Episodes Of Bloodstream Infection Research Articles

Laboratory-confirmed bloodstream infections in two large neonatal units in sub-Saharan Africa

BackgroundEpidemiological data on neonatal bloodstream infections (BSI) in sub-Saharan Africa are extremely limited. MethodsA comparative analysis of laboratory-confirmed neonatal BSI episodes was conducted retrospectively in two large neonatal units in Botswana and South Africa (January 1 to December 31, 2017). Routine laboratory and ward register data were used to determine BSI rates, the pathogen spectrum, and BSI outcomes. ResultsIn 2017, the Princess Marina Hospital (PMH) and Tygerberg Hospital (TBH) neonatal units admitted 1187 and 2826 neonates, respectively. The BSI incidence rate was 12.1/1000 patient-days (95% confidence interval (CI) 10.2–14.3) at PMH and 3.5/1000 patient-days (95% CI 2.9–4.1) at TBH (p < 0.0001). Most BSI episodes were hospital-acquired (260/284; 91.6%). The blood culture contamination rate was substantially higher at PMH than TBH (152/1116 (13.6%) vs 122/2559 (4.8%); p < 0.001). The crude mortality rate in neonates with BSI was 21.2% (53/250) and significantly higher at TBH than PMH (38/128 (29.7%) vs 15/122 (12.3%), p = 0.001). Factors independently associated with death were birth weight <1500 g (adjusted odds ratio (aOR) 2.8, 95% CI 1.3–6.4; p = 0.02) and male sex (aOR 2.1, 95% CI 1.1–3.7; p = 0.01). Klebsiella pneumoniae was the dominant BSI pathogen in both units, accounting for two-thirds of BSI, and was associated with a large infection outbreak at PMH. Antibiotic resistance rates were substantial in both neonatal units, particularly for K. pneumoniae (98/122 (80.3%), extended-spectrum beta-lactamase (ESBL)-producers) and Staphylococcus aureus (22/33 (66.7%), methicillin-resistant). ConclusionsBSI rates and associated mortality were substantial in these two neonatal units in sub-Saharan Africa. ESBL-producing K. pneumoniae remains a leading BSI and outbreak pathogen.

Management of Bloodstream Infections in Left Ventricular Assist Device Recipients: To Suppress, or Not to Suppress?

BackgroundAscertaining involvement of left ventricular assist device (LVAD) in a patient presenting with bloodstream infection (BSI) can be challenging, frequently leading to use of chronic antimicrobial suppressive (CAS) therapy. We aimed to assess the efficacy of CAS therapy to prevent relapse of BSI from LVAD and non-LVAD sources. MethodsWe retrospectively screened adults receiving LVAD support from 2010 through 2018, to identify cases of BSI. Bloodstream infection events were classified into LVAD-related, LVAD-associated, and non-LVAD BSIs.ResultsA total of 121 episodes of BSI were identified in 80 patients. Of these, 35 cases in the LVAD-related, 14 in the LVAD-associated, and 46 in the non-LVAD BSI groups completed the recommended initial course of therapy and were evaluated for CAS therapy. Chronic antimicrobial suppressive therapy was prescribed in most of the LVAD-related BSI cases (32 of 35, 91.4%) and 12 (37.5%) experienced relapse. Chronic antimicrobial suppressive therapy was not prescribed in a majority of non-LVAD BSI cases (33, 58.9%), and most (31, 93.9%) did not experience relapse. Chronic antimicrobial suppressive therapy was prescribed in 9 of 14 (64.2%) cases of LVAD-associated BSI and none experienced relapse. Of the 5 cases in this group that were managed without CAS, 2 had relapse.ConclusionsPatients presenting with LVAD-related BSI are at high risk of relapse. Consequently, CAS therapy may be a reasonable approach in the management of these cases. In contrast, routine use of CAS therapy may be unnecessary for non-LVAD BSIs.

Clinical and economic impact of intensive care unit-acquired bloodstream infections in Taiwan: a nationwide population-based retrospective cohort study

ObjectivesTo estimate the clinical and economic impact of intensive care unit-acquired bloodstream infections in Taiwan.DesignRetrospective cohort study.SettingNationwide Taiwanese population in the National Health Insurance Research Database and the Taiwan Nosocomial...

Clonal replacement of meticillin-resistant Staphylococcus aureus during repeated outbreaks in a long-term care facility

Meticillin-resistant Staphylococcus aureus (MRSA) is common among residents of long-term care facilities (LTCFs). Analysing the spa types of 22 isolates, mostly bloodstream infections (BSI), revealed five temporally distinct clonal outbreaks occurring in one ward of our local LTCF between 2012 and 2019. Each clone caused episodes of BSI for several months until replaced by another clone. A high MRSA carriage rate of 32% among healthcare workers in this ward was documented during the investigation of the 2019 outbreak. Clonal replacement of MRSA and the role of healthcare workers in transmission are discussed.

