Late-onset Bloodstream Infections Research Articles

P-1597. Timing and Microbiology of Late Positive Blood Cultures in Hematology/Oncology Patients with Persistent Febrile Neutropenia

Abstract Background The optimal frequency of repeating blood cultures in persistent febrile neutropenia (FN) is unknown. We aim to characterize timing and microbiology of positive blood cultures in persistent FN to inform diagnostic stewardship of blood cultures at our cancer center. Flow diagram outlining methods for selecting patients to include in the study. Among qualifying FN episodes, only the first FN episode per patient was included in the analysis. Abbreviation: FN (febrile neutropenia). Methods This is a retrospective cohort study of adult hematology/oncology patients with a FN episode lasting > 3 days between March 31, 2021 - August 31, 2023. A day of FN was defined as a day with a patient temperature of ≥ 38C and an absolute neutrophil count ≤ 500 cells/µL within 24 hours of the qualifying temperature. Day 1 of FN was the first day a patient met FN criteria; the end of the FN episode was the last day of FN that was followed by ≥ 2 consecutive days where the patient no longer met FN criteria. All blood cultures collected during each FN episode were extracted from the medical record. Results Among 459 patients included (Figure 1), 420 (91%) had a hematologic malignancy (Table 1). The median FN duration was 5 days (interquartile range (IQR) 4-7). A median of 12 blood culture bottles were collected per patient during FN (IQR 8-18). At least 1 positive blood culture at any time during the FN episode occurred in 126 (27%) patients; 23 (5%) patients had ≥ 1 positive blood culture after FN day 3. For 12 of these 23 patients the positive blood culture(s) that occurred after FN day 3 were the first positive cultures during the FN episode. The percent of patients with ≥ 1 positive blood culture declined from 25% on FN day 1 to < 10% on FN days 2-4 and < 5% on FN days 5-8 (Figure 2). Among the 23 patients with positive blood cultures after FN day 3, gram positive bacteria were observed most frequently after FN day 3 (12 patients), with coagulase negative Staphylococci occurring most often. Gram negative bacteria and yeast were isolated in blood cultures after FN day 3 from 8 and 5 patients, respectively (Table 2). Bar chart depicting the number of patients on each day of FN who had at least one positive blood culture, no positive blood cultures, and no blood cultures collected. The table below the bar chart shows the total number of patients who met criteria for FN on each FN day, the number of those patients with at least one positive blood culture on a given FN day, and the percent of patients on each FN day who had at least one positive blood culture (among the patients who had at least one blood culture collected on the given FN day). Percentages were only calculated for days where there were ≥ 30 patients who had at least one blood culture collected (FN days 1-8). Abbreviation: FN (febrile neutropenia). Conclusion Few patients had a positive blood culture beyond day 3 of FN. Gram positive organisms, particularly coagulase negative Staphylococci, were most often isolated, raising the possibility that some of these late positive cultures may be skin contaminants rather than true bloodstream infections (BSI). Additional studies are needed to determine optimal frequency of blood culturing in persistent FN and to identify patients at high risk of late onset BSI. Disclosures Frank Tverdek, PharmD, Merck: Advisor/Consultant Catherine Liu, MD, Pfizer: Grant/Research Support

Epidemiology of neonatal sepsis in two neonatal intensive care units in Krakow, Poland in 2016–2017 years

BackgroundSepsis in low-birth-weight neonates remains one of the most significant causes of neonatal morbidity and mortality. Approximately 3 million newborns suffer from sepsis globally every year. The aim of this study was to compare demographic and clinical features, as well as etiology and antibiotic susceptibility, of the main pathogens related to neonatal sepsis in two neonatal intensive units during a two-year period.MethodsWe observed early-onset (EO-BSI) and late-onset bloodstream infections (LO-BSI) cases in two high-reference neonatal intensive care units (NICU) over a 24-month period (2016–2017). Samples of patients’ blood were tested for the presence of the microorganisms. All bacterial isolates were tested for susceptibility to antibiotics.ResultsThe majority of sepsis cases weighed above 1000 g and were born by cesarean section. About 10% of the EO-BSI group died. There were differences in the EO-BSI /LO-BSI ratio in the compared wards due to differences among the admitted children. The most common pathogens isolated from blood were coagulase-negative staphylococci (CoNS) were represented by two dominating species: S. epidermidis and S. haemolyticus, followed by Klebsiella spp. strains and E.coli, which were mostly found in EO-BSI cases. No single S. agalactiae (GBS) strain was isolated. The majority of CoNS strains were resistant to methicillin, half were resistant to aminoglycosides, and one-third were resistant to macrolides and lincosamides. Half of the Gram-negative rods were resistant to beta-lactams.ConclusionsThe epidemiology of sepsis in two observed NICUs is comparable to data obtained from other studies with a predominance of methicillin-resistant CoNS in LO-BSI and beta-lactam resistant E. coli in EO-BSI. It is of importance that the campaign for controlling GBS carriage in pregnant women in Poland resulted in the disappearance of GBS as a cause of sepsis. Unfortunately, there are no such measures to control E.coli related sepsis.

