Bloodstream Infections In Patients Research Articles

Ten Years of KPC-Kp Bloodstream Infections Experience: Impact of Early Appropriate Empirical Therapy on Mortality.

In K. pneumoniae KPC (KPC-Kp) bloodstream infections (BSI), INCREMENT CPE score >7, Charlson Comorbidity Index (CCI) ≥3 and septic shock are recognized predictors of mortality, with a possible beneficial effect of combination therapy in seriously ill patients. We conducted a ten-year retrospective study including all KPC-Kp BSI in patients ≥18 years of age with the aim to evaluate the characteristics and impact of appropriate empirical therapy, either monotherapy or combination therapy, and targeted therapy on mortality. Appropriate therapy was defined as at least one active antimicrobial agent with in vitro activity against KPC-kp demonstrated by susceptibility testing, administered within 48 h from blood culture collection. The median age of the 435 analyzed patients was 66.09 years (IQR 54.87-73.98). The median CCI was 4. KPC-Kp colonization was present in 324 patients (74.48%). The probable origin of the KPC-Kp BSI was not identified in 136 patients (31.26%), whereas in 120 (27.59%) patients, it was CVC-related, and in 118 (27.13%), it was respiratory. Source control was achieved in 87 patients (72.5%) with CVC-related KPC-Kp BSI. The twenty-eight-day survival was 70.45% for empirical monotherapy, 63.88% for empirical combination therapy and 57.05% for targeted therapy (p = 0.0399). A probable source of KPC-Kp BSI other than urinary, CVC or abdominal [aHR 1.64 (IC 1.15-2.34) p = 0.006] and deferred targeted therapy [HR 1.67 (IC 1.12-2.51), p= 0.013] emerged as predictors of mortality, whereas source control [HR 0.62 (IC 0.44-0.86), p = 0.005] and ceftazidime/avibactam administration in empirical therapy [aHR 0.37 (IC 0.20-0.68) p = 0.002] appeared as protective factors. These data underline the importance of source control together with timing appropriateness in the early start of empirical therapy over the choice of monotherapy or combination therapy and the use of ceftazidime/avibactam against KPC-Kp BSI.

430. Oritavancin Activity Against Gram-positive Pathogens Causing Bloodstream Infections in Hematology/Oncology and Transplant Units in US Medical Centers (2010-2019)

Abstract Background Patients undergoing hematologic, oncologic, and/or transplant treatment are at risk for infections. Appropriate antimicrobial management is crucial for patients with suspected or confirmed bloodstream infections (BSI). We evaluated the in vitro activity of oritavancin (ORI) and comparators against Gram-positive (GP) isolates causing BSI in patients from hematology/oncology and transplant units (HTU) in US medical centers. Methods 1,217 isolates (1/patient) were consecutively collected from HTU patients in 33 US hospitals during 2010-2019. Isolates were identified by MALDI-TOF and/or standard microbiological testing methods, and susceptibility (S) tested by CLSI reference broth microdilution in a central laboratory. CLSI breakpoints were applied. Results Enterococcus spp. (overall, 36.1%; E. faecium [EFM], 20.2%; E. faecalis [EF], 14.3%) and S. aureus (SA, 35.7%; 36.4% methicillin-resistant [MRSA]) were the most common organism groups, followed by coagulase-negative Staphylococcus (CoNS; 11.8%; 76.4% MR), Viridans group streptococci (VHS; 9.6%), and beta-haemolytic streptococci (BHS; 3.5%). ORI inhibited 96.7%/98.9% of EFM/EF at ≤0.12mg/L (S breakpoint for vancomycin [VAN]-S EF). Ampicillin (100.0%S), linezolid (LZD; 100.0%S), daptomycin (DAP; 98.3%S), and VAN (97.1%S) were also active against EF. Only ORI (96.7%S) and LZD (100.0%S) remained active against EFM. A VRE phenotype and elevated daptomycin MIC (2-4 mg/L) were noted in 72.8% and 55.3% of EFM, with ORI inhibiting 95.5% and 95.6% of these isolates at ≤0.12mg/L, respectively. ORI displayed equivalent MIC50/90 (0.03/0.06 mg/L) values against MSSA (99.3%S) and MRSA (99.4%S). ORI inhibited 95.5% of MRCoNS at ≤0.12mg/L (SA breakpoint). VAN, DAP, and LZD remained active against MRSA and MRCoNS. ORI was also active against BHS (MIC50/90, 0.03/0.25 mg/L; 95.2%S) and VGS (MIC50/90, 0.015/0.25 mg/L; 96.6%S) as was VAN (100.0%), DAP (100.0%), and LZD (100.0%/99.1%S, respectively). Conclusion VRE EFM, MRCoNS, and MRSA rates were generally high in BSI GP isolates recovered from patients in HTU. ORI was highly active and inhibited > 95% of isolates at MIC of ≤ 0.12mg/L from this unique collection, including R subsets such as VAN-R EFM, EFM displaying elevated DAP MIC (2-4 mg/L), MRSA, and MRCoNS. Disclosures Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support Helio S. Sader, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support.

