Bacterial Bloodstream Infections Research Articles

Polymorphism in a lincRNA Associates with a Doubled Risk of Pneumococcal Bacteremia in Kenyan Children

Bacteremia (bacterial bloodstream infection) is a major cause of illness and death in sub-Saharan Africa but little is known about the role of human genetics in susceptibility. We conducted a genome-wide association study of bacteremia susceptibility in more than 5,000 Kenyan children as part of the Wellcome Trust Case Control Consortium 2 (WTCCC2). Both the blood-culture-proven bacteremia case subjects and healthy infants as controls were recruited from Kilifi, on the east coast of Kenya. Streptococcus pneumoniae is the most common cause of bacteremia in Kilifi and was thus the focus of this study. We identified an association between polymorphisms in a long intergenic non-coding RNA (lincRNA) gene (AC011288.2) and pneumococcal bacteremia and replicated the results in the same population (p combined = 1.69 × 10−9; OR = 2.47, 95% CI = 1.84–3.31). The susceptibility allele is African specific, derived rather than ancestral, and occurs at low frequency (2.7% in control subjects and 6.4% in case subjects). Our further studies showed AC011288.2 expression only in neutrophils, a cell type that is known to play a major role in pneumococcal clearance. Identification of this novel association will further focus research on the role of lincRNAs in human infectious disease.

Clinical and microbiological features of resistant gram-negative bloodstream infections in children.

Bloodstream infections (BSIs) caused by Gram-negative (GN) bacteria cause significant morbidity and mortality. There is a worldwide increase in the reported incidence of resistant microorganisms; therefore, surveillance programs are important to define resistance patterns of GN microorganisms causing BSIs. The objective of this study was to describe the clinical and microbiological features of resistant GN BSIs in a tertiary pediatric hospital in Turkey. Patients between 1 month and 18 years of age hospitalized between January 2005 and December 2012 were included in this study. The presence of ESBL and AmpC type beta-lactamase activity were evaluated using the Clinical and Laboratory Standards Institute (CLSI) disk diffusion and double-disk synergy tests. A total of 209 resistant GN bacterial BSI episodes were identified in 192 patients. Of 192 children, 133 (69.2%) were aged ≤48 months of age. Sixty-six (31.6%) of the BSIs were considered community-acquired and 143 (68.4%) were hospital-acquired infections. The most common isolates were non-fermenting GN bacteria (n=117, 55.9%). The major causative pathogens were Pseudomonas spp. in non-fermenting GN bacteria. The resistance rates to imipenem for Pseudomonas spp. and Acinetobacter spp. were 40.5% and 41.6%, respectively. The most common isolates in fatal patients were Pseudomonas spp. followed by Escherichia coli. The overall 28-day mortality rate was 16.3%. Although our study was performed at a single center and represents a local population, based on this study, it is concluded that surveillance programs and studies of novel antibiotics for resistant GN bacteria focusing on pediatric patients are required.

Terminal Complement Blockade after Hematopoietic Stem Cell Transplantation Is Safe without Meningococcal Vaccination

Eculizumab inhibits terminal complement-mediated intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria and complement-mediated thrombotic microangiopathy (TMA) in patients with atypical hemolytic uremic syndrome and is now used as a first-line therapy in these diseases. Eculizumab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) because of an increased risk of meningococcal infections in persons without adequate functional complement. Administration of meningococcal vaccine is required at least 2 weeks before administering the first dose of eculizumab, and this advice is included in the product label. Eculizumab use for treatment of TMA in hematopoietic stem cell transplantation (HSCT) recipients brings a significant dilemma regarding REMS required meningococcal vaccination. TMA after HSCT usually occurs within the first 100 days after transplantation when patients are severely immunocompromised and are not able to mount a response to vaccines. We evaluated 30 HSCT recipients treated with eculizumab for high-risk TMA without meningococcal vaccine. All patients received antimicrobial prophylaxis adequate for Neisseria meningitides during eculizumab therapy and for 8 weeks after discontinuation of the drug. Median time to TMA diagnosis was 28 days after transplant (range, 13.8 to 48.5). Study subjects received a median of 14 eculizumab doses (range, 2 to 38 doses) for HSCT-associated TMA therapy. There were no incidences of meningococcal infections. The incidences of bacterial and fungal bloodstream infections were similar in patients treated with eculizumab (n = 30) as compared with those with HSCT-associated TMA who did not receive any complement blocking therapy (n = 39). Our data indicate that terminal complement blockade in the early post-transplant period can be performed without meningococcal vaccination while using appropriate antimicrobial prophylaxis until complement function is restored after therapy completion.

