Differences in antimicrobial susceptibility testing complicating management of IMP carbapenemase-producing Enterobacterales infection.

OBJECTIVES: IMP-type carbapenemases are rarely detected in Europe and limited information is available to guide the treatment of infections caused by carbapenemase-producing Enterobacterales (CPE) producing these carbapenemases. Accurate antimicrobial susceptibility testing (AST) results are essential for optimal antibiotic management. Here we report discrepancies in AST of IMP-producing Enterobacterales (IMP-CPE) complicating the management of severe sepsis. METHODS: Antimicrobial susceptibilities were analysed by in-house VITEK® 2, Etest and broth microdilution (BMD). Carbapenemase-encoding genes were detected by PCR. Whole-genome sequencing (WGS) was performed using an Illumina MiSeq platform. RESULTS: Minimum inhibitory concentrations (MICs) determined by VITEK® 2 for Enterobacter hormaechei and Klebsiella oxytoca blood culture isolates were ≥16 mg/L for meropenem and ≤0.5 mg/L for ertapenem. In contrast, Etest analysis and BMD returned MICs of 2 mg/L and 1 mg/L, respectively. Both isolates tested positive for IMP carbapenemase-encoding genes by PCR. WGS revealed that both isolates carried the same blaIMP-4 gene. Based on VITEK® 2 susceptibilities, initial treatment was with tigecycline and amikacin. After subsequent deterioration, the patient was successfully treated with ertapenem and amikacin. CONCLUSION: This case highlights that automated AST by VITEK® 2 can over-report meropenem resistance for IMP carbapenemase-producers compared with Etest and BMD. Clinicians need to be cautious deciding against carbapenem treatment based on VITEK® 2 susceptibility testing results for IMP-positive Enterobacterales. Tigecycline was inferior to carbapenem treatment for pyelonephritis caused by isolates expressing IMP carbapenemases, however specific evidence guiding the treatment of these infections is lacking.

Can guidelines for the control of multi-drug-resistant Gram-negative organisms be put into practice? A national survey of guideline compliance and comparison of available guidelines.

Multi-drug-resistant Gram-negative organisms (MDRGNO) are an emerging global threat, reflected in the increasing incidence of infections in Ireland and elsewhere. The response to this threat has been the development of Infection Prevention and Control (IPC) guidelines. A survey of IPC teams in Ireland was undertaken to assess compliance with national guidelines. To place these survey results in context, IPC guidelines from the Irish Health Protection Surveillance Centre (HPSC) are compared with guidelines from Healthcare Infection Society (HIS), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Centre for Disease Control (CDC). Thirty-three percent of hospitals responded across a range of hospital types. The results highlight the variability in implementation of guidelines across Ireland, as well as the variability between guidelines internationally. Respondents are less than 90% compliant with the majority of MDRGNO screening guidelines. Hospitals have variable access to isolation facilities with an average of 29% single rooms available (range 2.6-100%), resulting in some patients with MDRGNO not being isolated. Broad variability in application of guidance on personal protective equipment was demonstrated. This survey gives an insight into the real-life applicability of HPSC guidelines. Survey results are placed in context with a comparison of five MDRGNO IPC guidelines. Although core tenets of IPC are standard across guidelines, research into which practices are efficient in reducing MDRGNO transmission while being cost-effective would be worthwhile.

Canis Caveat (Beware of the Dog) - Septic Shock Due To Capnocytophaga Canimorsus Contracted From A Dog Bite

We describe the case of a 61-year-old immunocompetent male who developed septic shock and multiorgan failure due to Capnocytophaga canimorsus (C. canimorsus) bloodstream infection, sustained from a dog bite. Unusually, this patient developed acute liver failure and splenic infarction in addition to many of the better-known clinical sequelae of C. canimorsus infection.

C-reactive protein is an independent prognostic marker in patients with tongue carcinoma - A retrospective study.