Changing epidemiology and prognosis of nosocomial bloodstream infection: A single-center retrospective study in Taiwan.

Nosocomial bloodstream infection (BSI) remains a significant cause of mortality and morbidity. We evaluate the trend of the pathogens of nosocomial BSI and investigate the distribution of the pathogens to demonstrate the risk factors of mortality. In this retrospective study, we collected data from a 2076-bed tertiary referral center that offers a full range of clinical services in central Taiwan during January, 2016 to December, 2017. Five hundred and eighty-four patients were identified with nosocomial BSI. Among the comorbidities of nosocomial BSI patients with, the most frequent were hypertension, in 294 patients (50.3%), malignancy, in 279 patients (47.8%); diabetes, in 278 patients (47.6%); chronic kidney disease, in 171 patients (29.3%); and liver cirrhosis, in 132 patients (22.6%). Gram-positive organisms caused 22.9% of these nosocomial BSIs, gram-negative organisms caused 69.2%, and fungi caused 6.8%. The most common organism causing nosocomial BSIs were Klebsiella spp. (14%), E coli. (14%), and Enterococcus spp. (11%). Multivariate analysis of risk factors for mortality displayed that comorbidity with low body weight, liver cirrhosis, and malignancy, high CRP level, high Charlson Comorbidity Index and internal medicine and hematology/oncology distribution were strikingly associated with mortality (P=0.0222, 0.0352, 0.0008, 0.0122, <0.001, and 0.041; [OR]=1.8097, 1.9268, 2.7156, 2.7585, 3.5431, and 2.2449, respectively). K. spp. and E coli. became the most common pathogens of nosocomial BSI in recent years. Comorbidities could be important roles to predictive the outcome of nosocomial BSI. The modifiable risk factors of nosocomial BSI may be investigated further to improve the outcome.

Clinical Characteristics, Microbiology, and Risk Factors for Mortality of Pre-Engraftment and Post-Engraftment Bloodstream Infection in Hematopoietic Stem Cell Transplantation Recipients.

Bloodstream infection (BSI) is a common and serious complication that may lead to high mortality during the different phases after hematopoietic stem cell transplant (HSCT). We investigated BSI in patients undergoing HSCT to provide an appropriate clinical anti-infection experience and improve the prognosis of recipients with BSI after HSCT. A total of 105 patients with BSI after HSCT at our center from January 2015 to June 2020 were included in this retrospective study. We analyzed the clinical and microbiological data, and the risk factors for mortality at 3 months after BSI. Of the 1141 HSCT recipients, 105 (9.2%) patients presented with 122 episodes of BSI, of which we isolated 85 (65.9%) gram-negative bacteria, 32 (24.8%) gram-positive bacteria and 12 (9.3%) fungi. Multidrug-resistant bacteria (MDR) were more than 70% of all pathogens and carbapenem-resistant organisms (CRO) were 25.6%. There were 55 episodes of BSI in the pre-engraftment phase and 67 episodes in the post-engraftment phase. The mortality of post-engraftment BSI was significantly higher than that of pre-engraftment (56.7% vs 32.7%, p = 0.005). Through multivariate analysis, the independent risk factors for all-cause mortality at 3 months after BSI were higher levels of procalcitonin (PCT), failure to cover appropriate antibiotics timely, and CRO BSI in pre-engraftment period or multidrug-resistant gram-negative bacteria (MDRGNB) BSI in post-engraftment period. Although the incidence of BSI was lower after HSCT, MDR-dominated BSI had a high mortality rate. Rapid identification of infection or pathogens' classification with various testing methods and the more sensible and timely antibiotic cover are critical to the outcome of BSI after HSCT.

Biomarker of neutrophil extracellular traps is associated with deep-seated infections and predicts mortality and cardiovascular morbidity in commensal streptococcal bacteremia.

