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Background & Objective: The Infectious Disease Society of America guidelines recommend vancomycin trough levels of 15-20 mg/L for severe methicillin-resistant Staphylococcus aureus. However, recent consensus guidelines of four infectious disease organizations no longer recommend vancomycin dosing using minimum serum trough concentrations. Therefore, this study aimed to evaluate the impact of low (< 15 mg/L) vs. high (≥ 15 mg/L) vancomycin trough levels on clinical outcomes in adult patients with sepsis or gram-positive bacterial infections., Method: A systematic literature review from inception to December 2022 was conducted using four online databases, followed by a meta-analysis. The outcomes of interest included clinical response/efficacy, microbial clearance, length of ICU stay, treatment failure, nephrotoxicity, and mortality., Results: Fourteen cohort studies met the inclusion criteria from which vancomycin trough concentration data were available for 5,228 participants. Our analysis found no association between vancomycin trough levels and clinical response [OR = 1.06 (95%CI 0.41-2.72], p = 0.91], microbial clearance [OR = 0.47 (95% CI 0.23-0.96), p = 0.04], ICU length of stay [MD=-1.01 (95%CI -5.73-3.71), p = 0.68], or nephrotoxicity [OR = 0.57 (95% CI 0.31-1.06), p = 0.07]. However, low trough levels were associated with a non-significant trend towards a lower risk of treatment failure [OR = 0.89 (95% CI 0.73-1.10), p = 0.28] and were significantly associated with reduced risk of all-cause mortality [OR = 0.74 (95% CI 0.62-0.90), p = 0.002]., Conclusion: Except for a lower risk of treatment failure and all-cause mortality at low vancomycin trough levels, this meta-analysis found no significant association between vancomycin trough levels and clinical outcomes in adult patients with sepsis or gram-positive bacterial infections., (© 2024. The Author(s).)

The aquaculture sector plays a vital role in global food security, yet it grapples with significant challenges posed by infectious diseases. Piscine lactococcosis is one of the significant threats in rainbow trout aquaculture due to its potential to cause severe economic losses through mortalities, reduced growth rates, and increased susceptibility to other pathogens. It poses challenges in disease management strategies, impacting the sustainability and profitability of rainbow trout farming. The current study focuses on the variations in serum blood parameters of farmed rainbow trout Oncorhynchus mykiss during a lactococcosis outbreak caused by Lactococcus garvieae. Blood samples were collected for biochemical analysis, fish were examined for parasites and bacteria, and DNA from bacterial colonies was PCR-amplified and sequenced for identification. Overall, 13 biochemical parameters, including proteins, enzymes, lipids, chemicals, and minerals, were measured in serum blood samples from both diseased and healthy fish. The results indicate significant alterations in the levels of these parameters during the outbreak, highlighting the impact of infections on the blood profile of farmed rainbow trout. Urea levels were significantly higher in diseased fish compared to controls, and creatinine, phosphorus, and magnesium also showed similar trends. Alanine aminotransferase and total protein levels were higher in control fish. Chloride levels differed significantly between groups. Iron levels were higher in controls and lower in diseased fish. No significant differences were found in other parameters. This study reveals significant changes in serum blood parameters of rainbow trout during a lactococcosis outbreak caused by L. garvieae. These changes highlight the potential of these parameters as tools for monitoring health status, stress, and aquaculture management. Continuous monitoring can provide valuable insights into disease severity and overall fish health, aiding in the development of improved management practices. The presented data contribute to understanding the pathophysiology of piscine lactococcosis and developing effective mitigation strategies for farmed rainbow trout., (© 2024 The Author(s). Journal of Fish Diseases published by John Wiley & Sons Ltd.)

DENOVA-score is useful to stratify the risk of infective endocarditis (IE) in Enterococcus faecalis bacteremia. Recently, time to positive (TTP) of blood cultures has also been related with a higher risk of IE. The objective was to evaluate DENOVA- score with TTP to improve its specificity. We performed a retrospective, case-control study in adult patients with E. faecalis bacteremia. Thirty-nine patients with definite E. faecalis IE and 82 with E. faecalis bacteremia were included. The addition of a TTP ≤ 8 h to DENOVA-score did not improve the diagnostic accuracy of this score., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Bifidobacterium breve is widely used as a probiotic in preterm infants and children with congenital surgical conditions, however, some cases of probiotics-induced bacteremia have been reported recently., Objectives: To examine the clinical and bacteriologic features of Bifidobacterium breve bacteremia caused by a probiotic (BBG-01) in term and preterm infants., Methods: We included 298 patients who were admitted to the neonatal intensive care unit of Miyagi Children's Hospital and were given BBG-01 as a probiotic within the period June 2014 to February 2019. We experienced six cases of B. breve bacteremia and assessed their features retrospectively., Results: The incidence rate of B. breve bacteremia in our hospital was 2% (6/298), higher than reported previously. The median age at onset, corrected age, and weight of the patients was 8 days (range: 5-27 days), 35 weeks (range: 26-39 weeks), and 1,940 g (range: 369-2734 g), respectively. The bacteremia triggers were gastrointestinal perforations in two cases, food protein-induced enterocolitis syndrome in two cases, adhesive ileus in one case, ileal volvulus in one case, and aspiration pneumonia following esophageal atresia repair in one case. B. breve was detected on blood cultures after a median of 5 days 13 hours (range: 4 days 18 hours-9 days 13 hours). No patient demonstrated serious symptoms, such as septic shock. All patients received antibiotics and recovered without any sequelae., Conclusions: Ileus and intestinal mucosal damage, such as enteritis, can cause B. breve bacteremia. The incidence of B. breve bacteremia may be higher than reported previously and detection via culture may require a longer time than typically needed for more common bacteria. It is associated with a good prognosis., Competing Interests: The authors declare no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

This study aimed to review the clinical characteristics of patients with Aerococcus spp. detected by blood culture, and drug susceptibility of Aerococcus spp. All cases of Aerococcus spp. determined using blood culture between June 2013 and May 2020 in a single institution were included; patient information (age, sex, comorbidities, outcome, diagnosis, antimicrobial agents) was analyzed. The cohort comprised 25 patients (18 [72%] men and 7 [28%] women; median age, 84.5 [range, 75-87] years). Thirteen (52%) patients had urinary tract infections(UTI) caused by Aerococcus spp. All patients had a favorable prognosis, except 1 who died owing to infective endocarditis. Drug susceptibility testing showed that most isolates were susceptible to β-lactams except 1. However, 24 (96%) cases were resistant to trimethoprim-sulfamethoxazole and 10 (40%) to quinolones. Aerococcus spp. are important causative agents of bacteremia and UTI. The increasing reports of Aerococcus spp. infections could lead to better treatment schemes and facilitate diagnosis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aim: To establish a highly sensitive time-resolved fluorescence immunoassay of heparin-binding protein (HBP-TRFIA) and evaluate its application value for bacterial or fungal infections in tumor patients., Methods: Two types of HBP monoclonal specific antibodies against different epitopes of the antigen molecule were used as coating antibodies and Eu 3+ -labeled antibodies, respectively. The double-antibody sandwich method was used in establishing HBP-TRFIA, and the methodology was evaluated. The established HBP-TRFIA was used in detecting HBP concentration in the plasma samples of healthy individuals, patients with bacterial or fungal infections, and infected or uninfected patients with various types of tumors., Results: The linear range of HBP-TRFIA was (0.11-530 ng/mL). Plasma HBP concentrations detected through HBP-TRFIA were consistent with the results of fluorescence quantitative immunochromatography (ρ = 0.964). The plasma HBP concentrations of infected tumor patients were significantly higher than those of uninfected tumor patients (P < 0.01)., Conclusion: This study successfully established a highly sensitive HBP-TRFIA, which was highly comparable to commercially available fluorescent quantitative immunochromatographic kits and was able to facilitate the timely diagnosis of bacterial or fungal infections in patients with tumor., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction. Contamination of specimens and overuse of broad spectrum antibiotics contribute to false positives and false negatives, respectively. Therefore, useful and applicable biomarkers of bacteremia are still required. Hypothesis/Gap Statement. IL-6 can be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection. Aim. We aimed to evaluate the diagnostic efficiency of neutrophil/lymphocyte ratio (NLR), procalcitonin (PCT) and interleukin-6 (IL-6) in discriminating Gram-negative (G - ) bacteria from Gram-positive (G + ) bacteria and fungi in febrile patients. Methodology. A total of 567 patients with fever were evaluated. Serum levels of IL-6, PCT, NLR and CRP were compared among a G - group ( n =188), a G + group ( n =168), a fungal group ( n =38) and a culture negative group ( n =173). Sensitivity, specificity, Yuden's index and area under the Receiver operating characteristic (ROC) curve (AUC) were obtained to analyse the diagnostic abilities of these biomarkers in discriminating bloodstream infection caused by different pathogens. Results. Serum IL-6 and PCT in the G - group increased significantly when compared with both the G + group and fungal group ( P <0.05). AUC of IL-6 (0.767, 95 % CI:0.725-0.805) is higher than AUC of PCT (0.751, 95 % CI:0.708-0.796) in discriminating the G - group from G + group. When discriminating the G - group from fungal group, the AUC of IL-6 (0.695, 95 % CI:0.651-0.747) with a cut-off value of 464.3 pg ml -1 was also higher than the AUC of PCT (0.630, 95 % CI:0.585-0.688) with a cut-off value of 0.68 ng ml -1 . Additionally, AUC of NLR (0.685, 95 % CI:0.646-0.727) in discriminating the fungal group from G + group at the cut-off value of 9.03, was higher than AUC of IL-6, PCT and CRP. Conclusion. This study suggests that IL-6 could be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection. In addition, NLR is valuable to discriminate fungal infections from Gram-positive infections in febrile patients with a bloodstream infection.

