Impact of polymyxin B hemoperfusion therapy on high endotoxin activity level patients after successful infection source control: a prospective cohort study.

We sought to evaluate the clinical implication of endotoxin levels in gram-negative bacilli (GNB)-induced abdominal septic shock patients with polymyxin B-hemoperfusion (PMX-HP) treatment. A prospective cohort of 60 patients who received surgical infectious source control for abdominal sepsis from January 2019 to December 2020 was included in the study. Endotoxin activity (EA) levels and Sequential Organ Failure Assessment (SOFA) scores were assessed immediately after surgery (baseline), 24, and 48 h post baseline. With receiver operating characteristic curves, the patients were stratified into two groups by the EA cut-off value (high-risk group vs low-risk group) and the clinical outcomes were compared. Logistic regression was performed to identify the clinical impact of PMX-HP on in-hospital death. Among the 31 high-risk patients (EA level ≥ 0.54), 16 patients (51.6%) received PMX-HP treatment and showed significant decreases in EA levels compared to patients who underwent conventional treatment only (- 0.34 vs - 0.12, p = 0.01). SOFA scores also showed significant improvement with PMX-HP treatment (12.8-8.9, p = 0.007). Fourteen in-hospital deaths occurred (45.2%), and PMX-HP treatment had a protective effect on in-hospital death (odds ratio (OR) 0.04, p = 0.03). In 29 low-risk patients (EA level < 0.54), seven patients (24.1%) received PMX-HP treatment and showed significant decreases in EA levels (0.46-0.16, p = 0.018). However, SOFA scores and in-hospital deaths were not improved by PMX-HP treatment. EA level significantly decreased after PMX-HP treatment and it may represent a therapeutic option to improve organ impairment and in-hospital death in septic shock patients with EA levels exceeding 0.54.

Establishment of heparin-binding protein time-resolved immunoassay and some potential clinical applications.

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 Eu3+-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.

Serum biomarkers to differentiate Gram-negative, Gram-positive and fungal infection in febrile patients.

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.

Bloodstream infection due to Herbaspirillum sp.: case series and review of literature.

Herbaspirillum species are Gram-negative bacteria belonging to the class Betaproteobacteria, order Burkholderiales. The phylogenetic and phenotypic similarities among these groups easily lead to species misidentification. Herbaspirillum bacteraemia is an uncommon clinical entity. The objective of this review is to collect information to contribute to the management of this infection. We describe our own case series and review the cases reported in the literature. Cancer appears as the major underlying disease. The main source of bacteraemia was respiratory. Phenotypic identification methods often misidentify this species. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and molecular methods identify at genus level, but species assignment is not reliable. Herbaspirillum spp. showed a highly susceptible antimicrobial profile. ß-Lactams showed good activity with low MIC values, except ampicillin. All isolates were resistant to colistin, suggesting an intrinsic resistance mechanism. Herbaspirillum spp. is an uncommon pathogen. MALDI-TOF MS or molecular methods are necessary to achieve a reliable genus identification. These species are not multidrug resistant. Piperacillin/tazobactam or ceftazidime might be a good treatment for this microorganism.

Analysis of blood stream infections, antibiograms and clinical outcomes in haematological patients with febrile neutropenia: data from a tertiary care haematology institute in India.

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.

Procalcitonin as a predictor of early antibiotic treatment failure in patients with gram-negative bloodstream infections caused by urinary tract infections.

We retrospectively evaluated whether initial procalcitonin (PCT) levels can predict early antibiotic treatment failure (ATF) in patients with gram-negative bloodstream infections (GN-BSI) caused by urinary tract infections from January 2018 to November 2019. Early ATF was defined as the following: (1) hemodynamically unstable or febrile at Day 3; (2) the need for mechanical ventilation or continuous renal replacement therapy at Day 3; (3) patients who died within 3 days (date of blood culture: Day 0). The study included 189 patients; 42 showed early ATF. Independent risk factors for early ATF were initial admission to the intensive care unit (odds ratio: 7.735, 95% confidence interval: 2.567-23.311; P < 0.001) and PCT levels ≥30 ng/mL (odds ratio: 5.413, 95% confidence interval: 2.188-13.388; P < 0.001). Antibiotic factors were not associated with early ATF. Initial PCT levels may be helpful to predict early ATF in these patients.

