ResearchPad - bacteremia https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[<i>Escherichia coli</i> ST131 clones harbouring AggR and AAF/V fimbriae causing bacteremia in Mozambican children: Emergence of new variant of <i>fimH27</i> subclone]]> https://www.researchpad.co/article/elastic_article_14507 Escherichia coli ST131 has emerged as a globally disseminated multi-drug resistant clone associated with extra-intestinal infections acquired in the community or hospital. In Manhiça district, E. coli is among the top five leading bloodstream pathogens in children. We characterized E. coli strains causing bacteremia in young children in a rural hospital of Mozambique, providing novel information on the occurrence of a new subclone of ST131 harboring both ExPEC and EAEC related genes and belonging to commonly reported O25:H4 and other serotypes. These data suggest the need for further understanding of pathogenesis and clinical impact of this new entity to inform prompt recognition and appropriate treatment.

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<![CDATA[Age-related differences in clinical characteristics of invasive group G streptococcal infection: Comparison with group A and group B streptococcal infections]]> https://www.researchpad.co/article/5c8accd0d5eed0c48499008b

Purpose

Invasive Group G streptococcal infection (iGGS) has increasingly been recognized as a cause of severe disease, mainly among elderly people with chronic illnesses. This study aimed to examine age-related differences in clinical characteristics of iGGS and describe its characteristics among very elderly individuals (≥80 years).

Methods

Fifty-four iGGS patients for whom detailed clinical information was available were identified from 2002 to 2014 in a tertiary care hospital in Japan. iGGS (n = 54) was compared with invasive Group A (iGAS; n = 17) and B streptococcal infection patients (iGBS; n = 52) based on patient age.

Results

The incidence of iGGS in our catchment area significantly increased during the study period. The prevalence of iGGS in the very elderly population was higher than that of iGAS or iGBS (p<0.001). Among iGGS patients, cardiovascular disease, chronic kidney disease, oxygen demand, and bacteremia with unknown focus of infection were more frequent in the very elderly population (p = 0.009, p = 0.02, p = 0.04, and p = 0.04, respectively). Altered mental status was present in half of iGGS patients aged ≥60 years (p = 0.03). In contrast, alcohol drinking and liver cirrhosis were significantly more frequent in patients with iGGS aged <60 years than in other age groups (p<0.001, p = 0.001, respectively). Levofloxacin resistance in GBS isolates was significantly more frequent among very elderly patients than among other age groups (p<0.001).

Conclusions

The burden of iGGS has been increasing in our catchment area. Different iGGS-associated clinical characteristics were found in each age group. Unclear and atypical clinical manifestations and syndromes were likely to be observed in very elderly patients. Alcohol drinking and liver cirrhosis may contribute to iGGS even in patients aged <60 years. Understanding these age-related differences could be helpful for optimal diagnosis and treatment.

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<![CDATA[Epidemiological and clinical features of invasive pneumococcal disease caused by serotype 12F in adults, Japan]]> https://www.researchpad.co/article/5c78501ad5eed0c484007c91

Enhanced surveillance of invasive pneumococcal disease (IPD) in adults was conducted during April 2013–March 2018 in 10 of 47 prefectures in Japan, and a total of 1277 IPD patients were enrolled. An emergence of IPD caused by serotype 12F was identified during May 2015–March 2018 through this surveillance. 12F isolates were composed of four related sequence types. In total, 120 patients with 12F IPD were reported during this period. To characterize the clinical features of 12F IPD, the disease characteristics of these patients were compared with those of 1157 patients with non-12F IPD. Compared with the non-12F IPD patients, a significantly lower proportion of 12F IPD patients was aged 65 years or older (55% vs. 70%), vaccinated with 23-valent pneumococcal polysaccharide (4% vs. 14%), had comorbid illness (65% vs. 77%), or were immunocompromised (19% vs. 30%; all P < 0.05). No significant difference in the proportion of case fatalities was found between the two groups. The proportions of those aged 65 years or older (53% vs. 69%) and with bacteremic pneumonia (35% vs. 69%) were significantly lower in 17 patients who died from 12F IPD than in 205 patients who died from non-12F IPD (all P < 0.05). Differences in clinical features were similarly found between 12F IPD patients and patients in low- or intermediate-level invasive potential serogroups. Our data demonstrated that serotype 12F was associated with IPD in younger adults and a lower proportion of comorbid illness, including immunocompromised conditions, in adult IPD, suggesting the high invasive potential of the serotype 12F. In addition, patients who died from 12F IPD were younger and had proportionately more bacteremia without focus. These findings may provide new insight into the pathogenesis of IPD in adults caused by 12F serotype with a high invasive potential.