Background: Carnobacterium species are lactic acid-producing Gram-positive bacteria that have been approved by the US Food and Drug Administration and Health Canada for use as a food bio-preservative. The use of live bacteria as a food additive and its potential risk of infections in immunocompromised patients are not well understood., Case Presentation: An 81-year-old male with a history of metastatic prostate cancer on androgen deprivation therapy and chronic steroids presented to our hospital with a 2-week history of productive cough, dyspnea, altered mentation, and fever. Extensive computed tomography imaging revealed multifocal pneumonia without other foci of infection. He was diagnosed with pneumonia and empirically treated with ceftriaxone and vancomycin. Blood cultures from admission later returned positive for Carnobacterium inhibens. He achieved clinical recovery with step-down to oral amoxicillin/clavulanic acid for a total 7-day course of antibiotics., Conclusions: This is the fourth reported case of bacteremia with Carnobacterium spp. isolated from humans. This case highlights the need to better understand the pathogenicity and disease spectrum of bacteria used in the food industry for bio-preservation, especially in immunocompromised patients.

Timely administration of appropriate empirical antibiotics in febrile neutropenia is crucial for favourable patient outcomes. There are guidelines in place recommending such antibiotics. However, regional variations and local epidemiological data must be evaluated to tailor the antibiotics for best possible and rational use. In this study, we audited the clinical and microbiological data of febrile neutropenic episodes occurring at a tertiary care haematology institution. Three hundred and ninety-three febrile neutropenic episodes occurring in 123 patients over a 1-year period were analysed for microbial profile, sensitivity and resistance patterns, and finally clinical outcomes. Gram-negative bacilli (GNB) blood stream infections (46.9%) were more prevalent as compared to gram-positive infections (41.9%). Overall mortality due to complicated neutropenic sepsis was 19.5% (24/123 patients). Increased resistance to carbapenems, beta-lactam beta-lactamase inhibitor combinations, aminoglycosides, fluoroquinolones, and cephalosporins were observed. Cefepime and tigecycline resistance were seen in 20% and 15% GNB isolates, respectively. Chest was the most frequent focus of infection, and acute myeloid leukaemia (AML) was the most common underlying disorder which correlated with the likelihood of death (p < 0.01). Multidrug-resistant GNB (esp. Klebsiella sp.) are still most worrisome isolates in neutropenic patients. Single-agent cefepime or piperacillin-tazobactam/tigecycline combination may be considered empirical agents. Chest infections and AML were independent predictors of poor clinical outcome in neutropenic patients. Regular audit of infections and antibiotic susceptibility data is needed to improve clinical outcomes in patients with febrile neutropenia.

Enterococcus hirae , a member of the Enterococcus genus, is known to cause infections, including infective endocarditis (IE), in animal species. In humans, E. hirae is an uncommon pathogen, but has been associated with severe and recurrent disease. Here, we report the first Danish case of E. hirae native aortic valve IE in a 62-year-old woman with no history of heart disease. She presented to the hospital with symptoms of gastroenteritis but no signs of heart disease. Nevertheless, blood culture revealed growth of E. hirae , and a transoesophageal echocardiography demonstrated a mobile mass adherent to the aortic valve, compatible with a vegetation. The patient was successfully treated for E. hirae native aortic valve IE with 4 weeks of intravenous benzylpenicillin in combination with gentamicin for the initial 2 weeks. To the best of our knowledge, this is the first documented case of E. hirae IE in Denmark and the sixth documented case worldwide., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Gram-positive anaerobic (GPA) bacteria inhabit different parts of the human body as commensals but can also cause bacteremia. In this retrospective observational study, we analyzed GPA bacteremia pathogens before (2013-2015) and after (2016-2018) the introduction of the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS)., Method: We conducted a retrospective observational study by searching the microbiology database to identify all positive GPA blood cultures of patients with GPA bacteremia diagnosed using the new technique, MALDI-TOF MS, between January 1, 2016 and December 31, 2018; and using a conventional phenotypic method between January 1, 2013 and December 31, 2015 at a single tertiary center in Japan. Parvimonas micra (P. micra) (17.5%) was the second most frequently identified GPA (MALDI-TOF MS); we then retrospectively reviewed electronic medical records for 25 P. micra bacteremia cases at our hospital. We also conducted a literature review of published cases in PubMed from January 1, 1980, until December 31, 2019; 27 cases were retrieved., Results: Most cases of P. micra bacteremia were identified after 2015, both, at our institute and from the literature review. They were of mostly elderly patients and had comorbid conditions (malignancies and diabetes). In our cases, laryngeal pharynx (7/25, 28%) and gastrointestinal tract (GIT; 6/25, 24%) were identified as the most likely sources of bacteremia; however, the infection source was not identified in 9 cases (36%). P. micra bacteremia were frequently associated with spondylodiscitis (29.6%), oropharyngeal infection (25.9%), intra-abdominal abscess (14.8%), infective endocarditis (11.1%), septic pulmonary emboli (11.1%), and GIT infection (11.1%) in the literature review. Almost all cases were treated successfully with antibiotics and by abscess drainage. The 30-day mortalities were 4 and 3.7% for our cases and the literature cases, respectively., Conclusions: Infection sites of P. micra are predominantly associated with GIT, oropharyngeal, vertebral spine, intra-abdominal region, pulmonary, and heart valves. Patients with P. micra bacteremia could have good prognosis following appropriate treatment.

Tunneled central venous catheters (TCVCs) are colonized by Gram-positive organisms and form biofilm. Lipoteichoic acid (LTA) is a Gram-positive cell wall component that can be measured in serum. The purpose of this pilot study was to characterize LTA concentrations in hemodialysis (HD) patients with TCVCs compared to other access types and to evaluate biofilm morphology and microbiology in TCVCs removed by clinical decision. The study enrolled patients with TCVCs (18), grafts (19), and fistulas (18). Blood samples were collected before HD, at 30 minutes, 2 hours, and end of HD. Catheters removed by clinical decision were evaluated by scanning electron microscopy (SEM) for biofilm morphology, and portions of the catheter were cultured. LTA was detectable in all samples and concentrations increased significantly in all access types during HD (p < 0.05 for all comparisons). Patients with TCVCs that had a >30% increase in LTA concentration from baseline also had the greatest rate of increase (slope) compared to grafts and fistulas (p = 0.03 and p = 0.04, respectively). Catheters removed by clinical decision (n = 7) and examined by SEM had deposition of fibrin. Cultures revealed polymicrobial colonization. TCVCs had the highest rate of increase of LTA during HD. Further studies to determine the source of LTA in patients with AVG and AVF are warranted.

Sepsis is a high-mortality disease that is infected by bacteria, but pathogens in individual patients are difficult to diagnosis. Metabolomic changes triggered by microbial activity provide us with the possibility of accurately identifying infection. We adopted machine learning methods for training different classifiers with a clinical-metabolomic database from sepsis cases to identify the pathogen of sepsis. Records of clinical indicators and concentration of metabolites were obtained for each patient upon their arrival at the hospital. Machine learning algorithms were used in 100 patients with clear infection and corresponding 29 controls to select specific biosignatures to discriminate microorganism in septic patients. The sensitivity, specificity, and AUC value of clinical and metabolomic characteristics in predicting diagnostic outcomes were determined at admission. Our analyses demonstrate that the biosignatures selected by machine learning algorithms could have diagnostic value on the identification of infected patients and Gram-positive from Gram-negative; related AUC values were 0.94 ± 0.054 and 0.80 ± 0.085, respectively. Pathway and blood disease enrichment analyses of clinical and metabolomic biomarkers among infected patients showed that sepsis disease was accompanied by abnormal nitrogen metabolism, cell respiratory disorder, and renal or intestinal failure. The panel of selected clinical and metabolomic characteristics might be powerful biomarkers to discriminate patients with sepsis., Competing Interests: The authors declare that they have no conflicts of interest relevant to this study., (Copyright © 2020 Lingling Zheng et al.)