Organ dysfunction and mortality in preterm neonates with late-onset bloodstream infection.

Organ dysfunction (ODF) in late-onset bloodstream infection (LBSI) is associated with increased risk of adverse outcomes. However, no established definition of ODF exists among preterm neonates. Our objective was to describe an outcome-based ODF definition for preterm infants, and assess factors associated with mortality. This is a six-year retrospective study of neonates <35 weeks gestational age, >72 h of age, with non-CONS bacterial/fungal LBSI. Discriminatory ability of each parameter for mortality was evaluated: base deficit ≤-8 mmol/L (BD8), renal dysfunction (urine output <1 cc/kg/h or creatinine ≥100 μmol/L), hypoxic respiratory failure (HRF, ventilated, FiO2 = 1.0), or vasopressor/inotrope use (V/I). Multivariable logistic regression analysis was performed to derive a mortality score. One hundred and forty-eight infants had LBSI. BD8 had the highest individual predictive ability for mortality (AUROC = 0.78). The combination BD8 + HRF + V/I was used to define ODF (AUROC = 0.84). Fifty-seven (39%) infants developed ODF, among which 28 (49%) died. Mortality increased inversely relative to GA at LBSI-onset (aOR 0.81 [0.67, 0.98]) and directly relative to ODF occurrence (12.15 [4.48, 33.92]). Compared to no-ODF, ODF infants had lower GA and age at illness, and higher frequency of Gram-negative pathogen. Among preterm neonates with LBSI, significant metabolic acidosis, HRF, and vasopressor/inotrope use may identify infants high risk for mortality. These criteria could help identify patients for future studies of adjunctive therapies. Sepsis-related organ dysfunction is associated with increased risk of adverse outcomes. Among preterm neonates, significant metabolic acidosis, use of vasopressors/inotropes, and hypoxic respiratory failure may identify high-risk infants. This can be used to target research and quality improvement efforts toward the most vulnerable infants.

Gastroschisis and low incidence of early-onset infection: a case for antimicrobial stewardship.

Early onset infection (EOI) in gastroschisis is rare. Excess antibiotic exposure in neonates increases necrotizing enterocolitis and mortality. We evaluated antibiotic exposure and EOI in gastroschisis. Retrospective cohort analysis between 2010-2016 in the Children's Hospital Neonatal Database. Included: Infants ≥32 weeks with gastroschisis admitted <48 h. Excluded: major anomalies or surgical intervention prior to admission. EOI diagnosis (<72 h). In 2021 patients with gastroschisis, median gestational age was 36 weeks (IQR 35, 37). 93.9% patients received empiric antibiotics after delivery, with median 7 days duration (IQR 3, 9). Only 13 patients (0.64%) had early positive blood culture. The rate of late onset blood stream infection (7.08%) was higher, and higher in complex (18%) than simple gastroschisis (4.8%, p < 0.001). Despite low incidence of EOI and risks of excess antibiotic exposure, neonates with gastroschisis are exposed to long courses of empiric antibiotics. These data should stimulate interinstitution work to improve antibiotic prescribing.