Unexpectedly High Frequency of Enterococcal Bloodstream Infections in Coronavirus Disease 2019 Patients Admitted to an Italian ICU: An Observational Study.

We aimed to assess the frequency of ICU-acquired bloodstream infections in coronavirus disease 2019 patients. Retrospective observational study. The emergency expansion of an ICU from eight general beds to 30 coronavirus disease 2019 beds. Patients with coronavirus disease 2019 admitted to the ICU of Luigi Sacco Hospital (Milan, Italy) for greater than or equal to 48 hours between February 21, 2020, and April 30, 2020. None. The frequency of bloodstream infections per 1,000 days of ICU stay was calculated in 89 coronavirus disease 2019 patients, and the cumulative probability of bloodstream infection was estimated using death and ICU discharge as competing events. Sixty patients (67.4%) experienced at least one of the 93 recorded episodes of bloodstream infection, a frequency of 87 per 1,000 days of ICU stay (95% CI, 67-112).The patients who experienced a bloodstream infection had a higher Sequential Organ Failure Assessment score upon ICU admission (9.5; interquartile range, 8-12 vs 8, interquartile range, 5-10; p = 0.042), a longer median ICU stay (15 d; interquartile range, 11-23 vs 8, interquartile range, 5-12; p < 0.001), and more frequently required invasive mechanical ventilation (98.3% vs 82.8%; p = 0.013) than those who did not. The median time from ICU admission to the first bloodstream infection episode was 10 days. Gram-positive bacteria accounted for 74 episodes (79.6%), with Enterococcus species being the most prevalent (53 episodes, 55.8%). Thirty-two isolates (27.3%) showed multidrug resistance. Coronavirus disease 2019 seemed to increase the frequency of bloodstream infections (particularly Enterococcus-related bloodstream infection) after ICU admission. This may have been due to enteric involvement in patients with severe coronavirus disease 2019 and/or limitations in controlling the patient-to-patient transmission of infectious agents in extremely challenging circumstances.

MALDI-TOFMS-oriented early definitive therapy improves the optimal use of antibiotics for Enterococcus spp. bloodstream infection

Enterococci is one of a major cause of bloodstream infection (BSI). Because of its intrinsic drug-resistant nature, empiric antibiotic treatment tends to be inappropriate. We conducted a single-center retrospective cohort study to evaluate the impact of Matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOFMS) on the improvement of early antibiotic treatment for enterococcal infection. We also investigated the 28-day mortality, length of hospitalization and duration of antibiotic treatment for enterococcal bacteremia. A total of 173 BSI episodes (172 patients) between June 2012 and June 2019 were enrolled. Patients were divided into 2 groups before (n = 82) and after (n = 91) the implementation of MALDI-TOFMS (Control group and MALDI-TOF group, respectively). Almost an equal number of Enterococcus faecalis and Enterococcus faecium cases were identified in each group (51.2% and 48.8%, and 47.3% and 52.7% in each group). By implementing MALDI-TOFMS, the time to definitive antibiotic treatment was significantly improved (median 3 vs 1 days, p < 0.001). The 28-day mortality (29.3% vs 26.4%, p = 0.63) and length of hospitalization (median 16 vs 19 days, p = 0.58) were not significantly different. The duration of antibiotic treatment did not significantly differ between the two groups (median 11 vs 11 days, p = 0.78), but the duration was often shorter in older patients (>74 years old) in MALDI-TOF group, excluding those in the terminal phase of malignancy. By implementing MALDI-TOFMS, the time to definitive antibiotic treatment was significantly shortened. Although associated outcomes did not significantly differ, the duration of antibiotic treatment may be shortened.

A case series of rapidly growing mycobacterial catheter-related bloodstream infections among immunocompetent patients

Rapidly growing mycobacteria (RGM) are ubiquitous in the environment and can cause a variety of human infections. Catheter-related bloodstream infections (CRBSI) caused by RGM have been reported predominantly among immunocompromised patients. Removal of central lines and antimicrobial therapy with at least 2 active agents are generally recommended for immunocompromised patients. RGM bloodstream infections (BSIs) are rare in immunocompetent patients and clinical data are very limited. Retrospective medical record review was conducted on patients with blood cultures positive for RGM from July 2012 through March 2015 at Lemuel Shattuck Hospital, a public teaching hospital in Jamaica Plain, Massachusetts, United States. RGM was suspected by presence of beaded Gram-positive bacilli on Gram staining of positive conventional blood cultures and it was confirmed as RGM by Massachusetts State Public Health Laboratory. Nineteen episodes of RGM BSI were identified in 17 patients who had no known immunocompromised conditions that predispose them to opportunistic pathogens. They were predominantly young male with history of intravenous drug use. Peripherally inserted central catheter (PICC) was present in all episodes of RGM BSI and 74% of them clinically improved with PICC removal alone without specific antibiotic therapy for RGM. They were followed up for median duration of 45 days (interquartile range 25–385). The patients remained alive and asymptomatic until the end of follow-up periods. In immunocompetent patients, removal of catheters alone without adding specific antibiotics may be sufficient for RGM CRBSI.

