Gram-negative Bacterial Bloodstream Infections Research Articles

Prediction of carbapenem-resistant gram-negative bacterial bloodstream infection in intensive care unit based on machine learning

BackgroundPredicting whether Carbapenem-Resistant Gram-Negative Bacterial (CRGNB) cause bloodstream infection when giving advice may guide the use of antibiotics because it takes 2–5 days conventionally to return the results from doctor's order.MethodsIt is a regional multi-center retrospective study in which patients with suspected bloodstream infections were divided into a positive and negative culture group. According to the positive results, patients were divided into the CRGNB group and other groups. We used the machine learning algorithm to predict whether the blood culture was positive and whether the pathogen was CRGNB once giving the order of blood culture.ResultsThere were 952 patients with positive blood cultures, 418 patients in the CRGNB group, 534 in the non-CRGNB group, and 1422 with negative blood cultures. Mechanical ventilation, invasive catheterization, and carbapenem use history were the main high-risk factors for CRGNB bloodstream infection. The random forest model has the best prediction ability, with AUROC being 0.86, followed by the XGBoost prediction model in bloodstream infection prediction. In the CRGNB prediction model analysis, the SVM and random forest model have higher area under the receiver operating characteristic curves, which are 0.88 and 0.87, respectively.ConclusionsThe machine learning algorithm can accurately predict the occurrence of ICU-acquired bloodstream infection and identify whether CRGNB causes it once giving the order of blood culture.

In-patient evolution of a high-persister Escherichia coli strain with reduced in vivo antibiotic susceptibility.

Gram-negative bacterial bloodstream infections (GNB-BSI) are common and frequently lethal. Despite appropriate antibiotic treatment, relapse of GNB-BSI with the same bacterial strain is common and associated with poor clinical outcomes and high healthcare costs. The role of persister cells, which are sub-populations of bacteria that survive for prolonged periods in the presence of bactericidal antibiotics, in relapse of GNB-BSI is unclear. Using a cohort of patients with relapsed GNB-BSI, we aimed to determine how the pathogen evolves within the patient between the initial and subsequent episodes of GNB-BSI and how these changes impact persistence. Using Escherichia coli clinical bloodstream isolate pairs (initial and relapse isolates) from patients with relapsed GNB-BSI, we found that 4/11 (36%) of the relapse isolates displayed a significant increase in persisters cells relative to the initial bloodstream infection isolate. In the relapsed E. coli strain with the greatest increase in persisters (100-fold relative to initial isolate), we determined that the increase was due to a loss-of-function mutation in the ptsI gene encoding Enzyme I of the phosphoenolpyruvate phosphotransferase system. The ptsI mutant was equally virulent in a murine bacteremia infection model but exhibited 10-fold increased survival to antibiotic treatment. This work addresses the controversy regarding the clinical relevance of persister formation by providing compelling data that not only do high-persister mutations arise during bloodstream infection in humans but also that these mutants display increased survival to antibiotic challenge in vivo.

Changing epidemiology, microbiology and mortality of bloodstream infections in patients with haematological malignancies before and during SARS-CoV-2 pandemic: a retrospective cohort study

ObjectiveThis study was to explore the changes in bacterial bloodstream infection (BSI) in patients with haematological malignancies (HMs) before and during SARS-CoV-2 pandemic.DesignRetrospective cohort study between 2018 and 2021.SettingThe largest...

186. The Role of Repeated Blood Cultures in Hematologic Malignancy Patients with Neutropenic Fever due to Gram-Negative Bacterial Bloodstream Infections