Risk of cardiac device-related infection in patients with late-onset bloodstream infection. Analysis on a National Cohort

To determine the incidence of cardiac device-related infection (CDRI) among patients with cardiac device (CD) during late-onset bloodstream infection (BSI) and to identify the risk factors associated with CDRI. Patients with a CD (cardiac implantable electronic devices -CIED- and/or prosthetic heart valve -PHV-) and late-onset-BSI (>1 year after the CD implantation/last manipulation) were selected from the PROBAC project, a prospective, observational cohort study including adult patients with bacteraemia consecutively admitted to 26 Spanish hospitals from October 2016 to March 2017. Multivariate analyses using logistic regression were performed to identify the risk factors associated with CDRI. 317 BSI from patients carrying a CD were registered, 187 (56.2%) were late-onset-BSI. A total of 40 (21.4%) CDRI were identified during late-onset-BSI. The CDRI cumulative incidence in Gram-positive-BSI was 41.8% (38/91), with S. aureus, Enterococcus spp. and viridans streptococci showing the greatest percentages: 40% (12/30), 42% (11/26) and 75% (6/8), respectively. Independent predictors of CDRI were an unknown source of infection (OR: 2.88[CI 95%:1.18-7.06], p =0.02), Gram-positive-aetiology (23.1 [5.23-102.1], p<0.001) and persistent bacteraemia (4.81 [1.21-19], p=0.03). In an exploratory analysis, S. aureus (3.99 [1.37-11.65], p=0.011), Enterococcus spp. (5.21 [1.76-15.4], p=0.003) and viridans streptococci (28.7 [4.71-173.5], p<0.001) aetiology were also found to be risk factors for CDRI. CDRI during late-onset-BSI is a frequent phenomenon. Risk of CDRI differs among species, happening in almost half of the Gram-positive-BSI. An unknown source of the primary infection, Gram-positive-aetiology -especially S. aureus, Enterococcus spp. and viridans streptococci-, and persistent bacteraemia were identified as risk factors for CDRI.

Bacterial Etiology and Antibiotic Sensitivity Patterns in Late-Onset Neonatal Blood Infection

Introduction: The incidence and etiology of neonatal bloodstream infections vary globally. Early appropriate antibiotic therapy is crucial. An empiric antibiotic choice should be driven by accurate knowledge of the local spectrum of pathogens and susceptibilities. Methodology: A retrospective observational study was conducted on neonates born at local tertiary center from January 1, 2013, to December 31, 2018, with late-onset bloodstream infection (LBSI). Trends of causative organisms and antibiotic susceptibilities were analyzed. Results: A total of 696 LBSI occurred in 469 neonates. Overall incidence over the 6 years was 122/1000 admissions. The median time to LBSI was 13 days of life. Majority of infections occurred in infants &lt;32 weeks. About 75.9% were caused by Gram-positive and the rest by Gram-negative bacteria. The most common organism was coagulase-negative staphylococcus (CoNS) which showed an increase in resistance to amikacin over time, but with stable sensitivity patterns to teicoplanin. Klebsiella and Escherichia coli were the most common Gram-negative organisms. There was improving sensitivity to cephalosporin in Klebsiella species. Sixteen percent of Gram-negative isolates were extended spectrum beta-lactamase (ESBL) producing. Majority of the Gram-negative bacteria including ESBL-producing strains remained sensitive to amikacin. An empiric antibiotic combination of teicoplanin and amikacin was appropriate to cover the majority of LBSIs. Conclusions: The majority of late-onset neonatal bloodstream infections in this study cohort were caused by Gram-positive organisms of which CoNS was the most common. The empiric antibiotic choices for LBSI on our unit seem appropriate based on the data. In units where the organism and susceptibility patterns are similar, the same antibiotic choices may be justified.

Factors associated with antibiotic administration delay among preterm infants with late-onset bloodstream infection

Early antibiotic administration is an important modifiable factor in reducing mortality from late-onset bloodstream infections in preterm infants. In a cohort study including 142 infants with non-coagulase negative staphylococcus bloodstream infection at two tertiary neonatal intensive care units, we identified typical practice-related factors that may be targeted to prevent delays in antibiotic administration. Collection of cerebrospinal fluid or urine sample before administering antibiotics, a longer time taken to site a peripheral intravenous catheter among those without pre-existing access, and a longer time taken to administer fluid boluses were associated with a longer than median time to antibiotic administration.

C-Reactive Protein, Interleukin-6, and Procalcitonin in Diagnosis of Late-Onset Bloodstream Infection in Very Preterm Infants.