Epidemiology, Risk Factors, and Outcome of Bloodstream Infection Within the First Year After Kidney Transplantation

BackgroundMulti-drug resistant organisms have been emerging among kidney transplant (KT) recipients with bloodstream infections (BSI). The investigation for epidemiology, risk factors and outcome of these infections following KT was initiated. Materials and MethodsA retrospective study of all adult KT recipients who developed a BSI within the first year after KT in 2016 at a single transplant center was conducted. The cumulative incidence of BSI was estimated with Kaplan-Meier methodology. Clinical characteristics and outcome were extracted. Risk factors were analyzed with Cox proportional hazards models. ResultsAmong 171 KT recipients, there were 26 (15.2%) episodes of BSI. Fifty-nine percent were men and the mean ± SD age was 43 ± 12 years. The cumulative incidence of BSIs was 10.1% at 1 month, 13.5% at 6 months, and 15.2% at 12 months. Gram-negative bacteria were responsible for 92% of BSIs, Escherichia coli was the most common pathogen (65%) followed by Klebsiella pneumoniae (11%). Among those, 71% were resistant to extended-spectrum cephalosporins. The genitourinary tracts were the predominant source of BSIs (85%). The second kidney transplantation (HR, 4.55; 95% CI, 1.24–16.79 [P = 0.02]) and receiving induction therapy (HR, 3.05; 95% CI, 1.15‐8.10 [P < 0.03]) were associated with BSI in a multivariate analysis. One patient (4%) developed allograft rejection, allograft failure and death from septic shock. ConclusionsOne out of six KT recipients could develop BSI from gram-negative bacteria within the first year after transplant, particularly in those that received the second transplantation or induction therapy.

A Prevention Initiative to Reduce Healthcare-Associated Bloodstream Infections in a Spanish University Hospital

Background: Bloodstream infections are one of the main adverse effects of healthcare in Spain. In our hospital, we have reported that the mean incremental cost of patients who develop bacteremia during admission was €15,526 (US$18,314.62) per discharge, representing an annual increment in hospital cost of €1,108,190 (US$1,307,232) in 2005–2012. Moreover, we have also observed that only 15.4% of episodes of our bacteremia occur in intensive care units, with most of these infections (67%) occurring in conventional units.1 Therefore, we started several initiatives to reduce healthcare-associated bloodstream infections. Herein, we describe one of these initiatives, which is the implementation of the intravascular therapy team (ITT) and its effect on the observed healthcare-associated bloodstream infections. Methods: This retrospective analysis evaluated the incidence of healthcare-associated bloodstream infections in a University Hospital of 520 beds from January 2014 to June 2019. The ITT was implemented in 2017. This is a multidisciplinary team with 2 specialists in infection control and 2 specialists in intravascular therapy. We evaluated the annual incidence rate of healthcare-associated bloodstream infections (number of bacteremia episodes per 1,000 days of hospital stay) and its relation with the interventions carried out by the multidisciplinary team. Results: The annual incidences of healthcare-associated bloodstream infections (episodes per 1,000 days of hospital stay) were 0.50 (2014), 0.46 (2015), 0.58 (2016), 0.69 (2017), 0.60 (2018), 0.51 (first quarter 2019), and 0.38 (second quarter 2019, 0.38), respectively. The highest incidence of bacteremia was observed in 2017 when the ITT started the following actions: (1) following a clinical protocol to improve the appropriateness in the utilization of new devices such as a peripherally inserted central catheter (PICC) and Medline; (2) continuous training of healthcare professionals, particularly young staff; (3) feedback with hospitalization units; and (4) proactive surveillance of venous access manipulation and maintenance. The interventions were designed, implemented, and evaluated by the ITT and were well accepted by healthcare professionals. After the implementation of the ITT, the incidence of healthcare-associated bloodstream infections decreased. This trend was particularly relevant for parenteral nutrition catheters (episodes per 1,000 days of parenteral nutrition) (Fig. 1). Conclusions: The implementation of the ITT in our center has allowed us to considerably reduce the incidence of healthcare-associated bloodstream infections. From our experience, the interventions related to systematic evaluation, education, and feedback are key to obtain and maintain this improvement.Funding: NoneDisclosures: Carlota Hidalgo-Lopez reports that this study was partly funded by Diversey. The authors did not receive direct Funding: from the sponsor, Juan Pablo Horcajada reports consulting fees from MSD, Pfizerand, and Menarini, as well as speaker fees from MSD, Pfizer, and Zambon.