Abstract Background Several observational studies and a recent meta-analysis suggest there is a mortality benefit associated with acquiring repeat blood cultures for gram-negative bacterial bloodstream infections (GNBSI). However, limited data are available among patients with febrile neutropenia. We sought to evaluate the utility of obtaining follow-up blood cultures (FUBC) in GNBSI among neutropenic hematological malignancy patients. Methods A retrospective chart review was conducted to identify all patients with a hematologic malignancy admitted with a diagnosis of neutropenic fever due to gram-negative rod bacteremia (GNRB) from 2018-2021 at a large urban academic medical center. We collected demographics, cancer diagnosis and treatment data, microbiology and antibiotic information, and death at discharge, 30 days, and 90 days. Descriptive statistics and chi-square tests were used. Results A total of 47 episodes of GNBSI among 43 patients were included. Mean age was 57 years, 61% were male, 49% were White, and 14% were Latino. Most patients had AML (47%), and most common chemotherapy regimen was R-CHOP (19%). 32% of GNRB were due to K. pneumoniae, in the setting of long-term central venous catheter (53%), and from a gastrointestinal source (49%). FUBC were collected among most patients (87%), but only two patients (5%) had positive FUBC. ESBL resistance profiles were uncommon (6%), and most were treated with beta-lactams (55%). Patients who died at discharge were less likely to have FUBC collected (p< 0.001). We also found an association between acquiring FUBC and mortality at 30 (p=0.01) and 90 days (p=0.02). However, there was no association between having a positive FUBC and mortality at discharge (p=0.47), 30 days (p=0.93), and 90 days (p=1.00). Conclusion Among patients with neutropenic fever found to have GNBSI, acquiring repeat blood cultures was associated with decreased mortality. Due to their immunocompromised status, patients with neutropenic fever and GNRB should have repeat blood cultures collected. Disclosures All Authors: No reported disclosures

Use of Transcriptional Signatures to Differentiate Pathogen-Specific and Treatment-Specific Host Responses in Patients With Bacterial Bloodstream Infections.

Clinical outcomes in bacterial bloodstream infections (BSIs) are influenced by bacterial species, host immunity, and antibiotic therapy. The mechanisms by which such factors influence outcomes are poorly understood. We aimed to identify bacterial- and antibiotic-specific host transcriptional signatures in patients with bacterial BSI. RNA sequencing was performed on blood samples from patients with BSI due to gram-negative (GN) versus gram-positive (GP) pathogens: Escherichia coli (n = 30) or Klebsiella pneumoniae (n = 28) versus methicillin-susceptible Staphylococcus aureus (MSSA) (n = 24) or methicillin-resistant S. aureus (MRSA) (n = 58). Patients were matched by age, sex, and race. No significant host transcriptome differences were detected in patients with E. coli versus K. pneumoniae BSI, so these were considered together as GN BSI. Relative to S. aureus BSI, patients with GN BSI had increased activation of the classic complement system. However, the most significant signal was a reduction in host transcriptional signatures involving mitochondrial energy transduction and oxidative burst in MRSA versus MSSA. This attenuated host transcriptional signature remained after controlling for antibiotic therapy. Given the importance of immune cellular energetics and reactive oxygen species in eliminating hematogenous or intracellular MRSA, these findings may offer insights into its persistence relative to other bacterial BSIs.

Machine learning model for the prediction of gram-positive and gram-negative bacterial bloodstream infection based on routine laboratory parameters

BackgroundBacterial bloodstream infection is responsible for the majority of cases of sepsis and septic shock. Early recognition of the causative pathogen is pivotal for administration of adequate empiric antibiotic therapy and for the survival of the patients. In this study, we developed a feasible machine learning (ML) model to predict gram-positive and gram-negative bacteremia based on routine laboratory parameters.MethodsData for 2118 patients with bacteremia were obtained from the Medical Information Mart for Intensive Care dataset. Patients were randomly split into the training set and test set by stratified sampling, and 374 routine laboratory blood test variables were retrieved. Variables with missing values in more than 40% of the patients were excluded. Pearson correlation test was employed to eliminate redundant features. Five ML algorithms were used to build the model based on the selected features. Additionally, 132 patients with bacteremia who were treated at Qilu Hospital of Shandong University were included in an independent test cohort to evaluate the model.ResultsAfter feature selection, 32 variables remained. All the five ML algorithms performed well in terms of discriminating between gram-positive and gram-negative bacteremia, but the performance of convolutional neural network (CNN) and random forest (RF) were better than other three algorithms. Consider of the interpretability of models, RF was chosen for further test (ROC-AUC = 0.768; 95%CI = 0.715–0.798, with a sensitivity of 75.20% and a specificity of 63.79%). To expand the application of the model, a decision tree (DT) was built utilizing the major variables, and it achieved an AUC of 0.679 (95%CI = 0.632–0.723), a sensitivity of 66%, and a specificity of 67.82% in the test cohort. When tested in the Qilu Hospital cohort, the ROC-AUC of the RF and DT models were 0.666 (95%CI = 0.579–0.746) and 0.615 (95%CI = 0.526–0.698), respectively. Finally, a software was developed to make the RF- and DT-based prediction models easily accessible.ConclusionThe present ML-based models could effectively discriminate between gram-positive and gram-negative bacteremia based on routine laboratory blood test results. This simple model would be beneficial in terms of guiding timely antibiotic selection and administration in critically ill patients with bacteremia before their pathogen test results are available.