Late-onset bloodstream infection (LOBSI) is common in very preterm infants. Early and accurate diagnosis is crucial for prognosis and outcome. We aimed to analyze the accuracy of routinely used inflammatory biomarkers in the diagnosis of LOBSI as compared to uninfected controls. In this single-center, retrospective case-control study, interleukin-6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) were routinely measured, when infection was clinically suspected. The definition of LOBSI was based on positive blood culture, clinical signs of infection, and onset more than 72 hours after birth. Among 285 enrolled infants, 66 developed LOBSI. IL-6 was superior to other markers, and levels greater than 100 ng/L had a sensitivity of 94% and a specificity of 99% for the presence of LOBSI. Receiver operating characteristic curve of IL-6 had area under the curve of 0.988 (95% CI = 0.975-1.00, P < .001). The negative predictive value of IL-6, CRP, and PCT for optimal cutoff values was 99%, 95%, and 93%, respectively. The logistic regression model of IL-6 > 100 ng/L or CRP > 10 mg/L were successfully predicted LOBSI in 97.9% of cases. The combination of IL-6 and CRP seems to have great potential in routine rapid diagnosis of LOBSI development. High negative predictive value of all tested markers could encourage the early discontinuation of antibiotic treatment.

Nutritional management in newborn babies receiving therapeutic hypothermia: two retrospective observational studies using propensity score matching.

Therapeutic hypothermia is standard of care for babies with moderate to severe hypoxic-ischaemic encephalopathy. There is limited evidence to inform provision of nutrition during hypothermia. To assess the association during therapeutic hypothermia between (1) enteral feeding and outcomes, such as necrotising enterocolitis and (2) parenteral nutrition and outcomes, such as late-onset bloodstream infection. A retrospective cohort study using data held in the National Neonatal Research Database and applying propensity score methodology to form matched groups for analysis. NHS neonatal units in England, Wales and Scotland. Babies born at ≥ 36 gestational weeks between 1 January 2010 and 31 December 2017 who received therapeutic hypothermia for 72 hours or who died during treatment. Enteral feeding analysis - babies who were enterally fed during therapeutic hypothermia (intervention) compared with babies who received no enteral feeds during therapeutic hypothermia (control). Parenteral nutrition analysis - babies who received parenteral nutrition during therapeutic hypothermia (intervention) compared with babies who received no parenteral nutrition during therapeutic hypothermia (control). Primary outcomes were severe and pragmatically defined necrotising enterocolitis (enteral feeding analysis) and late-onset bloodstream infection (parenteral nutrition analysis). Secondary outcomes were survival at neonatal discharge, length of neonatal stay, breastfeeding at discharge, onset of breastfeeding, time to first maternal breast milk, hypoglycaemia, number of days with a central line in situ, duration of parenteral nutrition, time to full enteral feeds and growth. A total of 6030 babies received therapeutic hypothermia. Thirty-one per cent of babies received enteral feeds and 25% received parenteral nutrition. Seven babies (0.1%) were diagnosed with severe necrotising enterocolitis, and further comparative analyses were not conducted on this outcome. A total of 3236 babies were included in the matched enteral feeding analysis. Pragmatically defined necrotising enterocolitis was rare in both groups (0.5% vs. 1.1%) and was lower in babies who were fed during hypothermia (rate difference -0.5%, 95% confidence interval -1.0% to -0.1%; p = 0.03). Higher survival to discharge (96.0% vs. 90.8%, rate difference 5.2%, 95% confidence interval 3.9% to 6.6%; p < 0.001) and higher breastfeeding at discharge (54.6% vs. 46.7%, rate difference 8.0%, 95% confidence interval 5.1% to 10.8%; p < 0.001) rates were observed in enterally fed babies who also had a shorter neonatal stay (mean difference -2.2 days, 95% confidence interval -3.0 to -1.2 days). A total of 2480 babies were included in the matched parenteral nutrition analysis. Higher levels of late-onset bloodstream infection were seen in babies who received parenteral nutrition (0.3% vs. 0.9%, rate difference 0.6%, 95% confidence interval 0.1% to 1.2%; p = 0.03). Survival was lower in babies who did not receive parenteral nutrition (90.0% vs. 93.1%, rate difference 3.1%, 95% confidence interval 1.5% to 4.7%; p < 0.001). Propensity score methodology can address imbalances in observed confounders only. Residual confounding by unmeasured or poorly recorded variables cannot be ruled out. We did not analyse by type or volume of enteral or parenteral nutrition. Necrotising enterocolitis is rare in babies receiving therapeutic hypothermia, and the introduction of enteral feeding is associated with a lower risk of pragmatically defined necrotising enterocolitis and other beneficial outcomes, including rates of higher survival and breastfeeding at discharge. Receipt of parenteral nutrition during therapeutic hypothermia is associated with a higher rate of late-onset infection but lower mortality. These results support introduction of enteral feeding during therapeutic hypothermia. Randomised trials to assess parenteral nutrition during therapeutic hypothermia. Current Controlled Trials ISRCTN474042962. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 36. See the NIHR Journals Library website for further project information.