Bloodstream Infections with Typical Probiotic Organisms

Background: Probiotics are protective against Clostridioides difficile infection and antibiotic-associated diarrhea, and they may decrease risk of infections following complex abdominal surgeries. Infectious risks associated with probiotic use are not well described in the literature. We describe probiotic use among patients with bloodstream infections (BSIs) due to organisms typically found in probiotics. Methods: Patients with positive blood cultures with Lactobacillus spp, Saccharomyces spp, and Bifidobacterium spp at our large academic hospital from October 2016 through October 2019 were identified using Theradoc, a clinical surveillance tool. Clinical data and orders for probiotics, including probiotic capsules, probiotic yogurt, and kefir, were extracted from the electronic medical record. Cases were considered distinct if the cultures were collected 7 or more days apart. True infections were defined as positive cultures which were treated with antimicrobials and had provider documentation outlining clinical relevance of culture data. Results: Among 26 distinct episodes of BSI, 16 (62%) were considered true infections. The remaining 10 cases were interpreted as contaminants or of unclear significance. Of the 16 cases representing true infection in 14 patients, 6 (38%) had received probiotics in the hospital in the preceding month. Among these patients, 5 had Lactobacillus bacteremia and had received Lactobacillus capsules, probiotic yogurt, and/or kefir. One patient had Saccharomyces fungemia following receipt of probiotic yogurt and kefir. All 6 patients with BSI possibly related to probiotic use had an antecedent gastrointestinal procedure or surgery within a month of the BSI, and 2 had intra-abdominal abscesses from which the same organism was cultured. Of the 16 true BSIs, 9 occurred in immunocompromised hosts, but antecedent probiotic use was confirmed in only 1 of these cases. Two episodes caused by different organisms occurred within the same month; all other episodes were &gt;60 days apart. Conclusions: In our retrospective review of BSIs with organisms typically found in probiotics over a 3-year period at a large academic hospital, more than one-third of those with clinically relevant BSIs had antecedent probiotic use within the hospital. All patients with infections possibly related to probiotic use had recent gastrointestinal procedures or surgery, raising concern for probiotic use following interventions that increase the risk for gastrointestinal tract leakage or translocation. Further research is necessary to assess the risk of bloodstream infection in postoperative patients treated with probiotics.Funding: NoneDisclosures: None

Evaluation of Inflammatory Biomarkers in Pediatric Hematology-Oncology Patients With Bloodstream Infection.

Bloodstream infection (BSI) is a serious complication in pediatric hematology-oncology patients. To evaluate the clinical significance of C-reactive protein (CRP), procalcitonin (PCT), albumin, fibrinogen, and D-dimer as potential biomarkers to differentiate among various subtypes of BSIs in pediatric patients with hematologic and oncologic diseases, we retrieved and analyzed the medical records of pediatric hematology-oncology patients diagnosed with BSI at our hospital between January 2016 and December 2017. The demographic (sex and age) and clinical (primary diseases) characteristics, and laboratory test results (white blood cell and absolute neutrophil counts, and serum CRP, PCT, albumin, fibrinogen, and D-dimer levels) were compared between nosocomial and non-nosocomial; neutropenic and non-neutropenic; and Gram-positive and Gram-negative BSI episodes. A total of 125 BSI episodes were included, including 69 (55.2%) nosocomial cases, 94 (75.2%) neutropenic cases, and 49 (39.2%) Gram-positive episodes. Of the 5 potential biomarkers evaluated (CRP, PCT, albumin, fibrinogen, and D-dimer), PCT levels were significantly lower in neutropenic episodes and Gram-positive BSIs (P=0.008 and P=0.001, respectively). At a cutoff value of 0.67 ng/mL, the diagnostic sensitivity, specificity, and positive/negative predictive values of PCT for the differentiation of Gram-positive and Gram-negative bacterial sepsis were 74.2%, 64.6%, 70.8%, and 65.2%, respectively. We concluded that PCT might potentially serve as a biomarker to differentiate between Gram-positive and Gram-negative BSIs in pediatric hematology-oncology patients.

Bloodstream infections by gram-negative bacteria in kidney transplant patients: Incidence, risk factors, and outcome.

