ResearchPad - nosocomial-infections https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Within-patient plasmid dynamics in <i>Klebsiella pneumoniae</i> during an outbreak of a carbapenemase-producing <i>Klebsiella pneumoniae</i>]]> https://www.researchpad.co/article/elastic_article_15752 Knowledge of within-patient dynamics of resistance plasmids during outbreaks is important for understanding the persistence and transmission of plasmid-mediated antimicrobial resistance. During an outbreak of a Klebsiella pneumoniae carbapenemase-producing (KPC) K. pneumoniae, the plasmid and chromosomal dynamics of K. pneumoniae within-patients were investigated.MethodsDuring the outbreak, all K. pneumoniae isolates of colonized or infected patients were collected, regardless of their susceptibility pattern. A selection of isolates was short-read and long-read sequenced. A hybrid assembly of the short-and long-read sequence data was performed. Plasmid contigs were extracted from the hybrid assembly, annotated, and within patient plasmid comparisons were performed.ResultsFifteen K. pneumoniae isolates of six patients were short-read whole-genome sequenced. Whole-genome multi-locus sequence typing revealed a maximum of 4 allele differences between the sequenced isolates. Within patients 1 and 2 the resistance gene- and plasmid replicon-content did differ between the isolates sequenced. Long-read sequencing and hybrid assembly of 4 isolates revealed loss of the entire KPC-gene containing plasmid in the isolates of patient 2 and a recombination event between the plasmids in the isolates of patient 1. This resulted in two different KPC-gene containing plasmids being simultaneously present during the outbreak.ConclusionDuring a hospital outbreak of a KPC-producing K. pneumoniae isolate, plasmid loss of the KPC-gene carrying plasmid and plasmid recombination was detected within the isolates from two patients. When investigating outbreaks, one should be aware that plasmid transmission can occur and the possibility of within- and between-patient plasmid variation needs to be considered. ]]> <![CDATA[Increased financial burdens and lengths of stay in patients with healthcare-associated infections due to multidrug-resistant bacteria in intensive care units: A propensity-matched case-control study]]> https://www.researchpad.co/article/elastic_article_15718 Incidence rates of healthcare-associated infections (HAIs) depend upon infection control policy and practices, and the effectiveness of the implementation of antibiotic stewardship. Amongst intensive care unit (ICU) patients with HAIs, a substantial number of pathogens were reported to be multidrug-resistant bacteria (MDRB). However, impacts of ICU HAIs due to MDRB (MDRB-HAIs) remain understudied. Our study aimed to evaluate the negative impacts of MRDB-HAIs versus HAIs due to non-MDRB (non-MRDB-HAIs).MethodsAmong 60,317 adult patients admitted at ICUs of a 2680-bed medical centre in Taiwan between January 2010 and December 2017, 279 pairs of propensity-score matched MRDB-HAI and non-MRDB-HAI were analyzed.Principal findingsBetween the MDRB-HAI group and the non-MDRB-HAI group, significant differences were found in overall hospital costs, costs of medical and nursing services, medication, and rooms/beds, and in ICU length-of-stay (LOS). As compared with the non-MDRB-HAI group, the mean of the overall hospital costs of patients in the MDRB-HAI group was increased by 26%; for categorized expenditures, the mean of costs of medical and nursing services of patients in the MDRB-HAI group was increased by 8%, of medication by 26.9%, of rooms/beds by 10.3%. The mean ICU LOS in the MDRB-HAI group was increased by 13%. Mortality rates in both groups did not significantly differ.ConclusionsThese data clearly demonstrate more negative impacts of MDRB-HAIs in ICUs. The quantified financial burdens will be helpful for hospital/government policymakers in allocating resources to mitigate MDRB-HAIs in ICUs; in case of need for clarification/verification of the medico-economic burdens of MDRB-HAIs in different healthcare systems, this study provides a model to facilitate the evaluations. ]]> <![CDATA[Nosocomial transmission of extensively drug resistant Acinetobacter baumannii strains in a tertiary level hospital]]> https://www.researchpad.co/article/N9f3b656c-39ce-49ef-bced-db8369f1110d

Acinetobacter baumannii is an opportunistic infectious agent that affects primarily immunocompromised individuals. A. baumannii is highly prevalent in hospital settings being commonly associated with nosocomial transmission and drug resistance. Here, we report the identification and genetic characterization of A. baumannii strains among patients in a tertiary level hospital in Mexico. Whole genome sequencing analysis was performed to establish their genetic relationship and drug resistance mutations profile. Ten genetically different, extensively drug resistant strains were identified circulating among seven wards. The genetic profiles showed resistance primarily against aminoglycosides and beta-lactam antibiotics. Importantly, no mutants conferring resistance to colistin were observed. The results highlight the importance of implementing robust classification schemes for advanced genetic characterization of A. baumannii clinical isolates and simultaneous detection of drug resistance markers for adequate patient’s management in clinical settings.