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<![CDATA[Penicillin skin testing in methicillin-sensitive staphylococcus aureus bacteremia: A cost-effectiveness analysis]]> https://www.researchpad.co/article/5c3d0135d5eed0c48403937e

Background

Beta-lactams are the mainstay for treating methicillin-susceptible Staphylococcus aureus (MSSA) infections complicated by bacteremia due to superior outcomes compared with vancomycin. With approximately 11% of inpatients reporting a penicillin (PCN) allergy, many patients receive suboptimal treatment for MSSA bacteremia.

Objective

Evaluate the cost-effectiveness of penicillin skin testing (PST) in adult patients with self-reported PCN allergy in an inpatient setting undergoing treatment for MSSA bacteremia.

Methods

A decision analytic model was developed comparing an acute care PST intervention to a scenario with no confirmatory allergy testing. The primary outcome was the incremental cost-effectiveness ratio (ICER) from the health-sector perspective over a 1-year time horizon using quality-adjusted life years (QALYs) as the measure for effectiveness. One-way and probabilistic sensitivity analyses were conducted to assess the uncertainty of the ICER estimation.

Results

Over a 1-year time horizon, PST services applied to all MSSA bacteremia patients reporting a PCN-allergy would result in a cost per patient of $12,559 and 0.73 QALYs while no PST services would have a higher cost per patient of $13,219 and 0.66 QALYs per patient. This resulted in a cost-effectiveness estimate of -$9,429 per QALY gained. Varying the cost of implementing PST services determined a break-even point of $959.98 where any PST cost less than this amount would actually be cost saving.

Conclusions

Patients reporting a PCN allergy on admission may receive sub-optimal alternative therapies to beta-lactams, such as vancomycin, for MSSA bacteremia. This economic analysis demonstrates that inpatient PST services confirming PCN allergy are cost-effective for patients with MSSA bacteremia.

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<![CDATA[Time to positivity of blood cultures supports early re-evaluation of empiric broad-spectrum antimicrobial therapy]]> https://www.researchpad.co/article/5c3667ebd5eed0c4841a6940

Background

Blood cultures are considered the gold standard to distinguish bacteremia from non-bacteremic systemic inflammation. In current clinical practice, bacteraemia is considered unlikely if blood cultures have been negative for 48–72 hours. Modern BC systems have reduced this time-to-positivity (TTP), questioning whether the time frame of 48–72 hrs is still valid. This study investigates the distribution of TTP, the probability of blood culture positivity after 24 hours, and identifies clinical predictors of prolonged TTP.

Methods

Adult patients with monomicrobial bacteremia in an academic hospital were included retrospectively over a three-year period. Clinical data were retrieved from the medical records. Predictors of TTP >24 hours were determined by uni- and multivariate analyses. The residual probability of bacteremia was estimated for the scenario of negative BCs at 24 hours after bedside collection.

Results

The cohort consisted of 801 patients, accounting for 897 episodes of bacteremia. Mean age was 65 years (IQR 54–73), 534 (59.5%) patients were male. Median TTP was 15.7 (IQR 13.5–19.3) hours. TTP was ≤24 hours in 85.3% of episodes. Antibiotic pre-treatment (adjusted OR 1.77; 95%CI 1.14–2.74, p<0.01) was independently associated with prolonged TTP. The probability of bacteremia, if BC had remained negative for 24 hours, was 1.8% (95% CI 1.46–2.14).

Conclusion

With adequate hospital logistics, the probability of positive blood cultures after 24 hours of negative cultures was low. Combined with clinical reassessment, knowledge of this low probability may contribute to prioritization of the differential diagnosis and decisions on antimicrobial therapy. As a potential antibiotic stewardship tool, this strategy warrants further prospective investigation.

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<![CDATA[Cost-effectiveness of PCV13 vaccination in Belgian adults aged 65-84 years at elevated risk of pneumococcal infection]]> https://www.researchpad.co/article/5b4a28a3463d7e4513b89811

Background

The Belgian Superior Health Council (SHC) recently added a 13-valent pneumococcal conjugate vaccine (PCV13) to its recommendations for adult pneumococcal vaccination. This study addresses the policy question regarding whether a single dose of PCV13 should be reimbursed among Belgian adults aged 65–84 years with chronic comorbidities (“moderate-risk”) or immunosuppression (“high-risk”).

