External Validation of Difficult-to-Treat Resistance Prevalence and Mortality Risk in Gram-Negative Bloodstream Infection Using Electronic Health Record Data From 140 US Hospitals.
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ABSTRACT:
SUBMITTER: Kadri SS
PROVIDER: S-EPMC6441782 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
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External Validation of Difficult-to-Treat Resistance Prevalence and Mortality Risk in Gram-Negative Bloodstream Infection Using Electronic Health Record Data From 140 US Hospitals.
Kadri Sameer S SS Lai Yi Ling Elaine YLE Ricotta Emily E EE Strich Jeffrey R JR Babiker Ahmed A Rhee Chanu C Klompas Michael M Dekker John P JP Powers John H JH Danner Robert L RL Adjemian Jennifer J
Open forum infectious diseases 20190228 4
Difficult-to-treat resistance (DTR; ie, co-resistance to all first-line antibiotics) in gram-negative bloodstream infection (GNBSI) is associated with decreased survival in administrative data models. We externally validated DTR prevalence and associated mortality risk in GNBSI using detailed clinical data from electronic health records to adjust for baseline differences in acute illness severity. ...[more]
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Project description:BackgroundTo compare the prognostic utility of the new definition of difficult-to-treat resistance (DTR) vs established definitions in a cohort of patients with Gram-negative bloodstream infections (GNBSIs).MethodsThis was a retrospective single-center study of adult patients with monomicrobial GNBSI, hospitalized from 2013 to 2016. DTR was defined as isolate demonstrating intermediate or resistant phenotype to all reported agents in the carbapenem, beta-lactam, and fluoroquinolone classes. Carbapenem resistance (CR) was defined according to 2015 Centers for Disease Control and Prevention criteria. Each isolate was further classified according to the Magiorakos et al. criteria as non-multidrug-resistant (non-MDR), MDR, extensively drug-resistant (XDR), or pan-drug-resistant (PDR). The primary outcome was all-cause 30-day mortality.ResultsOverall, 1576 patients were analyzed. Enterobacteriaceae accounted for 88.7% of BSIs, with Escherichia coli (n = 941) and Klebsiella pneumoniae (n = 326) being the most common pathogens. Pseudomonas aeruginosa was the most common nonfermentative bacteria (n = 130, 8.2%). Overall, 11% of strains were defined as DTR and 13% as CR. Episodes were further classified as non-MDR (68.8%), MDR (21.9%), XDR (8.8%), and PDR (0.4%). The prevalence rates of DTR, CR, and XDR were similar among Enterobacteriaceae and Acinetobacter baumannii, whereas they differed in P. aeruginosa. All the analyzed resistance definitions significantly improved prediction of 30-day mortality when introduced into a baseline multivariate model, to a similar degree: 9%, 10%, and 11% for DTR, Magiorakos, and CR definitions, respectively.ConclusionsDTR seems a promising tool to identify challenging GNBSIs, mainly those due to P. aeruginosa. With the availability of new agents for CR infections, further multicenter assessments of DTR are needed.
| S-EPMC6916520 | biostudies-literature
Project description:BackgroundResistance to all first-line antibiotics necessitates the use of less effective or more toxic "reserve" agents. Gram-negative bloodstream infections (GNBSIs) harboring such difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for ?1 active first-line antibiotic.MethodsThe Premier Database was analyzed for inpatients with select GNBSIs. DTR was defined as intermediate/resistant in vitro to all ß-lactam categories, including carbapenems and fluoroquinolones. Prevalence and aminoglycoside resistance of DTR episodes were compared with carbapenem-resistant, extended-spectrum cephalosporin-resistant, and fluoroquinolone-resistant episodes using CDC definitions. Predictors of DTR were identified. The adjusted relative risk (aRR) of mortality was examined for DTR, CDC-defined phenotypes susceptible to ?1 first-line agent, and graded loss of active categories.ResultsBetween 2009-2013, 471 (1%) of 45011 GNBSI episodes at 92 (53.2%) of 173 hospitals exhibited DTR, ranging from 0.04% for Escherichia coli to 18.4% for Acinetobacter baumannii. Among patients with DTR, 79% received parenteral aminoglycosides, tigecycline, or colistin/polymyxin-B; resistance to all aminoglycosides occurred in 33%. Predictors of DTR included urban healthcare and higher baseline illness. Crude mortality for GNBSIs with DTR was 43%; aRR was higher for DTR than for carbapenem-resistant (1.2; 95% confidence interval, 1.0-1.4; P = .02), extended-spectrum cephalosporin-resistant (1.2; 1.1-1.4; P = .001), or fluoroquinolone-resistant (1.2; 1.0-1.4; P = .008) infections. The mortality aRR increased 20% per graded loss of active first-line categories, from 3-5 to 1-2 to 0.ConclusionNonsusceptibility to first-line antibiotics is associated with decreased survival in GNBSIs. DTR is a simple bedside prognostic measure of treatment-limiting coresistance.