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<![CDATA[The burden of Staphylococcus aureus among Native Americans on the Navajo Nation]]> https://www.researchpad.co/article/5c8823e9d5eed0c4846392b2

Introduction

Native Americans in the southwestern United States have a higher risk for many infectious diseases and may be at higher risk for Staphylococcus aureus due to the high prevalence of risk factors for S. aureus. Recent data on invasive S. aureus infections among Native Americans are limited.

Methods

Active population- and laboratory-based surveillance was conducted in 2016–2017 on the Navajo Nation to document the rate of invasive S. aureus. A case of invasive S.aureus infection was defined as a Native American individual with S. aureus isolated from a normally sterile body site whose reported community of residence was on or around the Navajo Nation.

Results

One hundred and fifty-nine cases of invasive S. aureus from 152 individuals were identified. The median age of cases was 56.3 years and 35% were female. Thirty-five percent of cases had community-acquired infections. Ninety-three percent of cases had underlying medical conditions, including diabetes (60%) and obesity (42%), 28% of cases had a documented prior S. aureus infection, and 33% were infected with methicillin-resistant S. aureus. The annual incidence of invasive S. aureus and of invasive methicillin-resistant S. aureus was 64.9/100,000 persons and 21.2/100,000 persons, respectively.

Conclusions

This community has a high burden of invasive S. aureus infections. Further research is needed to identify prevention strategies and opportunities for intervention.

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<![CDATA[Evidence of transmission of Clostridium difficile in asymptomatic patients following admission screening in a tertiary care hospital]]> https://www.researchpad.co/article/5c6b262bd5eed0c4842894b4

Background

Clostridium difficile (CD) is the leading cause of infectious health-care associated diarrhea. However, little is known regarding CD carriage and transmission amongst asymptomatic colonizers. We evaluated carriage, characterized strains and examined epidemiologic linkages in asymptomatic colonized CD patients.

Methods

Rectal swabs from asymptomatic patients admitted to the general medicine ward from April 1-June 30 2012 were collected. PCR-confirmed CD colonies were ribotyped and characterized by Modified-Multi Locus Variable Number Tandem Repeat Analysis (MMLVA).

Results

1549-swabs were collected from 474-patients. Overall, 50/474(10.6%) were CD PCR-positive, 24/50 were colonized at admission, while 26/50 were first identified > = 72 hours after admission. Amongst the 50 CD PCR-positive patients, 90% were asymptomatically colonized and 80% of individuals carried toxigenic CD-strains, including ribotype-027 (5/45:11%). MMLVA revealed five-clusters involving 15-patients harboring toxigenic (4/5) and non-toxigenic CD strains (1/5). In two clusters, patients were CD positive on admission while in the other three clusters involving 10 patients, we observed CD transmission from asymptomatically colonized patients to 8 previously CD-negative patients.

Conclusions

We identified increasing rates of colonization during admission to medical wards. MMLVA typing effectively discriminated between strains and suggests that 20% of patients with CD colonization acquired their strain(s) from asymptomatically colonized individuals in hospital.

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<![CDATA[Assessment of displacement ventilation systems in airborne infection risk in hospital rooms]]> https://www.researchpad.co/article/5c5b5260d5eed0c4842bc715

Efficient ventilation in hospital airborne isolation rooms is important vis-à-vis decreasing the risk of cross infection and reducing energy consumption. This paper analyses the suitability of using a displacement ventilation strategy in airborne infection isolation rooms, focusing on health care worker exposure to pathogens exhaled by infected patients. The analysis is mainly based on numerical simulation results obtained with the support of a 3-D transient numerical model validated using experimental data. A thermal breathing manikin lying on a bed represents the source patient and another thermal breathing manikin represents the exposed individual standing beside the bed and facing the patient. A radiant wall represents an external wall exposed to solar radiation. The air change efficiency index and contaminant removal effectiveness indices and inhalation by the health care worker of contaminants exhaled by the patient are considered in a typical airborne infection isolation room set up with three air renewal rates (6 h-1, 9 h-1 and 12 h-1), two exhaust opening positions and two health care worker positions. Results show that the radiant wall significantly affects the air flow pattern and contaminant dispersion. The lockup phenomenon occurs at the inhalation height of the standing manikin. Displacement ventilation renews the air of the airborne isolation room and eliminates the exhaled pollutants efficiently, but is at a disadvantage compared to other ventilation strategies when the risk of exposure is taken into account.