High Burden of Bloodstream Infections Associated With Antimicrobial Resistance and Mortality in the Neonatal Intensive Care Unit in Pune, India.

BackgroundAntimicrobial resistance (AMR) is a growing threat to newborns in low- and middle-income countries (LMIC).MethodsWe performed a prospective cohort study in 3 tertiary neonatal intensive care units (NICUs) in Pune, India, to describe the epidemiology of neonatal bloodstream infections (BSIs). All neonates admitted to the NICU were enrolled. The primary outcome was BSI, defined as positive blood culture. Early-onset BSI was defined as BSI on day of life (DOL) 0–2 and late-onset BSI on DOL 3 or later.ResultsFrom 1 May 2017 until 30 April 2018, 4073 neonates were enrolled. Among at-risk neonates, 55 (1.6%) developed early-onset BSI and 176 (5.5%) developed late-onset BSI. The majority of BSIs were caused by gram-negative bacteria (GNB; 58%); among GNB, 61 (45%) were resistant to carbapenems. Klebsiella spp. (n = 53, 23%) were the most common cause of BSI. Compared with neonates without BSI, all-cause mortality was higher among neonates with early-onset BSI (31% vs 10%, P < .001) and late-onset BSI (24% vs 7%, P < .001). Non–low-birth-weight neonates with late-onset BSI had the greatest excess in mortality (22% vs 3%, P < .001).ConclusionsIn our cohort, neonatal BSIs were most commonly caused by GNB, with a high prevalence of AMR, and were associated with high mortality, even in term neonates. Effective interventions are urgently needed to reduce the burden of BSI and death due to AMR GNB in hospitalized neonates in LMIC.

Early- and Late-Onset Bloodstream Infections in the Intensive Care Unit: A Retrospective 5-Year Study of Patients at a University Hospital in China.

Limited data are available regarding the current microbiological characteristics of bloodstream infections (BSIs) in intensive care units (ICUs) in China. This retrospective study aimed to determine the epidemiology of early- and late-onset BSIs in our ICU. We retrospectively collected data about ICU patients with BSI from 2013 to 2017. The patients were divided into the early- and late-onset BSI groups according to if BSI occurred within or beyond 48 hours after ICU admission. Univariate and multivariate logistic regression analyses were used to assess the risk factors for infection with multidrug resistant organisms (MDROs). Of 5474 ICU admissions, 486 (8.9%) patients with BSIs and with 500 microorganisms were included in this study, 246 (50.6%) of whom had early-onset BSIs. Two hundred and seventy patients were infected with MDROs. The proportion of MDRO infections was significantly higher among patients with late-onset BSIs than among those with early-onset BSIs (57.9% vs. 41.5%, P = .017). The ICU mortality rate was significantly higher in the late-onset BSI group (44.6% vs. 33.8%, P = .014) and early and appropriate antimicrobial treatment significantly improved the survival rate among patients with BSI (P < .001). MDROs affected more than half of patients with BSI in the ICU. Early appropriate empirical antimicrobial therapy could improve clinical outcome of patients with BSIs.

Early versus late onset bloodstream infection during neutropenia after high-dose chemotherapy for hematologic malignancy.