Predictors and Outcomes of Multidrug-Resistant Gram-Negative Bacterial Bloodstream Infections in Pediatric Oncology Patients

Background Pediatric patients with cancer are at great risk of infection either from disease process or after being immuno-suppressed by chemotherapy and radiotherapy, this is especially with gram negative and multidrug resistant (MDR) pathogens. The primary aim of our study is to detect the frequency of multidrug resistant gram negative bacteria (MDR-GNB) infections at the Pediatric Oncology Department. The secondary aim is to identify the patterns of resistance of different pathogens to commonly used antimicrobials and detect the risk factors and outcomes of MDR-GNB infections in pediatric oncology patients. Patients and Methods We studied episodes of fever and /or bacteremia in children (aged 1 m to 18 y) with hematologic and solid malignancies in the pediatric oncology department in Ain Shams University Hospital between January 2020 and March 2021. We studied different risks for MDR-GNB including sex, age, underlying malignancy, the presence of indwelling catheter, absolute neutrophil count and other laboratory investigations. Results MDR bacteria were isolated in about 15% samples. The most commonly detected MDR-GNB pathogens were Klebsiella (61.1%) and Acintobacter (22.2%). Among studied patients, MDR-GNB were significantly reported among patients with T-lymphoblastic lymphoma (p = 0.006). Although most patients were neutropenic, neutrophil count was not significantly correlated (p = 0.981). Low serum albumin on the other hand was significantly correlated with MDR-GNB (p = 0.009). Conclusion MDR-GNB is a significant threat to pediatric oncology patients. Contact precautions for all patients with colonization or infection with MDR pathogens and an antimicrobial stewardship based on local epidemiology should be implemented to prevent MDR infections.

Microbiology and Clinical Outcome of Bloodstream Infections in Patients After Hematopoietic Stem Cell Transplantation.

Patients after hematopoietic stem cell transplantation (HSCT) are often followed by bloodstream infections (BSIs). BSI is an important cause of non-relapse mortality (NRM) in HSCT patients. We conducted a retrospective cohort study of patients (aged >14 years) who underwent HSCT at our hospital from 2017 to 2021. Population characteristics, BSI microbiology, resistance to common antibiotics, and 30-day all-cause mortality were analyzed. Of 3054 patients, 169 (5.5%) had BSIs after HSCT. Male, not in complete remission at transplantation and longer duration of neutropenia were risk factors for the development of BSI after HSCT. These BSIs were Gram-negative bacterial (n=123, 69.49%), Gram-positive bacterial (n=27, 15.25%), fungal (n=11, 6.36%), and polymicrobial (n=16, 9.25%). Among the Gram-negative bacteria, the proportions of isolates resistant to ceftazidime, cefepime, and piperacillin-tazobactam were similar (72.93%, 74.80%, and 77.42%, respectively). The overall drug resistance rates of amikacin and imipenem were 16.13% and 43.90%, respectively. Staphylococcus isolates were methicillin-resistant. In Enterococcus isolates, the penicillin resistance rate was 84.62%. Eleven isolates of Candida tropicalis were resistant to fluconazole and were sensitive to amphotericin B and flucytosine. The 30-day all-cause mortality rate of the 169 patients with BSIs was 8.88%. The 30-day all-cause mortality of patients with Gram-negative bacterial BSIs was 7.32%, 25.00% for polymicrobial BSIs, and 36.36% for fungal BSIs. The 30-day all-cause mortality of patients with fungal BSIs was significantly higher than that of patients with Gram-negative (P=0.0023) and Gram-positive bacteria (P=0.0023). Fungal BSI and non-Hodgkin's lymphoma (NHL) were associated with higher 30-day mortality. Our study reveals the microbiological characteristics and 30-day all-cause mortality in patients with bloodstream infections after HSCT. Our data provides strong support for empirical antimicrobial therapy and infection prevention strategies for patients with BSIs after HSCT.