Methods

A cohort model was developed to project lifetime risks, consequences, and costs of invasive pneumococcal disease (IPD) and pneumococcal community-acquired pneumonia (CAP). Parameter values were estimated using published literature and available databases, and were reviewed by Belgian experts. PCV13 effectiveness was assumed to be durable during the first 5 years following receipt, and to progressively decline thereafter with 15 years protection. The Belgian National Health Insurance perspective was employed.

Results

Use of PCV13 (vs. no vaccine) in moderate/high-risk persons aged 65–84 years (n = 861,467; 58% vaccination coverage) would be expected to prevent 527 cases of IPD, 1,744 cases of pneumococcal CAP and 176 pneumococcal-related deaths, and reduce medical care costs by €20.1 million. Vaccination costs, however, would increase by €36.9 million and thus total overall costs would increase by €16.8 million. Cost per QALY gained was €17,126. In probabilistic sensitivity analyses, use of PCV13 was cost-effective in 97% of 1,000 simulations.

Conclusions

Reimbursement of PCV13 in moderate/high-risk Belgian adults aged 65–84 years would be cost-effective from the Belgian healthcare perspective.

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<![CDATA[Etiology of Severe Non-malaria Febrile Illness in Northern Tanzania: A Prospective Cohort Study]]> https://www.researchpad.co/article/5989da15ab0ee8fa60b7adaa

Introduction

The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes.

Methods and Findings

We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis.

Conclusions

Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts.

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<![CDATA[Fatal Outcome in Bacteremia is Characterized by High Plasma Cell Free DNA Concentration and Apoptotic DNA Fragmentation: A Prospective Cohort Study]]> https://www.researchpad.co/article/5989da27ab0ee8fa60b813a1

Introduction

Recent studies have shown that apoptosis plays a critical role in the pathogenesis of sepsis. High plasma cell free DNA (cf-DNA) concentrations have been shown to be associated with sepsis outcome. The origin of cf-DNA is unclear.

Methods

Total plasma cf-DNA was quantified directly in plasma and the amplifiable cf-DNA assessed using quantitative PCR in 132 patients with bacteremia caused by Staphylococcus aureus, Streptococcus pneumoniae, ß-hemolytic streptococcae or Escherichia coli. The quality of cf-DNA was analyzed with a DNA Chip assay performed on 8 survivors and 8 nonsurvivors. Values were measured on days 1–4 after positive blood culture, on day 5–17 and on recovery.

Results

The maximum cf-DNA values on days 1–4 (n = 132) were markedly higher in nonsurvivors compared to survivors (2.03 vs 1.26 ug/ml, p<0.001) and the AUCROC in the prediction of case fatality was 0.81 (95% CI 0.69–0.94). cf-DNA at a cut-off level of 1.52 ug/ml showed 83% sensitivity and 79% specificity for fatal disease. High cf-DNA (>1.52 ug/ml) remained an independent risk factor for case fatality in a logistic regression model. Qualitative analysis of cf-DNA showed that cf-DNA displayed a predominating low-molecular-weight cf-DNA band (150–200 bp) in nonsurvivors, corresponding to the size of the apoptotic nucleosomal DNA. cf-DNA concentration showed a significant positive correlation with visually graded apoptotic band intensity (R = 0.822, p<0.001).

Conclusions

Plasma cf-DNA concentration proved to be a specific independent prognostic biomarker in bacteremia. cf-DNA displayed a predominating low-molecular-weight cf-DNA band in nonsurvivors corresponding to the size of apoptotic nucleosomal DNA.

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<![CDATA[Effectiveness and Limitations of Hand Hygiene Promotion on Decreasing Healthcare–Associated Infections]]> https://www.researchpad.co/article/5989da16ab0ee8fa60b7b621

Background

Limited data describe the sustained impact of hand hygiene programs (HHPs) implemented in teaching hospitals, where the burden of healthcare-associated infections (HAIs) is high. We use a quasi-experimental, before and after, study design with prospective hospital-wide surveillance of HAIs to assess the cost effectiveness of HHPs.

