Binary toxin and its clinical importance in <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection,Belgium

Binary toxin-producing Clostridium difficile strains such as ribotypes 027 and 078 have been associated with increased Clostridium difficile infection (CDI) severity. Our objective was to investigate the association between presence of the binary toxin gene and CDI severity and recurrence. We performed a laboratory-based retrospective study including patients between January 2013 and March 2015 whose fecal samples were analyzed by polymerase chain reaction (PCR) for the presence of the genes for toxin B and binary toxin and a deletion in the tcdC gene, specific for ribotype 027. Clinical and epidemiological characteristics were compared between 33 binary toxin-positive CDI patients and 33 binary toxin-negative CDI patients. Subsequently, the characteristics of 66 CDI patients were compared to those of 66 diarrhea patients who were carriers of non-toxigenic C. difficile strains. Fifty-nine of 1034 (5.7 %) fecal samples analyzed by PCR were binary toxin-positive, belonging to 33 different patients. No samples were positive for ribotype 027. Binary toxin-positive CDI patients did not differ from binary toxin-negative CDI patients in terms of disease recurrence, morbidity, or mortality, except for a higher peripheral leukocytosis in the binary toxin-positive group (16.30?×?10⁹/L vs. 11.65?×?10⁹/L; p?=?0.02). The second part of our study showed that CDI patients had more severe disease, but not a higher 30-day mortality rate than diarrhea patients with a non-toxicogenic C. difficile strain. In our setting with a low prevalence of ribotype 027, the presence of the binary toxin gene is not associated with poor outcome.     

<Emphasis Type="Italic">Acinetobacter baumannii</Emphasis> bacteraemia in patients with haematological malignancy: a multicentre retrospective study from the Infection Working Party of Jiangsu Society of Hematology

Acinetobacter baumannii (Ab) bacteraemia in patients with haematological malignancies is fatal but rarely reported. We explored the clinical characteristics, drug resistances and prognostic factors in these patients. This multicentre, retrospective study was conducted at the department of haematology wards of 18 tertiary hospitals in China from January 2014 to June 2015. The total clinical isolates from every source were collected from patients with haematological malignancy. Haematological malignancy patients diagnosed with Ab bacteraemia were analysed. During the study period, 40 patients with Ab bacteraemia were identified, accounting for 2.9% (40/1358) of bacteraemia cases, of which 25 (62.5%) had acute leukaemia (AL) and 27 (67.5%) had neutropaenia. Compared with non-neutropaenic patients, neutropaenic patients showed higher Acute Physiology and Chronic Health Evaluation (APACHE) scores and 30-day mortality rates (p?<?0.05). The in vitro antibiotic susceptibility of Ab to colistin was highest, at 100%, followed by that of tigecycline (91.30%) and amikacin (75.86%). Compared with the patients who had carbapenem-susceptible Ab infections, patients infected with carbapenem-resistant Ab (CRAB) had significantly longer hospital stays and were more likely to have had exposure to carbapenem before bacteraemia (p?<?0.05). The 30-day mortality rate was 32.5%. CRAB, neutropaenia, higher APACHE score, Pitt bacteraemia score and inappropriate initial antimicrobial therapy were significantly associated with 30-day mortality. Multivariable analysis showed that APACHE score and CRAB were independent predictors of 30-day mortality. Haematologic patients with AL and febrile neutropaenia were at high risk of Ab bacteraemia. More attention should be paid to CRAB, which is an independent risk factor for mortality in haematological malignancy patients with Ab bacteraemia.     

Molecular-based diagnosis of <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection is associated with reduced mortality

Polymerase chain reaction (PCR) for the diagnosis of Clostridium difficile infection (CDI) might result in overdiagnosis. The clinical outcomes of symptomatic CDI patients diagnosed by PCR remain uncertain. We aimed to determine whether patients whose diagnosis of CDI was based on PCR had different characteristics and clinical outcomes than those diagnosed by toxin immunoassay. Consecutive CDI patients, hospitalized at Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel, between January 2013 and January 2016, were identified retrospectively and included in the study. Diagnosis of CDI was based on PCR or diagnosis by immunoassay for C. difficile toxin. The main outcome was 30- and 90-day all-cause mortality. The PCR group included 165 patients and the immunoassay group included 157 patients. In comparison to the immunoassay group, patients in the PCR group were more likely to be younger, to be independent, to undergo previous abdominal surgery, and to use laxatives. The 30-day mortality rate in the PCR group was significantly lower than that in the immunoassay group, 29/165 (18%) vs 49/157 (31%), respectively; p?=?0.028. On multivariate analysis, PCR diagnosis was associated with reduced mortality, OR 0.48 (95% CI 0.26–0.88). PCR-based diagnosis of CDI is associated with reduced all-cause mortality rates. Further studies are needed to determine the management of patients with discrepant immunoassay and PCR diagnosis of CDI.     