Kidney transplant recipients (KTRs) are at increased risk of infections. The aims of this study were to describe the incidence of bloodstream infections (BSIs) by gram-negative bacteria in a cohort of KTRs, the risk factors for BSI due to multi-drug-resistant (MDR) gram-negative bacteria, and the predictors for unfavorable outcome, defined as death or nephrectomy or return to dialysis, within 30days from BSI. We conducted a retrospective cohort study at the renal transplant unit of a tertiary care hospital in Athens, Greece. In a total of 1962 KTRs, we recorded 195 BSI episodes in 182 single patients (male/female=97/85), with a median (interquartile range) age of 57.2 (44-64.9) years. The incidence was 1.393/100 patient-years. The most common source of infection was urinary tract (70.9%), and Escherichia coli (63.7%) was the most common pathogen. 19.2% of the infecting organisms were MDR; previous antibiotic use (OR 8.2; CI 2.1-32.9) and previous stay in the intensive care unit (OR 34.2; CI 1.6-730.2) were associated with MDR BSIs. 6% of patients died, and 2.2% underwent nephrectomy, while no patients had to return to dialysis. Diabetes mellitus (OR 8.1; 95% CI 1.3-50.3), Pseudomonas aeruginosa BSI (OR 46.1; 95% CI 3.9-552.3), and septic shock (OR 46.7; 95% CI 1.7-1304.9) were independent predictors of unfavorable outcome. Bloodstream infections in KTRs have a significant impact on allograft and patients outcome.

Bloodstream infections in critically ill patients with COVID-19.

BackgroundLittle is known about the incidence and risk of intensive care unit (ICU)‐acquired bloodstream infections (BSI) in critically ill patients with coronavirus disease 2019 (COVID‐19).Materials and methodsThis retrospective, single‐centre study was conducted in Northern Italy. The primary study objectives were as follows: (a) to assess the incidence rate of ICU‐acquired BSI and (b) to assess the cumulative risk of developing ICU‐acquired BSI.ResultsOverall, 78 critically ill patients with COVID‐19 were included in the study. Forty‐five episodes of ICU‐acquired BSI were registered in 31 patients, with an incidence rate of 47 episodes (95% confidence interval [CI] 35‐63) per 1000 patient‐days at risk. The estimated cumulative risk of developing at least one BSI episode was of almost 25% after 15 days at risk and possibly surpassing 50% after 30 days at risk. In multivariable analysis, anti‐inflammatory treatment was independently associated with the development of BSI (cause‐specific hazard ratio [csHR] 1.07 with 95% CI 0.38‐3.04 for tocilizumab, csHR 3.95 with 95% CI 1.20‐13.03 for methylprednisolone and csHR 10.69 with 95% CI 2.71‐42.17 for methylprednisolone plus tocilizumab, with no anti‐inflammatory treatment as the reference group; overall P for the dummy variable = 0.003).ConclusionsThe incidence rate of BSI was high, and the cumulative risk of developing BSI increased with ICU stay. Further study will clarify if the increased risk of BSI we detected in COVID‐19 patients treated with anti‐inflammatory drugs is outweighed by the benefits of reducing any possible pro‐inflammatory dysregulation induced by SARS‐CoV‐2.

Trends of Pediatric Bloodstream Infections in Stockholm, Sweden: A 20-year Retrospective Study.

The etiology of bloodstream infections (BSIs) changes over time due to updated immunization programs, new antibiotic-use strategies, changes in patient mix and travel. Continuous surveillance can guide empiric therapy and identify targets for prevention. We conducted a descriptive retrospective analysis among children <18 years of age who were detected with BSI between July 1998 and June 2018 for changes in the incidence, risk factors, and etiology of BSI in a Swedish tertiary hospital (Karolinska University Hospital). We evaluated 2079 episodes of BSI. During the study period, the incidence of BSI in children 0-17 years of age decreased (τ = -0.45, P = 0.016), which was most evident among children 3 months to 2 years of age (τ = -0.59, P = 0.0006) and in early neonatal period (0-7 days; τ = -0.44, P = 0.0069). These were explained by the reduced occurrence of Streptococcus pneumoniae in children 3 months to 2 years of age and Streptococcus agalactiae and Candida spp. in neonates. Staphylococcus aureus was the commonest pathogen, accounting for 31.6% of episodes. The proportion of hospital-acquired infection was higher in patients with underlying risk factors (47.6% vs. 2.6%). The etiology of hospital-acquired infection BSI was more diverse than that of community-acquired infections and was related to underlying risk factors. The crude mortality rate was 5.7%. For children admitted to the neonatal ward, the mortality was 17.6%, but declined (τ = -0.469, P = 0.004) over the study period. There was a decreasing trend of pediatric BSI and mortality over last 20 years, which was associated with pneumococcal immunization and antimicrobial prophylaxis for high-risk patients.