An eleven-year cohort of bloodstream infections in 552 febrile neutropenic patients: resistance profiles of Gram-negative bacteria as a predictor of mortality.

Antimicrobial stewardship is of major importance in patients with febrile neutropenia (FN). In this study, we aimed to investigate the trends in resistance and the relationship with mortality rates in patients with FN. The single-center surveillance data of inpatients with FN and diagnosed as microbiologically confirmed bloodstream infections (BSIs) between 2006 and 2016 were reviewed retrospectively. A total of 950 episodes in 552 patients with BSIs were analyzed. Of whom, 55.9% were male, the median age was 43 years, and 35.6% had acute myeloid leukemia. In total, 1016 microorganisms were isolated from blood cultures. Gram-negatives accounted for 42.4% (n = 403) of the episodes. Among Gram-negatives, Enterobacteriaceae accounted for 346 (86%) (E. coli, n = 197; 34% extended-spectrum ß-lactamases (ESBL) producers, and Klebsiella spp., n = 120; 48.3% ESBL producers). Also, 24 (20.0%) of Klebsiella spp. had carbapenemase activity. There were 6 (5.0%) colistin-resistant Klebsiella spp. Thirteen (26.5%) of Pseudomonas spp. and 17 (60.7%) of Acinetobacter spp. had carbapenemase activity. There were 2 (5.6%) colistin-resistant Acinetobacter spp. The 30-day mortality rates were 12.0%, 21.5%, 34.6%, and 29.0% in BSIs due to Gram-positive, Gram-negative bacterial, fungal, and polymicrobial etiology respectively (p = 0.001). BSIs with ESBL-producing (p = 0.001) isolates, carbapenem (p < 0.001), and colistin-resistant isolates (p < 0.001) were associated with increased mortality risk. The tremendous rise in resistance rates among Gram-negatives is dreadfully related to increasing mortality and leads to sharp shifts toward extreme restrictions of unnecessary antibiotic uses. Antimicrobial stewardship in patients with FN requires vigilance and tailoring of treatment upon local surveillance data.

Plasma pharmacokinetics of ceftolozane/tazobactam in pediatric patients with cystic fibrosis.

BACKGROUND: The antipseudomonal cephalosporin/ß-lactamase inhibitor combination ceftolozane/tazobactam could be a potential treatment option for cystic fibrosis (CF) pulmonary exacerbations. The pharmacokinetics (PK) of ceftolozane/tazobactam in children with CF merits further evaluation. METHODS: This is a retrospective subgroup analysis of a phase 1, noncomparative trial that characterized PK, safety, and tolerability of single intravenous doses of ceftolozane/tazobactam in pediatric patients. This analysis compares ceftolozane and tazobactam plasma PK parameters, estimated from a population PK model, between patients with and without CF enrolled in that trial. Individual attainment of PK/pharmacodynamic (PD) targets of ceftolozane and tazobactam (free ceftolozane concentration >4 µg/mL for >30% and free tazobactam concentration >1 µg/mL for 20% of the dosing interval) in patients with and without CF were evaluated. RESULTS: The study enrolled 18 patients aged greater than or equal to 2 to less than 18 years old, which included 9 with CF. Weight-normalized ceftolozane PK parameters were similar between patients with CF (clearance: 0.16 L/h/kg, half-life: 1.54 hours, volume of distribution: 0.26 L/kg) and without CF (clearance: 0.15 L/h/kg, half-life: 1.62 hours, volume of distribution: 0.26 L/kg), as were most weight-normalized tazobactam PK parameters. Weight-normalized tazobactam clearance was higher in patients with CF (0.73 L/h/kg) than patients without CF (0.42 L/h/kg). All patients achieved the prespecified PK/PD targets for ceftolozane and tazobactam. CONCLUSIONS: This retrospective analysis demonstrated generally similar weight-normalized plasma PK parameters for ceftolozane and tazobactam among children with and without CF; thus, projected doses for treatment of pediatric hospital-acquired/ventilator-associated pneumonia, which are higher than the pediatric complicated urinary tract infection/intra-abdominal infection doses, may be appropriate for treatment of CF pulmonary exacerbation.