Prognostic impact of hyperglycemia at onset of methicillin-sensitive <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> bacteraemia

Previous reports have associated hyperglycemia to poor outcome among aged and comorbid Staphylococcus aureus bacteraemia (SAB) patients. However, the prognostic impact of hyperglycemia in SAB irrespective of age and underlying conditions including a diagnosis of diabetes has received little attention. The objective here was to evaluate the prognostic relevance of hyperglycemia at onset of methicillin-sensitive SAB (MS-SAB). It was a retrospective study of MS-SAB patients. Blood glucose was measured within 24 h of positive blood cultures. The patient cohort was analyzed en bloc and by categorization according to age, underlying conditions and a diagnosis of diabetes. Altogether 161 patients were identified. High initial blood glucose levels were observed among diabetics (p?<?0.001), patients with deep infections (p?<?0.05) and poor outcome at 28- or 90-days (p?<?0.05). Receiver operating characteristics presented the glucose cut-off level of 7.2 mmol/L as a significant predictor of mortality with an area under the curve of 0.63 (95% CI 0.52–0.75, p?<?0.05). Blood glucose ≥7.2 mmol/L connected to higher 28- (9 vs. 20%, p?<?0.05) and 90-day (14 vs. 29%, p?<?0.01) mortality. In Cox proportional hazard regression the blood glucose cut-off value of 7.2 mmol/L significantly predicted 90-day mortality (HR, 2.12; 95% CI, 1.01–4.46; p?<?0.05). Among young and healthy non-diabetics the negative prognostic impact of high glucose was further accentuated (HR 7.46, p?<?0.05). High glucose levels had no prognostic impact among diabetics. Hyperglycemia at SAB onset may associate to poor outcome. The negative prognostic impact is accentuated among young and healthy non-diabetics.     

Impact of malignancy on <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection

Purpose

The purpose of this study was to investigate the impact of malignancy and chemotherapy on the clinical and microbiological characteristics of Clostridium difficile infections (CDI).

Methods

CDI patients with a history of malignancy within 5 years were defined as the cancer group. The characteristics of the patients were compared according to the presence of malignancy.

Results

Of 580 patients with CDI, 159 (27.4 %) belonged to the cancer group and 421 (72.6 %) to the non-cancer group. More of the patients in the cancer group than those in the non-cancer group had been hospitalized within the prior 2 months (P?<?0.001). Leukocytosis was more common in the non-cancer group (P?=?0.034), while infection by PCR ribotype 017 strains was more common in the cancer group, with marginal significance (P?=?0.07). Recurrence was more frequent in the cancer group (20.4 % vs. 9.5 %, P =0.005) and cancer was an independent risk factor for recurrence of CDI (OR?=?2.66, 95 % CI 1.34-5.29, P =0.005). Age also contributed to the recurrence of CDI (OR?=?1.03, 95 % CI 1.00-1.06, P =0.026).

Conclusions

Malignancy and age are independent risk factors for recurrence of CDI. Cancer patients require careful observation for recurrence after treatment of CDI.