The prognostic significance of bacterial DNA in patients with decompensated cirrhosis and suspected infection.

Circulating and peritoneal fragments of microbial DNA (bactDNA) are evidence for bacterial translocation in decompensated cirrhosis and may serve as a rational approach for antibiotic therapy when infection is suspected. Prospective multicenter study to investigate whether identification of bactDNA from blood or ascitic fluid (AF) by multiplex polymerase chain reaction (PCR) is associated with increased 90-day mortality in 218 patients with cirrhosis and signs of infection. BactDNA in either compartment was detected in 134 (61%) patients, comprising 54 with bactDNA in blood and AF, 48 with AF bactDNA only, and 32 with blood bactDNA only. BactDNA was associated with spontaneous bacterial peritonitis and blood stream infections (SBP/BSI), acute-on-chronic liver failure (ACLF), encephalopathy and markers of inflammation. The prevalence of bactDNA in patients with proven SBP/BSI (36/49; 73%) was similar to that in patients with sterile ACLF (37/52; 71%). Actuarial 90-day survival was 56 ± 5% in the absence of bactDNA in both compartments and did not differ if bactDNA was detected in blood only (63 ± 9%), AF only (63 ± 7%), or in blood and AF (52 ± 7%). Predictors of 90-day mortality were SBP (HR = 3.10; 95% CI: 1.90-5.06), BSI (HR = 4.94; 95% CI: 2.71-9.02), and ACLF (HR = 2.20; 95% CI: 1.44-3.35). The detection of resistance genes in blood or AF in the absence of SBP/BSI (n = 11) was associated with poor 1-year survival (HR = 2.35; 95% CI: 1.03-5.35). BactDNA in sterile body fluids did not indicate increased mortality in cirrhotic patients with suspected infection. Using multiplex PCR for risk stratification cannot be recommended in these patients.

Potential Impact of Bacterial Bloodstream Infection (BSI) on Outcomes of Allogeneic Hematopoietic Progenitor Cell Transplant – Single Pediatric Center Experience

Potential Impact of Bacterial Bloodstream Infection (BSI) on Outcomes of Allogeneic Hematopoietic Progenitor Cell Transplant – Single Pediatric Center Experience

A Study of Impact of Bacterial Blood Stream Infections (BBSI) and Antibiotic Resistance on Transplant Related Mortality (TRM) Following Allogeneic Hematopoietic Cell Transplantation (alloHCT) in Children: A Multicenter Study

A Study of Impact of Bacterial Blood Stream Infections (BBSI) and Antibiotic Resistance on Transplant Related Mortality (TRM) Following Allogeneic Hematopoietic Cell Transplantation (alloHCT) in Children: A Multicenter Study

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.

Risk Factors for and Clinical Outcomes of Multidrug-Resistant Gram-Negative Bacterial Bloodstream Infections: Initial Results From a 12-Year Prospective Cohort Study

Risk Factors for and Clinical Outcomes of Multidrug-Resistant Gram-Negative Bacterial Bloodstream Infections: Initial Results From a 12-Year Prospective Cohort Study

Causes of non-malarial febrile illness in outpatients in Tanzania.

ObjectiveIn sub‐Saharan Africa, the use of malaria rapid diagnostic tests (mRDT) has raised awareness of alternative fever causes in children but few studies have included adults. To address this gap, we conducted a study of mRDT‐negative fever aetiologies among children and adults in Tanzania.MethodsA total of 1028 patients aged 3 months to 50 years with a febrile illness and negative mRDT were enrolled from a Tanzanian hospital outpatient department. All had a physical examination and cultures from blood, nasopharynx/throat and urine. Patients were followed on Days 7 and 14 and children meeting WHO criteria for pneumonia were followed on Day 2 with chest radiology.ResultsRespiratory symptoms were the most frequent presenting complaint, reported by 20.3% of adults and 64.0% (339/530) of children. Of 38 X‐rayed children meeting WHO pneumonia criteria, 47.4% had a normal X‐ray. Overall, only 1.3% of 1028 blood cultures were positive. Salmonella typhi was the most prevalent pathogen isolated (7/13, 53.8%) and S. typhi patients reported fever for a median of 7 days (range 2–14). Children with bacteraemia did not present with WHO symptoms requiring antibiotic treatment. Young children and adults had similar prevalences of positive urine cultures (24/428 and 29/498, respectively).ConclusionFew outpatient fevers are caused by blood stream bacterial infection, and most adult bacteraemia would be identified by current clinical guidelines although paediatric bacteraemia may be more difficult to diagnose. While pneumonia may be overdiagnosed, urinary tract infection was relatively common. Our results emphasise the difficulty in identifying African children in need of antibiotics among the majority who do not.