Neutrophil extracellular traps (NETs) play important roles in sepsis and deep-seated infections, but whether NET formation correlates with clinical outcomes of patients with streptococcal bloodstream infections (BSIs) is unclear. We analyzed serum levels of complexes of myeloperoxidase and DNA (MPO-DNA) in patients with streptococcal-BSIs. Invitro assay of NET induction by serum from BSI patients was performed. MPO-DNA values for the Streptococci-BSI group (n=59) were significantly higher than those for healthy controls (p<0.00001) and matched control groups (n=59, p=0.004). The rate of higher MPO-DNA levels (>1.87μg/mL) were higher in abscess-prone streptococcal groups (streptococcus milleri group) (72.2% vs. 52.5%, p=0.02). For patients with BSIs due to highly infective endocarditis (IE)-prone pathogens, the values of serum MPO-DNA were also higher in patients diagnosed of IE compared to their counterparts (p=0.009). Notably, serum from patients with leukopenia could induce higher amounts of invitro NET formation, despite having low MPO-DNA levels, suggesting that NET formation could be influenced by WBC counts. Therefore, we combined WBC counts with MPO-DNA to predict all-cause 30-day mortality in patients with commensal streptococcal-BSIs. The mortality risk was lowest among patients who had neither high MPO-DNA levels nor abnormal WBC counts (p=0.058). Furthermore, this group of patients also had a favorable composite outcome consisting of major adverse cardiovascular events (MACE) and all-cause mortality (p=0.026). Together, these study data suggested that serum MPO-DNA can be a biomarker for predicting a composite outcome consisting of MACE and all-cause mortality in patients with commensal streptococcal-BSIs.

Epidemiological and Clinical Characteristics of Non-Typhoidal Salmonella Bloodstream Infections in Central Israel: A Case-Control Study.

Non-typhoidal Salmonella (NTS) infection continues to be a significant cause of morbidity. In addition to gastroenteritis (GE), NTS may cause bloodstream infections (BSI). Our goals were to characterize the demographics, clinical characteristics and outcome of NTS-BSI in central Israel. The study was a retrospective, case-control study conducted at the Tel Aviv Sourasky Medical Center between 2001–2018. Cases with NTS-BSI were matched by age and compared with two control groups, hospitalized patients with NTS-GE and patients with E. coli BSI. The NTS-BSI group included 34 patients who were compared with 69 and 68 patients in the NTS-GE and E. coli BSI groups, respectively. In the NTS-BSI group, the median age was 59 years, with 20% of patients below 20 years of age. Diarrhea was less common in NTS-BSI patients compared with NTS-GE: 53% vs. 80% (p < 0.01). Compared with NTS-GE patients, NTS-BSI patients had a higher rate of recent antimicrobial use: 21% vs. 5.9%, p = 0.03, respectively. They also had a slightly higher Charlson Comorbidity Index score, and history of past malignancy and steroid use, but these differences were not statistically significant. Antimicrobial treatment was documented in 30/34 of the NTS-BSI patients vs. 55/69 of the NTS-GE patients (p < 0.001). NTS-BSI patients had higher rates of in-hospital death (23% vs. 4%, p < 0.01) and a longer length of stay (8 vs. 4 days, p < 0.001) compared with NTS-GE. There was no significant difference in the outcome compared with the E. coli BSI group. In conclusion, our study found relatively low rates of pediatric cases compared with previous studies in Israel. NTS-BSI patients had slightly higher rates of comorbidities compared with NTS-GE patients, and a similar prognosis to E. coli BSI patients.

Risk factors for bloodstream infection (BSI) in patients with severe acute respiratory distress syndrome (ARDS) supported by veno–venous extracorporeal membrane oxygenation (VV–ECMO)

BackgroundThere were relatively few studies about the incidence and risk factors for bloodstream infection (BSI) in patients with severe acute respiratory distress syndrome (ARDS) supported by veno–venous extracorporeal membrane oxygenation (VV–ECMO).MethodsPatients who were diagnosed with severe ARDS and received VV–ECMO treatment in the medical intensive care unit of China–Japan Friendship Hospital from August 2013 to March 2019 were retrospectively studied. The pathogens isolated from blood culture (BC) were identified and analyzed for drug sensitivity. The risk factors for BSI were analyzed by logistic regression.ResultsA total of 105 patients were included in this single–center retrospective cohort study. Among them, 23 patients (22%) had BSIs. 19 cases were identified as primary BSI; while the other 4 cases were as secondary BSI. A total of 23 pathogenic strains were isolated from BCs, including gram–negative (G–) bacilli in 21 (91%) cases, gram–positive (G+) cocci in 1 case, fungus in 1 case, and multidrug–resistant (MDR) organisms in 8 cases. Compared with patients without BSI, patients with BSI had a higher Murray score (odds ratio = 6.29, P = 0.01) and more blood transfusion (odds ratio = 1.27, P = 0.03) during ECMO.ConclusionsThe incidence of BSI in patients with severe ARDS supported by VV–ECMO was 22%. G– bacilli was the main pathogen, and most of them were MDR–G– bacilli (MDR–GNB). Higher Murray score and more blood transfusion may be the independent risk factors for BSI.

