Bacteria Bloodstream Infections Research Articles

Adult acute leukemia patients with gram-negative bacteria bloodstream infection: Risk factors and outcomes of antibiotic-resistant bacteria.

This study aims to analyze the risk factors for the development of multidrug-resistant (MDR) and carbapenem-resistant (CR) bacteria bloodstream infection (BSI) in a patient with acute leukemia (AL) and the mortality in gram-negative bacteria (GNB) BSI. This is a retrospective study conducted at West China Hospital of Sichuan University, which included patients diagnosed with AL and concomitant GNB BSI from 2016 to 2021. A total of 206 patients with GNB BSI in AL were included. The 30-day mortality rate for all patients was 26.2%, with rates of 25.8% for those with MDR GNB BSI and 59.1% for those with CR GNB BSI. Univariate and multivariate analyses revealed that exposure to quinolones (Odds ratio (OR) = 3.111, 95% confidence interval (95%CI): 1.623-5.964, p = 0.001) within the preceding 30 days was an independent risk factor for MDR GNB BSI, while placement of urinary catheter (OR = 6.311, 95%CI: 2.478-16.073, p< 0.001) and exposure to cephalosporins (OR = 2.340, 95%CI: 1.090-5.025, p = 0.029) and carbapenems (OR = 2.558, 95%CI: 1.190-5.497, p = 0.016) within the preceding 30 days were independently associated with CR GNB BSI. Additionally, CR GNB BSI (OR = 2.960, 95% CI: 1.016-8.624, p = 0.047), relapsed/refractory AL (OR = 3.035, 95% CI: 1.265-7.354, p = 0.013), septic shock (OR = 5.108, 95% CI: 1.794-14.547, p = 0.002), platelets < 30 × 109/L before BSI (OR = 7.785, 95% CI: 2.055-29.492, p = 0.003), and inappropriate empiric antibiotic therapy (OR = 3.140, 95% CI: 1.171-8.417, p = 0.023) were independent risk factors for 30-day mortality in AL patients with GNB BSI. Prior antibiotic exposure was a significant factor in the occurrence of MDR GNB BSI and CR GNB BSI. CR GNB BSI increased the risk of mortality in AL patients with GNB BSI.

Intravenous Fosfomycin as Adjunctive Therapy for Gram-Negative Bacteria Bloodstream Infections: A Propensity Score Adjusted Retrospective Cohort Study

The role of intravenous fosfomycin (iv-FOS) as a part of combination therapy for Gram-negative bacteria bloodstream infections (GNB-BSI) needs to be evaluated in clinical practice, as in vitro data show potential efficacy. All consecutive patients with a GNB-BSI from 01 January 2021 to 01 April 2023 were included. Primary outcome was 30-day mortality. A Cox regression analysis was used to identify predictors of mortality; an inverse-probability of treatment-weighting (IPTW) analysis was also performed. Overall, 363 patients were enrolled: 211 (58%) males, with a median (q1-q3) age of 68 (57-78) years, and a median Charlson comorbidity index of 5 (3-7). At GNB-BSI onset, the median SOFA score was 5 (2-7) and 122 patients (34%) presented with septic shock. Pathogens were principally Klebsiella pneumoniae (42%), Escherichia coli (28%) and Pseudomonas aeruginosa (17%); of them, 36% were carbapenem-resistant. The therapy included carbapenems (40%), cephalosporins (37%) and beta-lactams/beta-lactamases-inhibitors (19%); a combination with iv-FOS was used in 98 (27%) cases at a median dosage of 16 (16-18) g/daily. The use of iv-FOS was not associated with reduced crude mortality (21% vs 29%, P = 0.147). However, on multivariable Cox-regression, combination therapy with iv-FOS resulted in protection for mortality (aHR 0.51, 95% CI 0.28-0.92), but not other combo-therapies (HR 0.69, 95% CI 0.44-1.16). This result was also confirmed with the IPTW-adjusted Cox model (aHR 0.52, 95% CI 0.31-0.91). Subgroup analysis suggested a benefit in severe infections (SOFA > 6, PITT ≥ 4) and when iv-FOS was initiated within 24 hours of GNB-BSI onset. Fosfomycin in combination therapy for GNB-BSI may have a role in improving survival. These results justify the development of further clinical trials.

Distribution and Drug Resistance of Pathogens Causing Bloodstream Infection in Patients with Hematological Malignancies