Bloodstream gram-negative bacterial infections in adult patients with leukemia: A retrospective review of medical records in a tertiary care hospital in Western Saudi Arabia

BackgroundPatients with neutropenic cancers are at high risk of acquiring infections, especially if on chemotherapy. Gram-negative bacterial infections are associated with high mortality. This study aimed to assess clinical characteristics, outcomes, and epidemiology of gram-negative bacterial (GNB) bloodstream infections (BSI) in adult patients with leukemia. MethodsThis single-center, retrospective study included 102 adult patients diagnosed with leukemia between 2017 and 2019. The patients’ demographics, infection diagnosis, leukemia diagnosis, comorbidities, and infection outcomes were collected from electronic medical records. ResultsThe most common GNB were Klebsiella pneumoniae (33.3 %), Pseudomonas aeruginosa (23.5 %), and Escherichia coli (17.6 %). Additionally, 36.7 % of infections were multidrug resistant. The most common comorbidities were cardiovascular diseases (36.7 %), diabetes mellitus (33.3 %), and liver diseases (24.1 %). GNB-infected patients had a higher mortality than noninfected patients (35.3 % and 11.8 %, respectively, p = 0.005). In a multivariable analysis, patients with acute myeloid leukemia and acute lymphoid leukemia were significantly more likely to acquire GNB BSI (p = 0.01), while patients with chronic myelogenous leukemia and chronic lymphocytic leukemia had a lower likelihood of developing GNB BSI. In addition, low hemoglobin level was an independent risk factor of GNB BSI (p = 0.001). Chemotherapeutic agents showed an association with increased risk of GNB BSI. ConclusionsPatients with acute leukemia and low hemoglobin levels have increased risk of GNB BSI, which was associated with increased mortality. Prospective studies are needed to further assess the effect of co-morbidities and chemotherapy medications on the occurrence of GNB BSI according to the type of leukemia.

Characteristics, Outcomes, and Clinical Indicators of Bloodstream Infections in Neutropenic Patients with Hematological Malignancies: A 7-Year Retrospective Study.

The aim of this study was to investigate the current epidemiology, its changes during the study years, and inflammatory biomarkers of bacterial bloodstream infections (BSIs) in neutropenic patients with hematological malignancies. We assessed mortality risk factors and multidrug-resistant (MDR) gram-negative BSI predictors. We conducted a retrospective study from January 2015 to December 2021, which included adult neutropenic oncohematological patients with confirmed BSIs. We used univariable and multivariable analyses to analyze the risk factors. Each index's reliability for bacterial BSI diagnosis was assessed using the receiver-operating characteristic curve and area under the curve. A total of 514 isolates were obtained from the 452 patients. The average mortality was 17.71%. Gram-negative organisms were the predominant causes of BSI. Escherichia coli was the most common microorganism (49.90%). The overall variation trend of the isolation rate of MDR and carbapenem-resistant gram-negative bacteria increased. Multivariate analysis indicated that: 1) neutropenia that lasted for more than 7 days, patients ≥ 60 years of age, septic shock, hospitalization for >20 days, BSI with a carbapenem-resistant strain, and treatment with linezolid or vancomycin in infections lasting less than 30 days were independent mortality risk factors; 2) severe neutropenia exceeding 7 days, unreasonable empirical therapy, and receipt of aminoglycosides or 3rd or 4th generation cephalosporins in infections lasting less than 30 days were independent risk factors of MDR gram-negative bacteria. Procalcitonin, absolute neutrophil count, and white blood cell indicate higher diagnostic accuracy for BSIs. Moreover, bacteria time to detection was better at differentiating Gram-negative and Gram-positive bacterial infections. We analyzed the risk factors for BSI neutropenic patients with hematological malignancies, the distribution of bacteria, antibiotic resistance, and the changes in clinical parameters. This single-center retrospective study may provide clinicians with novel insights into the diagnosis and treatment of BSI to improve future clinical outcomes.

Microbiology and prognostic prediction model of bloodstream infection in patients with hematological malignancies.