Methods and Findings

A 4-year hospital-wide HHP, with particular emphasis on using an alcohol-based hand rub, was implemented in April 2004 at a 2,200-bed teaching hospital in Taiwan. Compliance was measured by direct observation and the use of hand rub products. Poisson regression analyses were employed to evaluate the densities and trends of HAIs during the preintervention (January 1999 to March 2004) and intervention (April 2004 to December 2007) periods. The economic impact was estimated based on a case-control study in Taiwan. We observed 8,420 opportunities for hand hygiene during the study period. Compliance improved from 43.3% in April 2004 to 95.6% in 2007 (p<.001), and was closely correlated with increased consumption of the alcohol-based hand rub (r = 0.9399). The disease severity score (Charlson comorbidity index) increased (p = .002) during the intervention period. Nevertheless, we observed an 8.9% decrease in HAIs and a decline in the occurrence of bloodstream, methicillin-resistant Staphylococcus aureus, extensively drug-resistant Acinetobacter baumannii, and intensive care unit infections. The intervention had no discernable impact on HAI rates in the hematology/oncology wards. The net benefit of the HHP was US$5,289,364, and the benefit-cost ratio was 23.7 with a 3% discount rate.

Conclusions

Implementation of a HHP reduces preventable HAIs and is cost effective.

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<![CDATA[Predictive Value of C-Reactive Protein (CRP) in Identifying Fatal Outcome and Deep Infections in Staphylococcus aureus Bacteremia]]> https://www.researchpad.co/article/5989da6bab0ee8fa60b92db9

Introduction

Clear cut-off levels could aid clinicians in identifying patients with a risk of fatal outcomes or complications such as deep infection foci in Staphylococcus aureus bacteremia (SAB). Cut-off levels for widely used clinical follow-up parameters including serum C-reactive protein (CRP) levels and white blood cell counts (WBC) have not been previously studied.

Methods

430 adult SAB patients in Finland took part in prospective multicentre study in which their CRP levels and WBC counts were measured on the day of the positive blood culture, every other day during the first week, twice a week during hospitalization and at 30 days. Receiver operating characteristic (ROC) analysis was used to evaluate the prognostic value of CRP and WBC on the day of the positive blood culture and at days 4, 7, and 14 in predicting mortality and the presence of deep infections at 30 days. Adjusted hazard ratios (HR) for CRP level and WBC count cut-off values for mortality were calculated by the Cox regression analysis and adjusted odds ratios (OR) for cut-off values to predict the presence of deep infection by the binary logistic regression analysis.

Results

The succumbing patients could be distinguished from the survivors, starting on day 4 after the positive blood culture, by higher CRP levels. Cut-off values of CRP for day 30 mortality in adjusted analysis, that significantly predicted fatal outcome were at day 4 CRP >103 mg/L with sensitivity of 77%, specificity of 55%, and HR of 3.5 (95% CI, 1.2–10.3; p = 0.024), at day 14 CRP >61 mg/L with a sensitivity of 82%, specificity of 80% and HR of 3.6 (95% CI, 1.1–10.3; p<0.039) and cut-off value of WBC at day 14 >8.6 x109/L was prognostic with sensitivity of 77%, specificity of 78% and HR of 8.2 (95% CI, 2.9–23.1; p<0.0001). Cut-off values for deep infection in adjusted analysis were on the day of the positive blood culture CRP >108 mg/L with sensitivity of 77%, specificity of 60%, and HR of 2.6 (95% CI, 1.3–4.9; p = 0.005) and at day 14 CRP >22 mg/L with sensitivity of 59%, specificity of 68%, and HR of 3.9 (95% CI, 1.6–9.5; p = 0.003). The lack of decline of CRP in 14 days or during the second week were neither prognostic nor markers of deep infection focus.

Conclusions

CRP levels have potential for the early identification of SAB patients with a greater risk for death and deep infections.