To investigate distribution and drug resistance of pathogens of bloodstream infection in patients with hematological malignancies, in order to provide reference for clinical infection control and treatment. The clinical information of blood culture patients in the hematology department of our hospital from January 2016 to December 2021 was reviewed. They were divided into transplantation group and non-transplantation group according to whether they had undergone hematopoietic stem cell transplantation. The types of pathogens and their drug resistance were analyzed. Two hundred and ninety-nine positive strains of pathogenic bacteria were detected. In the transplantation group, Gram-negative bacteria accounted for 68.5% (50/73), Gram-positive bacteria accounted for 6.8% (5/73), and fungi accounted for 24.7% (18/73). The resistance rate of Escherichia coli to the third-generation cephalosporins was 77.8%, and 11.5% to carbapenems. The resistance rate of Klebsiella pneumoniae to the third-generation cephalosporins was 50.0%, and 56.2% to carbapenems. In the non-transplantation group, Gram-negative bacteria accounted for 64.1% (145/226), Gram-positive bacteria accounted for 31.0% (70/226), and fungi accounted for 4.9% (11/226). Gram-positive bacteria were mainly Enterococcus faecium (6.6%, 15/226) and Coagulase-negative Staphylococci (6.2%, 14/226). The fungi were all Candida tropicalis. The resistance rate of Escherichia coli to the third-generation cephalosporins was 63.8%, and 10.3% to carbapenems. The resistance rate of Klebsiella pneumoniae to the third-generation cephalosporins was 46.3%, and 26.8% to carbapenems. The types of pathogenic bacteria in bloodstream infection in patients with hematological malignancies are varied. Gram-negative bacteria is the main pathogenic bacteria. The resistance of pathogenic bacteria to antibiotics is severe. Antibiotics should be used scientifically and reasonably according to the detection and resistance of pathogenic bacteria.

Rectal culture could predict carbapenem-resistant organism bloodstream infection and reduce the mortality in haematological patients: A retrospective cohort study

The objective is to explore the correlation between rectal swab culture and the overall 30-d survival of hematologic patients diagnosed with carbapenem-resistant organism (CRO) bloodstream infection. A total of 434 haematological patients who were complicated with Gram-negative bacilli (GNB) bloodstream infections (BSIs) caused by Gram-negative bacteria between January 2020 and December 2021 were included in our retrospective study. Based on their drug susceptibility results, we classified patients into CRO BSIs and non-CRO BSIs cases. Through group comparison, to uncover the correlation between the positive screening of rectal swabs and reducing the mortality of CRO BSI in patients with haematological diseases. Among the 434 cases of Gram-negative bacteria bloodstream infection, 96 were identified as carbapenem-resistant bloodstream infection, which consisted of 57 cases of carbapenem-resistant Klebsiella pneumoniae (CR-KP), 19 cases of carbapenem-resistant Pseudomonas aeruginosa (CR-PA), 11 cases of carbapenem-resistant Escherichia coli (CR-CO), 5 cases of carbapenem-resistant Acinetobacter baumannii (CR-AB), and 4 cases of other Enterobacteriaceae. Before the onset of CRO bloodstream infection, rectal swab cultures were conducted on 36 patients, and the positive result rate was 75.0% (27/36), with 20 cases of CR-KP, 6 cases of CR-CO, and one case of carbapenem-resistant Enterobacter cloacae. It was observed that the rectal and blood cultures had matching outcomes in 75.0% of cases. The mortality rate within 30 d for CRO BSIs was 53.1% (51/96), while for carbapenem-resistant Enterobacteriaceae (CRE) BSIs it was 62.5% (45/72). Univariate analysis showed that 30-d mortality was significantly reduced when there were positive rectal culture results preceding bloodstream infection (P < 0.001), as well as preemptive anti-infection treatment (P < 0.001). Multivariate analysis demonstrated that preemptive adjustment to an effective antibiotic regimen, guided by positive rectal culture results, had a significant effect on decreasing 30-d mortality following CRO BSIs (P= 0.002). Furthermore, for the management of CRE BSIs, antibiotic treatments utilising ceftazidime/avibactam (CAV/AVI) may be more beneficial compared to those that use tigecycline (TGC) or polymyxin (PMB). CRO BSI, especially CRE BSI, can be life-threatening for those with haematological diseases. Utilising rectal culture can effectively identify CRO strains with high sensitivity and specificity. Adjusting antibiotic treatment based on the preemptive positive rectal culture results may significantly decrease 30-d mortality rates for haematological patients with CRO BSIs.

Loading dose plus continuous/extended infusion versus intermittent bolus of β-lactams for the treatment of Gram-negative bacteria bloodstream infections: a propensity score-adjusted retrospective cohort study.

Optimal β-lactam dosing for the treatment of Gram-negative bacteria bloodstream infections (GNB-BSIs) remains a debated issue. Herein, the efficacy and safety of a loading dose (LD) followed by extended/continuous infusion (EI/CI) versus intermittent bolus (IB) of these drugs for the treatment of GNB-BSIs was evaluated. This is a retrospective observational study enrolling patients with GNB-BSIs treated with β-lactams from 1 October 2020 to 31 March 2022. The 30 day infection-related mortality rate was assessed with Cox regression, while mortality risk reduction was evaluated by an inverse probability of treatment weighting regression adjustment (IPTW-RA) model. Overall, 224 patients were enrolled: 140 and 84 in the IB and EI/CI groups, respectively. β-Lactam regimens were chosen according to pathogen antibiogram, clinical judgement and current guidelines. Interestingly, the LD + EI/CI regimen was associated with a significant lower mortality rate (17% versus 32%, P = 0.011). Similarly, β-lactam LD + EI/CI was significantly associated with a reduced risk of mortality at multivariable Cox regression [adjusted HR (aHR) = 0.46; 95%CI = 0.22-0.98; P = 0.046]. Finally, the IPTW-RA (adjusted for multiple covariates) was performed, showing a significant risk reduction in the overall population [-14% (95% CI = -23% to -5%)]; at the subgroup restricted analysis, a significant risk reduction (>15%) was observed in the case of GNB-BSI in severely immunocompromised patients (P = 0.003), for SOFA score > 6 (P = 0.014) and in septic shock (P = 0.011). The use of LD + EI/CI of β-lactams in patients with a GNB-BSI may be associated with reduced mortality; also in patients with severe presentation of infection or with additional risk factors, such as immunodepression.