Association Between Time to Appropriate Antimicrobial Treatment and 30-day Mortality in Patients With Bloodstream Infections: A Retrospective Cohort Study.

Effective antimicrobial treatment is key for survival in bloodstream infection (BSI), but the impact of timing of treatment remains unclear. Our aim was to assess the association between time to appropriate antimicrobial treatment and 30-day mortality in BSI patients. This was a retrospective cohort study using electronic health record data from a large academic center in Sweden. Adult patients admitted between the years 2012 and 2019, with onset of BSI at the emergency department or general wards, were included. Pathogen-antimicrobial drug combinations were classified as appropriate or inappropriate based on reported in vitro susceptibilities. To avoid immortal time bias, the association between appropriate therapy and mortality was assessed with multivariable logistic regression analysis at pre-specified landmark times. We included 10 628 BSI-episodes, occurring in 9192 unique patients. The overall 30-day mortality was 11.8%. No association in favor of a protective effect between appropriate therapy and mortality was found at the 1, 3 and 6 hours landmark after blood culture collection. At 12 hours, the risk of death increased with inappropriate treatment (adjusted odds ratio 1.17 [95% confidence interval {CI}, 1.01-1.37]) and continued to increase gradually at 24, 48, and 72 hours. Stratifying by high or low SOFA score generated similar odds ratios, with wider confidence intervals. Delays in appropriate antimicrobial treatment were associated with increased 30-day mortality after 12 hours from blood culture collection, but not at 1, 3, and 6 hours, in BSI. These results indicate a benchmark for providing rapid microbiological diagnostics of blood cultures.

Molecular epidemiology and carbapenem resistance characteristics of Acinetobacter baumannii causing bloodstream infection from 2009 to 2018 in northwest China.

Bloodstream infection (BSI) caused by Acinetobacter baumannii poses a serious threat to health and is correlated with high mortality in patients with hospital-acquired infections, so the molecular epidemiology and antimicrobial resistance characteristics of this pathogen urgently need to be explored. A. baumannii isolates from BSI patients were collected in three tertiary hospitals in northwest China from 2009 to 2018. Antimicrobial susceptibility testing was used to determine the MICs of the A. baumannii isolates. Whole-genome sequencing based on the Illumina platform was performed for molecular epidemiological analyses and acquired resistance gene screening. The efflux pump phenotype was detected by examining the influence of an efflux pump inhibitor. The expression of efflux pump genes was evaluated by RT-PCR. In total, 47 A. baumannii isolates causing BSI were collected and they presented multidrug resistance, including resistance to carbapenems. Clone complex (CC) 92 was the most prevalent with 30 isolates, among which a cluster was observed in the phylogenetic tree based on the core genome multi-locus sequence type, indicating the dissemination of a dominant clone. BSI-related A. baumannii isolates normally harbour multiple resistance determinants, of which oxacillinase genes are most common. Except for the intrinsic blaOXA-51 family, there are some carbapenem-resistant determinants in these A. baumannii isolates, including blaOXA-23, which is encoded within the Tn2006, Tn2008 or Tn2009 transposon structures and blaOXA-72. The transfer of blaOXA-72 was suggested by XerC/D site-specific recombination. The AdeABC efflux pump system contributed to carbapenem resistance in A. baumannii isolates, as evidenced by the high expression of some of its encoding genes. Both the clone dissemination and carbapenem resistance mediated by oxacillinase or efflux pumps suggest an effective strategy for hospital infection control.

Clinical and Epidemiological Characteristics of Bloodstream Infections in Head and Neck Cancer Patients: A Decadal Observational Study.

This retrospective study aims to describe the clinico-epidemiological characteristics of bloodstream infections (BSIs) and the risk factors in patients with head and neck cancer (n = 227) treated at the Department of Otolaryngology, Head and Neck Surgery, Tohoku University Hospital between April 2011 and March 2021. Overall, 23.3% of blood cultures were positive. In the culture-positive group, catheter-related bloodstream infections (CRBSIs) were the most common (38.8%), followed by respiratory tract infections (19.4%), and catheter-associated urinary tract infections (6.0%). Methicillin-resistant Staphylococcus aureus (26.9%), Staphylococcus epidermidis (17.9%), and Pseudomonas aeruginosa (10.4%) infections were common. The most frequent treatment for head and neck cancer was surgery (23.9%), followed by treatment interval or palliative care (19.4%), and single radiotherapy (13.4%). The 30-day mortality rate was significantly higher in the BSI than in the non-BSI group (10.4% vs. 1.8%, respectively). CRBSIs are the most frequent source of BSIs in patients with head and neck cancer. In conclusion, central venous catheters or port insertion should be used for a short period to prevent CRBSIs. The risk of developing BSI should be considered in patients with pneumonia. Understanding the epidemiology of BSIs is crucial for diagnosing, preventing, and controlling infections in patients with head and neck cancer.