OBJECTIVES: Reliable prognostic markers are lacking for tongue carcinoma. C-reactive protein (CRP) and a ratio from neutrophils/lymphocytes (NLR) are biomarkers, associated with prognosis in solid cancers. Aim of this work was to investigate the role of CRP and NLR in prognosis of patients with tongue carcinoma. DESIGN: Retrospective cohort study. SETTING: We retrospectively analysed data of patients treated for tongue carcinoma at our institution. Levels of CRP, Neutrophils and Lymphocytes were measured pretherapeutic. PARTICIPANTS: 197 patients treated for squamous cell carcinoma of the tongue between 2002 and 2015. MAIN OUTCOME MEASURES: Overall survival, disease-free survival. RESULTS: Elevated CRP was significantly associated with shorter overall survival in our cohort in uni- and multivariate analysis. NLR was not associated with prognosis. CONCLUSION: In the present study we could confirm the role of CRP as an independent prognostic marker in patients with tongue carcinoma. Incorporating this marker in prognostication could represent a valuable and moreover inexpensive tool for improved decisions making concerning therapy in the future.

Cognitive Effects of Air Pollution Exposures and Potential Mechanistic Underpinnings.

PURPOSE OF REVIEW: This review sought to address the potential for air pollutants to impair cognition and mechanisms by which that might occur. RECENT FINDINGS: Air pollution has been associated with deficits in cognitive functions across a wide range of epidemiological studies, both with developmental and adult exposures. Studies in animal models are significantly more limited in number, with somewhat inconsistent findings to date for measures of learning, but show more consistent impairments for short-term memory. Potential contributory mechanisms include oxidative stress/inflammation, altered levels of dopamine and/or glutamate, and changes in synaptic plasticity/structure. Epidemiological studies are consistent with adverse effects of air pollutants on cognition, but additional studies and better phenotypic characterization are needed for animal models, including more precise delineation of specific components of cognition that are affected, as well as definitions of critical exposure periods for such effects and the components of air pollution responsible. This would permit development of more circumscribed hypotheses as to potential behavioral and neurobiological mechanisms.

Benchmarking Lumbar Puncture Fluoroscopy Time during Fellowship Training.

We sought to establish a guide for identifying fellowship competency in performing fluoroscopically guided lumbar punctures. With a linear mixed-effects model, we compared the fluoroscopy time between the first and last 3 months of neuroradiology training. During 7 years, 55 fellows performed 1142 and 861 lumbar punctures in the first and last quarters of training. A target fluoroscopy time of 0.26 minutes, the upper 95% confidence interval, can serve as a fellowship benchmark for successfully achieving competence in fluoroscopically guided lumbar punctures.

Developmental neurotoxicity of inhaled ambient ultrafine particle air pollution: Parallels with neuropathological and behavioral features of autism and other neurodevelopmental disorders.

Accumulating evidence from both human and animal studies show that brain is a target of air pollution. Multiple epidemiological studies have now linked components of air pollution to diagnosis of autism spectrum disorder (ASD), a linkage with plausibility based on the shared mechanisms of inflammation. Additional plausibility appears to be provided by findings from our studies in mice of exposures from postnatal day (PND) 4-7 and 10-13 (human 3rd trimester equivalent), to concentrated ambient ultrafine (UFP) particles, considered the most reactive component of air pollution, at levels consistent with high traffic areas of major U.S. cities and thus highly relevant to human exposures. These exposures, occurring during a period of marked neuro- and gliogenesis, unexpectedly produced a pattern of developmental neurotoxicity notably similar to multiple hypothesized mechanistic underpinnings of ASD, including its greater impact in males. UFP exposures induced inflammation/microglial activation, reductions in size of the corpus callosum (CC) and associated hypomyelination, aberrant white matter development and/or structural integrity with ventriculomegaly (VM), elevated glutamate and excitatory/inhibitory imbalance, increased amygdala astrocytic activation, and repetitive and impulsive behaviors. Collectively, these findings suggest the human 3rd trimester equivalent as a period of potential vulnerability to neurodevelopmental toxicity to UFP, particularly in males, and point to the possibility that UFP air pollution exposure during periods of rapid neuro- and gliogenesis may be a risk factor not only for ASD, but also for other neurodevelopmental disorders that share features with ASD, such as schizophrenia, attention deficit disorder, and periventricular leukomalacia.

Whatever Happened to Formal Methods for Security?

We asked 7 experts 7 questions to find out what has occurred recently in terms of applying formal methods (FM) to security-centric, cyber problems. We are continually reminded of the 1996 paper by Tony Hoare "How did Software Get So Reliable Without Proof?" [1] In that vein, how did we get so insecure with proof? Given daily press announcements concerning new malware, data breaches, and privacy loss, is FM still relevant or was it ever? Our experts answered with unique personal insights. We were curious as to whether this successful methodology in "safety-critical" has succeeded as well for today's "build it, hack it, patch it" mindset. Our experts were John McLean (Naval Research Labs), Paul Black (National Institute of Standards and Technology), Karl Levitt (University of California at Davis), Joseph Williams (CloudEconomist.Com), Connie Heitmeyer (Naval Research Labs), Eugene Spafford (Purdue University), and Joseph Kiniry (Galois, Inc.). The questions and responses follow.