To identify the molecular characteristics of Gram-positive cocci isolated from blood cultures and clinical outcome among critically ill patients. This retrospective study was conducted in the general intensive care unit of the University General Hospital of Patras, Greece, during a 5-year period (2012-2016). All adult patients with a Gram-positive BSI were included. PCR was applied to identify mecA gene (staphylococci); vanA, vanB, and vanC genes (enterococci). Linezolid-resistant S. epidermidis, MRSA, and VRE were further typed by multilocus sequence typing. Mutations in region V of 23S rDNA and ribosomal protein L4were investigated by PCR and sequencing analysis. The presence of the cfr gene was tested by PCR. In total, 141 Gram-positive BSIs were included. Coagulase-negative staphylococci predominated (n = 69; 65 methicillin-resistant, 23 linezolid-resistant carrying both C2534T and T2504A mutations and belonging to the ST22 clone), followed by enterococci (n = 46; 11 vancomycin-resistant carrying vanA gene, classified into four clones), S. aureus (n = 22; 10 methicillin-resistant, classified into three clones) and streptococci (n = 4). The most common type of infection was catheter-related (66; 46.8%), followed by primary BSI (28; 19.9%). Overall 14-day fatality was 24.8%. Multivariate analysis revealed septic shock as independent predictor of fatality, while appropriate empiric antimicrobial treatment and catheter-related BSI were identified as a predictor of good prognosis. Even though most of Gram-positive cocci were multidrug-resistant, fatality rate was low, associated with catheter-related BSIs. Among CNS, LR isolates represented one-third of BSIs due to the dissemination of ST22 S. epidermidis propagated by utilization of linezolid.

Background: Although various methods have been developed to directly identify bacteria from positive blood cultures by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), the necessity of using commercial kits still leads to a high cost and long assay time. Moreover, few evaluations of these methods have been conducted. This study aimed to evaluate the feasibility of an optimized MALDI-TOF MS method for direct identification of bacteria in positive blood cultures., Methods: A total of 829 non-repeated positive cultures were collected from July 2018 to August 2019, and direct identification was performed by an optimized MALDI-TOF MS method. The same positive blood cultures were sub-cultivated to obtain a single bacterial colony and identified by classical biochemical BD testing, which is the gold standard to compare the accuracy of direct identification of positive blood cultures by MALDI-TOF MS., Results: After excluding 7 false-positive samples from the 829 positive blood cultures, the most accurate rate of direct identification by this optimized MALDI-TOF MS method was for gram-negative bacteria (91.5%), followed by gram-positive bacteria (88.3%), fungi (84.8%), anaerobic bacteria (80%), and other rare bacteria (66.67%)., Conclusion: Common bacteria in positive blood cultures can be identified directly within 1 hour by MALDI-TOF MS, and thus, this optimized method can be used as a primary identification method by clinicians. Routine implementation of this method may significantly increase the optimal utilization rate of antibiotics and decrease mortality in bacteremia patients., (© 2019 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.)

Bacillus cereus is a gram positive microorganism commonly involved in gastrointestinal infection but capable of causing severe infections and bacteremia. We describe here a case of bacteremia caused by B. cereus in a previously healthy young woman admitted to the intensive care unit following emergency surgery due to a penetrating abdominal stab wound and subsequent hepatic lesion. She developed fever during admission and cultures were taken. B. cereus was isolated in blood and hepatic fluid collection cultures. Treatment was adjusted according to the isolate, with good clinical results. It is important to highlight the pathogenic potential of this microorganism and not underestimate it as a contaminant when it is isolated from blood samples., (Copyright © 2019 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.)

The definition of sepsis continues to be as dynamic as the management strategies used to treat this. Sepsis-3 has replaced the earlier systemic inflammatory response syndrome (SIRS)-based diagnoses with the rapid Sequential Organ Failure Assessment (SOFA) score assisting in predicting overall prognosis with regards to mortality. Surgeons have an important role in ensuring adequate source control while recognizing the threat of carbapenem-resistance in gram-negative organisms. Rapid diagnostic tests are being used increasingly for the early identification of multi-drug-resistant organisms (MDROs), with a key emphasis on the multidisciplinary alert of results. Novel, higher generation antibiotic agents have been developed for resistance in ESKCAPE ( Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , and Enterobacter species) organisms while surgeons have an important role in the prevention of spread. The Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial has challenged the previous paradigm of length of antibiotic treatment whereas biomarkers such as procalcitonin are playing a prominent role in individualizing therapy. Several novel therapies for refractory septic shock, while still investigational, are gaining prominence rapidly (such as vitamin C) whereas others await further clinical trials. Management strategies presented as care bundles continue to be updated by the Surviving Sepsis Campaign, yet still remain controversial in its global adoption. We have broadened our temporal and epidemiologic perspective of sepsis by understanding it both as an acute, time-sensitive, life-threatening illness to a chronic condition that increases the risk of mortality up to five years post-discharge. Artificial intelligence, machine learning, and bedside scoring systems can assist the clinician in predicting post-operative sepsis. The public health role of the surgeon is key. This includes collaboration and multi-disciplinary antibiotic stewardship at a hospital level. It also requires controlling pharmaceutical sales and the unregulated dispensing of antibiotic agents globally through policy initiatives to control emerging resistance through prevention.

Especially in immunocompromised and intensive care patients VRE sepsis is associated with high mortality. The GeneXpert vanA/vanB assay is marketed for fast molecular surveillance of VRE colonization in peri-anal and rectal swabs. The aim of this study was to evaluate this assay for its usefulness for rapid identification of the vanAB determinant from positive blood cultures. During an evaluation phase, 33/34 blood cultures (negative = 13; vanA = 1; and vanB = 19) were correctly identified. In the validation phase 205/211 blood cultures were correctly identified (negative, n = 160; vanA, n = 2; vanB, n = 43). Sensitivity and specificity calculated from valid tests was 100% (95% CI: 90.2-100%) and 100% (95% CI: 97.1-100%), respectively. The error rate was 2.8%. The Xpert vanA/vanB cartridge is a reliable tool in the rapid molecular identification of the vanA and vanB determinant from positive blood cultures with moderate inhibition rates (2.8%) and high PPV and NPV. However, additional methods for species identification are required., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Early-onset sepsis (EOS) in neonates is a serious disease with severe complications. The increased severity of EOS and risk of death in newborns in recent years signify that continued monitoring to detect possible changes in the pathogen etiology, disease severity, and disease outcome is particularly important. We conducted a retrospective study on early-onset infection among infants (birth weights > 800 g) who were hospitalized in the Children's Hospital of Soochow University from January 1, 2011, to December 31, 2017. Multivariable analysis was performed to determine the significant predictors of mortality. The most frequent early-onset pathogen was Group B Streptococcus (GBS) (28.1%), followed by Escherichia coli (21.6%), Listeria monocytogenes (11.8%), and Klebsiella pneumoniae (7.8%). Most infants (85.6%) with early-onset infections survived until hospital discharge, while 44 (14.4%) patients died. Multivariable logistic regression analysis showed that the significant predictors of mortality were the pathogen (GBS, E. coli, or other pathogens) and birth weight (both P < 0.01). GBS remains the most frequent pathogen known to infect infants. E coli was the most common pathogen associated with neonatal mortality. Prevention of E. coli sepsis, specifically among preterm infants, remains a challenge.

Background: Late-onset sepsis (LOS) remains an important cause of morbidity and mortality in preterm infants. In this study, our aim was to investigate the red-cell distribution width (RDW) levels during a LOS episode, and its association with the type of growing microorganism and mortality., Methods: Preterm infants with culture-proven sepsis during their neonatal intensive care unit stay were enrolled. Red-cell distribution width levels were obtained in the first 4 h of postnatal life and at the onset of the LOS episode, and compared for these time frames. The study cohort was divided into two groups according to the type of the growing microorganism. The RDW levels were then assessed in intra- and inter-group analyses., Results: Eighty-six infants were included in the final analysis. RDW levels were increased in the study cohort after a LOS attack (P < 0.001). Infants with Gram-negative sepsis showed a significant increase in their RDW levels, but they remained unchanged in infants with Gram-positive sepsis (P < 0.001 and P = 0.4, respectively). An RDW cut-off of >19.50% was related with a sensitivity of 87% and a specificity of 81% for predicting late-onset Gram-negative sepsis (P < 0.001). Logistic regression analysis showed a positive association of RDW with mortality when adjusted for covariants (adjusted odds ratio: 1.40; 95% confidence interval: 1.02-1.80; P = 0.03)., Conclusions: Our findings show that RDW levels increased during a LOS episode in preterm infants, which was especially evident in Gram-negative infections. We believe that these findings may be of importance in the early diagnosis and prognosis of LOS in preterm infants., (© 2019 Japan Pediatric Society.)