Incidence of bloodstream infections in patients with COVID-19: a retrospective cohort study of risk factors and outcomes.

Prior evidence found that bloodstream infections (BSIs) are common in viral respiratory infections and can lead to heightened morbidity and mortality. We described the incidence, risk factors, and outcomes of BSIs in patients with COVID-19. This was a single-center retrospective cohort study of adults consecutively admitted from March to June 2020 for COVID-19 with BSIs. Data were collected by electronic medical record review. BSIs were defined as positive blood cultures (BCs) with a known pathogen in one or more BCs or the same commensal organism in two or more BCs. We evaluated 290 patients with BCs done; 39 (13.4%) had a positive result. In univariable analysis, male sex, black/African American race, admission from a facility, hemiplegia, altered mental status, and a higher Charlson Comorbidity Index were positively associated with positive BCs, whereas obesity and systolic blood pressure (SBP) were negatively associated. Patients with positive BCs were more likely to have severe COVID-19, be admitted to the intensive care unit (ICU), require mechanical ventilation, have septic shock, and higher mortality. In multivariable logistic regression, factors that were independent predictors of positive BCs were male sex (OR=2.8, p=0.030), hypoalbuminemia (OR=3.3, p=0.013), ICU admission (OR=5.3, p<0.001), SBP<100 mmHg (OR=3.7, p=0.021) and having a procedure (OR=10.5, p=0.019). Patients with an abnormal chest X-ray on admission were less likely to have positive BCs (OR=0.3, p=0.007). We found that male sex, abnormal chest X-ray, low SBP, and hypoalbuminemia upon hospital admission, admission to ICU, and having a procedure during hospitalization were independent predictors of BSIs in patients with COVID-19.

P1575: DEVELOPMENT OF A RISK PREDICTION MODEL OF SUBSEQUENT BLOOLDSTREAM INFECTION AFTER CARBAPENEM-RESISTANT ENTEROBACTERIACEASE ISOLATED FROM PERIANAL SWABS IN PATIENTS WITH HEMATOLOGICAL DISEASES

Background: Hematological patients are at higher risk of developing carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infection (BSI) and associated with high mortality. Prediction model for a subsequent CRE BSI in hematological patients with CRE isolated from previous perianal swab samples can provide timely and useful target treatment strategies. Aims: To developing a quantified risk prediction model based on the risk factors of subsequent BSI in CRE carriers will help clinicians better identify specific individuals who would truly benefit from early, empiric CRE-targeted treatment. Methods: The data were extracted from patients with CRE isolated from perianal swab samples at the Hematopoietic Stem Cell Transplantation Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences between July 2017 to October 2020 January. Patients who developed subsequent CRE BSI were compared with those who did not develop BSI. Univariate logistic analysis, multivariate logistic analysis and stepwise regression analysis were carried on a variety of clinical factors. Results: A total of 215 cases were included and 29 (13.4%) patients of them with CRE isolated from perianal swab samples developed CRE BSI subsequently. Multivariate analysis showed that C-reactive protein(CRP)﹥30mg/l(OR 10.613，95%CI 2.965~37.985，P=0.000）, perianal infection(OR 6.450, 95%CI 2.223~18.714, P=0.001), concomitant gastrointestinal symptoms (OR 4.175，95%CI 1.476~11.813，P=0.007），age﹥44 years (OR 3.415，95%CI 1.222~9.541，P=0.007）and neutrophil count﹤0.025×109/L (OR 4.583，95%CI 0.939~22.369，P=0.060）were risk factors for CRE BSI in patients with CRE isolated from perianal swab samples (P<0.01). They were included in the Logistic regression model to predict BSI. According to receiver operating characteristic (ROC) curve analysis, the cut-off value of the model was 0.921 (0.851-0.968，P<0.001). Image:Summary/Conclusion: Hematological patients with CRE isolated from perianal swab samples have a relatively low incidence of subsequent BSI but a relatively high risk of death. The risk prediction model based on CRP, perianal infection, concomitant gastrointestinal symptoms, age and valley absolute neutrophil may be used for predicting subsequent CRE BSI in patients with isolated from perianal swab samples and provide timely and effective treatment reference for this kind of patients.

Indwelling Central Venous Catheters Drive Bloodstream Infection During Veno-venous Extracorporeal Membrane Oxygenation Support.

