Incidence Of Bacterial Bloodstream Infections Research Articles

Incidence, causative organisms, and risk factors of bloodstream infections in pediatric liver transplant patients: a systematic review.

Bacterial bloodstream infections (BSI) are the leading cause of mortality and morbidity in pediatric solid organ transplant recipients. This systematic review aimed to pool global data from leading transplant institutions and identify the overall incidence, risk factors, and causative organisms of BSI in pediatric liver transplant recipients. A systematic review of the PubMed and OVID databases was conducted from 2000 to 2022. The initial search yielded 252 unique articles, which were independently reviewed by 2 authors. Articles that reported pediatric-specific data on BSI in isolated liver transplant patients were included, including the incidence of BSI, isolated organisms, and involved risk factors involved. This systematic review was registered with PROSPERO (ID: CRD42023403206). Fourteen articles from the United States, France, Iran, Japan, Korea, South Africa, Thailand, and Turkey were included. A total of 4,812 liver transplants were included in the final analysis. The mean patient age was 25 months (age range, 0-18 years), and 50.9% were male. The overall incidence of BSI was 23.5% (range, 14.7%-55%). The most commonly reported organisms were Staphylococcus epidermidis, Enterococcus, Klebsiella spp., and Escherichia coli. Among the risk factors studied, postoperative biliary complications, a medical history of biliary atresia, and younger age were the risk factors most commonly associated with BSI. Bacterial BSI after pediatric liver transplantation occur at a high incidence, with a unique organism profile notable for a higher percentage of gram-negative organisms. Further studies are required to determine the most appropriate prophylactic and empirical antibiotic management strategies for this population.

#20 Bloodstream Infection is Associated with Prior Gut Microbiome Colonization of the Same Strain in the Neonatal Intensive Care Unit

Abstract Background Infants hospitalized in neonatal intensive care units (NICUs) have high incidence of bacterial bloodstream infections (BSIs) leading to up to 15% mortality and substantial morbidity. Common etiologies of BSI in the NICU are pathogens also capable of colonizing the preterm infant gut. However, differentiating susceptible neonates from those in the same environment remains challenging. We hypothesized that the same strains causing BSI increase in abundance in the gut of affected neonates prior to bacteremia and increased above controls in the same environment. Method We performed shotgun metagenomic sequencing on 462 fecal samples from 19 infants with BSI and 37 controls in the same NICUs paired for gestational age, days of life, antibiotic exposure, delivery mode, and sex. We whole genome sequenced the BSI isolate from 19 cases (6 Staphylococcus aureus, 3 Streptococcus agalactiae, 3 Serratia marcescens, 2 Enterococcus faecalis, 2 Klebsiella pneumoniae, 2 Escherichia coli, and 1 Enterobacter cloacae). We utilized MetaPhLan3 to infer taxonomy and InStrain to track the whole genome sequence of the BSI pathogen within the fecal metagenomes longitudinally. We performed generalized linear mixed effect models with MaAsLin2 to determine significant associations between the microbiome and metadata with subject as a random effect. Results We found no differences in gut microbiome diversity or richness between cases and controls relative to bacteremia day of life. However, infants who experience a BSI possess significantly higher median relative abundances of the causative species in their gut relative to paired controls in the 2 weeks prior to bacteremia (Figure 1A, median 21.4% IQR 0.33-52 vs. 0.4% IQR 0.23-10.5, p<0.05 Wilcoxon). 10/19 infants produced at least 1 stool before bacteremia containing an organism with 0-1 genomic substitutions from the BSI isolate, establishing isogenicity between gut residing and invasive pathogen. The coverage (abundance) of the BSI isolate increased in the stool of affected neonates in the 10 days before infection to an average maximum of 0.48/1.0 (Figure 1B, linear mixed effect model p<0.05). We observed the strongest associations between high gut microbiome abundance of E. faecalis, Klebsiella spp., E. coli, and S. marcescens in the gut microbiome of cases whose BSI was caused by that organism compared to all other samples (p<0.01). Conclusion We show high relative abundance of the same strain in stool prior to bacteremia in hospitalized neonates. The relative abundance of the causative species is higher in cases versus paired controls. These data suggest the potential of gut microbial surveillance and management to identify blooms of gut pathogens to limit the incidence of bacteremia.