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Project description:BackgroundClusters of bloodstream infections caused by Burkholderia cepacia and Stenotrophomonas maltophilia are uncommon, but have been previously identified in hemodialysis centers that reprocessed dialyzers for reuse on patients. We investigated an outbreak of bloodstream infections caused by B cepacia and S maltophilia among hemodialysis patients in clinics of a dialysis organization.Study designOutbreak investigation, including matched case-control study.Setting & participantsHemodialysis patients treated in multiple outpatient clinics owned by a dialysis organization.PredictorsMain predictors were dialyzer reuse, dialyzer model, and dialyzer reprocessing practice.OutcomesCase patients had a bloodstream infection caused by B cepacia or S maltophilia; controls were patients without infection dialyzed at the same clinic on the same day as a case; results of environmental cultures and organism typing.Results17 cases (9 B cepacia and 8 S maltophilia bloodstream infections) occurred in 5 clinics owned by the same dialysis organization. Case patients were more likely to have received hemodialysis with a dialyzer that had been used more than 6 times (matched OR, 7.03; 95% CI, 1.38-69.76) and to have been dialyzed with a specific reusable dialyzer (Model R) with sealed ends (OR, 22.87; 95% CI, 4.49-∞). No major lapses during dialyzer reprocessing were identified that could explain the outbreak. B cepacia was isolated from samples collected from a dialyzer header-cleaning machine from a clinic with cases and was indistinguishable from a patient isolate collected from the same clinic, by pulsed-field gel electrophoresis. Gram-negative bacteria were isolated from 2 reused Model R dialyzers that had undergone the facility's reprocessing procedure.LimitationsLimited statistical power and overmatching; few patient isolates and dialyzers available for testing.ConclusionsThis outbreak was likely caused by contamination during reprocessing of reused dialyzers. Results of this and previous investigations demonstrate that exposing patients to reused dialyzers increases the risk for bloodstream infections. To reduce infection risk, providers should consider implementing single dialyzer use whenever possible.
| S-EPMC5441929 | biostudies-literature
Project description:Carbapenem resistance in Gram-negative bacteria has come into sight as a serious global threat. Carbapenem-resistant Gram-negative pathogens and their main representatives Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa are ranked in the highest priority category for new treatments. The worrisome phenomenon of the recent years is the presence of difficult-to-treat resistance (DTR) and pandrug-resistant (PDR) Gram-negative bacteria, characterized as non-susceptible to all conventional antimicrobial agents. DTR and PDR Gram-negative infections are linked with high mortality and associated with nosocomial infections, mainly in critically ill and ICU patients. Therapeutic options for infections caused by DTR and PDR Gram-negative organisms are extremely limited and are based on case reports and series. Herein, the current available knowledge regarding treatment of DTR and PDR infections is discussed. A focal point of the review focuses on salvage treatment, synergistic combinations (double and triple combinations), as well as increased exposure regimen adapted to the MIC of the pathogen. The most available data regarding novel antimicrobials, including novel β-lactam-β-lactamase inhibitor combinations, cefiderocol, and eravacycline as potential agents against DTR and PDR Gram-negative strains in critically ill patients are thoroughly presented.