Molecular epidemiology of Mycobacterium abscessus complex isolates in Ireland.

BACKGROUND: The Mycobacterium abscessus complex are the rapidly growing mycobacteria (RGM) most commonly causing lung disease, especially in cystic fibrosis (CF) patients. Ireland has the world's highest CF incidence. The molecular epidemiology of M. abscessus complex in Ireland is unreported. METHODS: We performed rpoB gene sequencing and multi-locus sequence typing (MLST) on M. abscessus complex strains isolated from thirty-six patients in 2006-2012 (eighteen known CF patients). RESULTS: Twenty-eight strains (78%) were M. abscessus subsp. abscessus, eight M. abscessus subsp. massiliense, none were M. abscessus subsp. bolletii. Sequence type 1 (ST1) and ST26 (M. abscessus subsp. abscessus) were commonest. Seven M. abscessus subsp. abscessus STs (25%) were novel (two with novel alleles). Seven M. abscessus subsp. massiliense STs were previously reported (88%), including two ST23, the globally successful clone. In 2012, of 552 CF patients screened, eleven were infected with M. abscessus complex strains (2%). CONCLUSIONS: The most prevalent M. abscessus subsp. abscessus and M. abscessus subsp. massiliense strains in Ireland belong to widely-distributed STs, but there is evidence of high M. abscessus subsp. abscessus diversity.

First outbreak of linezolid-resistant vancomycin-resistant Enterococcus faecium in an Irish hospital, February to September 2014.

An outbreak of linezolid-resistant vancomycin-resistant Enterococcus faecium (LRVREfm) occurred in the hepatology ward of a tertiary referral hospital in Ireland between February and September 2014. LRVREfm was isolated from 15 patients; pulsed-field gel electrophoresis confirmed spread of a single clone. This is the first report of an outbreak of linezolid-resistant vancomycin-resistant enterococcus in Ireland.

Epidemiology and molecular typing of VRE bloodstream isolates in an Irish tertiary care hospital.

OBJECTIVES: Ireland has the highest rate of vancomycin-resistant Enterococcus faecium (VREfm) isolated from blood of nosocomial patients in Europe, which rose from 33% (110/330) in 2007 to 45% (178/392) in 2012. No other European country had a VREfm rate from blood cultures of >25%. Our aim was to elucidate the reasons for this significantly higher rate in Ireland. METHODS: The epidemiology and molecular typing of VRE from bloodstream infections (BSIs) was examined in a tertiary care referral hospital and isolates were compared with those from other tertiary care referral centres in the region. RESULTS: The most common source of VRE BSIs was intra-abdominal sepsis, followed by line-related infection and febrile neutropenia. Most of the isolates were positive for vanA; 52% (43/83) possessed the esp gene and 12% (10/83) possessed the hyl gene. Genotyping by SmaI macrorestriction analysis (PFGE) of isolates revealed clonal relatedness between bloodstream isolates and environmental isolates. VRE BSI isolates from two other tertiary care hospitals in the Dublin region showed relatedness by PFGE analysis. MLST revealed four STs (ST17, ST18, ST78 and ST203), all belonging to the clonal complex of hospital-associated strains. CONCLUSIONS: Irish VRE BSI isolates have virulence factor profiles as previously reported from Europe. Typing analysis shows the spread of individual clones within the hospital and between regional tertiary care hospitals. Apart from transmission of VRE within the hospital and transfer of colonized patients between Irish hospitals, no other explanation for the persistently high VREfm BSI rate in Ireland has been found.

Epidemiology of infection and current guidelines for infection prevention in cystic fibrosis patients.