Blood stream infection (BSI) is a potentially lethal complication in patients receiving extracorporeal membrane oxygenation (ECMO). It may be particularly common in patients with veno-venous ECMO due to their long hospitalization in the intensive care unit. Given that these patients have concurrent indwelling central venous catheters (CVC), it is unclear whether the ECMO circuit, CVC, or both, contribute to BSI. This study evaluated the risk factors associated with BSI in patients receiving veno-venous ECMO in a single institution study of 61 patients from 2016 through 2019. All ECMO catheters and the circuit oxygenator fluid were aseptically collected and analyzed for microorganisms at the time of decannulation. New BSI was diagnosed in 15 (24.6%) patients and increased mortality by threefold. None of the ECMO catheters or oxygenator fluid were culture positive. BSI increased with CVC use of over 8 days and was significantly lowered when CVC were exchanged by day 8 compared with patients with exchanges at later points (15.0% vs. 42.8%, p = 0.02). Median length of CVC use in the BSI-negative and BSI-positive group were 6.3 ± 5.0 and 9.4 ± 5.1, respectively (p = 0.04). In summary, BSI is a potentially lethal complication in patients receiving ECMO. Indwelling CVC, not the ECMO circuitry, is the likely contributor for BSI, and exchanging CVC by day 8 can reduce the incidence of BSI.

The Threat of Carbapenem-Resistant Gram-Negative Bacteria in Patients with Hematological Malignancies: Unignorable Respiratory Non-Fermentative Bacteria-Derived Bloodstream Infections.

BackgroundCarbapenem-resistant Gram-negative bacteria (CRGNB) bloodstream infection (BSI) pose a significant threat to the prognosis of hematologic malignancies (HM) patients. Understanding the distribution of pathogenic bacteria, changes in carbapenem-resistant trends, risk factors for CRGNB infections, and exploring the early detection measures can help reduce mortality.MethodsWe conducted a multicenter retrospective study of Gram-negative bacteria (GNB) BSI in patients with HM in three university-affiliated hospitals in Hunan Province, China, from January 2010 to December 2020. Demographic and clinical data were collected from the hospital electronic medical records system.ResultsCRGNB caused 138 (15.3%) of 902 GNB BSI. The detection rate of CRGNB increased from 6.4% in 2010–2012 to 35.4% in 2019–2020. The 7-day mortality rate was significantly higher in patients with CRGNB BSI than in patients with carbapenem-susceptible Gram-negative bacteria (CSGNB) BSI [31.9% (44/138) vs 9.7% (74/764), P < 0.001], and the mortality rate in patients with carbapenem-resistant non-fermenting bacteria (CRNFB) bloodstream infections was generally higher than that of carbapenem-resistant Enterobacteriaceae (CRE). Urinary catheter (OR, 2.814; CI=1.395–5.680; P=0.004) and prior exposure to carbapenem (OR, 4.372; CI=2.881–6.635; P<0.001) were independent risk factors for CRGNB BSI. Analysis of co-infections showed that 50%–85% of patients with CRGNB BSI had pulmonary infections, sputum culture results suggested that sputum culture positivity rate was as high as 57.1%–66.7% in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) and Stenotrophomonas maltophilia BSI, and the results of antimicrobial susceptibility testing of sputum cultures were consistent with the blood cultures.ConclusionCarbapenem resistance has dramatically increased in HM patients with GNB BSI in recent years and is associated with a worse outcome, especially for non-fermenting bacteria. In high-risk patients, early screening of the respiratory tract specimens may help to detect CRNFB colonization and protect patients from breakthrough BSI.

Influence of daptomycin doses on the outcomes of VRE bloodstream infection treated with high-dose daptomycin.

The CLSI recommended high-dose daptomycin (8-12 mg/kg) for treating Enterococcus faecium bloodstream infections (BSI). The current study was designed to determine the safety and efficacy of increasing the daptomycin dose for VRE BSI patients receiving ≥8 mg/kg. We conducted a multicentre prospective observational study of patients who received a ≥8 mg/kg dose of daptomycin for treatment of VRE BSI. The primary outcome was 28 day mortality. A total of 661 patients were included. The 28 day mortality rate was 45.1%. The survivors received higher doses of daptomycin than non-survivors (10.1 versus 9.8 mg/kg; P < 0.001). An increase in the daptomycin dose independently predicted lower mortality [adjusted OR (aOR) = 0.85; 95% CI = 0.73-0.99; P = 0.03]. Eighty-six survivors (23.7%) and 43 non-survivors (14.4%) received a ≥11 mg/kg dose of daptomycin (P = 0.003). The 8 to <11 and ≥11 mg/kg doses of daptomycin differed in the 28 day mortality in the higher MIC group (≥2 mg/L) (49.4% versus 33.3%; P = 0.004), but not in the lower MIC group (≤1 mg/L) (29.3% versus 29.4%; P = 0.99). A dose of ≥11 mg/kg was associated with a higher (3.9%) rate of highly elevated creatine kinase (>2000 U/L) compared with 1.1% with 8 to <11 mg/kg (P = 0.04). The efficacy of daptomycin is dose dependent. A high daptomycin dose, especially at ≥11 mg/kg, improved survival in patients with VRE BSI, but was associated with highly elevated creatine kinase. We recommend a ≥11 mg/kg dose of daptomycin be considered for treatment of VRE BSI, particularly for isolates with higher MICs.