| S-EPMC9394369 | biostudies-literature
Project description:Bloodstream infections (BSI) are a major public health burden due to high mortality rates and the cost of treatment. The impact of BSI is further compounded by a rise in antibiotic resistance among Gram-negative species associated with these infections. Escherichia coli, Serratia marcescens, Klebsiella pneumoniae, Enterobacter hormaechei, Citrobacter freundii, and Acinetobacter baumannii are all common causes of BSI, which can be recapitulated in a murine model. The objective of this study was to characterize infection kinetics and bacterial replication rates during bacteremia for these six pathogens to gain a better understanding of bacterial physiology during infection. Temporal observations of bacterial burdens of the tested species demonstrated varied abilities to establish colonization in the spleen, liver, or kidney. K. pneumoniae and S. marcescens expanded rapidly in the liver and kidney, respectively. Other organisms, such as C. freundii and E. hormaechei, were steadily cleared from all three target organs throughout the infection. In situ replication rates measured by whole-genome sequencing of bacterial DNA recovered from murine spleens demonstrated that each species was capable of sustained replication at 24 h postinfection, and several species demonstrated <60-min generation times. The relatively short generation times observed in the spleen were in contrast to an overall decrease in bacterial burden for some species, suggesting that the rate of immune-mediated clearance exceeded replication. Furthermore, bacterial generation times measured in the murine spleen approximated those measured during growth in human serum cultures. Together, these findings provide insight into the infection kinetics of six medically important species during bacteremia. IMPORTANCE Bloodstream infections are a global public health problem. The goal of this work was to determine the replication characteristics of Gram-negative bacterial species in the host following bloodstream infection. The number of bacteria in major organs is likely determined by a balance between replication rates and the ability of the host to clear bacteria. We selected a cohort of six species from three families that represent common causative agents of bloodstream infections in humans and determined their replication rates in a murine bacteremia model. We found that the bacteria grow rapidly in the spleen, demonstrating that they can obtain the necessary nutrients for growth in this environment. However, the overall number of bacteria decreased in most cases, suggesting that killing of bacteria outpaces their growth. Through a better understanding of how bacteria replicate during bloodstream infections, we aim to gain insight into future means of combating these infections.
| S-EPMC8406280 | biostudies-literature
Project description:BackgroundExtensively drug-resistant Gram-negative bacterial (XDR-GNB) bloodstream infection (BSI) is difficult to treat and is associated with a high mortality rate in patients with hematological diseases. The aim of this study is to investigate the predisposing risk factors and the efficacy of the antibiotic treatment in these patients, including exploration of efficacy and adverse effects of high-dose tigecycline.MethodsBetween January 2013 and December 2017, 27 XDR-GNB BSI patients with hematological diseases were diagnosed and retrospectively reviewed in the current study.ResultsClinical response in patients with severe complications (such as severe neutropenia >10 days, grade III-IV acute graft-versus-host disease (aGVHD), and concurrent pneumonia) was significantly lower than in patients without or with only mild complications (P=0.033). The efficacy rate was 62.5% (10/16) in patients with tigecycline-based combination therapy regimen, 77.8% (7/9) with a high-dose tigecycline regimen, and 42.9% (3/7) with a standard-dose tigecycline regimen (P=0.36). The 30-day survival rates of patients undergoing high-dose or standard-dose tigecycline treatment were 66.7% (95% CI: 28.2-87.8) and 57.1% (95% CI: 17.2-83.7), respectively, (P=0.603). Patients with mild complications were associated with superior 30-day survival rates than patients with severe complications (93.8% vs 36.4%, P=0.001), >10 days of neutropenia (90.9% vs 33.3%, P=0.012), severe aGVHD (100% vs 40%, P=0.049), and concurrent pneumonia (84.6% vs 57.1%, P=0.048).ConclusionOur study indicated that XDR-GNB BSI in patients of hematological diseases with severe complications, such as long duration of neutropenia (>10 days) and severe aGVHD were associated with poor clinical response and short survival. We first indicated that these patients undergoing high-dose tigecycline treatment had an improved clinical response and an increased 30-day survival rate compared with the standard-dose group, although the differences were not statistically significant. This might be due to more severe complicated patients enrolled in high-dose group and the limited number size in our study.