In recent years, with the continuous development of treatments for hematological malignancies (HMs), the remission and survival rates of patients with HMs have been significantly improved. However, because of severe immunosuppression and long-term recurrent neutropenia during treatment, the incidence and mortality of bloodstream infection (BSI) were all high in patients with HMs. Therefore, we analyzed pathogens' distribution and drug-resistance patterns and developed a nomogram for predicting 30-day mortality in patients with BSIs among HMs. In this retrospective study, 362 patients with positive blood cultures in HMs were included from June 2015 to June 2020 at West China Hospital of Sichuan University. They were randomly divided into the training cohort (n = 253) and the validation cohort (n = 109) by 7:3. A nomogram for predicting 30-day mortality after BSIs in patients with HMs was established based on the results of univariate and multivariate logistic regression. C-index, calibration plots, and decision curve analysis were used to evaluate the nomogram. Among 362 patients with BSIs in HMs, the most common HM was acute myeloid leukemia (48.1%), and the most common pathogen of BSI was gram-negative bacteria (70.4%). The final nomogram included the septic shock, relapsed/refractory HM, albumin <30g/l, platelets <30×109/l before BSI, and inappropriate empiric antibiotic treatment. In the training and validation cohorts, the C-indexes (0.870 and 0.825) and the calibration plots indicated that the nomogram had a good performance. The decision curves in both cohorts showed that the nomogram model for predicting 30-day mortality after BSI was more beneficial than all patients with BSIs or none with BSIs. In our study, gram-negative bacterial BSIs were predominant in patients with HMs. We developed and validated a nomogram with good predictive ability to help clinicians evaluate the prognosis of patients.

Efficacy and safefy of Polymyxin B treatment for neutropenic patients suffering from refractory Gram-negative bacterial bloodstream infection

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.

Difficult-to-treat resistant gram-negative blood stream infections – the beginning of a superbug era – a prospective observational study

IntroductionCarbapenem resistant gram-negative bacterial infections are a growing concern worldwide. However, India is already in the era of a shortage of effective antibiotics for the management of these infections. Moreover, Difficult-to-Treat Resistance (DTR) gram-negative infections, which are not much studied, further complicate the scenario. This study emphasized the incidence and outcomes of DTR infections. MethodologyThis is a single-center prospective observational study. The study included hospitalised patients aged ≥18 years with gram-negative bacterial bloodstream infections (GNBSI). Blood cultures with the growth of contaminants and/or single positive culture taken from the femoral site were excluded. Incidences of DTR infections and outcomes in the form of 30-day mortality were analysed. ResultsTwo hundred forty patients with GNBSI episodes were recorded. The Incidence of DTR GNBSI was 37.9% (91/240). Multivariate analysis found that Hospital-acquired infections, ICU admission and mechanical ventilation were independent risk factors for DTR GNBSI. The most common DTR GNB isolates were Klebsiella pneumoniae (31/49, 63.3%) and Acinetobacter baumannii (26/52, 50%). The adjusted relative risk of mortality was remarkably high in DTR GNBSI (aRR 3.9; 95% CI 1.9–7.9) as compared to CR+/DTR- GNBSI (aRR 0.3; 95% CI 0.1–1.0) and ESCR/CS GNBSI (aRR 1.1; 95% CI 0.5–2.4). ConclusionDTR GNB infections are growing concern in India and this need to be evaluated in multicentric studies. Moreover, DTR GNBSI was associated with significantly higher mortality and there is need of further empowerment of antibiotic stewardship practices.

Association of Follow-up Blood Cultures With Mortality in Patients With Gram-Negative Bloodstream Infections

Obtaining follow-up blood cultures (FUBCs) in patients with Staphylococcus aureus bloodstream infection (BSI) is standard practice, although its utility in patients with gram-negative bacterial BSI (GN-BSI) is unclear. To examine whether obtaining FUBCs is associated with decreased mortality (key question [KQ] 1) and whether positive vs negative FUBCs are associated with increased mortality (KQ2). MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, and gray literature were searched from inception to March 11, 2022. Two investigators used predefined eligibility criteria to independently screen titles, abstracts, and relevant full texts. Randomized clinical trials or observational studies that matched or statistically adjusted for differences in, at minimum, level of acute illness between patients in the intervention (eg, FUBCs obtained) and control (eg, FUBCs not obtained) groups were included in primary analyses. Articles published in languages other than English were excluded. Data abstraction and quality assessments were performed by one investigator and verified by a second investigator. Risk of bias was assessed with the Newcastle-Ottawa Scale. Effect sizes were pooled using random-effects models. The study followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. Mortality before hospital discharge or up to 30 days from the index blood culture. From 3495 studies, 15 were included (all nonrandomized). In the 5 studies (n = 4378 patients) that met criteria for the KQ1 primary analysis, obtaining FUBCs was associated with decreased mortality (hazard ratio, 0.56; 95% CI, 0.45-0.71). For KQ2, 2 studies met criteria for the primary analysis (ie, matched or statistically adjusted for differences in patients with positive vs negative FUBCs), so an exploratory meta-analysis of all 9 studies that investigated KQ2 (n = 3243 patients) was performed. Positive FUBCs were associated with increased mortality relative to negative blood cultures (odds ratio, 2.27; 95% CI, 1.54-3.34). Limitations of the literature included a lack of randomized studies and few patient subgroup analyses. In this systematic review and meta-analysis, obtaining FUBCs in patients with GN-BSI was associated with decreased mortality. The benefit of FUBCs may stem from identification of patients with positive FUBCs, which was a poor prognostic marker.