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<![CDATA[Molecular epidemiology of Staphylococcus aureus bacteremia in a single large Minnesota medical center in 2015 as assessed using MLST, core genome MLST and spa typing]]> https://www.researchpad.co/article/5989db5cab0ee8fa60be02c2

Staphylococcus aureus is a leading cause of bacteremia in hospitalized patients. Whether or not S. aureus bacteremia (SAB) is associated with clonality, implicating potential nosocomial transmission, has not, however, been investigated. Herein, we examined the epidemiology of SAB using whole genome sequencing (WGS). 152 SAB isolates collected over the course of 2015 at a single large Minnesota medical center were studied. Staphylococcus protein A (spa) typing was performed by PCR/Sanger sequencing; multilocus sequence typing (MLST) and core genome MLST (cgMLST) were determined by WGS. Forty-eight isolates (32%) were methicillin–resistant S. aureus (MRSA). The isolates encompassed 66 spa types, clustered into 11 spa clonal complexes (CCs) and 10 singleton types. 88% of 48 MRSA isolates belonged to spa CC-002 or -008. Methicillin-susceptible S. aureus (MSSA) isolates were more genotypically diverse, with 61% distributed across four spa CCs (CC-002, CC-012, CC-008 and CC-084). By MLST, there was 31 sequence types (STs), including 18 divided into 6 CCs and 13 singleton STs. Amongst MSSA isolates, the common MLST clones were CC5 (23%), CC30 (19%), CC8 (15%) and CC15 (11%). Common MRSA clones were CC5 (67%) and CC8 (25%); there were no MRSA isolates in CC45 or CC30. By cgMLST analysis, there were 9 allelic differences between two isolates, with the remaining 150 isolates differing from each other by over 40 alleles. The two isolates were retroactively epidemiologically linked by medical record review. Overall, cgMLST analysis resulted in higher resolution epidemiological typing than did multilocus sequence or spa typing.

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<![CDATA[Azithromycin and Ciprofloxacin Resistance in Salmonella Bloodstream Infections in Cambodian Adults]]> https://www.researchpad.co/article/5989d9d2ab0ee8fa60b64ab0

Background

Salmonella enterica is a frequent cause of bloodstream infection (BSI) in Asia but few data are available from Cambodia. We describe Salmonella BSI isolates recovered from patients presenting at Sihanouk Hospital Centre of Hope, Phnom Penh, Cambodia (July 2007–December 2010).

Methodology

Blood was cultured as part of a microbiological prospective surveillance study. Identification of Salmonella isolates was performed by conventional methods and serotyping. Antibiotic susceptibilities were assessed using disk diffusion, MicroScan and E-test macromethod. Clonal relationships were assessed by Pulsed Field Gel Electrophoresis; PCR and sequencing for detection of mutations in Gyrase and Topoisomerase IV and presence of qnr genes.

Principal Findings

Seventy-two Salmonella isolates grew from 58 patients (mean age 34.2 years, range 8–71). Twenty isolates were identified as Salmonella Typhi, 2 as Salmonella Paratyphi A, 37 as Salmonella Choleraesuis and 13 as other non-typhoid Salmonella spp. Infection with human immunodeficiency virus (HIV) was present in 21 of 24 (87.5%) patients with S. Choleraesuis BSI. Five patients (8.7%) had at least one recurrent infection, all with S. Choleraesuis; five patients died. Overall, multi drug resistance (i.e., co-resistance to ampicillin, sulphamethoxazole-trimethoprim and chloramphenicol) was high (42/59 isolates, 71.2%). S. Typhi displayed high rates of decreased ciprofloxacin susceptibility (18/20 isolates, 90.0%), while azithromycin resistance was very common in S. Choleraesuis (17/24 isolates, 70.8%). Two S. Choleraesuis isolates were extended spectrum beta-lactamase producer.

Conclusions and Significance

Resistance rates in Salmonella spp. in Cambodia are alarming, in particular for azithromycin and ciprofloxacin. This warrants nationwide surveillance and revision of treatment guidelines.

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<![CDATA[Infectious Complications during Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Children with High-Risk or Recurrent Solid Tumors]]> https://www.researchpad.co/article/5989da3aab0ee8fa60b879f5

We retrospectively analyzed infectious complications during tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in children and adolescents with high-risk or recurrent solid tumors. A total of 324 patients underwent their first HDCT/auto-SCT between October 2004 and September 2014, and 283 of them proceeded to their second HDCT/auto-SCT (a total of 607 HDCT/auto-SCTs). During the early transplant period of 607 HDCT/auto-SCTs (from the beginning of HDCT to day 30 post-transplant), bacteremia, urinary tract infection (UTI), respiratory virus infection, and varicella zoster virus (VZV) reactivation occurred in 7.1%, 2.3%, 13.0%, and 2.5% of HDCT/auto-SCTs, respectively. The early transplant period of the second HDCT/auto-SCT had infectious complications similar to the first HDCT/auto-SCT. During the late transplant period of HDCT/auto-SCT (from day 31 to 1 year post-transplant), bacteremia, UTI, and VZV reactivation occurred in 7.5%, 2.5%, and 3.9% of patients, respectively. Most infectious complications in the late transplant period occurred during the first 6 months post-transplant. There were no invasive fungal infections during the study period. Six patients died from infectious complications (4 from bacterial sepsis and 2 from respiratory virus infection). Our study suggests that infectious complications are similar following second and first HDCT/auto-SCT in children.