Acinetobacter baumannii Genes Required for Bacterial Survival during Bloodstream Infection.

Acinetobacter baumannii is emerging as a leading global multiple-antibiotic-resistant nosocomial pathogen. The identity of genes essential for pathogenesis in a mammalian host remains largely unknown. Using transposon-directed insertion-site sequencing (TraDIS), we identified A.baumannii genes involved in bacterial survival in a leukopenic mouse model of bloodstream infection. Mice were inoculated with a pooled transposon mutant library derived from 109,000 mutants, and TraDIS was used to map transposon insertion sites in the genomes of bacteria in the inoculum and of bacteria recovered from mouse spleens. Unique transposon insertion sites were mapped and used to calculate a fitness factor for every insertion site based on its relative abundance in the inoculum and postinfection libraries. Eighty-nine transposon insertion mutants that were underrepresented after experimental infection in mice compared to their presence in the inocula were delineated as candidates for further evaluation. Genetically defined mutants lacking feoB (ferrous iron import), ddc (d-ala-d-ala-carboxypeptidase), and pntB (pyridine nucleotide transhydrogenase subunit) exhibited a fitness defect during systemic infection resulting from bacteremia. In vitro, these mutants, as well as a fepA (ferric enterobactin receptor) mutant, are defective in survival in human serum and within macrophages and are hypersensitive to killing by antimicrobial peptides compared to the survival of the parental strain under these conditions. Our data demonstrate that FepA is involved in the uptake of exogenous enterobactin in A.baumannii. Genetic complementation rescues the phenotypes of mutants in assays that emulate conditions encountered during infection. In summary, we have determined novel A.baumannii fitness genes involved in the pathogenesis of mammalian infection. IMPORTANCE A.baumannii is a significant cause of bacterial bloodstream infection in humans. Since multiple antibiotic resistance is becoming more common among strains of A.baumannii, there is an urgent need to develop novel tools to treat infections caused by this dangerous pathogen. To develop knowledge-guided treatment approaches for A.baumannii, a thorough understanding of the mechanism by which this pathogen causes bloodstream infection is required. Here, using a mouse model of infection, we report the identification of A.baumannii genes that are critical for the ability of this pathogen to cause bloodstream infections. This study lays the foundation for future research on A.baumannii genes that can be targeted to develop novel therapeutics against this emerging human pathogen.

Bloodstream Infections and Frequency of Pretreatment Associated With Age and Hospitalization Status in Sub-Saharan Africa.

The clinical diagnosis of bacterial bloodstream infections (BSIs) in sub-Saharan Africa is routinely confused with malaria due to overlapping symptoms. The Typhoid Surveillance in Africa Program (TSAP) recruited febrile inpatients and outpatients of all ages using identical study procedures and enrollment criteria, thus providing an opportunity to assess disease etiology and pretreatment patterns among children and adults. Inpatients and outpatients of all ages with tympanic or axillary temperatures of ≥38.0 or ≥37.5°C, respectively, and inpatients only reporting fever within the previous 72 hours were eligible for recruitment. All recruited patients had one blood sample drawn and cultured for microorganisms. Data from 11 TSAP surveillance sites in nine different countries were used in the analysis. Bivariate analysis was used to compare frequencies of pretreatment and BSIs in febrile children (<15 years old) and adults (≥15 years old) in each country. Pooled Cochran Mantel-Haenszel odds ratios (ORs) were calculated for overall trends. There was no significant difference in the odds of a culture-proven BSI between children and adults among inpatients or outpatients. Among both inpatients and outpatients, children had significantly higher odds of having a contaminated blood culture compared with adults. Using country-pooled data, child outpatients had 66% higher odds of having Salmonella Typhi in their bloodstream than adults (OR, 1.66; 95% confidence interval [CI], 1.01-2.73). Overall, inpatient children had 59% higher odds of pretreatment with analgesics in comparison to inpatient adults (OR, 1.59; 95% CI, 1.28-1.97). The proportion of patients with culture-proven BSIs in children compared with adults was similar across the TSAP study population; however, outpatient children were more likely to have Salmonella Typhi infections than outpatient adults. This finding points to the importance of including outpatient facilities in surveillance efforts, particularly for the surveillance of typhoid fever. Strategies to reduce contamination among pediatric blood cultures are needed across the continent to prevent the misdiagnosis of BSI cases in children.

