Dysbiosis, or disruption of the normal ecology of this microbiome, has been directly implicated in the pathogenesis of entities such as Clostridium difficile infections, graft-versus-host disease, and most recently disease relapse, all of which are major causes of morbidity and mortality in patients undergoing allogeneic stem cell transplant. In this review, we elucidate the key origins of microbiotic alterations and discuss how dysbiosis influences complications following allogeneic stem cell transplant. Our emerging understanding of the importance of a balanced and diverse intestinal microbiota is prompting investigation into the appropriate treatment of dysbiosis, reliable and early detection of such, and ultimately its prevention in patients to improve the outcome following allogeneic hematopoietic stem cell transplant. This article is protected by copyright. All rights reserved.
Stem Cell Research (6) Graft vs Host Disease (2), Infections (2), more mentions
OBJECTIVES: The aim was to investigate an unusual outbreak of 5 patients with in total 8 episodes of a Clostridium difficile infection (CDI) on a gastro intestinal surgical ward of a Dutch tertiary care university affiliated hospital.
METHODS: Clinical case investigations and laboratory analyses were performed. Laboratory analyses included PCR ribotyping, MLVA typing, toxinotyping, antimicrobial susceptibility testing and whole genome sequencing.
RESULTS: The outbreak was associated with recurrent and severe disease in 2 out of 5 patients. All episodes were due to a unique ribotype that was not recognized in the collection of an international network of reference laboratories and was assigned PCR ribotype 826. PCR ribotype 826 is a toxin A, toxin B and binary toxin positive ribotype which according to molecular typing belongs to clade 5 and resembles the so called "hypervirulent " ribotype 078. The presence of a clonal outbreak was confirmed by whole genome sequencing, yet the source of this newly identified ribotype remained unclear.
CONCLUSION: This newly identified C. difficile PCR ribotype 826 is part of clade 5 and might as well have increased virulence. The recognition of this outbreak highlights the need of ongoing CDI surveillance to monitor new circulating ribotypes with assumed increased virulence.
Pseudomonas aeruginosa, a prevalent pathogen in nosocomial infections and a major burden in cystic fibrosis, uses three interconnected quorum-sensing systems to coordinate virulence processes. At variance with other Gram-negatives, one of these systems relies on alkylquinolones (Pseudomonas Quinolone Signal, PQS) and may hence be an attractive target for new anti-infectives. Here, we report crystal structures of the N-terminal domain of anthranilate-CoA ligase PqsA, the first enzyme of PQS biosynthesis, in complex with anthraniloyl-AMP and 6-fluoroanthraniloyl-AMP (6FABA-AMP) at 1.4 and 1.7 Å resolution. We find that PqsA belongs to an unrecognized subfamily of anthranilate-CoA ligases that recognizes the amino group of anthranilate through a water-mediated hydrogen bond. The complex with 6FABA-AMP explains why 6FABA, an inhibitor of PQS biosynthesis, is a good substrate of PqsA. Together, our data may pave a way to new pathoblockers in P. aeruginosa infections.
Cystic Fibrosis (1), Hospital Infections (1), Infections (1), more mentions
OBJECTIVES: Despite the gradual increase in the incidence of non-ampullary duodenal adenocarcinoma (NADAC), the associated characteristics and risk factors remain poorly understood. The aim of this study was to clarify the clinical characteristics and risk factors of sporadic NADAC.
MATERIALS AND METHODS: In this retrospective case-control study, we enrolled 156 Japanese NADAC patients with 160 lesions from our hospital's cancer registry over 13 years. The patient demographics and clinical findings were compared to 468 age- and sex-matched controls selected from our medical health checkup recipients.
RESULTS: The ratio of men to women among the NADAC patients was 2:1, the median age was 64 years (range 31 to 90 years), the majority of the lesions were located in the second portion of the duodenum, and well-differentiated adenocarcinoma was the dominant histology. A univariate analysis revealed that smoking was a common risk factor for both men and women, whereas Helicobacter pylori (HP) infection and a history of colorectal cancer (CRC) were risk factors for the men. The multivariate analysis revealed that smoking, a history of CRC, and HP positivity were also individual risk factors for NADAC.
CONCLUSIONS: Smoking, a history of CRC, and HP positivity were identified as risk factors for NADAC.
OBJECTIVE: Gastric cancer is one of the most common causes of cancer-related death worldwide. Medicinal plants are one of the main sources for discovery of new pharmacological agents especially for treatment of cancers. The aim of the present study is to review pharmacotherapeutic aspects of three mostly studied phytochemicals including curcumin, quercetin, and allicin for management of gastric cancer.
METHODS: Scopus, PubMed, Web of Science, and Google Scholar were searched for the effects of curcumin, quercetin, allicin, and their analogs in gastric cancer. Data were collected up to November 2015. The search terms were "curcumin," "quercetin," "allicin," and "gastric cancer" or "cancer."
RESULTS: Curcumin demonstrated anti-angiogenic, anti-proliferative, anti-metastatic, pro-apoptotic, and anti-helicobacter activities. Quercetin inhibited cell growth and induced apoptosis, necrosis, and autophagy as well as anti-Helicobacter activity. Allicin showed apoptotic and anti-Helicobacter properties. All three natural compounds had low bioavailability.
CONCLUSIONS: Although preclinical studies demonstrated the activity of curcumin, quercetin, and allicin in gastric cancer, clinical trials are needed to confirm their effectiveness. Applying their possible synergistic action and suitable drug delivery system in clinical studies can be also an attractive approach with the purpose of finding new extremely efficient anti-gastric cancer agents. Curcumin, quercetin, and allicin seem to be good candidates for management of gastric cancer through their pro-apoptotic, anti-proliferative, and anti-helicobacter activities.