| S-EPMC6396657 | biostudies-literature
Project description:This study evaluated routine laboratory biomarkers (RLB) to predict the infectious bacterial group, Gram-positive (GP) or Gram-negative (GN) associated with bloodstream infection (BSI) before the result of blood culture (BC). A total of 13,574 BC of 6787 patients (217 BSI-GP and 238 BSI-GN) and 68 different RLB from these were analyzed. The logistic regression model was built considering BSI-GP or BSI-GN as response variable and RLB as covariates. After four filters applied total of 320 patients and 16 RLB remained in the Complete-Model-CM, and 4 RLB in the Reduced-Model-RM (RLB p > 0.05 excluded). In the RM, only platelets, creatinine, mean corpuscular hemoglobin and erythrocytes were used. The reproductivity of both models were applied to a test bank of 2019. The new model presented values to predict BSI-GN of the area under the curve (AUC) of 0.72 and 0.69 for CM and RM, respectively; with sensitivity of 0.62 and 0.61 (CM and RM) and specificity of 0.67 for both. These data confirm the discriminatory capacity of the new models for BSI-GN (p = 0.64). AUC of 0.69 using only 4 RLB, associated with the patient's clinical data could be useful for better targeted antimicrobial therapy in BSI.
| S-EPMC9474441 | biostudies-literature
Project description:BackgroundHemogram parameters and procalcitonin (PCT) play auxiliary roles in the diagnosis and outcome of sepsis. However, it is not clear whether these indicators can quickly distinguish bacterial classification or guide the choice of empirical antibiotics.MethodsWe retrospectively enrolled 381 patients with bloodstream infections (BSI), divided into Gram-positive bloodstream infections (GP-BSI) and Gram-negative bloodstream infections (GN-BSI). Demographic parameters, hemogram parameters, and PCT were recorded and compared between the two groups.ResultsThe mean platelet volume (MPV), platelet distribution width (PDW), and PCT in the GN-BSI group were significantly higher than those in the GP-BSI group, while the platelet count (PLT), plateletcrit, platelet count-to-white blood cell count ratio (PWR), platelet count-to-neutrophil count ratio (PNR), platelet count-to-PCT ratio (PLT/PCT), and mean platelet volume-to-PCT ratio (MPV/PCT) were significantly lower in the GN-BSI group. Multivariate stepwise logistic regression analysis revealed that the independent predictors of GN-BSI were MPV, PWR, and PCT. The areas under the curve (AUC) for this prediction model was 0.79, with sensitivity =0.75 and specificity =0.71.ConclusionsThere were significant differences in terms of PCT, platelet parameters, and platelet-related index-PCT ratio between GN-BSI and GP-BSI. Combined PCT and hemogram parameters are more conducive to the early differential diagnosis of bacterial classification of BSI.
| S-EPMC8418508 | biostudies-literature
Project description:THE CORRELATION BETWEEN ANTIBIOTIC SUSCEPTIBILITY, VIRULOME, AND CLINICAL OUTCOME IN EUROPEAN INFANTS LESS THAN 90 DAYS AFFECTED BY BLOODSTREAM INFECTIONS CAUSED BY ENTEROBACTERALES
| PRJEB44870 | ENA
Project description:BackgroundThe management of non-fermentative gram-negative bloodstream infection (NFGN-BSI) offers numerous challenges. In this study the aim is to analyse a large cohort of patients with NFGN-BSI recruited in the northern Italy to describe epidemiology, etiological and susceptibility pattern, therapeutic management and outcome.MethodsMulticentre retrospective cohort study of patients hospitalised at three large teaching hospitals in northern Italy in a fourth year period.Results355 BSI episodes were analyzed, due to P. aeruginosa (72.7%), A. baumannii (16.6%), and Stenotrophomonas maltophilia (10.7%). Overall, 21.4% of isolates were defined as DTR, highest rate among A. baumannii (64.4%). All-cause 30-day mortality rate was 17.5%. Rates of XDR or DTR A. baumannii isolation were significantly higher in non-surviving patients. Independent risk factors for 30-day mortality were: age (HR 1.03, 95%CI 1.00-1.04, p = 0.003), septic shock (HR 2.84, 95%CI 1.67-4.82, p < 0.001) and BSI due to Acinetobacter baumannii (HR 2.23, 95%CI 1.27-3.94, p = 0.005).ConclusionThe overall prevalence of DTR was high in the NFGN BSI cohort analyzied, mainly among Acinetobacter baumannii episodes (64.4%). Acinetobacter baumannii is showed to be an independent predictor of mortality. These evidences marked the urgent need of new therapeutic options against this pathogen.Trial registration number79/2017/O/OssN. Approved: March14th, 2017.
| S-EPMC8359066 | biostudies-literature