     

Oral teicoplanin versus oral vancomycin for the treatment of severe <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection: a prospective observational study

The aim of this study was to compare clinical cure rate, recurrence rate and time to resolution of diarrhea in patients with severe and severe-complicated Clostridium difficile infection (CDI) treated with teicoplanin or vancomycin. This two-year prospective observational study included patients with first episode or first recurrence of CDI who had severe or severe-complicated CDI and were treated with teicoplanin or vancomycin. Primary outcomes of interest were clinical cure rate at discharge and recurrence rate after eight weeks follow up, and secondary outcomes were all-cause mortality and time to resolution of diarrhea. Among 287 study patients, 107 were treated with teicoplanin and 180 with vancomycin. The mean age of patients was 73.5?±?10.6 years. One hundred eighty six patients (64.8%) had prior CDI episode. Severe complicated disease was detected in 23/107 (21.5%) and 42/180 (23.3%) patients treated with teicoplanin and vancomycin, respectively. There was no statistically significant difference in time to resolution of diarrhea between two treatment arms (6.0?±?3.4 vs 6.2?±?3.1 days, p?=?0.672). Treatment with teicoplanin resulted in significantly higher clinical cure rate compared to vancomycin [90.7% vs 79.4%, p?=?0.013, odds ratio (OR) (95% confidence interval (CI)) 2.51 (1.19–5.28)]. Recurrence rates were significantly lower in patients treated with teicoplanin [9/97 (9.3%) vs 49/143 (34.3%), p?<?0.001, OR (95%CI) 0.20 (0.09–0.42)]. There was no statistically significant difference in overall mortality rate. Teicoplanin might be a good treatment option for patients with severe CDI. Patients treated with teicoplanin experienced remarkably lower recurrence rates compared to vancomycin-treated patients.     

Is there a relationship between the presence of the binary toxin genes in <Emphasis Type="Italic">Clostridium difficile</Emphasis> strains and the severity of <Emphasis Type="Italic">C. difficile</Emphasis> infection (CDI)?

Some strains of Clostridium difficile produce a binary toxin, in addition to the main C. difficile virulence factors (toxins A and B). There have been conflicting reports regarding the role of binary toxin and its relationship to the severity of C. difficile infection (CDI). Samples, isolates and clinical data were collected as part of a prospective multicentre diagnostic study. Clostridium difficile isolates (n = 1259) were tested by polymerase chain reaction (PCR) assay to detect binary toxin genes cdtA and cdtB. The PCR binary toxin gene results were compared with clinical severity and outcome data, including 30-day all-cause mortality. The 1259 isolates corresponded to 1083 different patients (October 2010 to September 2011). The prevalence of binary toxin positive strains was significantly higher in faecal samples with detectable toxin A/B than in those without toxin but that were positive by cytotoxigenic culture (26.3% vs. 10.3%, p < 0.001). The presence of binary toxin correlated moderately with markers of CDI severity (white cell count, serum albumin concentration and serum creatinine concentration). However, the risk ratio for all-cause mortality was 1.68 for binary toxin positive patients and patients were significantly less likely to survive if they had CDI caused by a binary toxin gene positive strain, even after adjusting for age (p < 0.001). The presence of binary toxin genes does not predict the clinical severity of CDI, but it is significantly associated with the risk of all-cause mortality.     

Risk factors and outcome of levofloxacin-resistant <Emphasis Type="Italic">Elizabethkingia meningoseptica</Emphasis> bacteraemia in adult patients in Taiwan

Elizabethkingia meningoseptica is an emerging nosocomial pathogen associated with high mortality and inherently resistant to many antimicrobial agents. Levofloxacin has been considered as a therapeutic agent based on in vitro susceptibility. We aim to investigate the risk factors and outcomes for levofloxacin-resistant E. meningoseptica bacteraemia. Adult patients with E. meningoseptica bacteraemia were identified retrospectively in a medical centre in Taiwan from January 2011 to July 2015. These strains were identified by the Vitek2 automated system or matrix-assisted laser desorption-ionization time-of-flight mass spectrometry. We compared clinical features and outcomes of patients with levofloxacin-resistant (MIC >2 μg/mL) and levofloxacin-susceptible (MIC ≤2 μg/mL) E. meningoseptica bacteraemia. A total of 93 patients were identified, including 51 (54.8%) with levofloxacin-resistant E. meningoseptica bacteraemia. The APACHE II score (OR, 1.08; 95% CI, 1.02–1.14; p?=?0.008) was the only independent risk factor for levofloxacin-resistant E. meningoseptica bacteraemia. The 14-day mortality for patients with levofloxacin-resistant E. meningoseptica bacteraemia (attributable mortality: 30.7%) was significantly higher than that for patients with the levofloxacin-susceptible strain (56.9% versus 26.2%, p?=?0.003). In the multivariate analysis of risk factors for mortality, appropriate definite antibiotic use was the only factor associated with 14-day survival (OR, 0.11; 95% CI, 0.02–0.55, p?=?0.007). The levofloxacin-resistant strain was borderline significantly associated with mortality (OR, 3.09; 95% CI, 0.88–10.91, p?=?0.079). The early identification of levofloxacin resistance in E. meningoseptica isolates is important to tackle this multi-drug resistance pathogen.     