Rapid diagnosis to rule out bacterial bloodstream infection in neonates

Sepsis is an important cause of morbidity and mortality in neonates, especially in premature babies. Rapid and accurate diagnosis of neonatal sepsis is essential to prevent severe and life-threatening complications. However, diagnosis is often difficult as the clinical manifestations of this condition are often subtle and can overlap with those of non-infectious conditions. As a result, clinicians frequently administer empiric antibiotics to symptomatic or “at risk” infants while waiting culture results, which are currently the gold standard to identify bloodstream infection. Prolonged and inappropriate use of antibiotics is associated with various and well documented complications and adverse events. Therefore, it is mandatory not only to rapidly treat a suspected neonatal sepsis, but also to rule out the infection as soon as possible, in order to stop unnecessary antibiotics.

Infections after Transplantation of Bone Marrow or Peripheral Blood Stem Cells from Unrelated Donors.

Infection is a major complication of hematopoietic cell transplantation. Prolonged neutropenia and graft-versus-host disease are the 2 major complications with an associated risk for infection, and these complications differ according to the graft source. A phase 3, multicenter, randomized trial (Blood and Marrow Transplant Clinical Trials Network [BMT CTN] 0201) of transplantation of bone marrow (BM) versus peripheral blood stem cells (PBSC) from unrelated donors showed no significant differences in 2-year survival between these graft sources. In an effort to provide data regarding whether BM or PBSC could be used as a preferential graft source for transplantation, we report a detailed analysis of the infectious complications for 2years after transplantation from the BMT CTN 0201 trial. A total of 499 patients in this study had full audits of infection data. A total of 1347 infection episodes of moderate or greater severity were documented in 384 (77%) patients; 201 of 249 (81%) of the evaluable patients had received a BM graft and 183 of 250 (73%) had received a PBSC graft. Of 1347 infection episodes, 373 were severe and 123 were life-threatening and/or fatal; 710 (53%) of these episodes occurred on the BM arm and 637 (47%) on the PBSC arm, resulting in a 2-year cumulative incidence 84.7% (95% confidence interval [CI], 79.6 to 89.8) for BM versus 79.7% (95% CI, 73.9 to 85.5) for PBSC, P=.013. The majority of these episodes, 810 (60%), were due to bacteria, with a 2-year cumulative incidence of 72.1% and 62.9% in BM versus PBSC recipients, respectively (P= .003). The cumulative incidence of bloodstream bacterial infections during the first 100days was 44.8% (95% CI, 38.5 to 51.1) for BM versus 35.0% (95% CI, 28.9 to 41.1) for PBSC (P= .027). The total infection density (number of infection events/100 patient days at risk) was .67 for BM and .60 for PBSC. The overall infection density for bacterial infections was .4 in both arms; for viral infections, it was .2in both arms; and for fungal/parasitic infections, it was .04 and .05 for BM and PBSC, respectively. The cumulative incidence of infection before engraftment was 47.9% (95% CI, 41.5 to 53.9) for BM versus 32.8% (95% CI, 27.1 to 38.7) for PBSC (P= .002), possibly related to quicker neutrophil engraftment using PBSC.Infections remain frequent after unrelated donor hematopoietic cell transplantation, particularly after BM grafts.

Epidemiology of community-onset bloodstream infections in Bouaké, central Côte d’Ivoire

Bacterial bloodstream infections (BSI) account for considerable morbidity worldwide, but epidemiological data from resource-constrained tropical settings are scarce. We analysed 293 blood cultures from patients presenting to a regional referral hospital in Bouaké, central Côte d’Ivoire, to determine the aetiology of community-onset BSI. The prevalence of bacteraemia was 22.5%, with children being most commonly affected. Enterobacteriaceae (predominantly Klebsiella pneumoniae and Salmonella enterica) accounted for 94% of BSI. Staphylococcus aureus was the only relevant Gram-positive pathogen. Clinical signs and symptoms were not significantly associated with blood culture positivity after controlling for malaria.