Impact of the COVID-19 Pandemic on Antimicrobial Consumption and Hospital-Acquired Candidemia and Multidrug-Resistant Bloodstream Infections.

During the COVID-19 pandemic, the implementation of antimicrobial stewardship strategies has been recommended. This study aimed to assess the impact of the COVID-19 pandemic in a tertiary care Spanish hospital with an active ongoing antimicrobial stewardship programme (ASP). For a 20-week period, we weekly assessed antimicrobial consumption, incidence density, and crude death rate per 1000 occupied bed days of candidemia and multidrug-resistant (MDR) bacterial bloodstream infections (BSI). We conducted a segmented regression analysis of time series. Antimicrobial consumption increased +3.5% per week (p = 0.016) for six weeks after the national lockdown, followed by a sustained weekly reduction of −6.4% (p = 0.001). The global trend for the whole period was stable. The frequency of empirical treatment of patients with COVID-19 was 33.7%. No change in the global trend of incidence of hospital-acquired candidemia and MDR bacterial BSI was observed (+0.5% weekly; p = 0.816), nor differences in 14 and 30-day crude death rates (p = 0.653 and p = 0.732, respectively). Our work provides quantitative data about the pandemic effect on antimicrobial consumption and clinical outcomes in a centre with an active ongoing institutional and education-based ASP. However, assessing the long-term impact of the COVID-19 pandemic on antimicrobial resistance is required.

Bacterial bloodstream infections in pediatric allogeneic hematopoietic stem cell recipients before and after implementation of a central line-associated bloodstream infection protocol: A single-center experience.

There are only few reports describing the influence of central line-associated bloodstream infection (CLABSI) prevention strategies on the incidence of bacterial bloodstream infections (BBSIs). We performed a retrospective cohort study among pediatric recipients of allogeneic hematopoietic stem cell transplantation (allo-HCT) to assess potential changes in BBSI rates during 3 time periods: pre-CLABSI prevention era (era 1, 2004-2005), CLABSI prevention implementation era (era 2, 2006-2009), and maintenance of CLABSI prevention era (era 3, 2010-2012). BBSI from day 0-365 following allo-HCT were studied. The comparison of person-years incidence rates among different periods was carried out by Poisson regression analysis. The mean age of patients was 10.0 years. During the study period, 126 (65%) of 190 patients had at least a single BBSI. From day 0-30, day 31-100, day 101-180, and day 181-365, 20%, 28%, 30%, and 17% of patients, respectively, experienced BBSIs. The rate of Staphylococcus epidermidis and gram-negative pathogens significantly declined from 3.16-0.93 and 6.32-2.21 per 100 person-months during era 1 and era 3, respectively (P = .001). Patients undergoing allo-HCT during era 3 were associated with decreased risk of BBSI (P = .012). Maintenance of CLABSI protocols by nursing staff and appropriate education of other care providers is essential to lower incidence of BBSI in this high-risk population, and further strategies to decrease infection burden should be studied.

Clinical and microbiological characteristics of bloodstream infections in hematological cancer patients

Introduction. Bloodstream infections (BSI) are life-threatening illness for immunocompromised patients with hematological malignancies. The aim of the study was to compare epidemiology, causative pathogens and outcome of hospital-acquired BSI and clarifying the role of herpes group of viruses in their development. Materials and methods. During the period 1991–2013 438 bacterial strains obtained from 360 patients (pts) with hematological malignancies wеre studied. All blood cultures were incubated in the continuous monitoring system for 7 days before discard. The real-time PCR was used for human herpesviruses DNA detection: Herpes simplex viruses types 1 and 2 (HSV 1, 2), Cytomegalovirus (CMV), Epstein–Barr virus (EBV) and Herpesvirus 6 (HHV-6). In this study 64 hematological cancer patients with infectious complications who fulfilled criteria of systemic inflammatory response syndrome with positive peripheral blood cultures were investigated. All pts received empirical anti-infectious therapy with subsequent correction based on the bacteriological, virological and mycological analyses. Results and discussion. A total Gram-positive (G+) accounted for 69.2 % of BSI, Gram-negative (G–) for 30.8 %. Among G+ BSI Coagulase Negative Staphylococci and Staphylococcus aureus were the most frequent pathogens (58.8 %), among G– BSI Escherichia coli (13.0 %) was predominant. It is shown that the development of bacteremia were significantly more frequently occurs in the case of cytomegalovirus and the Epstein–Barr virus detection. Conclusion. Further epidemiological surveillance is warranted in order emerging resistant strains and related mortality. Reactivation of CMV and EBV is significantly associated with higher incidence of bacterial BSI.