The length of neutropenia has a significant impact on the incidence of bloodstream infection (BSI) in cancer patients, but limited information is available about the pathogen distribution in late BSI. Between 2002 and 2014, BSI episodes in patients with neutropenia receiving chemotherapy for hematologic malignancies were prospectively identified by multicenter, active surveillance in Germany, Switzerland and Austria. The incidence of first BSI episodes, their microbiology and time to BSI onset during the first episode of neutropenia of 15,988 patients are described. The incidence rate of BSI episodes was 14.7, 8.7, and 4.7 per 1000 patient-days in the first, second, and third week of neutropenia, respectively. BSI developed after a median of 5 days of neutropenia (interquartile range [IQR] 3-10days). The medium duration of neutropenia to BSI onset was 4 days in Escherichiacoli (IQR 3-7days), Klebsiella spp. (2-8days), and Staphylococcus aureus (3-6days). In contrast, BSI due to Enterococcus faecium occurred after a median of 9 days (IQR 6-14days; p < 0.001 vs. other BSI). Late onset of BSI (occurring after the first week of neutropenia) was also observed for Stenotrophomonas maltophilia (12days, IQR 7-17days; p < 0.001), and non-albicans Candida spp. (13days, IQR 8-19days; p < 0.001). Over the course of neutropenia, the proportion of difficult to treat pathogens such as E. faecium, S. maltophilia, and Candida spp. increased. Among other factors, prior duration of neutropenia may help to guide empiric antimicrobial treatment in febrile neutropenia.

Study protocol: optimising newborn nutrition during and after neonatal therapeutic hypothermia in the United Kingdom: observational study of routinely collected data using propensity matching

IntroductionTherapeutic hypothermia is standard of care for infants born ≥36 weeks gestation with hypoxic ischaemic encephalopathy (HIE); consensus on optimum nutrition during therapeutic hypothermia is lacking. This results in variation...

Characteristics and Risk Factors of Late-onset Bloodstream Infection Beyond 6 Months After Liver Transplantation in Children.

Bloodstream infection (BSI) is a major cause of morbidity and mortality after pediatric liver transplantation (LT). However, most studies have focused on BSI occurring within a few months after LT. In this study, we evaluated the characteristics of BSI occurring beyond 6 months after pediatric LT. We conducted a retrospective cohort study at a pediatric LT center in Japan from November 2005 to March 2016. We evaluated the causative organisms and site of late-onset BSI in children ≤ 18 years of age. The risk factors for developing late-onset BSI and the associations of late-onset BSI with long-term outcomes were also evaluated. Three hundred forty cases of LT were evaluated. Thirty-eight BSI developed in 29 (9%) LT recipients. There were 42 organisms (nine Gram-positive cocci, 33 Gram-negative rods) isolated from the blood cultures of recipients with late-onset BSI. The most frequent sites of late-onset BSI was intraabdominal infection (18/38; 47%). There were also 14 (39%) episodes with no apparent focus. In multivariate analysis, a prolonged operative time > 12 hours (odds ratio [OR] = 3.55; P = 0.04) and biliary stenosis (OR = 4.60; P = 0.006) were independent risk factors for developing late-onset BSI. Late-onset BSI was associated with increased retransplantation rate (P = 0.04) and mortality (P < 0.001). Late-onset BSI developed in 9% of recipients after pediatric LT. Gram-negative rods accounted for the majority of late-onset BSI as a consequence of abdominal infection, but the focus was often unclear. Prolonged operative time at LT and biliary stenosis were independent risk factors for developing late-onset BSI.

Epidemiology and impact of bloodstream infections among kidney transplant recipients: A retrospective single-center experience.