Bloodstream bacterial infection among outpatient children with acute febrile illness in north-eastern Tanzania.

BackgroundFever is a common clinical symptom in children attending hospital outpatient clinics in rural Tanzania, yet there is still a paucity of data on the burden of bloodstream bacterial infection among these patients.MethodsThe present study was conducted at Korogwe District Hospital in north-eastern Tanzania. Patients aged between 2 and 59 months with a history of fever or measured axillary temperature ≥37.5°C attending the outpatient clinic were screened for enrolment into the study. Blood culturing was performed using the BACTEC 9050® system. A biochemical analytical profile index and serological tests were used for identification and confirmation of bacterial isolates. In-vitro antimicrobial susceptibility testing was performed using the Kirby-Bauer disc diffusion method. The identification of Plasmodium falciparum malaria was performed by microscopy with Giemsa stained blood films.ResultsA total of 808 blood cultures were collected between January and October 2013. Bacterial growth was observed in 62/808 (7.7%) of the cultured samples. Pathogenic bacteria were identified in 26/808 (3.2%) cultures and the remaining 36/62 (58.1%) were classified as contaminants. Salmonella typhi was the predominant bacterial isolate detected in 17/26 (65.4%) patients of which 16/17 (94.1%) were from patients above 12 months of age. Streptococcus pneumoniae was the second leading bacterial isolate detected in 4/26 (15.4%) patients. A high proportion of S.typhi 11/17 (64.7%) was isolated during the rainy season. S. typhi isolates were susceptible to ciprofloxacin (n = 17/17, 100%) and ceftriaxone (n = 13/17, 76.5%) but resistant to chloramphenicol (n = 15/17, 88.2%). P. falciparum malaria was identified in 69/808 (8.5%) patients, none of whom had bacterial infection.ConclusionBloodstream bacterial infection was not found to be a common cause of fever in outpatient children; and S. typhi was the predominant isolate. This study highlights the need for rational use of antimicrobial prescription in febrile paediatric outpatients presenting at healthcare facilities in rural Tanzania.

Bacteriological profile and antimicrobial susceptibility patterns of blood culture isolates among febrile patients in Mekelle Hospital, Northern Ethiopia.

Bacterial bloodstream infections are a major public health problem, which leads to high morbidity and mortality of patients. On time diagnosis and appropriate medication will be the best way to save the lives of affected ones. The aim of the present study was to determine the bacterial profile of bloodstream infections and their antibiotic susceptibility pattern in Mekelle Hospital. Cross sectional study method was carried out in 514 (269 females and 245 males) febrile patients in Mekelle hospital from March to October 2014. Standard bacteriological methods were used for blood collection, bacterial isolation and antimicrobial susceptibility pattern. Out of the total 514 febrile patients, 144 (28%) culture positive were isolated. Staphylococcus aureus 54 (37.5%), Coagulase-negative staphylococci 44 (30.6%), Escherichia coli 16 (3.1%), Citrobacter spp. 9 (1.7%) and Salmonella typhi 8 (1.6%) were the most dominant isolates, collectively accounting for >90% of the isolates. Antimicrobial resistance pattern for gram positive and gram negative bacteria was 0–83.3% and 0–100%, respectively. High resistance was seen to Trimethoprim-sulphamethoxazole 101 (70.1%), Oxacillin 65 (62.5%), Ceftriaxone 79 (58.9%) and Doxycycline 71 (49.3%). Fifty-nine percent of the isolated bacteria in this study were multi drug resistant. Most bacterial isolates were sensitive to Gentamicin, Ciprofloxacin and Amoxicillin clavulanic acid. All gram positive isolates in this current study were sensitive to vancomycin. Prevalence of bacterial isolates in blood was high. It also reveals isolated bacteria species developed multi drug resistance to most of the antibiotics tested, which highlights for periodic surveillance of etiologic agent, antibiotic susceptibility to prevent further emergence and spread of resistant bacterial pathogens.

Etiology of Severe Febrile Illness in Low- and Middle-Income Countries: A Systematic Review.