The spectrum of bacterial pathogens encountered in cystic fibrosis (CF) lung disease has expanded over the last decade. In addition to established pathogens, such as Pseudomonas aeruginosa, Burkholderia cepacia complex and Staphylococcus aureus, novel Gram-negative non-fermenter bacteria and non-tuberculous mycobacteria have gained in clinical significance. Air sampling performed in inpatient and outpatient clinics, and analysis of cough aerosols expelled by CF patients provides evidence for potential airborne transmission of CF pathogens. Two outbreaks of 'Mycobacterium abscessus subsp. massiliense' have been reported among CF patients, raising the question of airborne transmission of non-tuberculous mycobacteria. In response to newer epidemiological evidence, international infection control guidance documents have changed. Guideline documents agree on the importance of specifications for ventilation when planning new CF inpatient facilities. New CF units should consider providing negative-pressure inpatient and outpatient rooms to diminish the risk of airborne contamination of ward corridors and communal areas. Air exchange rates of inpatient rooms and pulmonary function testing rooms need to be considered and optimized whenever possible. International guidelines disagree as to whether patients should be requested to wear masks in the hospital environment.

Detection and characterization of extended-spectrum beta-lactamase-producing Enterobacteriaceae in high-risk patients in an Irish tertiary care hospital.

BACKGROUND: Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are Gram-negative, multi-drug-resistant organisms that are of major clinical significance among immunocompromised patients in high-risk areas in hospital settings. In Ireland, the number of ESBL-E bloodstream infections is increasing. AIMS: To conduct a prevalence study of ESBL-E among immunocompromised patients in high-risk areas [intensive care unit (ICU), liver transplantation and haematology/oncology wards], characterize any ESBL genes detected by polymerase chain reaction (PCR), and perform epidemiological typing using pulsed-field gel electrophoresis (PFGE). METHODS: In total, 317 non-duplicate rectal swabs from patients in high-risk wards were screened anonymously for ESBL-E carriage. Positive isolates were characterized using PCR to detect blaCTX-M, blaTEM, blaOXA-1 and blaSHV ESBL-E genes. Clonal relationships of these isolates were investigated using PFGE. FINDINGS: Fifty (15.8%) high-risk patients were found to harbour ESBL-E. Prevalence rates of 21.9% (N = 28), 14.3% (N = 15) and 8.3% (N = 7) of ESBL-E were isolated from patients on the liver transplantation, ICU and haematology/oncology wards, respectively. Seventy percent of ESBL-E isolates carried more than one resistance gene. Of the 25 ESBL-producing Escherichia coli isolates typed by PFGE, two pairs of two isolates demonstrated >80% homology, and four of the five ESBL-producing Enterobacter cloacae isolates typed by PFGE demonstrated >80% homology, suggesting clonal relatedness and potential cross-transmission from individual patients. CONCLUSION: A significant proportion of the patients screened were found to be colonized with ESBL-E. Typing revealed three incidents of potential cross-infection. Therefore, timely detection of ESBL-E among patients in high-risk wards is critical for treatment and infection control.

Detection and epidemiology of plasmid-mediated AmpC ß-lactamase producing Escherichia coli in two Irish tertiary care hospitals.

This study determined the prevalence and distribution of plasmid-mediated AmpC (pAmpC) ß-lactamases in Irish Escherichia coli isolates. Clinical E. coli isolates (n=95) that were intermediate or resistant to cefoxitin and/or flagged by VITEK® 2 as potential AmpC-producers underwent confirmation using a MASTDISCS™ ESBL and AmpC Detection Kit. Multiplex PCR capable of detecting family-specific plasmid ampC genes was performed to detect the presence of these genes. Five PCR-negative isolates were selected for promoter analysis. PFGE and MLST were performed on E. coli isolates that harboured a plasmid ampC gene to determine their clonal relatedness. Plasmid ampC genes were detected in 19% (18/95) of phenotypic AmpC producing E. coli isolates. The CIT group was the most common plasmid family type (n=14); DHA (n=3) and ACC (n=1) groups were also detected. Promoter analysis showed that four isolates had multiple point mutations and one had a 1 bp insertion in the -10 box. PFGE demonstrated a polyclonal pattern for E. coli isolates. Furthermore, with the exception of two isolates with an identical sequence type (ST720), MLST analysis revealed that these isolates were not clonally related. This study revealed that there was a marked prevalence of pAmpC E. coli among phenotypic AmpC producing E. coli isolates but no evidence of cross-transmission of a single strain. Establishing the prevalence and clonality of these organisms is important in order to implement evidence-based infection control measures that reduce the spread of pAmpC ß-lactamase resistance in the hospital environment.

Investigation of the first outbreak of OXA-48-producing Klebsiella pneumoniae in Ireland.