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<![CDATA[ESBL colonization and acquisition in a hospital population: The molecular epidemiology and transmission of resistance genes]]> https://www.researchpad.co/article/5c466564d5eed0c484518ef0

A prospective cohort study (German Clinical Trial Registry, No. 00005273) was performed to determine pre-admission colonization rates, hospital acquisition risk factors, subsequent infection rates and colonization persistence including the respective molecular epidemiology and transmission rates of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (EPE). A total of 342 EPEs were isolated from rectal swabs of 1,334 patients on admission, at discharge and 6 months after hospitalization. Inclusion criteria were patients’ age > 18 years, expected length of stays > 48 hours, external referral. The EPEs were characterized by routine microbiological methods, a DNA microarray and ERIC-PCR. EPE colonization was found in 12.7 % of admitted patients, with the highest rate (23.8 %) in patients from nursing homes. During hospitalization, 8.1 % of the patients were de novo EPE colonized, and invasive procedures, antibiotic and antacid therapies were independent risk factors. Only 1/169 patients colonized on admission developed a hospital-acquired EPE infection. Escherichia coli was the predominant EPE (88.9 %), and 92.1% of the ESBL phenotypes could be related to CTX-M variants with CTX-M-1/15 group being most frequent (88.9%). A corresponding β-lactamase could not be identified in five isolates. Hospital-acquired EPE infections in patients colonized before or during hospitalization were rare. The diversity of the EPE strains was much higher than that of the underlying plasmids. In seven patients, transmission of the respective plasmid across different species could be observed indicating that the current strain-based surveillance approaches may underestimate the risk of inter-species transmission of resistance genes.

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<![CDATA[Length of stay following vaginal deliveries: A population based study in the Friuli Venezia Giulia region (North-Eastern Italy), 2005-2015]]> https://www.researchpad.co/article/5c37b7c6d5eed0c484490c88

Background

Lengths of hospital stay (LoS) after childbirth that are too long have a number of health, social and economic drawbacks. For this reason, in several high-income countries LoS has been reduced over the past decades and early discharge (ED) is increasingly applied to low-risk mothers and newborns.

Methods

We conducted a population-based study investigating LoS after chilbirth across all 12 maternity centres of Friuli Venezia-Giulia (FVG), North-Eastern Italy, using a database capturing all registered births in the region from 2005 to 2015 (11 years). Adjusting for clinical factors (clinical conditions of the mother and the newborn), socio-demographic bakground and obstetric history with multivariable logistic regression, we ranked facility centres for LoS that were longer than our proposed ED benchmarks (defined as >2 days for spontaneous vaginal deliveries and >3 days for instrumental vaginal deliveries). The reference was hospital A, a national excellence centre for maternal and child health.

Results

The total number of births examined in our database was 109,550, of which 109,257 occurred in hospitals. During these 11 years, the number of births significantly diminished over time, and the pooled mean LoS for spontaneous vaginal deliveries in the whole FVG was 2.9 days. There was a significantly decreasing trend in the proportion of women remaining admitted more than the respective ED cutoffs for both delivery modes. The percentage of women staying longer that the ED benchmarks varied extensively by facility centre, ranging from 32% to 97% for spontaneous vaginal deliveries and 15% to 64% for instrumental vaginal deliveries. All hospitals but G were by far more likely to surpass the ED cutoff for spontaneous deliveries. As compared with hospital A, the most significant adjusted ORs for LoS overcoming the ED thresholds for spontaneous vaginal deliveries were: 89.38 (78.49–101.78); 26.47 (22.35–31.36); 10.42 (9.49–11.44); 10.30 (9.45–11.21) and 8.40 (7.68–9.19) for centres B, D, I, K and E respectively. By contrast the OR was 0.77 (95%CI: 0.72–0.83) for centre G. Similar mitigated patterns were observed also for instrumental vaginal deliveiries.