Outcomes of <Emphasis Type="Italic">Clostridium difficile</Emphasis>-suspected diarrhea in a French university hospital

Clostridium difficile infection (CDI) produces a variety of clinical presentations ranging from mild diarrhea to severe infection with fulminant colitis, septic shock, and death. CDI puts a heavy burden on healthcare systems due to increased morbidity and mortality, and higher costs. We evaluated the clinical impact of CDI in terms of complications and mortality in a French university hospital compared with patients with diarrhea unrelated to CDI. A 3-year prospective, observational, cohort study was conducted in a French university hospital. Inpatients aged 18 years or older with CDI-suspected diarrhea were eligible to participate in the study and were followed for up to 60 days after CDI testing. Among the 945 patients with diarrhea included, 233 had confirmed CDI. Overall, 106 patients (11.2%) developed at least one of the following complications: colectomy, colitis, ileitis/rectitis, ileus, intestinal perforation, megacolon, multiorgan failure, pancolitis, peritonitis, pseudomembranous colitis, renal failure, and sepsis/septic shock. The complication rate was significantly higher in patients with diarrhea related to C. difficile than in non-CDI patients (26.6% vs 6.2%, P?<?0.001). At day 60, 137 (14.5%) patients had died, with 37 deaths among the CDI group (15.9%). Death was attributable to CDI in 15 patients (6.4%). Complications are more frequent among CDI cases than in patients with diarrhea not related to C. difficile. Assessment of CDI is necessary to ensure allocation of sufficient resources to CDI prevention.     

The impact of the introduction of fidaxomicin on the management of <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection in seven NHS secondary care hospitals in England: a series of local service evaluations

Clostridium difficile infection (CDI) is associated with high mortality. Reducing incidence is a priority for patients, clinicians, the National Health Service (NHS) and Public Health England alike. In June 2012, fidaxomicin (FDX) was launched for the treatment of adults with CDI. The objective of this evaluation was to collect robust real-world data to understand the effectiveness of FDX in routine practice. In seven hospitals introducing FDX between July 2012 and July 2013, data were collected retrospectively from medical records on CDI episodes occurring 12 months before/after the introduction of FDX. All hospitalised patients aged ≥18 years with primary CDI (diarrhoea with presence of toxin A/B without a previous CDI in the previous 3 months) were included. Recurrence was defined as in-patient diarrhoea re-emergence requiring treatment any time within 3 months after the first episode. Each hospital had a different protocol for the use of FDX. In hospitals A and B, where FDX was used first line for all primary and recurrent episodes, the recurrence rate reduced from 10.6 % to 3.1 % and from 16.3 % to 3.1 %, with a significant difference in 28-day mortality from 18.2 % to 3.1 % (p?<?0.05) and 17.3 % to 6.3 % (p?<?0.05) for hospitals A and B, respectively. In hospitals using FDX in selected patients only, the changes in recurrence rates and mortality were less marked. The pattern of adoption of FDX appears to affect its impact on CDI outcome, with maximum reduction in recurrence and all-cause mortality where it is used as first-line treatment.     

Fecal calprotectin concentrations in cancer patients with <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection

Fecal calprotectin (fCPT) has been used as a surrogate marker for assessment of intestinal inflammation. We explore the utility of fCPT values as a diagnostic aid in cancer patients with suspected Clostridium difficile infection (CDI). A total of 232 stool specimens submitted for GeneXpert C. difficile PCR testing were included in the study. All specimens were tested for fCPT and toxin/GDH antigens. Clinical severity of CDI cases was determined by the IDSA/SHEA criteria. Significant differences of median fCPT values between CDI (n?=?117, Median 183.6 μg/g) and non-CDI (n?=?115, 145.6 μg/g, p?=?0.006) patients were seen. In CDI patents, significantly lower fCPT values were found in patients with mild to moderate (n?=?95, 182.1 μg/g) than those with severe and severe to complicated (n?=?22, 218.5 μg/g, p?=?0.014) scores, and among those that were toxin positive (n?=?24, 200.2 μg/g) vs. toxin negative (n?=?86, 182.8 μg/g, p?=?0.044). Despite this overall trend, wide variations in fCPT values were found in all categories examined. A logistic regression analysis revealed that the fCPT values correlated independently with the severity of clinical manifestations (OR?=?2.021, 95%CI?=?1.132–3.608); however, it did not correlate with other clinical outcomes. Our study findings show that high fecal calprotectin levels correlate with toxin-positive and clinically severe CDI; however, wide variations in individual measurements preclude establishment of reliable cut-offs for routine diagnostic use in cancer patients.     