Cefepime Versus Cefepime Plus Amikacin as an Initial Antibiotic Choice for Pediatric Cancer Patients With Febrile Neutropenia in an Era of Increasing Cefepime Resistance.

BACKGROUND: We investigated the treatment outcomes before and after the addition of amikacin to cefepime monotherapy as an initial empirical antibiotic treatment in pediatric cancer patients with febrile neutropenia. METHODS: This was a retrospective historical cohort study. The subjects were pediatric cancer patients who visited the emergency room at the Samsung Medical Center, Seoul, Korea, due to chemotherapy-induced febrile neutropenia, between January 2011 and December 2016. Since September 2014, the empirical antimicrobial treatment regimen for febrile neutropenia was changed from high-dose cefepime monotherapy to combination therapy of adding a single dose of amikacin. RESULTS: Two hundred twenty-five bacteremia episodes in 164 patients were reported during the study period. Bacteremia caused by cefepime-resistant Gram-negative bacteria was observed in 16% of patients before September 2014 and in 21% of the patients after September 2014 (P = 0.331). Use of appropriate empirical antibiotic treatments increased from 62% to 83% following addition of amikacin to cefepime treatment (P = 0.003). The duration of fever was shorter in the cefepime plus amikacin group than in the cefepime group (22 vs. 34 hours, P = 0.014); however, rates of septic shock and pediatric intensive care unit hospitalizations were not significantly different between the 2 groups (septic shock, both 7%, P = 0.436; pediatric intensive care unit 3% vs. 1%, P = 0.647). CONCLUSIONS: We observed no additional benefit of amikacin addition to high-dose cefepime monotherapy. Therefore, adding amikacin to cefepime monotherapy in conditions where cefepime-resistant Gram-negative bacteremia amounts to 20% or less may not be justified.

Usefulness of infection biomarkers for diagnosing bacteremia in patients with a sepsis code in the emergency department.

The objective of this study was to assess the usefulness of the biomarkers lactate, C-reactive protein (CPR) and procalcitonin for the diagnosis of bacteremia in patients with suspected sepsis in the emergency department (ED) and according to the focus of infection. We conducted a retrospective study among patients included in the sepsis code of our ED between November 2013 and December 2017. We analyzed demographic variables, co-morbidity according to the Charlson Index and focus of infection, blood cultures and classification according to Gram staining. We determined the diagnostic performance of the biomarkers quantitatively and calculated the area under the curve (AUC) for global bacteremia and as a function of the focus of infection. We included 653 patients with a median age of 79 years (interquartile range: 66-86), of whom 287 (44.0% were women. The most frequent infectious focus was respiratory (36.1%]. Blood cultures were requested in 87.5% (569 cases). Of the tested samples, 31.3% were positive, of which 63.5% revealed Gram-negative (GN) bacteria. Procalcitonin obtained globally the best AUC 0.70 (95% CI: 0.65-0.75). The values with the best sensitivity and specificity were 2.54 ng/mL for procalcitonin, 4.1 mmol/L for lactate and 156 mg/L for CRP. We found an association between the median procalcitonin value and GN bacteria (6.02; IQR: 1.39-39.40) and Gram-positive bacteria (1.74; IQR: 0.22-15.61). Procalcitonin is the biomarker with the greatest capacity to diagnose bacteremia, particularly in GN infection. Stratification by focus is important since not all biomarkers discriminate in the same way.

Elevated serum procalcitonin predicts Gram-negative bloodstream infections in patients with burns.

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).