Objectives: The aim of this study was to investigate the effect of daptomycin against vancomycin-resistant Enterococcus faecium bacteraemia using computer modelling., Methods: Data obtained in vitro from time-kill curves were evaluated by PK/PD modelling and Monte Carlo simulations to determine the logarithmic reduction in the number of colony-forming units (CFU)/mL over 18 days of daptomycin treatment at 6, 8, and 10 mg/kg doses every 24 or 48 h and with variations in creatinine clearance (CL CR ) of 15-29, 30-49, and 50-100 mL/min/1.73 m 2 . Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) for an area under the unbound drug concentration-time curve/minimum inhibitory concentration (fAUC/MIC) > 36 at the same doses and CL CR ., Results: Static time-kill model was employed to investigate the antibacterial efficacy of constant daptomycin concentrations. The time-kill curve analysis was performed using mathematical modelling based on a Hill coefficient factor. There was an expressive reduction (> 2 Log CFU/mL) over 18 days of daptomycin treatment in 75th percentile of individuals with CL CR of 15-100 mL/min/1.73 m 2 ) with daptomycin 6-10 mg/kg/day, except for daptomycin every 48 h. Using fAUC/MIC > 36, PTA was > 90% at MICs ≤ 2 μg/mL., Conclusions: Higher daptomycin doses were associated with higher mortality in time-kill curves. The simulations indicated that independent of the CL CR the therapeutic responses of VRE occur with doses of daptomycin ≥ 6 mg/kg/day and daptomycin every 48 h is insufficient to treat enterococcal bacteraemia.

Background: Many studies have suggested that procalcitonin can predict bloodstream infection and also distinguish between Gram-negative, Gram-positive and fungal infections after burn. However, up to now, there is no literature on serum procalcitonin level of multidrug-resistant pathogens and non-multidrug-resistant pathogens among Gram-negative bloodstream infections after burn. The purpose of this study is to explore the value of serum procalcitonin in identifying Gram-negative bloodstream infection in patients with febrile critical burn and then to investigate the difference of serum procalcitonin level between multidrug-resistant pathogens and non-multidrug-resistant pathogens among Gram-negative bloodstream infections after burn., Methods: Patients with febrile critical burn admitted to the burn department of our hospital from 1 January 2014 to 1 August 2018 were retrospectively analysed. Patients with positive blood culture whose blood samples were collected for simultaneous blood culture and procalcitonin testing were enrolled. All strains were identified by an automatic microorganism analyser, and procalcitonin was analysed by an automatic electrochemiluminescence immunoassay., Results: Overall, a total of 119 patients with positive blood culture met the inclusion criteria. There were 64 Gram-negative bacilli, 38 Gram-positive bacteria, 8 C. albicans and 9 polymicrobial bloodstream infections. The median procalcitonin value in Gram-negative bloodstream infections (2.67 ng/mL, interquartile range (IQR) 1.58-6.08) was significantly higher than that in Gram-positive bloodstream infections (1.04 ng/mL, IQR 0.35-1.60, P < 0.01), or C. albicans bloodstream infections (1.09 ng/mL, IQR 0.82-2.30, P < 0.05). Receiver operating characteristic curve (ROC) analysis showed that in addition to polymicrobial bloodstream infections, the area of procalcitonin under the curve distinguishing Gram-negative bloodstream infections from all other blood culture-positive bloodstream infections was 0.761, the best critical value was 1.73 ng/mL, the sensitivity was 73%, the specificity was 74%, the positive predictive value was 80%, the negative predictive value was 67%, The level of procalcitonin was significantly higher in multidrug-resistant Gram-negative bacilli (A. baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa) (2.76 ng/mL, IQR 2.01-7.76) than in non-multidrug-resistant bacilli (1.01 ng/mL, IQR 0.58-1.56, P < 0.01)., Conclusion: Elevated serum procalcitonin can identify Gram-negative bloodstream infections in patients with febrile critical burn. In Gram-negative bloodstream infections, high procalcitonin levels may be associated with multidrug-resistant Gram-negative bacilli (A. baumannii, K. pneumoniae and P. aeruginosa)., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction. Among the causative agents of bloodstream infections (BSIs), methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) are the key causative pathogens. Their rapid detection directly from Gram-positive cocci-positive blood culture specimens will promote timely treatment and help to implement effective infection control measures. Aim. We aim to develop a PCR-dipstick technique for the rapid detection of MRSA and VRE directly from positive blood culture specimens. Methodology. PCR-dipstick is a PCR-based multiplex detection technique where DNA-DNA hybridization is employed, and the results are interpreted with the naked eye. It was designed to target three drug resistance genes: mecA in MRSA and vanA / vanB in VRE from positive blood culture specimens. A total of 120 clinical isolates were used to evaluate the sensitivity and specificity of PCR-dipstick. Then, PCR-dipstick was examined for MRSA and VRE detection directly from positive blood cultures. Results. PCR-dipstick showed 100 % sensitivity and specificity in detecting mecA , vanA and vanB genes directly from bacterial colonies in comparison with multiplex PCR for genomic DNA followed by agarose gel electrophoresis. Further, it could differentially detect multiple resistant genes in pooled bacterial colonies ( n =10). Ultimately, PCR-dipstick could detect MRSA and VRE in positive blood cultures in ~3 h. Conclusion. The results of the current study substantiate that PCR-dipstick can be used as an efficient detection system for MRSA and VRE directly from Gram-positive cocci-positive blood cultures. Its affordability and rapidity indicate that PCR-dipstick can be an effective tool for controlling nosocomial pathogens.

Background: Lipopolysaccharide (LPS), also known as endotoxin, is cell wall component of Gram-negative (GN) bacteria, which may contribute to the progression of a local infection to sepsis. Previous studies demonstrate that LBP is detectable in peritoneal effluents of peritoneal dialysis (PD) patients and it is significantly elevated in PD patients with peritonitis caused by both GN and Gram-positive (GP) bacteria., Aim: The aim of this study was to evaluate LPS levels in PD patients; in particular, we investigated different LPS levels in the context of GP and GN peritonitis., Material and Methods: We enrolled 49PD (61% Continuous Ambulatory PD and 39% Automated PD) patients: 37 with peritonitis and 12 without. Quantitative determination of LPS was performed by Enzyme-linked Immunosorbent Assay Kitin peritoneal and plasma samples., Results: Quantitative analysis of peritoneal and plasma LPS showed significantly higher levels in PD patients with peritonitis compared to patients without (p = 0.001). Furthermore, we divided patients with peritonitis in 2 groups on the basis of Gram staining (GP 27; GN 12). Peritoneal and plasma LPS levels showed significantly lower levels in PD patients with GP peritonitis than in patients with GN (p = 0.001). The median level of LPS showed no significant differences between patients without peritonitis and with GP peritonitis (p = 0.195). On the contrary, LPS levels showed significantly higher levels in PD patients with GN peritonitis compared to patients without peritonitis (p = 0.001). A significant positive correlation was observed between peritoneal white blood cells count (pWBC) and peritoneal LPS (Spearman's rho = 0,412, p = 0.013). However, no statistically significant correlation was observed between plasma LPS and WBC count., Conclusion: We observed LPS presence in all PD patients. In particular, our results demonstrated that LPS is significantly elevated in PD patients with GN peritonitis. Furthermore, pWBC and LPS levels increased proportionally in PD patients with peritonitis. Peritoneal and plasma LPS levels could be a useful marker for diagnosis and management of GN peritonitis in PD patients., (© 2020 S. Karger AG, Basel.)