Antimicrobial combination treatment including ciprofloxacin decreased the mortality rate of <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> bacteraemia: a retrospective cohort study

Ineffective antimicrobial therapy of Pseudomonas aeruginosa bacteraemia increases mortality. Recent studies have proposed the use of antimicrobial combination therapy composed of a beta-lactam with either ciprofloxacin or tobramycin. To determine if combination therapy correlates to lower mortality and is superior compared to monotherapy, we investigated the effect of antimicrobial treatment regimens on 30-day mortality in a cohort with Pseudomonas aeruginosa bacteraemia. All cases of P. aeruginosa bacteraemia (n?=?292) in southwest Skåne County, Sweden (years 2005–2010, adult population 361,112) and the whole county (2011–2012, 966,130) were identified. Available medical and microbiological records for persons aged 18 years or more were reviewed (n?=?235). Antimicrobial therapy was defined as empiric at admission or definitive after culture results and was correlated to 30-day mortality in a multivariate regression model. The incidence and mortality rates were 8.0 per 100,000 adults and 22.9% (67/292), respectively. As expected, multiple comorbidities and high age were associated with mortality. Adequate empiric or definitive antipseudomonal treatment was associated with lower mortality than other antimicrobial alternatives (empiric p?=?0.02, adj. p?=?0.03; definitive p?<?0.001, adj. p?=?0.007). No difference in mortality was seen between empiric antipseudomonal monotherapy or empiric combination therapy. However, definitive combination therapy including ciprofloxacin correlated to lower mortality than monotherapy (p?=?0.006, adj. p?=?0.003), whereas combinations including tobramycin did not. Our results underline the importance of adequate antipseudomonal treatment. These data also suggest that P. aeruginosa bacteraemia should be treated with an antimicrobial combination including ciprofloxacin when susceptible.     

Association between dementia and reduced walking ability and 30-day mortality in patients with extended-spectrum beta-lactamase-producing <Emphasis Type="Italic">Escherichia coli</Emphasis> bacteremia

Previous studies have shown controversial results of factors associated with short-term mortality in patients with extended-spectrum beta-lactamase (ESBL)-producing E. coli bacteremia and no research has investigated the impact of the geriatric assessment criteria on short-term mortality. Our objective was to determine whether dementia and walking ability are associated with 30-day mortality in patients with ESBL-producing E. coli bacteremia. All blood bottle cultures, analyzed from January 2008 to April 2015, in the Bacteriology Department of a 2,600-bed, university-affiliated center, Nantes, France, were retrospectively extracted. Factors associated with short-term mortality in patients with ESBL-producing E. coli bacteremia: 140 patients with an ESBL-producing E. coli bloodstream infection were included; 22 (15.7%) patients died within 30 days following the first positive blood bottle culture of ESBL-producing E.coli. In multivariate analysis, a reduced ability to walk (OR = 0.30; p = 0.021), presence of dementia (OR = 54.51; p = 0.040), a high Sepsis-related Organ Failure Assessment (SOFA) score (OR = 1.69; p < 0.001), presence of neutropenia (OR = 12.94; p = 0.049), and presence of a urinary tract infection (OR = 0.07; p = 0.036), were associated with 30-day mortality. Our findings provide new data showing an independent association between 30-day mortality with dementia and reduced walking ability, in patients with ESBL-producing E. coli bacteremia. These criteria should be considered in the therapeutic management of patients with ESBL-producing E. coli bacteremia.     