Is current initial empirical antibiotherapy appropriate to treat bloodstream infections in short-duration chemo-induced febrile neutropenia?

INTRODUCTION: Fever of unknown origin is by far the most common diagnosis in low-risk febrile neutropenic patients undergoing chemotherapy. The current empirical regimen combines amoxicillin-clavulanic acid and fluoroquinolones in low-risk neutropenic patients. The aim of this study was to assess the appropriateness of antibiotherapy and the outcome of bloodstream infections (BSI) in patients with expected neutropenia of short duration. METHODS: This 2-year monocentric retrospective study included all consecutive neutropenic febrile adult patients with expected duration of neutropenia ≤ 7 days. They were classified into low- and high-risk groups for complications using the MASCC index. Appropriateness of initial empirical antibiotic regimen was assessed for each BSI. Multivariate analysis was performed to identify factors associated with mortality. RESULTS: Over the study period, 189 febrile episodes with positive blood cultures in neutropenic patients were reported, of which 44 occurred during expected duration of neutropenia ≤ 7 days. Patients were classified as high-risk (n = 27) and low-risk (n = 17). Gram-negative bacteria BSI represented 57% of cases, including only two multidrug-resistant bacteria in high-risk patients. Initial empirical antibiotherapy was appropriate in 86% of cases, and inappropriate in the event of coagulase-negative Staphylococcus BSI (14%), although the outcome was always favorable. In low-risk patients, no deaths and only 12% of severe complications were reported, contrasting with mortality and complication rates of 48% (p < 0.001) and 63% in high-risk patients (p < 0.001), respectively. CONCLUSIONS: Outcome of BSI is favorable in low-risk febrile neutropenic patients, even with inappropriate empirical initial antibiotic regimen for coagulase-negative Staphylococcus BSI. Initial in-hospital assessment and close monitoring of these patients are however mandatory.

The Causative Organisms of Bacterial Meningitis and their Antimicrobial Resistance Profiles in Iranian Children in 2011-2016.

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.

Role of procalcitonin in predicting etiology in bacteremic patients: Report from a large single-center experience.

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.

Clinical Features, Outcomes, and Risk Factors of Bloodstream Infections due to Stenotrophomonas maltophilia in a Tertiary-Care Hospital of China: A Retrospective Analysis.

Background. Stenotrophomonas maltophilia bacteremia (SMB) is the most perilous situation as compared to other types of S. maltophilia infection. The present study aimed to investigate the clinical features, distribution, drug resistance, and predictors of survival of SMB in a tertiary-care hospital of China. Methods. SMB that occurred in a tertiary-care hospital in Beijing, China, within 9 years (2010-2018) was investigated in a retrospective study. Demographics, incidence, commodities, drug resistance, mortality, as well as antibiotics administration were summarized according to the electronic medical records. The risk factors for survival were analyzed by Chi-square test, Kaplan-Meier curve and Cox regression. Results. A total of 76 episodes of SMB were analyzed. The overall incidence of SMB fluctuated from 3.4 to 15.4 episodes per 1000 admissions over 9 years. Malignancy was the most common comorbidity. High in vitro sensitivity was observed to minocycline (96.1%), levofloxacin (81.6%), and trimethoprim-sulfamethoxazole (89.5%). Central venous catheter (CVC) (p = 0.004), mechanical ventilation (MV) (p = 0.006), hemodialysis (p = 0.024), and septic shock (p = 0.016) were significantly different between survival and death group. The 30-day mortality was 34.2% within 30 days after confirmation of blood culture. Factors such as hemodialysis (OR 0.287, 95% CI: 0.084-0.977, p = 0.046), T-tube (OR 0.160, 95% CI: 0.029-0.881, p = 0.035), and septic shock (OR 0.234, 95% CI: 0.076-0.719, p = 0.011) were associated with survival. Conclusions. S. maltophilia is the major nosocomial blood stream infectious pathogenic bacteria. Trimethoprim-sulfamethoxazole and minocycline are optimal antibiotics for the treatment of SMB. T-tube, hemodialysis, and septic shock were the risk factors associated with survival of SMB patients.