Clinical and Molecular Analyses of Recurrent Gram-Negative Bloodstream Infections.

The causes and clinical characteristics of recurrent gram-negative bacterial bloodstream infections (GNB-BSI) are poorly understood. We used a cohort of patients with GNB-BSI to identify clinical characteristics, microbiology, and risk factors associated with recurrent GNB-BSI. Bacterial genotyping (pulsed-field gel electrophoresis [PFGE] and whole-genome sequencing [WGS]) was used to determine whether episodes were due to relapse or reinfection. Multivariable logistic regression was used to identify risk factors for recurrence. Of the 1423 patients with GNB-BSI in this study, 60 (4%) had recurrent GNB-BSI. Non-White race (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.38-4.01; P = .002), admission to a surgical service (OR, 2.18; 95% CI, 1.26-3.75; P = .005), and indwelling cardiac device (OR, 2.73; 95% CI, 1.21-5.58; P = .009) were associated with increased risk for recurrent GNB-BSI. Among the 48 patients with recurrent GNB-BSI whose paired bloodstream isolates underwent genotyping, 63% were due to relapse (30 of 48) and 38% were due to reinfection (18 of 48) based on WGS. Compared with WGS, PFGE correctly differentiated relapse and reinfection in 98% (47 of 48) of cases. Median time to relapse and reinfection was similar (113 days; interquartile range [IQR], 35-222 vs 174 days; IQR, 69-599; P = .13). Presence of a cardiac device was associated with relapse (relapse: 7 of 27, 26%; nonrelapse: 65 of 988, 7%; P = .002). In this study, recurrent GNB-BSI was most commonly due to relapse. PFGE accurately differentiated relapse from reinfection when compared with WGS. Cardiac device was a risk factor for relapse.

Antimicrobial Resistance and Associated Risk Factors of Gram-Negative Bacterial Bloodstream Infections in Tikur Anbessa Specialized Hospital, Addis Ababa.

BackgroundBloodstream infections (BSIs) are significant causes of morbidity and mortality in Ethiopia and worldwide. Alarming is the rapid global spread of antimicrobial resistance (AMR) in bacteria.ObjectiveTo determine the microbial profile, antimicrobial susceptibility pattern, and associated risk factors for bloodstream infections in Tikur Anbessa Specialized Hospital (TASH) Addis Ababa Ethiopia.MethodsA cross-sectional study was conducted between September 2018 and March 2019. Blood collected twice from each septicemia suspected patient were processed following standard bacteriological procedures. AST was performed by using the disk diffusion test according to CLSI 2017 and 2018 guidelines. Data captured in Epidata were cleaned and analyzed by SPSS version 21 software.ResultsThe prevalence of BSI was 28.06% and a higher proportion of pathogene detected were gram-negative bacteria (GNB) (54.5%) and gram-positive bacteria (GPB) (45.43%). The most abundant bacterial species were Klebsiella pneumoniae 17.6%, CoNS 15.2%, and Acinetobacter spp 11.0%. Culture positivity was associated with age below 6 years, neonates AOR p=<0.001, infants AOR p=<0.001, Pre-school P=0.002, ICU admission COR p=<0.001, length of admission >5 days COR P=0.016, temperature greater than 38°C, AOR p=0.013, instrument usage during medical care AOR, p=<0.001, chronic illness AOR p=0.027, and neonatal incubation AOR p=0.013. GNB average drug resistance rate was 57.9% of the commonly used antibiotics and the most efficient and inefficient drugs were amikacin (10.8%) and ampicillin (94.6%). The gram-negative isolates showed a 95.3% rate of multi-drug resistance; and MDR, XDR, and PDR were observed at 55.8%, 32.2%, and 7.3%, of isolates respectively. This finding shows children especially neonates were highly affected by drug resistant BSI.ConclusionPediatric patients and ICU patients are more affected by BSI, and drug-resistant bacteria are a major problem. Therefore, appropriate intervention approaches need to be implemented.