Analysis of pathogens and clinical characteristics of bloodstream infection in neutropenic children with hematological malignancies from 2014 to 2018

目的探讨儿童血液病患者在中性粒细胞缺乏（粒缺）期发生血流感染时的病原学分布、耐药情况，为该类患者合理使用抗菌药物提供数据支持。方法回顾性分析2014年1月至2018年12月中国医学科学院血液病医院收治的儿童血液病患者粒缺期发生血流感染时的临床特征、病原菌分布和药物敏感性数据。结果427例儿童血液病患者在粒缺期共发生537次血流感染，30 d全因死亡率为3.7%。其中44.7%例次血流感染的临床特征仅表现为发热，其病原菌以肠杆菌科细菌为主。血流感染常伴口腔黏膜、呼吸道及消化道症状，比例分别为20.7%、20.5%和14.3%。伴不同症状的血流感染病原菌分布不同（χ2=40.561，P=0.001）。共分离出550株病原菌，位于前5位的细菌分别为草绿色链球菌（109株，19.8%）、大肠埃希菌（99株, 18.0%）、表皮葡萄球菌（75株，13.6%）、肺炎克雷伯菌（67株，12.2%）和金黄色葡萄球菌（32株，5.8%）。耐药方面，肠肝菌科细菌及铜绿假单胞菌对于哌拉西林/他唑巴坦、碳青霉烯类药物的耐药率<5%。金黄色葡萄球菌中耐甲氧西林金黄色葡萄球菌（MRSA）的比例为9.7%。结论儿童恶性血液病患者粒缺期发生血流感染病原菌革兰阳性球菌与阴性杆菌比例大致相同，提示经验性抗菌药物使用应具有广谱性，常见分离菌耐药性仍处于较低水平，常用的碳青霉烯类、糖肽类、酶抑制剂复合物类药物如哌拉西林/他唑巴坦等仍具有较好效果。

Low molecular weight heparin for prevention of central venous catheter-related thrombosis in children.

The prevalence of children diagnosed with thrombotic events has been increasing in the last decades. The most common thrombosis risk factor in neonates, infants and children is the placement of a central venous catheter (CVC). It is unknown if anticoagulation prophylaxis with low molecular weight heparin (LMWH) decreases CVC-related thrombosis in children. This is an update of the Cochrane Review published in 2014. To determine the effect of LMWH prophylaxis on the incidence of CVC-related thrombosis and major and minor bleeding complications in children. Further objectives were to determine the effect of LMWH on occlusion of CVCs, number of days of CVC patency, episodes of catheter-related bloodstream infection (CRBSI), other side effects of LMWH (allergic reactions, abnormal coagulation profile, heparin-induced thrombocytopaenia and osteoporosis) and mortality during therapy. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 7 May 2019. We undertook reference checking of identified trials to identify additional studies. We included randomised controlled trials (RCTs) and quasi-randomised trials comparing LMWH to no prophylaxis (placebo or no treatment), or low-dose unfractionated heparin (UFH) either as continuous infusion or flushes (low-dose UFH aims to ensure the patency of the central line but has no systemic anticoagulation activity), given to prevent CVC-related thrombotic events in children. We selected studies conducted in children aged 0 to 18 years. Two review authors independently identified eligible studies, which were assessed for study methodology including bias, and extracted unadjusted data where available. In the data analysis step, all outcomes were analysed as binary or dichotomous outcomes. The effects of interventions were summarised with risk ratios (RR) and their respective 95% confidence intervals (CI). We assessed the certainty of evidence for each outcome using the GRADE approach. One additional study was included for this update bringing the total to two included studies (with 1135 participants). Both studies were open-label RCTs comparing LMWH with low-dose UFH to prevent CVC-related thrombosis in children. We identified no studies comparing LMWH with placebo or no treatment. Meta-analysis found insufficient evidence of an effect of LMWH prophylaxis in reducing the incidence of CVC-related thrombosis in children with CVC, compared to low-dose UFH (RR 0.68, 95% CI 0.27 to 1.75; 2 studies; 787 participants; low-certainty evidence). One study (158 participants) reported symptomatic and asymptomatic CVC-related thrombosis separately and detected no evidence of a difference between LMWH and low-dose UFH (RR 1.03, 95% CI 0.21 to 4.93; low-certainty evidence; RR 1.17, 95% CI 0.45 to 3.08; low-certainty evidence; for symptomatic and asymptomatic participants respectively). There was insufficient evidence to determine whether LMWH impacts the risk of major bleeding (RR 0.27, 95% CI 0.05 to 1.67; 2 studies; 813 participants; low-certainty evidence); or minor bleeding. One study reported minor bleeding in 53.3% of participants in the LMWH arm and in 44.7% of participants in the low-dose UFH arm (RR 1.20, 95% CI 0.91 to 1.58; 1 study; 158 participants; very low-certainty evidence), and the other study reported no minor bleeding in either group (RR: not estimable). Mortality during the study period was reported in one study, where two deaths occurred during the study period. Both were unrelated to thrombotic events and occurred in the low-dose UFH arm. The second study did not report mortality during therapy per arm but showed similar 5-year overall survival (low-certainty evidence). No additional adverse effects were reported. Other pre-specified outcomes (including CVC occlusion, patency and CRBSI) were not reported. Pooling data from two RCTs did not provide evidence to support the use of prophylactic LWMH for preventing CVC-related thrombosis in children (low-certainty evidence). Evidence was also insufficient to confirm or exclude a difference in the incidence of major and minor bleeding complications in the LMWH prophylaxis group compared to low-dose UFH (low and very low certainty respectively). No evidence of a clear difference in overall mortality was seen. Studies did not report on the outcomes catheter occlusion, days of catheter patency, episodes of CRBSI and other side effects of LMWH (allergic reactions, abnormal coagulation profile, heparin-induced thrombocytopaenia and osteoporosis). The certainty of the evidence was downgraded due to risk of bias of the included studies, imprecision and inconsistency, preventing conclusions in regards to the efficacy of LMWH prophylaxis to prevent CVC-related thrombosis in children.