Diagnosis of Bloodstream Infections: An Evolution of Technologies towards Accurate and Rapid Identification and Antibiotic Susceptibility Testing.

Bloodstream infections (BSI) are a leading cause of death worldwide. The lack of timely and reliable diagnostic practices is an ongoing issue for managing BSI. The current gold standard blood culture practice for pathogen identification and antibiotic susceptibility testing is time-consuming. Delayed diagnosis warrants the use of empirical antibiotics, which could lead to poor patient outcomes, and risks the development of antibiotic resistance. Hence, novel techniques that could offer accurate and timely diagnosis and susceptibility testing are urgently needed. This review focuses on BSI and highlights both the progress and shortcomings of its current diagnosis. We surveyed clinical workflows that employ recently approved technologies and showed that, while offering improved sensitivity and selectivity, these techniques are still unable to deliver a timely result. We then discuss a number of emerging technologies that have the potential to shorten the overall turnaround time of BSI diagnosis through direct testing from whole blood—while maintaining, if not improving—the current assay’s sensitivity and pathogen coverage. We concluded by providing our assessment of potential future directions for accelerating BSI pathogen identification and the antibiotic susceptibility test. While engineering solutions have enabled faster assay turnaround, further progress is still needed to supplant blood culture practice and guide appropriate antibiotic administration for BSI patients.

Evaluation of the EUCAST Rapid Antimicrobial Susceptibility Test for Enterobacterales -Containing Blood Cultures in China

ABSTRACTBloodstream infection (BSI) is defined by the presence of microbes in the bloodstream and has high mortality. Early antimicrobial therapy is key to treating BSI patients. Because of potential antimicrobial resistance, rapid evaluation for the most suitable antimicrobial therapy is important for appropriate treatment. In China, the current workflow of microbiological diagnosis in BSI involves blood culture, species identification, and antimicrobial susceptibility testing, which takes around 3 days. However, this delay could lead to worse symptoms. To rapidly and accurately assess antimicrobial susceptibility, in this study, we applied EUCAST rapid antimicrobial susceptibility testing (RAST) to determine the antimicrobial susceptibilities of the most frequently detected Enterobacterales sampled in China, including Escherichia coli and Klebsiella pneumoniae. Based on EUCAST guidelines, we evaluated its efficiencies with six commercially available antimicrobials, including imipenem (10 μg), meropenem (10 μg), ciprofloxacin (5 μg), levofloxacin (5 μg), amikacin (30 μg), and trimethoprim-sulfamethoxazole (1.25/23.75 μg), with bacterium-spiked blood cultures. In addition, we developed potential breakpoints for a recently introduced antimicrobial, 30/20 μg ceftazidime-avibactam, which has high potential for treating multidrug-resistant Enterobacterales. Our results showed that EUCAST RAST is a reliable method for rapidly determining the antimicrobial susceptibilities of BSI-causing bacteria in China, with an overall categorical agreement rate at 8 h of ≥90%. The breakpoints developed in this study can categorize the isolates sampled in this study with an accuracy of 93%. Results from our experiments can be applied to clinically determine the microbial susceptibility of BSI-causing bacteria within 8 h and benefit clinical diagnostics for BSI patients.

Mortality associated with third-generation cephalosporin resistance in Enterobacteriaceae bloodstream infections at one South African hospital