Bloodstream infection (BSI) represents an important source of morbidity and mortality, as well as an increasing therapeutic challenge, among solid organ transplant recipients. Understanding the epidemiological and microbiological characteristics of BSI following renal transplantation is paramount to the implementation of appropriate preventative and therapeutic measures. We conducted a retrospective review of all BSI episodes occurring between July 2009 and April 2016 in adult patients, who received a renal transplant at Royal Free London hospital. A total of 116 episodes of BSI occurred in 87 patients, 43 (49.4%) of them men. The mean age at BSI was 54.37±12.81years. Late-onset BSI (>12months post transplant) represented 55.2%, with the median time to BSI being 16.28month. Sixty-seven patients had single BSI and 20 had recurrent episodes. Enterobacteriaceae were responsible for 73.7% of BSI, with Escherichia coli the commonest causative organism (46.6%). The urinary tract was the most frequent source of infection in 56.9%. Among the E.coli infections, 100% of the tested isolates were sensitive to meropenem, ertapenem, tigecycline, and fosfomycin, and >90% were sensitive to piperacillin-tazobactam, amikacin, and colistin. Lower susceptibility rates were encountered for ceftriaxone (70.6%), amoxicillin-clavulanic acid (48.1%), cotrimoxazole (40.4%), trimethoprim (37.3%), and amoxicillin (21.6%). During BSI, the median serum creatinine increased from a reference of 131μmol/L to a peak of 219μmol/L. Acute kidney injury (AKI) complicated 75/116 BSI episodes (64.7%)-stage 1: 34, stage 2: 31, and stage 3 AKI: 10 episodes. After 3months, the median creatinine remained elevated at 146μmol/L. The 3-month mortality rate was 8% (7/87), and the death-censored graft loss was 6.9% (6/87). No significant difference was seen between BSI of urinary and non-urinary sources in the incidence of AKI (χ2 =0.24, P=.6) or the percentage of creatinine change between baseline and peak and 3-month creatinines (P=.2 and .7 respectively). Urinary tract infection remains the commonest source of systemic infection among kidney transplant recipients and resistance to commonly used frontline antibiotics is common; thus, prevention and early detection are paramount. The appropriate choice of initial empirical antibiotic is vital to improve the outcome. Each unit needs to understand the epidemiology of organisms causing BSI in their transplant patients and their antibiotic susceptibilities.

Neonatal Escherichia coli Bloodstream Infections: Clinical Outcomes and Impact of Initial Antibiotic Therapy.

Escherichia coli is a common cause of bloodstream infections (BSIs) in infants and is associated with high mortality and morbidity among survivors. The clinical significance of antibiotic resistance and timing of appropriate antimicrobial therapy in this population is poorly understood. We identified all infants with E. coli BSIs discharged from 77 neonatal intensive care units managed by the Pediatrix Medical Group in 2012. We used multivariable logistic regression to evaluate the association between 30-day mortality and ampicillin-resistant E. coli BSI, as well as the number of active empiric antimicrobial agents administered, controlling for gestational age, small-for-gestational age status, early-onset versus late-onset BSI, oxygen requirement, ventilator support and inotropic support on the day of the first positive blood culture. We identified 258 episodes of E. coli BSI, including 123 (48%) ampicillin-resistant isolates. Unadjusted 30-day mortality did not significantly differ between infants with ampicillin-resistant versus ampicillin-susceptible E. coli BSI [11 of 123 (9%) vs. 7 of 135 (5%); P = 0.33; adjusted odds ratio = 1.37 (95% confidence interval: 0.39, 4.77)]. Among ampicillin-resistant E. coli BSIs, 30-day mortality was not significantly lower for infants treated with at least one empiric antimicrobial active against ampicillin-resistant E. coli versus infants receiving no active empiric agent [adjusted odds ratio = 1.50 (0.07, 33.6)]. In this population of infants with E. coli BSI, ampicillin resistance was not associated with significantly increased mortality. Among the subset of infants with ampicillin-resistant E. coli, appropriate empirical antibiotic therapy was not associated with lower mortality.

Genetic polymorphisms of IL-6-174 and IL-10-1082 in full term neonates with late onset blood stream infections

Genetically determined variation in the magnitude of inflammatory response may play a role in determining the risk of developing neonatal sepsis, as well as its outcome. To test the hypothesis that interleukin-6 (IL)-6 -174, IL-10 -1082 genetic polymorphisms are associated with the risk of sepsis and clinical outcomes in full-term neonates with blood stream infections (BSIs). A total of 54 full-term neonates with BSIs and 70 matched controls were included in this case/control study. DNA amplification using polymerase chain reaction with sequence-specific primers followed by NIaIII restriction enzyme digestion was done for detection of promoter single nucleotide polymorphism of IL-6 -174 G/C, amplification refractory mutation system-polymerase chain reaction assay was done for IL-10 -1082 G/A polymorphism in blood samples from all infants enrolled in the study. The IL-6 -174 and IL-10-1082 genotypes were not significantly different in neonates with BSIs compared to controls. Whereas, IL-6-174CC and IL-10-1082GG genotypes were associated with increased risk for mortality [Odds ratio (95% confidence intervals): 6.2 (1.3–28.4), P = 0.02 and 25.0 (2.0–74.3), P

Late-Onset Bloodstream Infection and Perturbed Maturation of the Gastrointestinal Microbiota in Premature Infants.