Comparison between hospital- and community-acquired septic shock in children: a single-center retrospective cohort study

BackgroundWe explored the differences in baseline characteristics, pathogens, complications, outcomes, and risk factors between children with hospital-acquired septic shock (HASS) and community-acquired septic shock (CASS) in the pediatric intensive care unit (PICU).MethodsThis retrospective study enrolled children with septic shock at the PICU of Beijing Children’s Hospital from January 1, 2016, to December 31, 2019. The patients were followed up until 28 days after shock or death and were divided into the HASS and CASS group. Logistic regression analysis was used to identify risk factors for mortality.ResultsA total of 298 children were enrolled. Among them, 65.9% (n = 91) of HASS patients had hematologic/oncologic diseases, mainly with Gram-negative bacterial bloodstream infections (47.3%). Additionally, 67.7% (n = 207) of CASS patients had no obvious underlying disease, and most experienced Gram-positive bacterial infections (30.9%) of the respiratory or central nervous system. The 28-day mortality was 62.6% and 32.7% in the HASS and CASS groups, respectively (P < 0.001). Platelet [odds ratio (OR) = 0.996, 95% confidence interval (CI) = 0.992–1.000, P = 0.028], positive pathogen detection (OR = 3.557, 95% CI = 1.307–9.684, P = 0.013), and multiple organ dysfunction syndrome (OR = 10.953, 95% CI = 1.974–60.775, P = 0.006) were risk factors for 28-day mortality in HASS patients. Lactate (OR = 1.104, 95% CI = 1.022–1.192, P = 0.012) and mechanical ventilation (OR = 8.114, 95% CI = 1.806–36.465, P = 0.006) were risk factors for 28-day mortality in patients with CASS.ConclusionsThe underlying diseases, pathogens, complications, prognosis, and mortality rates varied widely between the HASS and CASS groups. The predictors of 28-day mortality were different between HASS and CASS pediatric patients with septic shock.

A Desirability of Outcome Ranking Analysis of a Randomized Clinical Trial Comparing Seven Versus Fourteen Days of Antibiotics for Uncomplicated Gram-Negative Bloodstream Infection.

BackgroundAlthough a short course (7 days) of antibiotics has been demonstrated to be noninferior to a conventional course (14 days) in terms of mortality and infectious complications for patients with a Gram-negative bacterial bloodstream infection (GNB), it is unknown whether a shorter treatment duration can provide a better overall clinical outcome.MethodsWe applied a bloodstream infection-specific desirability of outcome ranking (DOOR) analysis to the results of a previously completed, randomized controlled trial comparing short versus conventional course antibiotic therapy for hospitalized patients with uncomplicated GNB. We determined the probability that a randomly selected participant in the short course group would have a more desirable overall outcome than a participant in the conventional duration group. We performed (1) partial credit analyses allowing for calculated and variable weighting of DOOR ranks and (2) subgroup analyses to elucidate which patients may benefit the most from short durations of therapy.ResultsFor the 604 patients included in the original study (306 short course, 298 conventional course), the probability of having a more desirable outcome with a short course of antibiotics compared with a conventional course was 51.1% (95% confidence interval, 46.7% to 55.4%), indicating no significant difference. Partial credit analyses indicated that the DOOR results were similar across different patient preferences. Prespecified subgroup analyses using DOOR did not reveal significant differences between short and conventional courses of therapy.ConclusionsBoth short and conventional durations of antibiotic therapy provide comparable clinical outcomes when using DOOR to consider benefits and risks of treatment options for GNB.

Patients' Experiences With Staphylococcus aureus and Gram-Negative Bacterial Bloodstream Infections: Results From Cognitive Interviews to Inform Assessment of Health-Related Quality of Life.