Haematological and acute-phase response of dogs with experimental skin <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> infection to treatment with antibiotic and parthenolide

Changes in white blood cells, leukogram patterns, the positive acute-phase protein (APP) fibrinogen and negative APPs (albumin and arylesterase) were monitored to evaluate their potential as sensitive indicators throughout the course of therapy in canine skin Pseudomonas aeruginosa infection. The study was performed on 15 male mixed-breed dogs, divided in three groups of 5 dogs each. Dogs from group A were injected subcutaneously with P. aeruginosa bacterial culture (1?×?10⁸ CFU/mL) at a dose of 0.3 mL/kg and treated with enrofloxacin (5 mg/kg, s.c.) on post infection hour 48 for 10 consecutive days. Dogs from group B were infected and treated with a combination of enrofloxacin (at above-mentioned dose and intervals) and parthenolide (feverfew extract 90 mg, 0.7 % parthenolide). The schedule consisted of daily oral intake of two capsules of feverfew beginning on post infection hour 4 and continued for 6 days. The control group C included healthy dogs, injected s.c. with 0.3 mL/kg physiological saline. The haematological indices and APPs were assayed before infection and on 4th, 24th, 48th and 72nd hours and on 7th, 10th and 14th days after infection. Infected and antibiotic-treated dogs responded with significant leukocytosis, left shift, eosinopaenia and lymphopaenia between hours 24 and 72. In this group, fibrinogen increased substantially by post infection hours 24 (p?<?0.01 vs 0 h; p?<?0.05 vs group C), 48 (p?<?0.001 vs 0 h; p?<?0.05 vs group C) and 72 (p?<?0.001 vs 0 h; p?<?0.01 vs group C) while albumin reduction was marked by hours 48 (p?<?0.05 vs 0 h) and 72 (p?<?0.05 vs 0 h; p?<?0.001 vs group C) and day 7 (p?<?0.01 vs 0 h; p?<?0.001 vs group C). The combination of enrofloxacin and parthenolide modified, at a significant extent, the deviations in studied parameters except for eosinophil percentage, which persisted low.     

The predictor of mortality outcome in adult patients with Ebola virus disease during the 2014–2015 outbreak in Guinea

The purpose of this study was to examine the association of any demographic and clinical factors with mortality outcome among adult patients with Ebola virus disease (EVD) in Guinea. This retrospective observational study analyzed medical records of laboratory confirmed EVD adult patients during the 2014–2015 EVD outbreak in Guinea. The associations between any demographic or clinical variables and mortality outcome of EVD were assessed using univariate and multivariate logistic regression analyses. Of 2,310 EVD adult patients included for analysis, the overall case fatality rate was 68.1%. Univariate analyses identified factors possibly associated with mortality outcome, including patient age (p?<?0.001), history of visiting or close contact with a suspected or confirmed EVD patient (p?=?0.035), and seven clinical symptoms on admission, i.e., fever (p?=?0.003), hiccups (p?<?0.001), vomiting (p?=?0.003), diarrhea (p?<?0.001), cough (p?=?0.001), sore throat (p?=?0.016), and unexplained bleeding (p?=?0.021). The multivariate analysis showed that patient age was independently associated with mortality outcome of EVD (OR?=?1.06; 95%CI?=?1.03–1.09; p?<?0.001), while none the of clinical symptoms on admission were significantly associated with the mortality outcome. Our analysis indicates that older age was the only independent factor associated with death among EVD adult patients in Guinea. This suggests that older EVD patients should receive intensive medical care and be carefully monitored.     

Population-based epidemiology of <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> bloodstream infection: clonal complex 30 genotype is associated with mortality