The clinical value of IL-3, IL-4, IL-12p70, IL17A, IFN-γ, MIP-1ß, NLR, P-selectin, and TNF-α in differentiating bloodstream infections caused by gram-negative, gram-positive bacteria and fungi in hospitalized patients: An Observational Study.

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 1ß (MIP-1ß), 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-1ß, 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-1ß 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-1ß, 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-1ß with an AUC of 0.703.NLR and MIP-1ß 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-1ß 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.

Population pharmacokinetics of amikacin in patients with pediatric cystic fibrosis.

INTRODUCTION: Amikacin is commonly used in patients with pediatric cystic fibrosis (CF) for the treatment of pulmonary exacerbations. Amikacin efficacy is related to maximum plasma concentration/minimum inhibitory concentration (Cmax/MIC) ratio >8. Pharmacokinetic data in patients with pediatric CF are scarce. The aim of this study was to develop a population pharmacokinetic (PopPK) model describing amikacin disposition in patients with pediatric CF. METHODS: CF patients under 18 years of age with pulmonary exacerbation who received amikacin were enrolled. Patients received different amikacin regimens (30 mg-1 kg-1 day-1 every 8, 12, or 24 hours) depending on the patient's status and hospital protocols. Amikacin serum levels were obtained for therapeutic drug monitoring. PopPK model was developed using MONOLIX Suite-2018R1 (Lixoft). RESULTS: A total of 39 patients (114 amikacin concentrations) were included in this study. Population estimates for the elimination rate constant (k) and the volume of distribution (V) were 0.541 hours-1 and 0.451 L/kg, respectively. Between-subject and between-occasion variability were 53% and 16.5% for k and 31% and 22% for V, respectively. Bodyweight was a significant covariate associated with V. Based on simulations, almost 70% of the patients receiving 30 mg-1 kg-1 day-1 every 24 hours would achieve a Cmax/MIC ratio >8 which is an appropriate therapeutic goal while no patient in the other two groups (Q8 and Q12) would achieve that objective. CONCLUSIONS: The regimen of 30 mg-1 kg-1 day-1 every 24 hours more adequately fulfilled the therapeutic target for amikacin. Although all our patients had good clinical results and a good adverse-events profile, further studies are necessary to redefine the optimal treatment strategy.

Simkania negevensis in Crohn's Disease.

BACKGROUND: Simkania negevensis is an obligate intracellular Gram-negative bacterium (family Simkaniaceae, order Chlamydiales) that has been isolated from domestic and mains water supplies, is able to infect human macrophages, and can induce an inflammatory response in the host. METHODS: From June to December 2016, in a single-center observational study, colonic Crohn's disease patients and controls (subjects undergoing screening for colorectal cancer) underwent blood tests to identify serum-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) to S. negevensis and a colonoscopy with biopsies for detection of S. negevensis DNA by polymerase chain reaction (PCR). RESULTS: Forty-three Crohn's disease patients and 18 controls were enrolled. Crohn's disease patients had higher prevalence of IgA antibodies to S. negevensis compared with controls (20.9% versus 0%, p = 0.04). Simkaniaceae negevensis DNA was detected in 34.9% and 5.6% of intestinal biopsies in Crohn's disease patients and controls, respectively (p = 0.02). All Crohn's disease patients with PCR-positive biopsies for S. negevensis were IgG seropositive, with specific IgA in 60% of them (p < 0.001). Immunosuppressive therapies, extraintestinal manifestations, or disease activity did not influence the presence of S. negevensis in the Crohn's disease population. CONCLUSIONS: We identified S. negevensis in Crohn's disease patients by demonstrating the presence of S. negevensis mucosal DNA and seropositivity to the bacterium. These results could support the presence of an acute or persistent S. negevensis infection and suggest a possible role in the pathogenesis of Crohn's disease.

Risk factors for surgical site infection after craniotomy: a prospective cohort study.

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.