Conclusions

For spontaneous vaginal deliveries the mean LoS in the whole FVG was shorter than 3.4 days, the average figure most recently reported for the whole of Italy, but higher than other countries’ with health systems similar to Italy’s. Since our results are controlled for the effect of all other factors, the between-hospital variability we found is likely attributable to the health care provider itself. It can be argued that some maternity centres of FVG may have had ecocomic interest in longer LoS after childbirth, although fear of medico-legal backlashes, internal organizational malfunctions of hospitals and scarce attention of ward staff on performance efficiency shall not be ruled out. It would be therefore important to ensure higher level of coordination between the various maternity services of FVG, which should follow standardized protocols to pursue efficiency of care and allow comparability of health outcomes and costs among them. Improving the performance of FVG and Italian hospitals requires investment in primary care services.

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<![CDATA[Evolution and mutations predisposing to daptomycin resistance in vancomycin-resistant Enterococcus faecium ST736 strains]]> https://www.researchpad.co/article/5c26972bd5eed0c48470ecf7

We recently identified a novel vancomycin-resistant Enterococcus faecium (VREfm) clone ST736 with reduced daptomycin susceptibility. The objectives of this study were to assess the population dynamics of local VREfm strains and genetic alterations predisposing to daptomycin resistance in VREfm ST736 strains. Multilocus sequence typing and single nucleotide variant data were derived from whole-genome sequencing of 250 E. faecium isolates from 1994–1995 (n = 43), 2009–2012 (n = 115) and 2013 (n = 92). A remarkable change was noticed in the clonality and antimicrobial resistance profiles of E. faecium strains between 1994–1995 and 2013. VREfm sequence type 17 (ST17), the prototype strain of clade A1, was the dominant clone (76.7%) recognized in 1994–1995. By contrast, clone ST736 accounted for 46.7% of VREfm isolates, followed by ST18 (26.1%) and ST412 (20.7%) in 2013. Bayesian evolutionary analysis suggested that clone ST736 emerged between 1996 and 2009. Co-mutations (liaR.W73C and liaS.T120A) of the liaFSR system were identified in all ST736 isolates (n = 111, 100%) examined. Thirty-eight (34.2%) ST736 isolates exhibited daptomycin-resistant phenotype, of which 13 isolates had mutations in both the liaFSR and cardiolipin synthase (cls) genes and showed high level of resistance with a daptomycin MIC50 of 32 μg/mL. The emergence of ST736 strains with mutations predisposing to daptomycin resistance and subsequent clonal spread among inpatients contributed to the observed high occurrence of daptomycin resistance in VREfm at our institution. The expanding geographic distribution of ST736 strains in other states and countries raises concerns about its global dissemination.

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<![CDATA[Critically ill healthcare workers with the middle east respiratory syndrome (MERS): A multicenter study]]> https://www.researchpad.co/article/5bf71feed5eed0c484dcbf89

Background

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) leads to healthcare-associated transmission to patients and healthcare workers with potentially fatal outcomes.

Aim

We aimed to describe the clinical course and functional outcomes of critically ill healthcare workers (HCWs) with MERS.

Methods

Data on HCWs was extracted from a multi-center retrospective cohort study on 330 critically ill patients with MERS admitted between (9/2012–9/2015). Baseline demographics, interventions and outcomes were recorded and compared between survivors and non-survivors. Survivors were approached with questionnaires to elucidate their functional outcomes using Karnofsky Performance Status Scale.

Findings

Thirty-Two HCWs met the inclusion criteria. Comorbidities were recorded in 34% (11/32) HCW. Death resulted in 8/32 (25%) HCWs including all 5 HCWs with chronic renal impairment at baseline. Non-surviving HCW had lower PaO2/FiO2 ratios 63.5 (57, 116.2) vs 148 (84, 194.3), p = 0.043, and received more ECMO therapy compared to survivors, 9/32 (28%) vs 4/24 (16.7%) respectively (p = 0.02).Thirteen of the surviving (13/24) HCWs responded to the questionnaire. Two HCWs confirmed functional limitations. Median number of days from hospital discharge until the questionnaires were filled was 580 (95% CI 568, 723.5) days.

Conclusion

Approximately 10% of critically ill patients with MERS were HCWs. Hospital mortality rate was substantial (25%). Patients with chronic renal impairment represented a particularly high-risk group that should receive extra caution during suspected or confirmed MERS cases clinical care assignment and during outbreaks. Long-term repercussions of critical illness due to MERS on HCWs in particular, and patients in general, remain unknown and should be investigated in larger studies.

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<![CDATA[Quality and technical efficiency do not evolve hand in hand in Spanish hospitals: Observational study with administrative data]]> https://www.researchpad.co/article/5b6da1c0463d7e4dccc5faf4

Objective

Recent evidence on the Spanish National Health System (SNHS) reveals a considerable margin for hospital efficiency and quality improvement. However, those studies do not consider both dimensions together. This study aims at jointly studying both technical efficiency (TE) and quality, classifying the public SNHS hospitals according to their joint performance.