Vancomycin is a glycopeptide antibiotic used for the treatment of Gram-positive infections. For adult patients, treatment with vancomycin requires effective therapeutic drug-monitoring (TDM) to achieve clinical outcomes and reduce the incidence of adverse effects. However, it remains still unclear whether the TDM with vancomycin is beneficial in yielding better clinical outcomes in pediatrics. The objective of our study was to evaluate whether the clinical response to treatment was associated with initial trough concentrations of vancomycin in pediatric patients. A retrospective observation study of 60 patients (age: 1 month-15 years) who had completed and qualified for analysis was conducted at Kyoto University Hospital. The response to treatment was assessed by the time to resolution of fever and time to 50% decline in C-reactive protein (CRP). In addition, we explored whether vancomycin trough level was associated with the baseline characteristics. Trend analysis showed that there were significant correlations between vancomycin trough level and age, body weight, estimated glomerular filtration rate, and serum albumin levels. The time to resolution of fever of the patients with higher initial trough level (≥ 5 µg/mL) was significantly lower than that of the patients with lower trough level (< 5 µg/mL). The higher vancomycin concentration tended to be associated with the shorter time to 50% decline in CRP. The findings suggest that initial trough concentration is important in achieving better outcomes with vancomycin treatment in pediatrics.

Objectives: The study aimed to describe the identity and antimicrobial resistance patterns of the causative agents of bacterial meningitis in children referred to Children's Medical Center (CMC) Hospital, Tehran, Iran., Methods: This retrospective study was performed at CMC Hospital during a six-year period from 2011 to 2016. The microbiological information of the patients with a diagnosis of bacterial meningitis was collected and the following data were obtained: patients' age, sex, hospital ward, the results of CSF and blood cultures, and antibiotic susceptibility profiles of isolated organisms., Results: A total of 118 patients with bacterial meningitis were admitted to CMC hospital. Sixty-two percent (n=73) of the patients were male. The median age of the patients was ten months (interquartile range [IQR]: 2 months-2 years) and the majority of them (n=92, 80%) were younger than two years of age. The highest number of patients (n=47, 40%) were admitted to the surgery department. Streptococcus epidermidis was the most frequent isolated bacterium (n=27/127, 21%), followed by Klebsiella pneumoniae (n=20/127, 16%), and Staphylococcus aureus (n=16/127, 12.5%). Blood culture was positive in 28% (n=33/118) of patients. Ampicillin-sulbactam and imipenem were the most effective antibiotics against Gram-negative bacteria isolated from CSF cultures. In the case of Gram-positive organisms, ampicillinsulbactam, vancomycin, and linezolid were the best choices. Imipenem was the most active drug against Gram-negative blood pathogens. Also, ampicillin and vancomycin had the best effect on Gram-positive bacteria isolated from blood cultures., Conclusion: Results of this study provide valuable information about the antibiotic resistance profiles of the etiologic agents of childhood meningitis, which can be used for prescription of more effective empirical therapies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Augmented renal clearance (ARC) refers to enhanced renal elimination of circulating solute has attracted attention widely and in recent years increasing attention has been paid to patients with ARC. A population pharmacokinetic (PPK) analysis was performed to provide a reference for clinical individual therapy of vancomycin in in ARC patients., Methods: Patients hospitalized in the First Affiliated Hospital of China Medical University from July 2013 to December 2015 and suspected or confirmed infection caused by gram-positive bacteria were enrolled in this study. The serum concentrations were determined by enzyme multiplied immunoassay technique. A nonlinear mixed effects model (NONMEM) was used to evaluate the influence of covariates on vancomycin pharmacokinetics and obtain the PPK model. Bootstrap, visual predictive checks and normalized prediction distribution errors were used to evaluate the estabolishe model., Results: A total of 186 vancomycin serum samples from 95 patients, including 24 females and 71 males were studied. The final model was as follows: [Formula: see text] and [Formula: see text] . The final PPK model in ARC patients was proved to be robust and reliable. Age was identified as the most significant covariate in the final model., Conclusions: In this study, a simple population pharmacokinetic (PPK) model of vancomycin in Chinese patients with ARC was established using a nonlinear mixed-effects model (NONMEM). The final PPK model could achieve a good predictive effect, which provides a reference for clinical individual therapy., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Procalcitonin (PCT) is routinely used for an early recognition of severe infections and for promoting appropriate use of antibiotics. However, limited data correlating values of PCT with etiology of infection has been reported., Methods: During 2016, all positive blood cultures (BC) were retrospectively extracted in a 1100-beds Italian tertiary-care hospital. PCT and C-reactive protein (CRP) values were recorded within 24h from BC collection. Primary endpoint of the study was to investigate the correlation between PCT and CRP values and the occurrence of bloodstream infections (BSI) caused by bacteria or fungi., Results: During the study period, 1296 positive BC were included: 712 (54.9%) due to Gram-positive (GP), 525 (40.5%) due to Gram-negative (GN) strains, and 59 (4.6%) caused by fungi. Among GN isolates, enterobacteriaceae were reported in 453 (86.3%) cases. PCT values were higher in patients with GN etiology (26.1±14.2ng/mL) compared to GP (6.9±4.5) and fungi (3.3±2.4). Mean values for CRP in GN, GP, and fungi were not different. Receiver Operating Characteristic (ROC) curves showed an area under curve (AUC) of 0.71 for PCT and 0.51 for CRP among GN isolates; an AUC of 0.7 for PCT and 0.52 for CRP among enterobacteriaceae. Lower AUC for PCT were reported for GP and fungi., Conclusions: PCT showed moderate performance in early detection (within 24h) of Gram-negative infections, especially those caused by enterobacteriaceae. Further prospective studies are mandatory to confirm these observations., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme controls blood cholesterol levels by downregulating the expression of the low-density lipoprotein receptor (LDLR). Pathogenic lipids (e.g. lipopolysaccharide) are removed from the circulation by an LDLR/PCSK9-dependent mechanism; thus, it has been suggested that PCSK9 inhibitors may be beneficial in the treatment of infections. We measured plasma PCSK9 levels in patients with culture-positive bacteraemia and explored pathogen-dependent and infection site-dependent effects as well as correlations between patient characteristics and outcome., Methods: Proprotein convertase subtilisin/kexin type 9 in the plasma was measured with an enzyme-linked immunosorbent assay from 481 patients with blood culture-positive infection on days 0 to 4 after admission to the emergency department. Patient outcome and clinical and laboratory data were gathered retrospectively from patient records., Results: The plasma PCSK9 level was elevated equally in patients with Gram-positive or Gram-negative bacterial infections; particularly high levels were seen in patients with a lower respiratory tract infection and Streptococcus pneumoniae bacteraemia. PCSK9 levels showed a significant positive correlation with C-reactive protein (CRP) level. Bacteraemia patients with liver disease or a history of alcohol abuse had significantly lower levels of plasma PCSK9. Reduced PCSK9 plasma responses in patients were significantly associated with mortality at days 7, 28 and 90., Conclusion: Proprotein convertase subtilisin/kexin type 9 is upregulated in blood culture-positive infections. Plasma PCSK9 resembles acute-phase proteins; its expression is induced during an infection, reduced in liver disease and correlates positively with CRP level. We have shown that PCSK9 levels are lower in patients with a fatal prognosis., (© 2019 The Association for the Publication of the Journal of Internal Medicine.)

While the clinical characteristics and treatment outcomes of Enterococcus faecalis and E. faecium bacteremia are well known, those of E. durans bacteremia are still largely unclear. We retrospectively identified 80 adult E. durans bacteremia cases treated at our 2700-bed tertiary care hospital between January 1997 and December 2016. We compared the clinical characteristics and treatment outcomes of the adult patients with E. durans bacteremia (case group) with those of E. faecalis and E. faecium bacteremia cases (two control groups). The case and control groups were matched for sex, age, and date of onset of bacteremia. E. durans was responsible for 1.2% of all enterococcal bacteremia cases at our hospital. Of 80 cases, 39 (48.8%) had biliary tract infection and 18 (22.5%) had urinary tract infection. Community-onset bacteremia was more frequent in the case group than in the control groups (56.2% vs. 35.0% vs. 21.2%, p < 0.01). Infective endocarditis tended to be more common in the E. durans group (7.5% vs. 1.2% vs. 1.2%, p = 0.05). The majority of E. durans isolates were susceptible to penicillin (66/76, 86.8%), ampicillin (67/76, 88.2%), and vancomycin (75/76, 98.7%). The case group had significantly lower all-cause mortality (20.0% vs. 31.2% vs. 42.5%, p < 0.01) and bacteremia-related mortality (2.5% vs. 16.2% vs. 18.8%, p < 0.01) than the control groups. E. durans bacteremia mainly originates from the biliary or urinary tract and is associated with a lower risk of mortality.