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<![CDATA[The Forgotten Role of Alcohol: A Systematic Review and Meta-Analysis of the Clinical Efficacy and Perceived Role of Chlorhexidine in Skin Antisepsis]]> https://www.researchpad.co/article/5989da8aab0ee8fa60b9d85a

Background

Skin antisepsis is a simple and effective measure to prevent infections. The efficacy of chlorhexidine is actively discussed in the literature on skin antisepsis. However, study outcomes due to chlorhexidine-alcohol combinations are often attributed to chlorhexidine alone. Thus, we sought to review the efficacy of chlorhexidine for skin antisepsis and the extent of a possible misinterpretation of evidence.

Methods

We performed a systematic literature review of clinical trials and systematic reviews investigating chlorhexidine compounds for blood culture collection, vascular catheter insertion and surgical skin preparation. We searched PubMed, CINAHL, the Cochrane Library, the Agency for Healthcare Research and Quality website, several clinical trials registries and a manufacturer website. We extracted data on study design, antiseptic composition, and the following outcomes: blood culture contamination, catheter colonisation, catheter-related bloodstream infection and surgical site infection. We conducted meta-analyses of the clinical efficacy of chlorhexidine compounds and reviewed the appropriateness of the authors′ attribution.

Results

In all three application areas and for all outcomes, we found good evidence favouring chlorhexidine-alcohol over aqueous competitors, but not over competitors combined with alcohols. For blood cultures and surgery, we found no evidence supporting chlorhexidine alone. For catheters, we found evidence in support of chlorhexidine alone for preventing catheter colonisation, but not for preventing bloodstream infection. A range of 29 to 43% of articles attributed outcomes solely to chlorhexidine when the combination with alcohol was in fact used. Articles with ambiguous attribution were common (8–35%). Unsubstantiated recommendations for chlorhexidine alone instead of chlorhexidine-alcohol were identified in several practice recommendations and evidence-based guidelines.

Conclusions

Perceived efficacy of chlorhexidine is often in fact based on evidence for the efficacy of the chlorhexidine-alcohol combination. The role of alcohol has frequently been overlooked in evidence assessments. This has broader implications for knowledge translation as well as potential implications for patient safety.

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<![CDATA[Evaluation of High-Throughput PCR and Microarray-Based Assay in Conjunction with Automated DNA Extraction Instruments for Diagnosis of Sepsis]]> https://www.researchpad.co/article/5989db27ab0ee8fa60bd0745

Background

High incidence of septic patients increases the pressure of faster and more reliable bacterial identification methods to adapt patient management towards focused and effective treatment options. The aim of this study was to assess two automated DNA extraction solutions with the PCR and microarray-based assay to enable rapid and reliable detection and speciation of causative agents in the diagnosis of sepsis.

Methodology/Principal Findings

We evaluated two automated DNA instruments NucliSENS® easyMAG® and NorDiag Arrow for the preparation of blood culture samples. A set of 91 samples flagged as positive during incubation was analyzed prospectively with the high-throughput generation of Prove-it™ Sepsis assay designed to identify over 60 Gram-negative and Gram-positive bacterial species as well as methicillin resistance marker from a blood culture. Bacterial findings were accurately reported from 77 blood culture samples, whereas 14 samples were reported as negative, containing bacteria not belonging to the pathogen panel of the assay. No difference was observed between the performance of NorDiag Arrow or NucliSENS® easyMAG® with regard to the result reporting of Prove-it™ Sepsis. In addition, we also assessed the quality and quantity of DNA extracted from the clinical Escherichia coli isolate with DNA extraction instruments. We observed only minor differences between the two instruments.