Methods

Stochastic frontier analysis is used to estimate TE and multilevel logistic regressions to build a low-quality composite measure (LQ), which considers in-hospital mortality and safety events. All hospitalizations discharged in Spain in 2003 and 2013, in 179 acute-care general hospitals, were studied. Four scenarios of resulting performance were built setting yearly medians as thresholds for the overall sample, and according to hospital-complexity strata.

Results

Overall, since 2003, median TE improved and LQ reduced -from TE2003:0.89 to TE2013:0.93 and, from LQ2003:42.6 to LQ2013:27.7 per 1,000 treated patients. The time estimated coefficient showed technical progress over the period. TE across hospitals showed scarce variability (CV2003:0.08 vs. CV2013:0.07), not so the rates of LQ (CV2003:0.64 vs. CV2013:0.76). No correlation was found between TE values and LQ rates. When jointly considering technical efficiency and quality, hospitals dealing with the highest clinical complexity showed the highest chance to be placed in optimal scenarios, also showing lesser variability between hospitals.

Conclusions

Efficiency and quality have improved in Spanish public hospitals. Not all hospitals experiencing improvements in efficiency equally improved their quality. The joint analysis of both dimensions allowed identifying those optimal hospitals according to this trade-off.

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<![CDATA[Using risk adjustment to improve the interpretation of global inpatient pediatric antibiotic prescribing]]> https://www.researchpad.co/article/5b4a287d463d7e4513b897f7

Objectives

Assessment of regional pediatric last-resort antibiotic utilization patterns is hampered by potential confounding from population differences. We developed a risk-adjustment model from readily available, internationally used survey data and a simple patient classification to aid such comparisons.

Design

We investigated the association between pediatric conserve antibiotic (pCA) exposure and patient / treatment characteristics derived from global point prevalence surveys of antibiotic prescribing, and developed a risk-adjustment model using multivariable logistic regression. The performance of a simple patient classification of groups with different expected pCA exposure levels was compared to the risk model.

Setting

226 centers in 41 countries across 5 continents.

Participants

Neonatal and pediatric inpatient antibiotic prescriptions for sepsis/bloodstream infection for 1281 patients.

Results

Overall pCA exposure was high (35%), strongly associated with each variable (patient age, ward, underlying disease, community acquisition or nosocomial infection and empiric or targeted treatment), and all were included in the final risk-adjustment model. The model demonstrated good discrimination (c-statistic = 0.83) and calibration (p = 0.38). The simple classification model demonstrated similar discrimination and calibration to the risk model. The crude regional pCA exposure rates ranged from 10.3% (Africa) to 67.4% (Latin America). Risk adjustment substantially reduced the regional variation, the adjusted rates ranging from 17.1% (Africa) to 42.8% (Latin America).

Conclusions

Greater comparability of pCA exposure rates can be achieved by using a few easily collected variables to produce risk-adjusted rates.

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<![CDATA[Clonality, virulence determinants, and profiles of resistance of clinical Acinetobacter baumannii isolates obtained from a Spanish hospital]]> https://www.researchpad.co/article/5989db5aab0ee8fa60bdf230

Introduction

Acinetobacter baumannii is a nosocomial pathogen that is showing increasing rates of carbapenem resistance. Multi-Drug Resistant (MDR) International Clones (ICs), associated with certain oxacillinases, are being reported globally. This organism also harbors numerous virulence determinants. In this study, we aim at characterizing A. baumannii isolated from a Spanish hospital in terms of antimicrobial susceptibility, clonality, carbapenemase genes harbored, and virulence determinants expressed.

Materials and methods

Fifty nine clinical bloodstream isolates were obtained from 2009 until 2013. Antimicrobial Susceptibility Testing was performed according to the CLSI guidelines. PFGE and tri-locus PCR typing were then performed in order to determine local and international clonality. PCRs for the detection of common carbapenemases were also performed. Production of hemolysis, biofilms, siderophores, surface motility, and proteolysis were determined phenotypically. Doubling times for selected strains were also calculated. Finally, statistical analysis for detecting associations between these factors was conducted.