Estimating the burden of antimicrobial resistance in Malawi: protocol for a prospective observational study of the morbidity, mortality and economic cost of third-generation cephalosporin resistant bloodstream infection.

Introduction: Antimicrobial resistance (AMR) is a global public health concern, but the problems are context specific, with each county or setting facing differing challenges. In sub-Saharan Africa, third-generation cephalosporin resistant Enterobacterales (3GCR-E) are of particular concern, given the widespread reliance on ceftriaxone for treatment of severe infection in this setting. In Malawi, despite rising prevalence of 3GCR-E, the health-impact of these infections has not been described. This study is designed to estimate attributable mortality, morbidity and economic cost of 3GCR-E bloodstream infection (BSI) in a large, urban hospital. Methods: This study will investigate the burden of AMR by recruiting a a prospective longitudinal cohort of patients who have bloodstream infection with 3GCR-E, at Queen Elizabeth Central Hospital, Blantyre, Malawi. Patients whose blood culture is positive for either third-generation cephalosporin susceptible (3GC-S) or third-generation resistant (3GC-R) Enterobacterales will be enrolled and provide clinical and healthcare economic data. Patients will be followed throughout their hospital stay and to 6-months post discharge. The primary outcomes for the study are mortality and morbidity from 3GCR-E. Healthcare economic outcomes will be assessed by comparing healthcare provider costs, indirect patient costs and health-related quality of life outcomes in patients with 3GC-S and 3GC-R BSI. Based on our observation that some patients with clinical suspicion of sepsis and 3GC-R BSI are surviving without an effective antibiotic, we review each patient prospectively and classify what role the isolated bacteria is playing in the patient's clinical presentation. Each BSI episode will be classified into the following categories: definite Gram-negative sepsis, probable Gram-negative sepsis, transient or occult bacteraemia, or contaminated blood culture. These classifications will be incorporated into our analysis. Ethics and dissemination: The study protocol has been approved by the Malawi College of Medicine Research Ethics Committee and by the Liverpool School of Tropical Medicine Research Ethics committee.

Epidemiologic changes in bloodstream infections in Andalucía (Spain) during the last decade

ObjectivesDuring the last decade, some changes in the epidemiology of invasive infections have been reported; however, specific studies with patient-level data are scarce. The aim of this study was to describe and evaluate the epidemiologic changes in bloodstream infections (BSI) during the last decade in Andalucía, Spain. MethodsData from two prospective cohorts of BSI in adults with the same methodology performed 10 years apart in 11 hospitals (eight tertiary and three community) in Andalucía, Spain, were compared; the 2006–7 cohort study was performed between October 2006 and March 2007, and the 2016–17 cohort study was performed between October 2016 and March 2017. Population-based incidence rates were calculated and extrapolated for 1 year. Relative risk ratios were calculated between the 2 periods. Multivariate analyses were performed by logistic regression. ResultsOverall, 1262 episodes of BSI were included, 563 (44.6%) in 2006–7 and 699 (55.3%) in 2016–17. Multivariate models selected the following changes in patients' features in 2016–17, after controlling for type of acquisition: higher age (odds ratio (OR) = 1.02; 95% confidence interval [CI] 1.01–1.03), lower urinary catheter (OR = 0.37; 95% CI, 0.26–0.48) and lower Pitt score (OR = 0.76; 95% CI, 0.71–0.82). Adjusted estimations considering patients' features and exposure to procedures showed a reduction in coagulase-negative staphylococci (OR = 0.47; 95% CI, 0.32–0.69), and an increase in Proteus spp. (OR = 3.12; 95% CI, 1.18–8.23) and Candida spp. (OR = 3.01; 95% CI, 1.03–8.86). ConclusionsWe found relevant epidemiologic changes in BSI in our area, including rates, frequency of acquisition types, changes in patient's profiles and aetiologic agents.