Community-Acquired Bacterial Bloodstream Infections in HIV-Infected Patients: A Systematic Review

Information on community-acquired bacterial bloodstream infections (BSIs) in individuals infected with human immunodeficiency virus (HIV) is limited. We conducted a systematic literature review. The case fraction of community-acquired bacterial BSIs in hospitalized patients is 20% and 30% in adults and children, respectively, compared to 9% in HIV-negative adults and children. Worldwide, the main pathogens of community-acquired BSI are nontyphoid salmonellae (NTS), Streptococcus pneumoniae, Escherichia coli, and Staphylococcus aureus, but regional differences are apparent, especially for S. pneumoniae. Compared to HIV-negative populations, HIV patients are particularly at risk to develop NTS bacteremia. Bacteremia incidence is related to immunosuppression, and antiretroviral therapy reduces the incidence of BSI in HIV patients (rate ratios, 0.63-0.02). Mortality rates varied between 7% and 46%. These results suggest that bacterial BSI is more likely to be found in HIV-positive than in HIV-negative patients upon hospitalization, and that causative pathogens vary by region.

Pediatric Bloodstream Infections in Cambodia, 2007 to 2011

Pediatric bacterial bloodstream infections (BSIs) are a major cause of morbidity and mortality worldwide. Epidemiological data from resource-limited settings in southeast Asia, such as Cambodia, are sparse but have important implications for treatment and public health strategies. We retrospectively investigated BSI in children at a pediatric hospital and its satellite clinic in Siem Reap, Cambodia, from January 1, 2007, to July 31, 2011. The range of bacterial pathogens and their antimicrobial susceptibility patterns were analyzed in conjunction with demographic, clinical and outcome data. Of 7682 blood cultures with results (99.9% of cultures taken), 606 (7.9%) episodes of BSI were identified in 588 children. The incidence of BSI increased from 14 to 50/1000 admissions (P < 0.001); this was associated with an increased sampling rate. Most BSI were community acquired (89.1%). Common pathogens included Salmonella Typhi (22.8% of all isolates), Staphylococcus aureus (12.2%), Streptococcus pneumoniae (10.0%), Klebsiella pneumoniae (6.4%) and Escherichia coli (6.3%). 21.5% of BSI were caused by a diverse group of uncommon organisms, the majority of which were environmental Gram-negative species. No Listeria monocytogenes or Group B streptococcal BSI were identified. Antimicrobial resistance, particularly among the Enterobacteriaceae, was common. Overall mortality was substantial (19.0%), higher in neonates (36.9%) and independently associated with meningitis/meningoencephalitis and K. pneumoniae infection. BSI is a common problem in Cambodian children attending hospital and associated with significant mortality. Further studies are needed to clarify the epidemiology of neonatal sepsis, the contribution of atypical organisms and the epidemiology of pneumococcal disease before the introduction of vaccine.

Deferasirox (Exjade®) Given During Conditioning Regimen (FLAMSA/Busulfan/ATG) Reduces the Appearance of Labile Plasma Iron in Patients Undergoing Allogeneic Stem Cell Transplantation