Pulmonary persistent adenoviral infections induce an immunosuppressive environment in the lung that renders CD8 T-cells dysfunctional. Innate cell activation during persistent infection re-invigorates effector T cell function leading to viral clearance and immune homeostasis.
BACKGROUND: Proton pump inhibitors (PPIs) have been identified as a significant risk factor for the development of Clostridium difficile infection (CDI). Probiotics given concurrently with antibiotics have been shown to have a moderate impact on preventing CDI.
OBJECTIVE: To evaluate the effectiveness of hospital-wide interventions designed to reduce PPI use and increase probiotics and whether these interventions were associated with a change in the incidence of hospital onset (HO)-CDI.
METHODS: This retrospective cohort study compared 2 fiscal years: July 2013 to June 2014 (FY14) and July 2014 to June 2015 (FY15). In July of FY15, global educational initiatives were launched targeting PPIs. Additionally, a HO-CDI prevention bundle was added to antibiotic-containing order sets targeting probiotics. Overall PPI use, probiotic use, and incidence of HO-CDI were recorded and compared for each cohort. Charts were also reviewed for patients who developed HO-CDI for the presence and appropriateness of a PPI and presence of probiotics.
RESULTS: The interventions resulted in a decrease in PPI use by 14% or 96 doses/1000 patient days (TPD; P = 0.0002) and a reduction in IV PPI use by 31% or 71 doses/TPD ( P = 0.0008). Probiotic use increased by 130% or 126 doses/TPD ( P = 0.0006). The incidence of HO-CDI decreased by 20% or 0.1 cases/TPD ( P = 0.04).
CONCLUSIONS: A collaborative, multifaceted educational initiative directed at highlighting the risks associated with PPI use was effective in reducing PPI prescribing. The implementation of a probiotic bundle added to antibiotic order sets was effective in increasing probiotic use. These interventions were associated with a decrease in incidence of HO-CDI.
Hematopoietic stem cell transplant (HSCT) recipients are uniquely threatened by the emergence of multidrug-resistant (MDR) bacteria because these patients rely on immediate active antimicrobial therapy to combat bacterial infections. This review describes the epidemiology and treatment considerations for three challenging MDR bacterial pathogens in HSCT recipients: MDR Enterobacteriaceae, including extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus (VRE). These bacteria are common causes of infection in this population and bacteremias caused by these organisms are associated with high mortality rates. Carbapenems remain the treatments of choice for serious infections due to ESBL-producing Enterobacteriaceae in HSCT recipients. Administration of β-lactam agents as an extended infusion is associated with improved outcomes in patients with severe infections caused by P. aeruginosa. Older agents used for the treatment of CRE and MDR P. aeruginosa infections, such as polymyxins and aminoglycosides, have major limitations. Newer agents, such as ceftazidime-avibactam and ceftolozane-tazobactam have great potential for the treatment of Klebsiella pneumoniae carbapemenase-producing CRE and MDR P. aeruginosa, respectively, but more pre-clinical and clinical data are needed to better evaluate their efficacy. Daptomycin dosages ≥ 8 mg/kg/day are recommended to treat VRE infections in this population, particularly in the setting of increasing daptomycin resistance. Strategies to prevent these infections include strict adherence to recommended infection control practices and multidisciplinary antimicrobial stewardship. Lastly, gastrointestinal screening to guide empirical therapy and the use of polymerase chain reaction-based rapid diagnostics may decrease the time to administration of appropriate therapy for these infections, thereby leading to improved outcomes. This article is protected by copyright. All rights reserved.
Stem Cell Research (3), Infectious Diseases (1) Infections (8), Bacterial Infection (1), more mentions
Bacterial genes that change in expression upon environmental disturbance have commonly been seen as those that must also phenotypically matter. However, several studies suggest that differentially expressed genes are rarely phenotypically important. We demonstrate, for Gram-positive and Gram-negative bacteria, that these seemingly uncoordinated gene sets are involved in responses that can be linked through topological network analysis. However, the level of coordination is stress dependent. While a well-coordinated response is triggered in response to nutrient stress, antibiotics trigger an uncoordinated response in which transcriptionally and phenotypically important genes are neither linked spatially nor in their magnitude. Moreover, a gene expression meta-analysis reveals that genes with large fitness changes during stress have low transcriptional variation across hundreds of other conditions, and vice versa. Our work suggests that cellular responses can be understood through network models that incorporate regulatory and genetic relationships, which could aid drug target predictions and genetic network engineering.
Methicillin-resistant Staphylococcus aureus (MRSA) infection is still a major global healthcare problem. Of concern is S. aureus bacteremia, which exhibits high rates of morbidity and mortality and can cause metastatic or complicated infections such as infective endocarditis or sepsis. MRSA is responsible for most global S. aureus bacteremia cases, and compared with methicillin-sensitive S. aureus, MRSA infection is associated with poorer clinical outcomes. S. aureus virulence is affected by the unique combination of toxin and immune-modulatory gene products, which may differ by geographic location and healthcare- or community-associated acquisition. Management of S. aureus bacteremia involves timely identification of the infecting strain and source of infection, proper choice of antibiotic treatment, and robust prevention strategies. Resistance and nonsusceptibility to first-line antimicrobials combined with a lack of equally effective alternatives complicates MRSA bacteremia treatment. This review describes trends in epidemiology and factors that influence the incidence of MRSA bacteremia. Current and developing diagnostic tools, treatments, and prevention strategies are also discussed.