BackgroundLate-onset bloodstream infection (LO-BSI) is a common complication of prematurity, and lack of timely diagnosis and treatment can have life-threatening consequences. We sought to identify clinical characteristics and microbial signatures in the gastrointestinal microbiota preceding diagnosis of LO-BSI in premature infants.MethodDaily faecal samples and clinical data were collected over two years from 369 premature neonates (<32 weeks gestation). We analysed samples from 22 neonates who developed LO-BSI and 44 matched control infants. Next-generation sequencing of 16S rRNA gene regions amplified by PCR from total faecal DNA was used to characterise the microbiota of faecal samples preceding diagnosis from infants with LO-BSI and controls. Culture of selected samples was undertaken, and bacterial isolates identified using MALDI-TOF. Antibiograms from bloodstream and faecal isolates were compared to explore strain similarity.ResultsFrom the week prior to diagnosis, infants with LO-BSI had higher proportions of faecal aerobes/facultative anaerobes compared to controls. Risk factors for LO-BSI were identified by multivariate analysis. Enterobacteriaceal sepsis was associated with antecedent multiple lines, low birth weight and a faecal microbiota with prominent Enterobacteriaceae. Staphylococcal sepsis was associated with Staphylococcus OTU faecal over-abundance, and the number of days prior to diagnosis of mechanical ventilation and of the presence of centrally-placed lines. In 12 cases, the antibiogram of the bloodstream isolate matched that of a component of the faecal microbiota in the sample collected closest to diagnosis.ConclusionsThe gastrointestinal tract is an important reservoir for LO-BSI organisms, pathogens translocating across the epithelial barrier. LO-BSI is associated with an aberrant microbiota, with abundant staphylococci and Enterobacteriaceae and a failure to mature towards predominance of obligate anaerobes.

Late-onset bloodstream infections in hospitalized term infants.

The epidemiology and incidence of late-onset blood stream infections (BSIs) in premature infants have been described, but studies describing late-onset BSI in term infants are sparse. We sought to describe the pathogens, incidence, risk factors and mortality of late-onset BSI in hospitalized term infants. A cohort study was conducted of infants ≥37 weeks gestational age and ≤120 days of age discharged from Pediatrix Medical Group neonatal intensive care units from 1997 to 2010. We examined all cultures obtained from day of life 4-120 and used multivariable regression to assess risk factors for late-onset BSI. We found a total of 206,019 infants cared for between day of life 4 and 120, and the incidence of late-onset BSI was 2.7/1000 admissions. We identified Gram-positive organisms in 64% of the cultures and Gram-negative organisms in 26%. We found a decreased risk of late-onset BSI in infants with the following characteristics: small for gestational age, delivery by Cesarean, antenatal antibiotic use and discharged in the later years of the study. Late-onset BSI increased the risk of death after controlling for confounders [odds ratio 8.43 (95% confidence interval 4.42-16.07)]. Our data highlight the importance of late-onset BSI in hospitalized term infants. We identified Gram-positive organisms as the most common pathogen, and late-onset BSI was an independent risk factor for death.

Timely empiric antimicrobials are associated with faster microbiologic clearance in preterm neonates with late-onset bloodstream infections.

The impact of timely empiric antimicrobial therapy on neonates is unclear. Our aim was to examine rates of effective timely empiric antimicrobial therapy on preterm neonates, together with the associated outcomes. We performed a single-centre retrospective study of preterm infants (<32weeks of gestational age) with a late-onset (>72h of age) bloodstream infection (BSI). Empiric antimicrobial administration took place before the results of blood culture were available and its timing was determined by the electronic medical records. Our cohort (n=105) was predominantly female (59%) and black (83%) with a mean (SD) gestational age of 27.4 (2.3) weeks and birthweight of 948 (335) g. Effective empiric antimicrobials were initiated in 114 (69%) of 165 BSI episodes, and a third of the BSIs without empiric antimicrobials were found to be fungal. Both antimicrobial timing (r=0.27, p=0.002) and fungal organism (r=0.35, p=0.0001) showed significant correlations and were independently associated with time to clearance. Neither variable was associated with survival or length of stay. Two-thirds of preterm infants with late-onset BSIs received effective empiric antimicrobials. Timely empiric antimicrobials were associated with shorter time to microbiologic clearance. These data suggest the need for standardised guidelines and quality improvement initiatives.