Results and discussion

Carbapenem non-susceptibility was 84.75%, suggesting the immediate need for intervention. PFGE showed the distribution of the majority of the isolates among 7 clusters. Although all three ICs were detected, IC II was predominant at 71.19%. blaOXA-24-like was the most prevalent carbapenemase (62.71%), followed by blaOXA-58-like (13.56%), and blaOXA-23-like (11.86%). Strains pertaining to IC II, and those harboring blaOXA-24-like, were positively associated with α-hemolysis, production of strong biofilms, and siderophore production. Harboring blaOXA-23-like and blaOXA-58-like was associated with attenuated virulence. These associations suggest that an interplay exists between these factors that could be locally exploited.

Conclusions

An alarmingly high rate of carbapenem non-susceptibility has been detected in this study. There was a predominance of IC II and blaOXA-24-like, and those factors were associated with heightened expression of virulence determinants. This association could be exploited for modifying treatment regimens and for improving on infection control protocols in this hospital.

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<![CDATA[The Potential Influence of Common Viral Infections Diagnosed during Hospitalization among Critically Ill Patients in the United States]]> https://www.researchpad.co/article/5989db44ab0ee8fa60bd7c58

Viruses are the most common source of infection among immunocompetent individuals, yet they are not considered a clinically meaningful risk factor among the critically ill. This work examines the association of viral infections diagnosed during the hospital stay or not documented as present on admission to the outcomes of ICU patients with no evidence of immunosuppression on admission. This is a population-based retrospective cohort study of University HealthSystem Consortium (UHC) academic centers in the U.S. from the years 2006 to 2009. The UHC is an alliance of over 90% of the non-profit academic medical centers in the U.S. A total of 209,695 critically ill patients were used in this analysis. Eight hospital complications were examined. Patients were grouped into four cohorts: absence of infection, bacterial infection only, viral infection only, and bacterial and viral infection during same hospital admission. Viral infections diagnosed during hospitalization significantly increased the risk of all complications. There was also a seasonal pattern for viral infections. Specific viruses associated with poor outcomes included influenza, RSV, CMV, and HSV. Patients who had both viral and bacterial infections during the same hospitalization had the greatest risk of mortality RR 6.58, 95% CI (5.47, 7.91); multi-organ failure RR 8.25, 95% CI (7.50, 9.07); and septic shock RR 271.2, 95% CI (188.0, 391.3). Viral infections may play a significant yet unrecognized role in the outcomes of ICU patients. They may serve as biological markers or play an active role in the development of certain adverse complications by interacting with coincident bacterial infection.

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<![CDATA[Non-Traditional Antibacterial Screening Approaches for the Identification of Novel Inhibitors of the Glyoxylate Shunt in Gram-Negative Pathogens]]> https://www.researchpad.co/article/5989db15ab0ee8fa60bccfcc

Antibacterial compounds that affect bacterial viability have traditionally been identified, confirmed, and characterized in standard laboratory media. The historical success of identifying new antibiotics via this route has justifiably established a traditional means of screening for new antimicrobials. The emergence of multi-drug-resistant (MDR) bacterial pathogens has expedited the need for new antibiotics, though many in the industry have questioned the source(s) of these new compounds. As many pharmaceutical companies' chemical libraries have been exhaustively screened via the traditional route, we have concluded that all compounds with any antibacterial potential have been identified. While new compound libraries and platforms are being pursued, it also seems prudent to screen the libraries we currently have in hand using alternative screening approaches. One strategy involves screening under conditions that better reflect the environment pathogens experience during an infection, and identifying in vivo essential targets and pathways that are dispensable for growth in standard laboratory media in vitro. Here we describe a novel screening strategy for identifying compounds that inhibit the glyoxylate shunt in Pseudomonas aeruginosa, a pathway that is required for bacterial survival in the pulmonary environment. We demonstrate that these compounds, which were not previously identified using traditional screening approaches, have broad-spectrum antibacterial activity when they are tested under in vivo-relevant conditions. We also show that these compounds have potent activity on both enzymes that comprise the glyoxylate shunt, a feature that was supported by computational homology modeling. By dual-targeting both enzymes in this pathway, we would expect to see a reduced propensity for resistance development to these compounds. Taken together, these data suggest that understanding the in vivo environment that bacterial pathogens must tolerate, and adjusting the antibacterial screening paradigm to reflect those conditions, could identify novel antibiotics for the treatment of serious MDR pathogens.

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<![CDATA[Correlating Cleaning Thoroughness with Effectiveness and Briefly Intervening to Affect Cleaning Outcomes: How Clean Is Cleaned?]]> https://www.researchpad.co/article/5989dab4ab0ee8fa60bac685

Objectives

The most efficient approach to monitoring and improving cleaning outcomes remains unresolved. We sought to extend the findings of a previous study by determining whether cleaning thoroughness (dye removal) correlates with cleaning efficacy (absence of molecular or cultivable biomaterial) and whether one brief educational intervention improves cleaning outcomes.