Abstract 3023In patients undergoing allogeneic stem cell transplantation (SCT) non-transferrin-bound iron (NTBI) has been shown to appear quickly after onset of chemotherapy, while not being detectable at baseline. This indicates that cytotoxic therapy is associated with release of catalytically active iron. Pre-transplant iron overload has been associated with a higher risk of complications like infections, liver dysfunction, veno-occlusive disease and acute graft-versus-host disease (GvHD). This could be due to released NTBI catalyzing the generation of reactive oxygen species and being an essential cofactor for pathogen growth.Labile plasma iron (LPI) represents the chelatable, redox-active and toxic fraction of NTBI. It has not yet been assessed in patients undergoing SCT. Treatment with deferasirox (DFR) has been shown to produce sustained reduction in LPI at doses > 20mg/kg/d in patients with β-thalassemia and myelodysplastic syndromes. The aim of this study was to investigate, whether DFR given off-label during conditioning regimen can prevent the formation of NTBI/LPI.A total of 9 patients - all receiving a conditioning regimen with fludarabine, amsacrine, cytosine-arabinoside, busulfan and anti-thymocyte globulin - were enrolled so far. Five consecutive patients received DFR in a mean dose of 16.8mg/kg/d (range 14.5 – 19.7) for the first 5 days of chemotherapy, while 4 patients served as control without DFR. Blood samples were taken daily during chemotherapy and following SCT on day +1, +4, +7 and +14 for assessing selected parameters of iron status (serum iron, transferrin, transferrin saturation (Tfs), serum ferritin) as well as renal and liver function (serum creatinine, ALT, AST, AP, bilirubin). Blood samples for assessment of NTBI and LPI were taken on second (d2) and fifth day (d5) of chemotherapy regimen and d+1 after SCT. NTBI was measured by graphite furnace atomic absorption spectrometry after mobilization of free iron by nitrilotriacetic acid (NTA) and centrifugal filtration of the iron-NTA complex. LPI levels were analyzed according to a previously reported method using an assay kit (Aferrix, Tel Aviv, Israel) that measures iron-specific redox activity in serum in the presence of ascorbate. LPI units > 0.4 were counted as weakly positive and > 0.6 as positive (according to Aferrix).Median baseline Tfs was below the threshold of 80% in both groups (DFR = 38% (range 28–88), control = 59% (range 18–91)). Therefore the presence of NTBI/LPI is very unlikely. During treatment with DFR no LPI was detectable on d2 and d5 whereas in control group 3/4 patients had positive LPI values. On day +1 LPI-values were higher in DFR-group with 3/5 LPI-positive samples (median 0.4 LPI units (range 0–2)) in contrast to 1 positive control sample (1.3 LPI units). Median NTBI-levels in DFR-group on d2 were 3.8 μM (range 3.3–4.8) and decreased notably in 3/5 patients until d5: median 2.1 μM (range 2.0–3.6). In the control group median NTBI values were higher on both days with a median of 5.0 μM (range 2.6–6.3) at d2 and of 4.1μM (range 2.9–6.0) at d5. On day +1 median NTBI-values were similar in both groups: 3.0 μM (range 2.3–4.0) in the DFR and 3.2 μM (range 2.0–3.5) in the control group.Regarding clinical effects the DFR-group had a lower incidence of bacterial bloodstream infections with 2/5 vs. 4/4 control patients.In total DFR was well tolerated and all patients completed chelator therapy. There were no differences between the groups in renal or liver function, except a higher (reversible) increase of bilirubin during ATG treatment in the DFR-group (4/5 patients with grade 3, 1 patient with grade 1 (CTC); median cmax 5.5mg/dl (range 1.4–10.4)) as compared to control (2/4 patients with grade 3, 2 with grade 2; median cmax 3.3mg/dl (range 1.9–4.9)). The DFR-group had a higher incidence of diarrhea during ATG (4/5 patients) and mucositis (5/ 5 patients) than control patients (2/4 and 1/4 patients, respectively). Moreover there were no differences in engraftment or development of acute GvHD.These findings suggest that DFR given during SCT conditioning regimen may prevent the appearance of LPI and reduce the level of NTBI. Therefore it may decrease the risk of infections and organ toxicity by iron-induced radical formation. These preliminary results should be verified in further studies. Disclosures:Off Label Use: Deferasirox (Exjade®) is an oral iron chelator for - the treatment of chronic iron overload due to frequent blood transfusions (≥7 ml/kg/month of packed red blood cells) in patients with beta thalassaemia major aged 6 years and older and - the treatment of chronic iron overload due to blood transfusions when deferoxamine therapy is contraindicated or inadequate in the following patient groups: patients with other anaemias, patients aged 2 to 5 years, patients with beta thalassaemia major with iron overload due to infrequent blood transfusions.