Prevalence and Clonal Distribution of Azole-Resistant Candida parapsilosis Isolates Causing Bloodstream Infections in a Large Italian Hospital.

The most prevalent cause of nosocomial bloodstream infection (BSI) among non-C. albicans Candida species, Candida parapsilosis, may not only be resistant to azole antifungal agents but also disseminate to vulnerable patients. In this survey of BSIs occurring at a large Italian hospital between May 2014 and May 2019, C. parapsilosis accounted for 28.5% (241/844) of all Candida isolates causing BSI episodes. The majority of episodes (151/844) occurred in medical wards. Across the 5 yearly periods, the rates of azole non-susceptibility were 11.8% (4/34), 17.8% (8/45), 28.6% (12/42), 32.8% (19/58), and 17.7% (11/62), respectively, using the Sensititre YeastOne® method. Among azole non-susceptible isolates (54/241; 22.4%), 49 were available for further investigation. Using the CLSI reference method, all 49 isolates were resistant to fluconazole and, except one (susceptible dose-dependent), to voriconazole. Forty (81.6%) isolates harbored the Erg11p Y132F substitution and nine (18.4%) isolates the Y132F in combination with the Erg11p R398I substitution. According to their genotypes, as defined using a microsatellite analysis based on six short tandem repeat markers, 87.7% of isolates (43/49) grouped in two major clusters (II and III), whereas 4.1% of isolates (2/49) belonged to a separate cluster (I). Interestingly, all the isolates from cluster II harbored the Y132F substitution, and those from cluster III harbored both Y132F and R398I substitutions. Of 56 non-Italian isolates included as controls, two Indian isolates with the Y132F substitution had a genotype clearly differing from that of the isolates from clusters II and I. In conclusion, these findings show the dominance of clonal Y132F isolates in our hospital and suggest detection of the Y132F substitution as helpful tool to prevent transmission among hospitalized patients at risk of BSI.

Estimating the burden of antimicrobial resistance in Malawi: protocol for a prospective observational study of the morbidity, mortality and economic cost of third-generation cephalosporin resistant bloodstream infection

Introduction: Antimicrobial resistance (AMR) is a global public health concern, but the problems are context specific, with each county or setting facing differing challenges. In sub-Saharan Africa, third-generation cephalosporin resistant Enterobacterales (3GCR-E) are of particular concern, given the widespread reliance on ceftriaxone for treatment of severe infection in this setting. In Malawi, despite rising prevalence of 3GCR-E, the health-impact of these infections has not been described. This study is designed to estimate attributable mortality, morbidity and economic cost of 3GCR-E bloodstream infection (BSI) in a large, urban hospital. Methods: This study will investigate the burden of AMR by recruiting a a prospective longitudinal cohort of patients who have bloodstream infection with 3GCR-E, at Queen Elizabeth Central Hospital, Blantyre, Malawi. Patients whose blood culture is positive for either third-generation cephalosporin susceptible (3GC-S) or third-generation resistant (3GC-R) Enterobacterales will be enrolled and provide clinical and healthcare economic data. Patients will be followed throughout their hospital stay and to 6-months post discharge. The primary outcomes for the study are mortality and morbidity from 3GCR-E. Healthcare economic outcomes will be assessed by comparing healthcare provider costs, indirect patient costs and health-related quality of life outcomes in patients with 3GC-S and 3GC-R BSI. Based on our observation that some patients with clinical suspicion of sepsis and 3GC-R BSI are surviving without an effective antibiotic, we review each patient prospectively and classify what role the isolated bacteria is playing in the patient’s clinical presentation. Each BSI episode will be classified into the following categories: definite Gram-negative sepsis, probable Gram-negative sepsis, transient or occult bacteraemia, or contaminated blood culture. These classifications will be incorporated into our analysis. Ethics and dissemination: The study protocol has been approved by the Malawi College of Medicine Research Ethics Committee and by the Liverpool School of Tropical Medicine Research Ethics committee.