Design

Before-after trial.

Setting

Newly built community hospital.

Intervention

90 minute training refresher with surface-specific performance results.

Methods

Dye removal, measured by fluorescence, and biomaterial removal and acquisition, measured with culture and culture-independent PCR-based assays, were clandestinely assessed for eight consecutive months. At this midpoint, results were presented to the cleaning staff (intervention) and assessments continued for another eight consecutive months.

Results

1273 surfaces were sampled before and after terminal room cleaning. In the short-term, dye removal increased from 40.3% to 50.0% (not significant). For the entire study period, dye removal also improved but not significantly. After the intervention, the number of rooms testing positive for specific pathogenic species by culturing decreased from 55.6% to 36.6% (not significant), and those testing positive by PCR fell from 80.6% to 53.7% (P = 0.016). For nonspecific biomaterial on surfaces: a) removal of cultivable Gram-negatives (GN) trended toward improvement (P = 0.056); b) removal of any cultivable growth was unchanged but acquisition (detection of biomaterial on post-cleaned surfaces that were contaminant-free before cleaning) worsened (P = 0.017); c) removal of PCR-based detection of bacterial DNA improved (P = 0.046), but acquisition worsened (P = 0.003); d) cleaning thoroughness and efficacy were not correlated.

Conclusion

At this facility, a minor intervention or minimally more aggressive cleaning may reduce pathogen-specific contamination, but not without unintended consequences.

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<![CDATA[Increased Virulence of an Epidemic Strain of Mycobacterium massiliense in Mice]]> https://www.researchpad.co/article/5989da39ab0ee8fa60b873ef

Background

Chronic pulmonary disease and skin/soft tissue infections due to non-tuberculous mycobacteria (NTM) of the Mycobacterium chelonae-abscessus-massiliense group is an emerging health problem worldwide. Moreover, the cure rate for the infections this group causes is low despite aggressive treatment. Post-surgical outbreaks that reached epidemic proportions in Brazil recently were caused by M. massiliense isolates resistant to high-level disinfection with glutaraldehyde (GTA). Understanding the differences in the virulence and host immune responses induced by NTM differing in their sensitivity to disinfectants, and therefore their relative threat of causing outbreaks in hospitals, is an important issue.

Methodology/Principal Finding

We compared the replication and survival inside macrophages of a GTA-susceptible reference Mycobacterium massiliense clinical isolate CIP 108297 and an epidemic strain from Brazil, CRM-0019, and characterized the immune responses of IFNγ knockout mice exposed to a high dose aerosol with these two isolates. CRM-0019 replicated more efficiently than CIP 108297 inside mouse bone marrow macrophages. Moreover, the animals infected with CRM-0019 showed a progressive lung infection characterized by a delayed influx of CD4+ and CD8+ T cells, culminating in extensive lung consolidation and demonstrated increased numbers of pulmonary CD4+ Foxp3+ regulatory T cells compared to those infected with the reference strain. Immunosuppressive activity of regulatory T cells may contribute to the progression and worsening of NTM disease by preventing the induction of specific protective immune responses.

Conclusions/Significance

These results provide the first direct evidence of the increased virulence in macrophages and mice and pathogenicity in vivo of the Brazilian epidemic isolate and the first observation that NTM infections can be associated with variable levels of regulatory T cells which may impact on their virulence and ability to persist in the host.

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<![CDATA[Severe Fever with Thrombocytopenia Syndrome in South Korea, 2013-2015]]> https://www.researchpad.co/article/5989d9ddab0ee8fa60b68484

Background

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was recently identified in China, South Korea and Japan. The objective of the study was to evaluate the epidemiologic and clinical characteristics of SFTS in South Korea.

Methods/Principal Findings

SFTS is a reportable disease in South Korea. We included all SFTS cases reported to the Korea Centers for Disease Control and Prevention (KCDC) from January 2013 to December 2015. Clinical information was gathered by reviewing medical records, and epidemiologic characteristics were analyzed using both KCDC surveillance data and patient medical records. Risk factors for mortality in patients with SFTS were assessed. A total of 172 SFTS cases were reported during the study period. SFTS occurred throughout the country, except in urban areas. Hilly areas in the eastern and southeastern regions and Jeju island (incidence, 1.26 cases /105 person-years) were the main endemic areas. The yearly incidence increased from 36 cases in 2013 to 81 cases in 2015. Most cases occurred from May to October. The overall case fatality ratio was 32.6%. The clinical progression was similar to the 3 phases reported in China: fever, multi-organ dysfunction, and convalescence. Confusion, elevated C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS. Two outbreaks of nosocomial SFTS transmission were observed.