Early differential diagnosis of bloodstream infections (BSIs) caused by different sources and species of bacteria in hospitalized patients is crucial for the timely targeted interventions including appropriate use of antibiotics. The aim of this study was to identify 9 biomarkers for the early differentiation of gram-negative-bloodstream infection (GN-BSI), gram-positive (GP)-BSI, and fungal-BSI.A prospective study was conducted for a total of 390 inpatients who underwent blood culture in the Chinese PLA General Hospital from September 2015 to March 2018. Patients with positive culture of a single pathogen were divided into GN-BSI, GP-BSI, and Fungal-BSI groups, and a culture-negative disease control group was also established. The serum levels of macrophage inflammatory protein 1β (MIP-1β), tumor necrosis factor α (TNF-α), interleukin (IL)-3, interferon (IFN)-γ, IL-17A, IL-4, IL-12p70, and P-selectin were detected and the NLR was calculated from routine blood test. Receiver-operating characteristic analysis was used to determine the efficacy of various indicators in the differential diagnosis of BSIs. Prediction and validation experiments on clinical patient samples (263 cases) were also performed.The level of IL-3 in the GP-BSI group was significantly higher than those in the other 3 groups. The level of IFN-γ in the fungal-BSI group was significantly higher than those in the other 3 groups. NLR, MIP-1β, TNF-α, IL-17A, and IL3 exhibited some efficacy when distinguishing between GN-BSI and GP-BSI and NLR had the largest area under curve (AUC) (0.728), followed by MIP-1β with an AUC of 0.679. IFN-γ and IL-3 exhibited some value in differential diagnosis between GN-BSI and Fungal-BSI. IL-3, MIP-1β, TNF-α, IFN-γ, NLR, IL-17A, and IL-4 exhibited some value in distinguishing fungal-BSI and GP-BSI, with IL-3 had the largest AUC (0.722), followed by MIP-1β with an AUC of 0.703.NLR and MIP-1β may be valuable in differentiating GN-BSI from GP-BSI in hospitalized patients. IFN-γ and IL-3 may be helpful in differential diagnosis GN-BSI and fungal-BSI. IL-3 and MIP-1β exhibited some diagnostic efficacy in distinguishing fungal-BSI and GP-BSI. Additionally, IL-3 with high serum level may be a marker for GP-BSI and IFN-γ with high serum level may be a valuable marker for the prediction of Fungal-BSI. The utility of these biomarkers to predict BSIs owing to different pathogens in hospitalized patients needs to be assessed in further studies.

Background: In Japan, blood cultures for children are performed by pediatric residents, and povidone-iodine (PI) is the recommended solution for skin preparation. Given that PI needs to be applied for 1.5-2 min before venipuncture, skin preparation may be suboptimal if this is not followed. In this study, we investigated the blood culture contamination rate after skin preparation with only 70% isopropyl alcohol (IPA) or IPA plus PI., Methods: We performed a retrospective study of patients aged ≤6 years who provided blood cultures in the emergency department or pediatric ward. Patients with indwelling central venous catheter were excluded. We evaluated the impact of changing the method of skin preparation, comparing the traditional method using IPA plus PI between 2008 and 2010 (IPA + PI group) with the simplified method using only IPA between 2015 and 2017 (IPA group)., Results: A total of 5,365 blood culture samples were eligible for this study. Of these, 171 (3.2%) had an organism identified in blood culture. Of the blood culture-positive samples, 68 (1.3%) were true positive and 103 (1.9%) were contaminated. Thirty-eight (1.6%) of 2,407 cultures in the IPA group were contaminated, whereas 65 (2.2%) of 2,958 cultures in the IPA + PI group were contaminated (OR, 0.72; 95%CI: 0.48-1.07; P = 0.1). Coagulase-negative Staphylococcus grew significantly less in the IPA group (1.7% vs 1.0%, P = 0.02)., Conclusions: A single application of 70% IPA may be the optimal skin preparation method for obtaining peripheral blood cultures from children in Japan., (© 2019 Japan Pediatric Society.)

Endotoxemia often occurs in patients with gram-positive infections. The possible mechanism is thought to be bacterial translocation after enterocyte hypoperfusion injury. However, the association between endotoxemia and enterocyte injury among patients with gram-positive septic shock has never been assessed. The aim of this study was to evaluate the association between endotoxemia and enterocyte injury in gram-positive septic shock patients and to evaluate the association among endotoxemia, subsequent clinical course, and other related factors.This was a posthoc analysis of a prospective observational study that evaluated the capability of intestinal fatty acid-binding protein (I-FABP), an indicator of enterocyte injury, to predict mortality. Among 57 patients in septic shock, those whose causative microorganisms were gram positive were included. The correlation between endotoxin activity (EA), which indicates endotoxemia, and I-FABP levels upon admission to the intensive care unit (ICU), the clinical course, and other related factors were evaluated.A total of 21 patients were examined. One-third of the patients presented with high EA levels at the time of ICU admission. However, there was no significant correlation between EA and I-FABP levels (Spearman ρ = 0.002, P = .993). Additionally, high EA levels were not associated with abdominal complications after ICU admission or mortality. Similarly, high EA levels were not associated with severity scores, inotropic scores, or lactate levels upon ICU admission, which were previously reported to be factors related to high EA levels.In this posthoc analysis, no correlation was observed between endotoxemia and enterocyte injury among patients in gram-positive septic shock. Additionally, high EA levels were not associated with the clinical course and reported factors related to endotoxemia. Although our results need to be validated in a large prospective cohort study, hypoperfusion enterocyte injury might not be a cause of endotoxemia in these patients. Thus, if there is no correlation between EA and I-FABP levels, other mechanisms that induce high EA levels among patients with gram-positive septic shock should be elucidated.

Background: Bacterial bloodstream infections (BSIs) cause high morbidity and mortality worldwide in humans, but the pathogenic spectrum varies from region to region. Long-term monitoring of the pathogenic spectrum and changes in bacterial antibiotic resistance is hugely important for effective clinical therapy and infection control. This study examined the data for BSIs in Tongji Hospital, one of the largest teaching hospitals in China, in an attempt to gain better understanding of bacterial antibiotic resistance in China, focusing on central China., Methods: Data from Tongji Hospital for a 20-year period (1998-2017) were used for a retrospective analysis to understand the pathogenic spectrum of BSIs and the changes occurring in antimicrobial resistance in central China. The disk diffusion and E test methods were used for antimicrobial susceptibility testing according to Clinical & Laboratory Standards Institute methodologies, and the data were analyzed by WHONET 5.6 software., Results: The isolated pathogens mainly came from hospitalized patients not treated in intensive care units (ICUs), and accounted for 81.5% of the total (9130/11200). The most common Gram-negative and Gram-positive bacterial BSI-causing pathogens were Escherichia coli and Staphylococcus aureus , respectively. The detection rate for methicillin-resistant S. aureus (MRSA) in the hospitalized non-ICU patients increased from 8.4% in 1998-2002 to 63% in 2013-2017, while the detection rate for carbapenem-resistant (CR) Klebsiella pneumoniae was below 5% in 1998-2012 but increased to 34.9% in 2013-2017. In contrast, worryingly, the detection rate for CR K. pneumoniae in ICU patients increased from 0% in 2013 to 75% in 2016. E. coli displayed the highest sensitivity rates to imipenem, meropenem and amikacin, all of which were > 90%, followed by cefoxitin at > 80%, and cefoperazone/sulbactam at > 70%. K. pneumoniae isolates were most sensitive to imipenem, meropenem and amikacin antibiotics, with sensitivity rates exceeding 60%. S. aureus isolates were most sensitive to vancomycin, teicoplanin and trimethoprim/sulfamethoxazole, with sensitivity rates exceeding 90%., Conclusions: BSIs caused by CR K. pneumoniae clearly posed a severe challenge to infection control and treatment of ICU and non-ICU patients in this retrospective study, while MRSA was an issue for non-ICU patients., Competing Interests: Competing interestsThe authors declare that they have no competing interest.