Enterobacteriaceae are common pathogens causing bloodstream infection (BSI) in sub-Saharan Africa and frequently express third-generation cephalosporin (3GC) resistance; however, the impact of 3GC resistance on clinical outcomes is rarely studied. We conducted a single-site prospective cohort study at Tygerberg Hospital, Cape Town, South Africa to examine the feasibility of measuring impacts of 3GC resistance in Enterobacteriaceae BSI. We included patients with 3GC-susceptible and 3GC-resistant BSIs and matched each BSI patient to two uninfected patients. We determined the concordance of initial antibiotic treatment with the corresponding isolate's susceptibility profile. We performed exploratory impact analysis using multivariable regression models. Between 1 June 2017 and 31 January 2018, we matched 177 Enterobacteriaceae BSI patients to 347 uninfected patients. Among these BSIs, 35% were phenotypically 3GC resistant. Parameters describing clinical comorbidity showed strong associations with mortality. We found that 18% of 3GC-R and 3% of 3GC-S BSI patient received non-concordant initial therapy. In multivariable Cox regression, we found a mortality impact over their matched patients for both 3GC-R (cause-specific hazard ratio 23.77; 95% CI 5.12-110.3) and 3GC-S (HR 7.49; 95%CI 3.08-18.19) BSI. There was a nonsignificant ratio of these ratios (HR 3.18; 95% CI 0.54-18.70), limited by the small sample size. This form of impact estimation was feasible in one hospital in South Africa where 3GC-R status was associated with non-concordant initial antibiotic treatment. There was a possible increase in mortality among individuals with 3GC-resistant Enterobacteriaceae, but with broad confidence intervals. These analytical approaches could be applied to larger datasets to improve precision of estimates.

Clinical and Microbiological Profile of Patients with Bloodstream Infections Caused by Burkholderia cepacia Complex.

Introduction Burkholderia cepacia complex (BCC) is an emerging pathogen causing nosocomial bloodstream infections (BSIs), and its treatment is challenging due to its multidrug resistance. In India, there is a dearth of data on BSIs caused by BCC, therefore, an updated study is required to know the clinical and microbiological profile of these patients. We aimed to study the clinical epidemiology and antibiotic susceptibility pattern of BCC isolated from blood samples in our hospital. Materials and Methods This observational study was conducted from January 2019 to December 2020 at a tertiary care center in northern India. All the blood cultures were done on an automated blood culture system. All BCC isolates of BSI were identified depending on their morphological properties and biochemical reactions, and underwent the matrix-assisted laser desorption ionization time-of-flight mass spectrometry system to confirm diagnosis. Antibiotic susceptibility testing was done as per Clinical Laboratory and Standards Institute guidelines. Results BCC was isolated from 30 BSI patients over a 2-year period. Sixty-six percent (20/30) of patients had cancer and a majority of them were undergoing chemotherapy. The most common predisposing factors were the use of steroids, immunosuppressive drugs, and chemotherapy (93.3%), central lines (83.3%), use of higher antibiotics (60%), and diabetes mellitus type 2 (60%). The most common species isolated were B. cepacia (64%) and B. cenocepacia (30%). Isolates showed highest sensitivity to minocycline (100%), ceftazidime (73.3%), and meropenem (70%) and the least to ticarcillin–clavulanate. Conclusion BCC is an emerging pathogen causing BSIs, especially in malignancy patients. Minocycline can be a good choice for these bacteria.

Risk Factors for a Hospital-Acquired Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infection: A Five-Year Retrospective Study.

PurposeThis study aimed to describe trends in Klebsiella pneumoniae (KP) resistance in bloodstream infections (BSI) and to identify risk factors for a hospital-acquired carbapenem-resistant Klebsiella pneumoniae (CRKP) BSI and 28-day mortality from a hospital-acquired KP BSI.Patients and MethodsWe recorded the results of antimicrobial susceptibility testing of 396 KP-positive blood cultures from January 2016 to December 2020. A total of 277 patients with a KP BSI were included in this study, of which 171 had a hospital-acquired infection and 84 had a hospital-acquired CRKP BSI. Multivariate logistic regression analysis was used to identify risk factors for a hospital-acquired CRKP BSI and 28-day mortality from a hospital-acquired KP BSI.ResultsThe proportion of hospital-acquired infections among KP BSI patients increased from 53.1% in 2016 to 72.8% in 2020. The detection rate of CRKP among KP BSI patients increased from 18.8% in 2016 to 37.7% in 2020. Multivariate logistic regression showed that β-lactam/β-lactamase inhibitor combinations (BLBLIs) exposure (P = 0.022, OR 2.863), carbapenems exposure (P = 0.007, OR 3.831) and solid organ transplantation (P <0.001, OR 19.454) were independent risk factors for a hospital-acquired CRKP BSI. Risk factors for a 28-day mortality from hospital-acquired KP BSI were CRKP BSI (P =0.009, OR 5.562), septic shock (P =0.002, OR 4.862), mechanical ventilation>96 hours (P =0.020, OR 8.765), and platelet counts <100×109/L (P =0.003, OR 4.464).ConclusionThe incidence of hospital-acquired KP BSI continues to rise and the proportion of CRKP BSI is also increasing. We believe that the use of the BLBLIs needs to be carefully evaluated in hospital-acquired infection. Hospital-acquired KP BSI Patients with CRKP BSI, septic shock, mechanical ventilation and deficiency of platelets are more likely to have a poor prognosis.