Staphylococcus aureus bloodstream infections (SABSI) are associated with a high burden of morbidity and mortality. The impact of specific S. aureus genotypes on outcome is unclear. The aim of this study was to evaluate the epidemiology and outcome of SABSI, with a special emphasis on the impact of bacterial clonal lineage on mortality. We conducted a 3-year population-based prospective study between 2011 and 2014, including 303 consecutive adult patients. Clinical data were obtained from interviews and medical records. S. aureus isolates were genotyped using DNA microarrays. The incidence rate of SABSI was 27.6 per 100,000 inhabitants [95 % confidence interval (CI) 24.6–31.0]. The median age of the patients was 71 years (interquartile range 56–81 years) and 61.4 % were male. Most SABSI (70.6 %) occurred in hospitals or associated to healthcare, and 34.1 % of these were associated with intravascular catheters. Only five (1.6 %) SABSI were caused by methicillin-resistant S. aureus (MRSA). The 30-day case fatality rate was 20.8 % (95 % CI 16.6–25.7). S. aureus clonal complex 30 [hazard ratio (HR) 3.9; 95 % CI 1.8–8.5, p?=?0.001], unknown focus of infection (HR 4.5; 95 % CI 1.9–10.8, p?=?0.001) and respiratory tract infection (HR 12.7; 95 % CI 4.6–34.6, p?<?0.001) were independent predictors of mortality in a Cox regression analysis after adjusting for age, sex and underlying conditions. A high proportion of potential preventable SABSI calls for effective infection control measures. S. aureus clonal complex 30 genotype was associated with mortality in patients with bloodstream infections. The genetic basis underlying this association remains to be demonstrated.     

Use of adenosine diphosphate receptor inhibitor prior to left ventricular assist device implantation is not associated with increased bleeding

Current guidelines recommend adenosine diphosphate receptor inhibitors (ADPRi) be discontinued 5–7 days prior to cardiac surgery due to increased bleeding events, rates of re-exploration, and transfusions. However, the risks of left ventricular assist device (LVAD) implantation in patients taking an ADPRi have not previously been studied. We retrospectively identified 134 eligible patients with ischemic cardiomyopathy that underwent LVAD implantation between July 2009 and August 2013. The cohorts received an ADPRi ≤5 days of surgery (n = 25) versus >5 days prior or not at all (n = 109). Subgroup analyses adjusted for differences in frequency of redo sternotomy between cohorts, excluded patients that received an ADPRi >1 year prior to surgery, and excluded patients with a redo sternotomy. The ADPRi and control groups did not have significant differences in the primary outcomes, intraoperative PRBC units transfused (3.0 vs. 4.0, p = 0.12) or chest tube output within 24 h of surgery (1.66 L vs. 1.80 L, p = 0.61). After adjusting for differences in frequency of redo sternotomy (ADPRi vs. control, 12 vs. 52%, p ≤ 0.001), no significant difference in PRBC units transfused (3.1 vs. 3.5, p = 0.59) or chest tube output (2.04 L vs. 2.04 L, p = 0.98) was seen. No significant difference in 30-day mortality (8.0 vs. 11.0%, p = 0.63), 90-day mortality (16.4 vs. 23.3%, p = 0.42), or length of stay (29.0 vs. 28.0, p = 0.61) was seen. In this single-center experience, use of an ADPRi ≤5 days prior to LVAD implantation was not associated with increased bleeding, length of stay, or mortality.     

Should all adjunctive corticosteroid therapy be avoided in the management of hemodynamically stabile <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> bacteremia?

The purpose of this study was to examine the prognostic impact of corticosteroids in hemodynamically stabile Staphylococcus aureus bacteremia (SAB). There were 361 hemodynamically stabile methicillin-sensitive SAB patients with prospective follow-up and grouping according to time-point, dose and indication for corticosteroid therapy. To enable analyses without external interfering corticosteroid therapy all patients with corticosteroid therapy equivalent to prednisone >10 mg/day for ≥1 month prior to positive blood culture results were excluded. Twenty-five percent (92) of patients received corticosteroid therapy of which 11 % (40) had therapy initiated within 1 week (early initiation) and 9 % (31) had therapy initiated 2–4 weeks after (delayed initiation) positive blood culture. Twenty-one patients (6 %) had corticosteroid initiated after 4 weeks and were not included in the analyses. A total of 55 % (51/92) received a weekly prednisone dose >100 mg. Patients with early initiated corticosteroid therapy had higher mortality compared to patients treated without corticosteroid therapy at 28 days (20 % vs. 7 %) (OR, 3.11; 95%CI, 1.27–7.65; p?<?0.05) and at 90 days (30 % vs. 10 %) (OR, 4.01; 95%CI, 1.82–8.81; p?<?0.001). Considering all prognostic markers, early initiated corticosteroid therapy predicted 28-day (HR, 3.75; 95%CI, 1.60–8.79; p?=?0.002) and 90-day (HR, 3.10; 95%CI, 1.50–6.39; p?=?0.002) mortality in Cox proportional hazards regression analysis. When including only patients receiving early initiated corticosteroid therapy with prednisone ≥100 mg/week the negative prognostic impact on 28-day mortality was accentuated (HR 4.8, p?=?0.001). Corticosteroid therapy initiation after 1 week of positive blood cultures had no independent prognostic impact. Early initiation of corticosteroid therapy may be associate to increased mortality in hemodynamically stabile SAB.     