Background: Although surgical site infection after craniotomy (SSI-CRAN) is a serious complication, risk factors for its development have not been well defined. We aim to identify the risk factors for developing SSI-CRAN in a large prospective cohort of adult patients undergoing craniotomy., Methods: A series of consecutive patients who underwent craniotomy at a university hospital from January 2013 to December 2015 were prospectively assessed. Demographic, epidemiological, surgical, clinical and microbiological data were collected. Patients were followed up in an active post-discharge surveillance programm e for up to one year after surgery. Multivariate analysis was carried out to identify independent risk factors for SSI-CRAN., Results: Among the 595 patients who underwent craniotomy, 91 (15.3%) episodes of SSI-CRAN were recorded, 67 (73.6%) of which were organ/space. Baseline demographic characteristics were similar among patients who developed SSI-CRAN and those who did not. The most frequent causative Gram-positive organisms were Cutibacterium acnes (23.1%) and Staphylococcus epidermidis (23.1%), whereas Enterobacter cloacae (12.1%) was the most commonly isolated Gram-negative agent. In the univariate analysis the factors associated with SSI-CRAN were ASA score > 2 (48.4% vs. 35.5% in SSI-CRAN and no SSI-CRAN respectively, p  = 0.025), extrinsic tumour (28.6% vs. 19.2%, p  = 0.05), and re-intervention (4.4% vs. 1.4%, p  = < 0.001). In the multivariate analysis, ASA score > 2 (AOR: 2.26, 95% CI: 1.32-3.87; p  = .003) and re-intervention (OR: 8.93, 95% CI: 5.33-14.96; p  < 0.001) were the only factors independently associated with SSI-CRAN., Conclusion: The risk factors and causative agents of SSI-CRAN identified in this study should be considered in the design of preventive strategies aimed to reduce the incidence of this serious complication., Competing Interests: The study only includes anonymised routine surveillance data. The need for informed consent and the information sheet were waived because the follow-up of patients undergoing craniotomy is part of the centre’s own surveillance programme. The study was approved by the Clinical Research Ethics Committee of Bellvitge University Hospital (Reference number PR334/18).Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objectives: The optimal treatment for serious infections due to Enterococcus spp. is unknown although combination antimicrobial therapy is often recommended for invasive infections to achieve bactericidal activity and improve clinical outcomes. Oritavancin is a novel lipoglycopeptide agent with in vitro activity against enterococci, including vancomycin-resistant VanA-type Enterococcus faecium. Data on its activity in combination with other antibacterials are limited. The objective of this study was to evaluate the activity of oritavancin alone and in combination with ceftriaxone, daptomycin, gentamicin, linezolid and rifampicin against vancomycin-susceptible and -resistant enterococci in in vitro time-kill analyses., Methods: Five enterococcal strains were used for all experiments: three vancomycin-resistant VanA-type E. faecium clinical bloodstream isolates, vancomycin-resistant VanA-type E. faecium ATCC 700221 and vancomycin-susceptible Enterococcus faecalis ATCC 29212. Individual drugs were tested at ¼, ½, 1, 2 and 4× MIC. Oritavancin combination experiments were performed with each agent at ¼× MIC., Results: Daptomycin was the most active single agent and was bactericidal against all strains at 4× MIC, followed by oritavancin, which was bactericidal against all three clinical VRE strains at ≥2× MIC. In combination experiments at ¼× MIC, oritavancin was synergistic with gentamicin against strains not displaying high-level aminoglycoside resistance. No other synergy against VRE strains was observed in any experiment. Strain- and drug-dependent antagonism was observed for many combinations., Conclusions: These in vitro data do not support the routine use of combination therapy with oritavancin in the treatment of infections due to VRE., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Despite the advancement in diagnostic modalities of sepsis, it is still a leading cause of morbidity and mortality. Differentiation between sepsis and non-infectious disease states remains a diagnostic challenge. Procalcitonin (PCT) is useful for the diagnosis of sepsis but it varies in cut-off ranges at different clinical settings. The aim of this study was to correlate serum PCT levels with cultures and to evaluate the best cut-off values with high sensitivity and specificity for PCT., Methodology: This prospective study included 305 patients from different medical wards; the patients were classified into group I: controls (n=46), group II: culture-negative sepsis (n=76) and group III: culture-positive sepsis (n=196). Mean p value <0.05 was considered significant., Results: PCT levels were significantly higher in group II and group III as compared with group I. In group II, the best cut-off point for PCT was 1.3ng/ml with 87.30% sensitivity and 78.26% specificity (area under curve 0.86). In group III, the best cut-off value of 2.20ng/ml with 98.47% sensitivity and 89.13% specificity was found (AUC 0.96)., Conclusion: Procalcitonin can accurately differentiate culture-negative and culture-positive sepsis from non-infectious diseases, thus making it a promising biomarker in diagnosis of bacterial sepsis., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Multidrug-resistant enterococcal strains emerged in the early 1980s and are now among the leading causes of drug-resistant bacterial infection worldwide. We used functional genomics to study an early bacterial outbreak in patients in a Wisconsin hospital between 1984 and 1988 that was caused by multidrug-resistant Enterococcus faecalis The goal was to determine how a clonal lineage of E. faecalis became adapted to growth and survival in the human bloodstream. Genome sequence analysis revealed a progression of increasingly fixed mutations and repeated independent occurrences of mutations in a relatively small set of genes. Repeated independent mutations suggested selection within the host during the course of infection in response to pressures such as host immunity and antibiotic treatment. We observed repeated independent mutations in a small number of loci, including a little studied polysaccharide utilization pathway and the cydABDC locus. Functional studies showed that mutating these loci rendered E. faecalis better able to withstand antibiotic pressure and innate immune defenses in the human bloodstream. We also observed a shift in mutation pattern that corresponded to the introduction of carbapenem antibiotics in 1987. This work identifies pathways that allow enterococci to survive the transition from the human gut into the bloodstream, enabling them to cause severe bacteremia associated with high mortality., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objectives: We aimed to describe the current time-to-positivity (TTP) of blood cultures in individuals with onco-haematological diseases with febrile neutropenia. We assessed the probability of having a multidrug-resistant Gram-negative bacilli (MDR-GNB) bloodstream infection (BSI) 24 h after cultures were taken, to use this information for antibiotic de-escalation strategies., Methods: BSI episodes were prospectively collected (2003-2017). When a patient experienced more than one BSI, only one episode was randomly chosen. Time elapsed from the beginning of incubation to a positive reading was observed; TTP was recorded when the first bottle had a positive result., Results: Of the 850 patient-unique episodes, 323 (38%) occurred in acute leukaemia, 185 (21.8%) in non-Hodgkin's lymphoma and 144 (16.9%) in solid neoplasms. Coagulase-negative staphylococci (225; 26.5%), Escherichia coli (207; 26.1%), Pseudomonas aeruginosa (136; 16%), Enterococcus spp. (81; 9.5%) and Klebsiella pneumoniae (67; 7.9%), were the most frequent microorganisms isolated. MDR-GNB were documented in 126 (14.8%) episodes. Median TTP was 12 h (interquartile range 9-16.5 h). Within the first 24 h, 92.1% of blood cultures were positive (783/850). No MDR-GNB was positive over 24 h. Of the 67 (7.9%) episodes with a TTP ≥24 h, 25 (37.3%) occurred in patients who were already receiving active antibiotics against the isolated pathogen. Most common isolations with TTP ≥24 h were coagulase-negative staphylococci, candidaemia and a group of anaerobic GNB., Conclusions: Currently, the vast majority of BSI in individuals with onco-haematological diseases with febrile neutropenia have a TTP <24 h, including all episodes caused by MDR-GNB. Our results support reassessing empiric antibiotic treatment in neutropenic patients at 24 h, to apply antibiotic stewardship de-escalation strategies., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: The smr and qacA/B genes in Staphylococcus aureus confer tolerance to antiseptics and are associated with nosocomial acquisition of infection and underlying medical conditions. Such antiseptic tolerance (AT) genes have also been reported in coagulase-negative staphylococci (CoNS) and enterococci, however, few data are available regarding their prevalence. We sought to describe the frequency of AT genes among bloodstream isolates of S. aureus, CoNS and enterococci at Texas Children's Hospital (TCH)., Methods: Banked CoNS, S. aureus and enterococci isolated from blood cultures collected bewteen October 1, 2016, and October 1, 2017, were obtained from the TCH clinical microbiology laboratory. All isolates underwent polymerase chain reaction (PCR) assay for the qacA/B and smr genes. Medical records were reviewed for all cases., Results: In total, 103 CoNS, 19 Enterococcus spp, and 119 S. aureus isolates were included in the study, and 80.6% of the CoNS possessed at least 1 AT gene compared to 37% of S. aureus and 43.8% of E. faecalis isolates (P &lt; .001). Among CoNS bloodstream isolates, the presence of either AT gene was strongly associated with nosocomial infection (P &lt; .001). The AT genes in S. aureus were associated with nosocomial infection (P = .025) as well as the diagnosis of central-line-associated bloodstream infection (CLABSI; P = .04) and recent hospitalizations (P &lt; .001). We found no correlation with genotypic AT in E. faecalis and any clinical variable we examined., Conclusions: Antiseptic tolerance is common among bloodstream staphylococci and E. faecalis isolates at TCH. Among CoNS, the presence of AT genes is strongly correlated with nosocomial acquisition of infection, consistent with previous studies in S. aureus. These data suggest that the healthcare environment contributes to AT among staphylococci.