BackgroundWe previously conducted a concept elicitation study on the impact of Staphylococcus aureus and gram-negative bacterial bloodstream infections (SAB/GNB) on health-related quality of life (HRQoL) from the patient’s perspective and found significant impacts on HRQoL, particularly in the physical and functional domains. Using this information and following guidance on the development of patient-reported outcome (PRO) measures, we determined which combination of measures and items (ie, specific questions) would be most appropriate in a survey assessing HRQoL in bloodstream infections.MethodsWe selected a variety of measures/items from the Patient-Reported Outcomes Measurement Information System (PROMIS) representing different domains. We purposefully sampled patients ~6–12 weeks post-SAB/GNB and conducted 2 rounds of cognitive interviews to refine the survey by exploring patients’ understanding of items and answer selection as well as relevance for capturing HRQoL.ResultsWe interviewed 17 SAB/GNB patients. Based on the first round of cognitive interviews (n = 10), we revised the survey. After round 2 of cognitive interviewing (n = 7), we finalized the survey to include 10 different PROMIS short forms/measures of the most salient HRQoL domains and 2 adapted questions (41 items total) that were found to adequately capture HRQoL.ConclusionsWe developed a survey from well-established PRO measures that captures what matters most to SAB/GNB patients as they recover. This survey, uniquely tailored to bloodstream infections, can be used to assess these meaningful, important HRQoL outcomes in clinical trials and in patient care. Engaging patients is crucial to developing treatments for bloodstream infections.

59. Risk Factors for Recurrent Gram-Negative Bacterial Bloodstream Infections

BackgroundGram-negative bacteria bloodstream infections (GNB-BSI) are a significant cause of morbidity and mortality. Recurrent GNB-BSI is an incompletely understood phenomenon. In this study we identify risk factors for recurrent GNB-BSI.MethodsPatients with GNB-BSI have been prospectively enrolled into the Bloodstream Infection Biorepository (BSIB) since 2002. From the BSIB, patients with >1 episode of GNB-BSI with the same bacterial species were identified. Chi-Square, Fisher Exact, and a multivariate linear regression models were used to identify clinical risk factors for recurrent GNB-BSI. Paired isolate samples from the initial and the recurrent episode of GNB-BSI in same patient underwent Pulsed Field Gel Electrophoresis (PFGE) to differentiate Relapse (paired isolates identical) from Reinfection (paired isolates different).ResultsAmong the 1,423 unique patients with GNB-BSI enrolled from 2002- 2015, 60 (4.2%) experienced recurrent GNB-BSI with the same bacterial species. Median time to recurrent GNB-BSI was 133 d (IQR: 40-284.75 days). Causes of recurrent-GNB-BSI included Escherichia coli (38%), Klebsiella species (30%), Pseudomonas aeruginosa (12%), and Serratia marcescens (5%) and did not differ from causes of non-recurrent GNB-BSI (Figure 1). Risk factors for recurrent GNB-BSI included Black race (OR: 2.45 [CI: 1.43-4.20]), implanted cardiac device (OR: 2.39 [CI: 1.00-5.07]), and admission to surgical service (OR: 2.16 [CI 1.24-3.75]). Forty-eight isolate-pairs from 43 patients with recurrent GNB-BSI underwent PFGE, relapse occurred in 31 (65%) and reinfection occurred in 17 (35%). Risk factors for GNB-BSI relapse included cardiac device (OR: 3.7 [CI: 1.7-8.3]), and admission to surgical service (OR: 3.7 [CI:1.3-9.4]).Figure 1: Species Breakdown Proportional comparison of the Gram-negative bacterial species identified in patients with recurrent and non-recurrent bloodstream infections.ConclusionRecurrent GNB-BSI is an uncommon complication of GNB-BSI. Recurrent GNB-BSI is most often driven by relapse, as opposed to reinfection, and is associated with associated with black race, implanted cardiac devices and admission to surgical service.Disclosures Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Grant/Research Support)Affinium (Consultant)Akagera (Consultant)Allergan (Grant/Research Support)Amphliphi Biosciences (Consultant)Aridis (Consultant)Armata (Consultant)Basilea (Consultant, Grant/Research Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Other Financial or Material Support, Educational fees)Contrafect (Consultant, Grant/Research Support)Debiopharm (Consultant, Other Financial or Material Support, Educational fees)Destiny (Consultant)Durata (Consultant, Other Financial or Material Support, educational fees)Genentech (Consultant, Grant/Research Support)Green Cross (Other Financial or Material Support, Educational fees)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)MedImmune (Consultant, Grant/Research Support)Merck (Grant/Research Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Grant/Research Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Grant/Research Support)sepsis diagnostics (Other Financial or Material Support, Pending patent for host gene expression signature diagnostic for sepsis.)Tetraphase (Consultant)Theravance (Consultant, Grant/Research Support, Other Financial or Material Support, Educational fees)Trius (Consultant)UpToDate (Other Financial or Material Support, Royalties)Valanbio (Consultant, Other Financial or Material Support, Stock options)xBiotech (Consultant)