Conclusions

Use of automated and standardized sample preparation methods together with rapid, multiplex pathogen detection offers a strategy to speed up reliably the diagnostics of septic patients. Both tested DNA extraction devices were shown to be feasible for blood culture samples and the Prove-it™ Sepsis assay, providing an accurate identification of pathogen within 4,5 hours when the detected pathogen was in the repertoire of the test.

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<![CDATA[Ultra-Fast and Sensitive Detection of Non-Typhoidal Salmonella Using Microwave-Accelerated Metal-Enhanced Fluorescence (“MAMEF”)]]> https://www.researchpad.co/article/5989db30ab0ee8fa60bd1f35

Certain serovars of Salmonella enterica subsp. enterica cause invasive disease (e.g., enteric fever, bacteremia, septicemia, meningitis, etc.) in humans and constitute a global public health problem. A rapid, sensitive diagnostic test is needed to allow prompt initiation of therapy in individual patients and for measuring disease burden at the population level. An innovative and promising new rapid diagnostic technique is microwave-accelerated metal-enhanced fluorescence (MAMEF). We have adapted this assay platform to detect the chromosomal oriC locus common to all Salmonella enterica subsp. enterica serovars. We have shown efficient lysis of biologically relevant concentrations of Salmonella spp. suspended in bacteriological media using microwave-induced lysis. Following lysis and DNA release, as little as 1 CFU of Salmonella in 1 ml of medium can be detected in <30 seconds. Furthermore the assay is sensitive and specific: it can detect oriC from Salmonella serovars Typhi, Paratyphi A, Paratyphi B, Paratyphi C, Typhimurium, Enteritidis and Choleraesuis but does not detect Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Streptococcus pneumoniae, Haemophilus influenzae or Acinetobacter baumanii. We have also performed preliminary experiments using a synthetic Salmonella oriC oligonucleotide suspended in whole human blood and observed rapid detection when the sample was diluted 1∶1 with PBS. These pre-clinical data encourage progress to the next step to detect Salmonella in blood (and other ordinarily sterile, clinically relevant body fluids).

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<![CDATA[Cross Border Comparison of MRSA Bacteraemia between The Netherlands and North Rhine-Westphalia (Germany): A Cross-Sectional Study]]> https://www.researchpad.co/article/5989da26ab0ee8fa60b80929

Background

We describe the impact of methicillin-resistant Staphylococcus aureus (MRSA) in two neighbouring regions in Europe with a comparable population size, North Rhine-Westphalia (NRW) in Germany and the Netherlands.

Methodology/Principal Findings

We compared the occurrence of MRSA in blood cultures from surveillance systems. In the Netherlands in 2009, 14 of 1,510 (0.9%) Staphylococcus aureus bacteraemia episodes under surveillance were MRSA. Extrapolation using the number of clinical admissions results in a total of 29 MRSA bacteraemia episodes in the Netherlands or 1.8 episodes per 1,000,000 inhabitants. In 2010 in NRW, 1,029 MRSA bacteraemias were reported, resulting in 57.6 episodes of MRSA bacteraemia per 1,000,000 inhabitants: a 32-fold higher incidence than in the Netherlands.

Conclusion/Significance

Based on an estimated attributable mortality of 15%, the Dutch approach would save approximately 150 lives per year by the prevention of bacteraemia only.

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<![CDATA[Protective and Pathogenic Roles of CD8+ T Lymphocytes in Murine Orientia tsutsugamushi Infection]]> https://www.researchpad.co/article/5989dacaab0ee8fa60bb3fc8

T cells are known to contribute to immune protection against scrub typhus, a potentially fatal infection caused by the obligate intracellular bacterium Orientia (O.) tsutsugamushi. However, the contribution of CD8+ T cells to protection and pathogenesis during O. tsutsugamushi infection is still unknown. Using our recently developed BALB/c mouse model that is based on footpad inoculation of the human-pathogenic Karp strain, we show that activated CD8+ T cells infiltrate spleen and lung during the third week of infection. Depletion of CD8+ T cells with monoclonal antibodies resulted in uncontrolled pathogen growth and mortality. Adoptive transfer of CD8+ T cells from infected animals protected naïve BALB/c mice from lethal outcome of intraperitoneal challenge. In C57Bl/6 mice, the pulmonary lymphocyte compartment showed an increased percentage of CD8+ T cells for at least 135 days post O. tsutsugamushi infection. Depletion of CD8+ T cells at 84 days post infection caused reactivation of bacterial growth. In CD8+ T cell-deficient beta 2-microglobulin knockout mice, bacterial replication was uncontrolled, and all mice succumbed to the infection, despite higher serum IFN-γ levels and stronger macrophage responses in liver and lung. Moreover, we show that CD8+ T cells but not NKT cells were required for hepatocyte injury: elevated concentrations of serum alanine aminotransferase and infection-induced subcapsular necrotic liver lesions surrounded by macrophages were found in C57Bl/6 and CD1d-deficient mice, but not in beta 2-microglobulin knockout mice. In the lungs, peribronchial macrophage infiltrations also depended on CD8+ T cells. In summary, our results demonstrate that CD8+ T cells restrict growth of O. tsutsugamushi during acute and persistent infection, and are required to protect from lethal infections in BALB/c and C57BL/6 mice. However, they also elicit specific pathologic tissue lesions in liver and lung.