BackgroundWith apparent declines in malaria worldwide during the last decade and more widespread use of malaria rapid diagnostic tests, healthcare workers in low-resource areas face a growing proportion of febrile patients without malaria. We sought to describe current knowledge and identify information gaps of the etiology severe febrile illness in low-and middle-income countries.Methods and FindingsWe conducted a systematic review of studies conducted in low-and-middle income countries 1980–2013 that prospectively assessed consecutive febrile patients admitted to hospital using rigorous laboratory-based case definitions. We found 45 eligible studies describing 54,578 patients; 9,771 (17.9%) had a positive result for ≥1 pathogen meeting diagnostic criteria. There were no eligible studies identified from Southern and Middle Africa, Eastern Asia, Oceania, Latin American and Caribbean regions, and the European region. The median (range) number of diagnostic tests meeting our confirmed laboratory case definitions was 2 (1 to 11) per study. Of diagnostic tests, 5,052 (10.3%) of 49,143 had confirmed bacterial or fungal bloodstream infection; 709 (3.8%) of 18,142 had bacterial zoonosis; 3,488 (28.5%) of 12,245 had malaria; and 1,804 (17.4%) of 10,389 had a viral infection.ConclusionsWe demonstrate a wide range of pathogens associated with severe febrile illness and highlight the substantial information gaps regarding the geographic distribution and role of common pathogens. High quality severe febrile illness etiology research that is comprehensive with respect to pathogens and geographically representative is needed.

Lower dose anti-thymocyte globulin for GvHD prophylaxis results in improved survival after allogeneic stem cell transplantation.

In vivo T-cell depletion with anti-thymocyte globulin (ATG) can attenuate GvHD but may increase infection and relapse risks. ATG-Fresenius (ATG-F) at a dose of 60 mg/kg was standard GvHD prophylaxis in unrelated donor hematopoietic stem cell transplantation (HSCT) at our institution. We changed to an incremental reduced dose regimen of 35 mg/kg and extended ATG prophylaxis to include older matched-related donor transplants considered to be at higher risk of GvHD. A total of 265 adults with hematological malignancies receiving a first allogeneic HSCT after myeloablative conditioning between 2009 and 2014 were analyzed in this cohort study. Patients had either received higher dose (n=32) or lower dose ATG-F (n=88) or no ATG (n=145). ATG-F was associated with slower engraftment and less chronic GvHD, whereas no effect was noted on acute grade II-IV GvHD and relapse incidence. Transplant-related mortality (TRM) was lower and survival higher with lower dose, but not with higher dose ATG-F. Both ATG-F groups were associated with more viral reactivation, viral disease and bacterial blood stream infection, but not invasive fungal infection, and with slower immune reconstitution. The recently adopted strategy of using lower doses of ATG-F in unrelated and older age-related donor HSCT appears to reduce TRM without increasing disease relapse, leading to slightly enhanced survival.

Analysis of correlation between inflammatory parameters and severity of sepsis caused by bacterial bloodstream infection in septic patients