Introduction: The majority of vancomycin-resistant Enterococcus faecium (VREfm) in Australia is of the vanB genotype. An outbreak of vanA VREfm emerged in our haematology/oncology unit between November 2014 and May 2015. The first case of daptomycin non-susceptible E. faecium (DNSEfm) detected was a patient with vanA VREfm bacteraemia who showed clinical failure of daptomycin therapy, prompting microbiologic testing confirming daptomycin non-susceptibility., Objectives: To describe the patient profiles, antibiotic susceptibility and genetic relatedness of vanA VREfm isolates in the outbreak., Methods: Chart review of vanA VREfm colonized and infected patients was undertaken to describe the demographics, clinical features and outcomes of therapy. Whole genome sequencing of vanA VREfm isolates involved in the outbreak was conducted to assess clonality., Results: In total, 29 samples from 24 patients tested positive for vanA VREfm (21 screening swabs and 8 clinical isolates). Five isolates were DNSEfm (four patients colonized, one patient with bacteraemia), with only one patient exposed to daptomycin previously. In silico multi-locus sequence typing of the isolates identified 25/26 as ST203, and 1/26 as ST796. Comparative genomic analysis revealed limited core genome diversity amongst the ST203 isolates, consistent with an outbreak of a single clone of vanA VREfm., Conclusions: Here we describe an outbreak of vanA VREfm in a haematology/oncology unit. Genomic analysis supports transmission of an ST203 vanA VRE clone within this unit. Daptomycin non-susceptibility in 5/24 patients left linezolid as the only treatment option. Daptomycin susceptibility cannot be assumed in vanA VREfm isolates and confirmatory testing is recommended.

Pathogenic bacteremia portends a high mortality risk in adult patients admitted to an Emergency Department (ED). This study aims to investigate the effect of adding high-sensitivity C-reactive protein (hs-CRP) to procalcitonin (PCT) and lactate in predicting bacteremia, Gram-negative (GNB) and Gram-positive bacteremia (GPB), using the optimal cutoff derived from the receiver operating characteristics analysis. We evaluated the diagnostic measures, including the positive-test likelihood (LR+), the negative-test likelihood (LR-), and the diagnostic odds ratio (DOR) using a single-center retrospective analysis design. This Standards for Reporting Diagnostic-compliant study comprised 886 consecutive adults who were admitted to the ED in 2010; to this cohort, a 22.2% prevalence of true bacteremia was subsequently confirmed. At the cutoff of 3.9 μg/L, PCT had a DOR of 5.3 (95% confidence interval [CI]: 3.76-7.61) and LR + of 2.8 (95% CI: 2.3-3.4) in predicting overall bacteremia. Elevated PCT and lactate (cutoff at 2 mmol/L), increased the DOR and LR + to 6.3 (95% CI: 4.27-9.29) and 4.0 (95% CI: 3.1-5.2). The DOR and LR + were further improved to 7.1 (95% CI: 4.2-11.95) and 5.6 (95% CI: 3.7-8.6), respectively, when hs-CRP at the cutoff of 1238 nmol/L was added to PCT plus lactate. High-sensitivity CRP at the cutoff of 1,255 nmol/L can enhance the discriminative power raising DOR and LR + values for GPB. The elevation of hs-CRP at the optimal cutoff might improve the diagnostic performance to predict unspecified bacteremia and GPB, but not GNB.

Background: Lipopolysaccharide (endotoxin) from the outer Gram-negative bacterial wall can induce a harmful immunologic response, involving hemodynamic deprivation, and is one important motor driving the septic cascade. The positively charged poly-imine ethylene layer on the oXiris membrane is capable of adsorbing negatively charged endotoxin molecules and removing them from the blood compartment. Endotoxin is detrimental and should be removed from blood., Summary: The adsorbable endotoxin fraction in blood arises from a tight balance between seeding from an infectious focus and removal by an overwhelmed immune system. The net sum of remaining endotoxin in blood is available for an adsorption process in the oXiris filter. Endotoxin data from 2 patients with severe Gram-negative septic shock and endotoxemia in this case series, speaks for a considerable share of the adsorption of the oXiris filter in the endotoxin net removal over time. Key Messages: Analysis of combined in vitro and in vivo data speaks for an effect of the oXiris filter in lowering endotoxin., (© 2019 The Author(s). Published by S. Karger AG, Basel.)

Vancomycin-resistant Enterococcus faecium (VREfm) is a major cause of nosocomial infection and is categorized as high priority by the World Health Organization global priority list of antibiotic-resistant bacteria. In the past, livestock have been proposed as a putative reservoir for drug-resistant E. faecium strains that infect humans, and isolates of the same lineage have been found in both reservoirs. We undertook cross-sectional surveys to isolate E. faecium (including VREfm) from livestock farms, retail meat, and wastewater treatment plants in the United Kingdom. More than 600 isolates from these sources were sequenced, and their relatedness and antibiotic resistance genes were compared with genomes of almost 800 E. faecium isolates from patients with bloodstream infection in the United Kingdom and Ireland. E. faecium was isolated from 28/29 farms; none of these isolates were VREfm, suggesting a decrease in VREfm prevalence since the last UK livestock survey in 2003. However, VREfm was isolated from 1% to 2% of retail meat products and was ubiquitous in wastewater treatment plants. Phylogenetic comparison demonstrated that the majority of human and livestock-related isolates were genetically distinct, although pig isolates from three farms were more genetically related to human isolates from 2001 to 2004 (minimum of 50 single-nucleotide polymorphisms [SNPs]). Analysis of accessory (variable) genes added further evidence for distinct niche adaptation. An analysis of acquired antibiotic resistance genes and their variants revealed limited sharing between humans and livestock. Our findings indicate that the majority of E. faecium strains infecting patients are largely distinct from those from livestock in this setting, with limited sharing of strains and resistance genes. IMPORTANCE The rise in rates of human infection caused by vancomycin-resistant Enterococcus faecium (VREfm) strains between 1988 to the 2000s in Europe was suggested to be associated with acquisition from livestock. As a result, the European Union banned the use of the glycopeptide drug avoparcin as a growth promoter in livestock feed. While some studies reported a decrease in VREfm in livestock, others reported no reduction. Here, we report the first livestock VREfm prevalence survey in the UK since 2003 and the first large-scale study using whole-genome sequencing to investigate the relationship between E. faecium strains in livestock and humans. We found a low prevalence of VREfm in retail meat and limited evidence for recent sharing of strains between livestock and humans with bloodstream infection. There was evidence for limited sharing of genes encoding antibiotic resistance between these reservoirs, a finding which requires further research., (Copyright © 2018 Gouliouris et al.)

Bacterial sepsis remains a major cause of mortality and blood cultures are the gold standard of laboratory diagnosis even though they lack sensitivity in neonates. Culturenegative sepsis, also known as clinical sepsis, has long been considered a diagnosis in neonatal intensive care units because, as well as culture-positive infants, culture-negative neonates have worse prognosis in comparison with non-infected ones. Quantitative amplifications are used to detect bacterial infections in neonates but results are considered only in a qualitative way (positive or negative). The aim of the present study was to determine and compare bacterial load levels in blood culture-positive and culture-negative neonatal sepsis. Seventy neonates with clinical and laboratory evidence of infection admitted at three neonatal intensive care units were classified as blood culture-positive or culture-negative. Blood samples obtained at the same time of blood cultures had bacterial load levels assessed through a 16S rDNA qPCR. Blood cultures were positive in 29 cases (41.4%) and qPCR in 64 (91.4%). In the 29 culture-positive cases, 100% were also positive by qPCR, while in the 41 culture-negative cases, 35 (85.4%) were positive by qPCR. Bacterial load levels were in general < 50 CFU/mL, but were significantly higher in culture-positive cases (Mann-Whitney, p = 0.013), although clinical and laboratory findings were similar, excepting for deaths. In conclusion, the present study has shown that blood culture-negative neonates have lower bacteria load levels in their bloodstream when compared to blood culture-positive infants.

In community hospitals, antimicrobial stewardship team notification of rapid diagnostic testing (RDT) results may not be feasible. A retrospective quasi-experimental study was conducted evaluating 252 adult inpatients with blood cultures positive for Gram-positive cocci in clusters (pre-RDT, n = 143; post-RDT, n = 109). The median time to appropriate therapy was significantly shorter in the post-RDT group (15 versus 0 h, P < 0.001), and the mean length of stay for patients with coagulase-negative staphylococcus was significantly shorter (10.5 versus 7.7 days; P = 0.015)., (Copyright © 2018 American Society for Microbiology.)