Clinical Impact of <Emphasis Type="Italic">p27</Emphasis><Superscript><Emphasis Type="Italic">Kip1</Emphasis></Superscript> and CaSR Expression on Primary Hyperparathyroidism

We aimed to investigate the expressions of p27 kinase inhibitory protein 1 (p27^Kip1) and calcium sensing receptor (CaSR) in adenomas and normal parathyroid tissue and to evaluate the relationship of these molecules with clinical and biochemical parameters in primary hyperparathyroidism (PHPT). Fifty-one patients with histopathologically confirmed parathyroid adenomas and 20 patients with normal parathyroid glands (which were removed incidentally during thyroid resection) were included. Immunohistochemical stainings of CaSR and p27^Kip1 were performed in surgical specimens. Clinical features, biochemical parameters, and BMD measurements of patients with PHPT were evaluated retrospectively. Expressions of p27^Kip1 and CaSR were decreased in parathyroid adenomas, compared to normal glands (p <?0.05). High intensity of CaSR staining (3+) was more frequent in normal parathyroid tissue (75%) than adenomas (12%) (p <?0.01). Hypertension was not observed in patients with high staining intensity of CaSR (p =?0.032). There was a negative association between CaSR expression and body mass index (BMI) (p =?0.027, r =???0.313). There was no significant relationship between p27^Kip1 and CaSR expressions, serum calcium, plasma parathormone, 25-hydroxy vitamin D levels, and bone density (p >?0.05). The expressions of p27^Kip1 and CaSR were decreased in PHPT patients. This reduction may play an important role in the pathogenesis of PHPT. However, neither p27^Kip1 nor CaSR expression was found to be useful in predicting prognosis or severity of disease.     

Women with familial risk for breast cancer have an increased frequency of aldehyde dehydrogenase expressing cells in breast ductules

Background

Knowledge is limited regarding the association between stem cells in histologically benign breast tissue and risk factors for breast cancer, and hence we addressed this issue in the present study. Recently, we assessed the histology of benign breast tissue from cancer and non-cancer patients for cells positive for the putative stem cell marker aldehyde dehydrogenase 1 A1 (ALDH), and the findings indicated an association between expression of ALDH and the hormonal factors menopause and hormone therapy. The current investigation examined possible associations between various known clinical and genetic risk factors for breast cancer and cellular expression of ALDH in ductules in benign human breast tissue.

Methods

The study included breast surgery patients that were BRCA1/2 mutation carriers without breast cancer (n?=?23), had BRCA1/2 (n?=?28) or sporadic (n?=?21) breast cancer, or required non-cancer-related mammoplasty (n?=?34). The distribution and frequency of ALDH-immunolabelled cells were correlated to patient subgroups with different risk factors, using mammoplasty patients as a control group. Statistical analyses comprised linear and logistic regression, Spearman’s rank test, Pearson’s test, and Fisher’s exact test. In two-tailed tests, p?<?0.05 was considered significant.

Results

A strong association was found between family history of breast cancer and a high frequency of ALDH+ cells (p?=?0.001) at all ductular levels in all groups, regardless of BRCA status, age, parity, or occurrence of cancer. In pre-menopausal non-BRCA cancer patients, the frequency of ALDH+ cells increased with age (p?<?0.01) but decreased with increasing parity (p?<?0.03). High frequencies of ALDH+ cells were found in the non-basal ductular levels in BRCA1 mutation carriers (p?=?0.03), but in the basal ductular level in BRCA2 cancer patients (p?=?0.02). Among post-menopausal patients, only on-going hormone replacement therapy was correlated with a high number of ALDH+ cells (p?<?0.03).

Conclusion

In histologically normal breast tissue, we found a positive association between the frequency of ductular ALDH+ cells and several breast cancer risk factors, particularly family history of this disease, which supports previous evidence that ALDH plays a role in breast cancer.