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) strains are encountered with increasing frequency in Europe. In November 2010 the European Centre for Disease Control (ECDC) graded Ireland as only having sporadic occurrence of CPE. AIM: To describe the epidemiological and molecular typing analysis of the first outbreak of OXA-48-producing Klebsiella pneumoniae in an Irish tertiary care referral centre. METHODS: Sixteen OXA-48-producing K. pneumoniae isolates were detected, from both clinical and screening specimens, and analysed by pulsed-field gel electrophoresis and by multi-locus sequence typing. FINDINGS: Typing analysis revealed that two outbreak strains were circulating in the hospital, one among surgical patients and one among medical patients. The 'medical strain' ST13 had already been identified as an internationally disseminated clone, whereas the 'surgical strain' ST221 had not previously been reported as an OXA-48-carrying strain. CONCLUSION: Although the outbreak on surgical wards was successfully controlled by implementing strict infection control measures, intermittent detection of individual patients carrying the 'medical strain' of OXA-48 K. pneumoniae has persisted since then. The experience from this outbreak suggests that OXA-48 K. pneumoniae is endemic at low level in the healthcare setting in the Dublin region.

Carbapenemase-producing Enterobacteriaceae in Irish critical care units: results of a pilot prevalence survey, June 2011.

The epidemiology of carbapenemase-producing Enterobacteriaceae (CPE) in Ireland is changing, with an increase in the number of reported cases in late 2010 and early 2011. Reported cases were predominantly linked to critical care units. In June 2011, a four-week national pilot survey took place in 40 Irish critical care units (37 adult and three paediatric) to examine the prevalence of rectal carriage of CPE and inform national CPE screening guidelines. A total of 760 screening swabs were taken over the study period, and CPE were not detected in any of the participating critical care units.

Frequency multiplexed superconducting quantum interference device readout of large bolometer arrays for cosmic microwave background measurements.

A technological milestone for experiments employing transition edge sensor bolometers operating at sub-Kelvin temperature is the deployment of detector arrays with 100s-1000s of bolometers. One key technology for such arrays is readout multiplexing: the ability to read out many sensors simultaneously on the same set of wires. This paper describes a frequency-domain multiplexed readout system which has been developed for and deployed on the APEX-SZ and South Pole Telescope millimeter wavelength receivers. In this system, the detector array is divided into modules of seven detectors, and each bolometer within the module is biased with a unique ∼MHz sinusoidal carrier such that the individual bolometer signals are well separated in frequency space. The currents from all bolometers in a module are summed together and pre-amplified with superconducting quantum interference devices operating at 4 K. Room temperature electronics demodulate the carriers to recover the bolometer signals, which are digitized separately and stored to disk. This readout system contributes little noise relative to the detectors themselves, is remarkably insensitive to unwanted microphonic excitations, and provides a technology pathway to multiplexing larger numbers of sensors.

First isolation and outbreak of OXA-48-producing Klebsiella pneumoniae in an Irish hospital, March to June 2011.

Five OXA-48-producing Klebsiella pneumoniae were detected in a tertiary referral hospital in Ireland between March and June 2011. They were found in the clinical isolates of five cases that were inpatients on general surgical wards. None of the cases had received healthcare at a facility outside of Ireland in the previous 12 months. This is the first report of OXA-48-producing K. pneumoniae in Ireland.

CT colonography and transient bacteraemia: implications for antibiotic prophylaxis.

OBJECTIVES: To determine the prevalence of transient bacteraemia after CT colonography (CTC). METHODS: Blood cultures were obtained at 5, 10 and 15 min after CTC from 100 consecutive consenting patients. Blood samples were cultured in both aerobic and anaerobic media and positive blood culture samples were analysed by a microbiologist. RESULTS: Blood culture samples were positive for growth in sixteen patients. All positive blood culture samples were confirmed skin contaminants. There were no cases of significant bacteraemia. The estimated significant bacteraemia rate as a result of CTC is 0-3.7%, based on 95% confidence intervals around extreme results using Wilson's score method. CONCLUSIONS: American Heart Association and National Institute for Clinical Excellence guidelines advise that antibiotic prophylaxis before lower gastrointestinal endoscopy is not indicated in patients with at risk cardiac lesions (ARCL) as the risk of a transient bacteraemia leading to infective endocarditis is low. These data show that the prevalence of transient bacteraemia after CTC is also low. It follows that patients with ARCL do not require antibiotic prophylaxis before CTC.