Conclusions

SFTS is an endemic disease in South Korea, with a nationwide distribution and a high case-fatality ratio. Confusion, elevated levels of C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS.

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<![CDATA[The Incidence, Clinical Outcomes, and Risk Factors of Thrombocytopenia in Intra-Abdominal Infection Patients: A Retrospective Cohort Study]]> https://www.researchpad.co/article/5989da62ab0ee8fa60b9146a

Background

Studies on the incidence and risk factors of thrombocytopenia among intra-abdominal infection patients remain absent, hindering efficacy assessments regarding thrombocytopenia prevention strategies.

Methods

We retrospectively studied 267 consecutively enrolled patients with intra-abdominal infections. Occurrence of thrombocytopenia was scanned for all patients. All-cause 28-day mortality was recorded. Variables from univariate analyses that were associated with occurrence of hospital-acquired thrombocytopenia were included in a multivariable logistic regression analysis to determine thrombocytopenia predictors.

Results

Median APACHE II score and SOFA score of the whole cohort was 12 and 3 respectively. The overall ICU mortality was 7.87% and the 28-day mortality was 8.98%. The incidence of thrombocytopenia among intra-abdominal infection patients was 21.73%. Regardless of preexisting or hospital-acquired one, thrombocytopenia is associated with an increased ICU mortality and 28-day mortality as well as length of ICU or hospital stay. A higher SOFA and ISTH score at admission were significant hospital-acquired thrombocytopenia risk factors.

Conclusions

This is the first study to identify a high incidence of thrombocytopenia in patients with intra-abdominal infections. Our findings suggest that the inflammatory milieu of intra-abdominal infections may uniquely predispose those patients to thrombocytopenia. More effective thrombocytopenia prevention strategies are necessary in intra-abdominal infection patients.

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<![CDATA[Faecal Carriage of Gram-Negative Multidrug-Resistant Bacteria among Patients Hospitalized in Two Centres in Ulaanbaatar, Mongolia]]> https://www.researchpad.co/article/5989db05ab0ee8fa60bc8167

Gram-negative multidrug-resistant organisms (GN-MDRO) producing β-lactamases (ESBL, plasmid-mediated AmpC β-lactamases and carbapenemases) are increasingly reported throughout Asia. The aim of this surveillance study was to determine the rate of bacterial colonization in patients from two hospitals in the Mongolian capital Ulaanbaatar. Rectal swabs were obtained from patients referred to the National Traumatology and Orthopaedics Research Centre (NTORC) or the Burn Treatment Centre (BTC) between July and September 2014, on admission and again after 14 days. Bacteria growing on selective chromogenic media (CHROMagar ESBL/KPC) were identified by MALDI-ToF MS. We performed susceptibility testing by disk diffusion and PCR (blaIMP-1, blaVIM, blaGES, blaNDM, blaKPC, blaOXA-48, blaGIM-1, blaOXA-23, blaOXA-24/40, blaOXA-51, blaOXA-58, blaOXA-143, blaOXA-235, blaCTX-M, blaSHV blaTEM and plasmid-mediated blaAmpC). Carbapenemase-producing isolates were additionally genotyped by PFGE and MLST. During the study period 985 patients in the NTORC and 65 patients in the BTC were screened on admission. The prevalence of GN-MDRO-carriage was 42.4% and 69.2% respectively (p<0.001). Due to the different medical specialities the two study populations differed significantly in age (p<0.029) and gender (p<0.001) with younger and more female patients in the burn centre (BTC). We did not observe a significant difference in colonization rate in the respective age groups in the total study population. In both centres most carriers were colonized with CTX-M-producing E. coli, followed by CTX-M-producing K. pneumoniae and CTX-M-producing E. cloacae. 158 patients from the NTORC were re-screened after 14 days of whom 99 had acquired a new GN-MDRO (p<0.001). Carbapenemases were detected in both centres in four OXA-58-producing A. baumannii isolates (ST642) and six VIM-2-producing P. aeruginosa isolates (ST235). This study shows a high overall prevalence of GN-MDRO in the study population and highlights the importance of routine surveillance, appropriate infection control practice and antibiotic prescribing policies to prevent further spread especially of carbapenemases.

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