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<![CDATA[Antibiotic Susceptibility Testing of Grown Blood Cultures by Combining Culture and Real-Time Polymerase Chain Reaction Is Rapid and Effective]]> https://www.researchpad.co/article/5989dae9ab0ee8fa60bbe75f

Background

Early administration of appropriate antibiotic therapy in bacteraemia patients dramatically reduces mortality. A new method for RApid Molecular Antibiotic Susceptibility Testing (RAMAST) that can be applied directly to positive blood cultures was developed and evaluated.

Methodology/Principal Findings

Growth curves and antibiotic susceptibility of blood culture isolates (Staphylococcus aureus, enterococci and (facultative) aerobic Gram-negative rods) were determined by incubating diluted blood cultures with and without antibiotics, followed by a quantitative universal 16S PCR to detect the presence or absence of growth. Testing 114 positive blood cultures, RAMAST showed an agreement with microbroth dilution of 96.7% for Gram-negative rods, with a minor error (false-susceptibility with a intermediate resistant strain) rate of 1.9%, a major error (false resistance) rate of 0.8% and a very major error (false susceptibility) rate of 0.6%. Agreement for S.aureus was 97.9%, with a very major error rate of 2.1%. Enterococcus species showed 95.0% agreement, with a major error rate of 5.0%. These agreements are comparable with those of the Phoenix system. Starting from a positive blood culture, the test was completed within 9 hours.

Conclusions/Significance

This new rapid method for antibiotic susceptibility testing can potentially provide accurate results for most relevant bacteria commonly isolated from positive blood cultures in less time than routine methods.

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<![CDATA[Burden of Pneumonia and Meningitis Caused by Streptococcus pneumoniae in China among Children under 5 Years of Age: A Systematic Literature Review]]> https://www.researchpad.co/article/5989da5dab0ee8fa60b905bd

Background and Methods

To understand the burden and epidemiology of Streptococcus pneumoniae disease among children between 1 and 59 months of age in China, we conducted a review of literature published between 1980 and 2008 applying standardized algorithms. Because of the absence of population-based surveillance for pneumococcal disease (PD), we identified all-cause pneumonia, bacteremia and meningitis burden, syndromes most commonly associated with S. pneumoniae, and applied the proportion of disease attributable to S. pneumoniae from studies that determined the etiology of these three syndromes to calculate PD burden. Because of the microbiologic difficulties in identifying S. pneumoniae–attributable pneumonia which likely underestimates the pneumonia burden, we also used the proportion obtained from vaccine efficacy trials.

Results

Between 1980 and 2008, there were 12,815 cases/100,000/year of all-cause pneumonia among children between 1 month and 59 months, with 526 deaths/100,000 annually. There were 14 meningitis cases/100,000/year. We estimate that as of 2000, there were 260,768 (113,000 to 582,382) and 902 (114–4,463) cases of pneumococcal pneumonia and meningitis, respectively with 10,703 (4,638–23,904) and 75 (9–370) pneumococcal pneumonia and meningitis deaths, respectively. Pneumococcal pneumonia cases and deaths were more than two-fold higher, 695,382 (173,845–1,216,918) and 28,542 (7,136–49,949), respectively, when parameters from efficacy trials were used. Serotypes 19F, 19A and 14 were the most common serotypes obtained from pneumonia/meningitis patients. Currently available vaccines are expected to cover 79.5% to 88.4% of the prevalent serotypes. With high antibiotic resistance, introducing pneumococcal vaccines to the routine immunization program should be considered in China. Population-based studies are warranted.

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