To discuss the differences of inflammatory parameters such as procalcitonin (PCT), C-reactive protein (CRP), endotoxin, white blood cell (WBC), neutrophil ratio (Neut%) in blood of septic patients caused by bacterial bloodstream infection, and their correlation with the severity of disease. 292 septic patients with positive blood culture were enrolled in Beijing Shijitan Hospital Affiliated to Capital Medical University from February 2012 to March 2015, and their gender, age, acute physiology and chronic health evaluation II (APACHEII) score, bacterial species and other general information were retrospectively collected. The differences in inflammatory parameters (PCT, CRP, endotoxin, WBC, Neut%) in septic patients caused by bacterial bloodstream infection were compared, their correlations with APACHEII scores within 24 hours were analyzed, and their diagnostic efficacies were also analyzed. (1) It was shown by Pearson correlation coefficients that positively statistical correlation was found between PCT (r=0.638), CRP (r=0.620), endotoxin (r=0.284), WBC (r=0.209) and APACHE II score (all P=0.000) in bacterial bloodstream infective patients (n=292), and positively statistical correlation was found between PCT (r=0.626), CRP (r=0.616), Neut% (r=0.297) and APACHE II score (all P<0.01 ) in Gram positive bacterial (G+) group (n=86), and positively statistical correlation was shown between PCT (r=0.631), CRP (r=0.616), endotoxin (r=0.301), WBC (r=0.226 ) and APACHE II score (all P<0.01) in Gram negative bacterial (G-) group (n=206). (2) It was shown that PCT and CRP of both G+/G- bacterial severe sepsis and septic shock subgroup were significantly higher than those of sepsis subgroup, respectively [G+ group: PCT (μg/L):0.92 (0.38, 4.75) vs. 0.43 (0.22, 1.00), CRP (mg/L): 118.45±62.60 vs. 57.97±32.41; G- group: PCT (μg/L):6.92 (1.94, 25.90) vs. 1.28 (0.27, 4.12), CRP (mg/L): 130.99±60.18 vs. 49.18±26.87, all P<0.01], and the endotoxin and WBC in G- bacterial severe sepsis and septic shock subgroup were significantly higher than those of sepsis subgroup [endotoxin (ng/L): 19.40 (9.62, 33.87) vs. 10.00 (5.00, 18.52), WBC (×10(9)/L): 12.13±6.72 vs. 9.61±5.01, both P<0.01]. The PCT and endotoxin in G- bacterial severe sepsis and septic shock subgroup were significantly higher than those in G+ severe sepsis and septic shock subgroup [PCT (μg/L): 6.92 (1.94, 25.90) vs. 0.92 (0.38, 4.75), endotoxin (ng/L): 19.40 (9.62, 33.87) vs. 2.56 (1.11, 4.01), both P<0.01]. (3) The diagnostic efficacy of inflammatory parameters for severe sepsis and septic shock subgroup were: PCT area under receiver operating characteristic (ROC) curve (AUC)=0.683, the cut-off point=0.55 μg/L, sensitivity 63.2%, specificity 69.0%; CRP AUC=0.802, the cut-off point=92.25 mg/L, sensitivity 73.7%, specificity 86.2%; WBC AUC=0.614, the cut-off point=7.35×10(9)/L, sensitivity 75.4%, specificity 48.3%; Neut% AUC=0.622, the cut-off point=0.882, sensitivity 43.9%, specificity 79.3% in G+ group. At the same time, it was shown that PCT AUC=0.780, the cut-off point=6.80 μg/L, sensitivity 51.0%, specificity 93.9%; CRP AUC=0.907, the cut-off point=90.10 mg/L, sensitivity 73.2%, specificity 95.9%; endotoxin AUC=0.694, the cut-off point=17.54 ng/L, sensitivity 57.3%, specificity 75.5%; WBC AUC=0.611, the cut-off point=10.54×10(9)/L, sensitivity 54.1%, specificity 69.4%; Neut% AUC=0.621, the cut-off point=0.843, sensitivity 65.6%, specificity 61.2% in G- group. The plasma PCT and CRP have the best correlation between inflammatory parameters and severity of disease in bloodstream infective sepsis patients. CRP has the best diagnostic effect in severe sepsis/septic shock patients with bloodstream infection.

Epidemiology and emerging resistance in bacterial bloodstream infections in patients with hematologic malignancies

Background: The objective of this study was determine the frequency of bloodstream infections (BSIs) and the causative bacteria and their resistance patterns in patients with hematological malignancies (HMs) in a large tertiary care university hospital in Turkey over a 5-year period. Methods: A total of 2098 patients with HMs with 3703 neutropenic episodes were included. Patients were classified as high-risk (n = 843) and low-risk (n = 1255) groups and evaluated for frequency of BSIs, causative bacteria, and their resistance patterns. Results: The frequency of BSIs was 14.5%. The frequency of gram-negative BSIs in high-risk and low-risk groups was 10.7% and 5.4% (p < 0.001), respectively. The frequency of gram-positive BSIs in high-risk and low-risk groups was 7.0% and 3.9% (p < 0.001), respectively. Gram-negative bacteria predominated (52.6%), with Escherichia coli (17.3%) and Klebsiella spp. (11.0%) as the most frequent organisms. Coagulase-negative staphylococci (10.4%) and Corynebacterium spp. (6.3%) were the most common gram-positive bacteria (35.8%). The rate of extended-spectrum beta-lactamase (ESBL) production was 45% for E. coli and 58% for Klebsiella spp. Quinolone resistance was 58% for E. coli and 11% for Klebsiella spp.. The overall frequency of ceftazidime resistance in Pseudomonas aeruginosa was 28%, and 87% of Acinetobacter spp. were multidrug-resistant. Of Staphylococcus aureus isolates, 24.8% were resistant to methicillin. Conclusion: The dominating causes of BSIs in patients with HMs in our hospital are resistant gram-negative bacteria, which has made empirical antimicrobial choice a highly challenging issue in this patient population.