Gram-negative ESKAPE bacteria bloodstream infections in patients during the COVID-19 pandemic.

Bloodstream infections due to bacteria are a highly consequential nosocomial occurrences and the organisms responsible for them are usually multidrug-resistant. The aims of this study were to describe the incidence of bacteremia caused by Gram-negative ESKAPE bacilli during the COVID-19 pandemic and characterize the clinical and microbiological findings including antimicrobial resistance. A total of 115 Gram-negative ESKAPE isolates were collected from patients with nosocomial bacteremia (18% of the total bacteremias) in a tertiary care center in Mexico City from February 2020 to January 2021. These isolates were more frequently derived from the Respiratory Diseases Ward (27), followed by the Neurosurgery (12), Intensive Care Unit (11), Internal Medicine (11), and Infectious Diseases Unit (7). The most frequently isolated bacteria were Acinetobacter baumannii (34%), followed by Klebsiella pneumoniae (28%), Pseudomonas aeruginosa (23%) and Enterobacter spp (16%). A. baumannii showed the highest levels of multidrug-resistance (100%), followed by K. pneumoniae (87%), Enterobacter spp (34%) and P. aeruginosa (20%). The bla CTX-M-15 and bla TEM-1 genes were identified in all beta-lactam-resistant K. pneumoniae (27), while bla TEM-1 was found in 84.6% (33/39) of A. baumannii isolates. The carbapenemase gene bla OXA-398 was predominant among carbapenem-resistant A. baumannii (74%, 29/39) and bla OXA-24was detected in four isolates. One P. aeruginosa isolate was bla VIM-2 gene carrier, while two K. pneumoniae and one Enterobacter spp were bla NDM gene carriers. Among colistin-resistant isolates mcr-1 gene was not detected. Clonal diversity was observed in K. pneumoniae, P. aeruginosa and Enterobacter spp. Two outbreaks caused by A. baumannii ST208 and ST369 were detected, both belonging to the clonal complex CC92 and IC2. A. baumannii was associated with a death rate of 72% (28/32), most of them (86%, 24/28) extensively drug-resistant or pandrug-resistant isolates, mainly in patients with COVID-19 (86%, 24/28) in the Respiratory Diseases Ward. A. baumannii isolates had a higher mortality rate (72%), which was higher in patients with COVID-19. There was no statistically significant association between the multidrug-resistant profile in Gram-negative ESKAPE bacilli and COVID-19 disease. The results point to the important role of multidrug-resistant Gram-negative ESKAPE bacteria causing bacteremia in nosocomial settings before and during the COVID-19 epidemic. Additionally, we were unable to identify a local impact of the COVID-19 pandemic on antimicrobial resistance rates, at least in the short term.

Development and validation of nomograms for predicting the risk probability of carbapenem resistance and 28-day all-cause mortality in gram-negative bacteremia among patients with hematological diseases.

Gram-negative bacteria (GNB) bloodstream infections (BSIs) are the most widespread and serious complications in hospitalized patients with hematological diseases. The emergence and prevalence of carbapenem-resistant (CR) pathogens has developed into a considerable challenge in clinical practice. Currently, nomograms have been extensively applied in the field of medicine to facilitate clinical diagnosis and treatment. The purpose of this study was to explore risk indicators predicting mortality and carbapenem resistance in hematological (HM) patients with GNB BSI and to construct two nomograms to achieve personalized prediction. A single-center retrospective case-control study enrolled 244 hospitalized HM patients with GNB-BSI from January 2015 to December 2019. The least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate logistic regression analysis were conducted to select potential characteristic predictors of plotting nomograms. Subsequently, to evaluate the prediction performance of the models, the prediction models were internally validated using the bootstrap approach (resampling = 1000) and 10-fold cross validation. Of all 244 eligible patients with BSI attributed to GNB in this study, 77 (31.6%) were resistant to carbapenems. The rate of carbapenem resistance exhibited a growing tendency year by year, from 20.4% in 2015 to 42.6% in 2019 (p = 0.004). The carbapenem resistance nomogram constructed with the parameters of hypoproteinemia, duration of neutropenia ≥ 6 days, previous exposure to carbapenems, and previous exposure to cephalosporin/β-lactamase inhibitors indicated a favorable discrimination ability with a modified concordance index (C-index) of 0.788 and 0.781 in both the bootstrapping and 10-fold cross validation procedures. The 28-day all-cause mortality was 28.3% (68/240). The prognosis nomogram plotted with the variables of hypoproteinemia, septic shock, isolation of CR-GNB, and the incomplete remission status of underlying diseases showed a superior discriminative ability of poorer clinical prognosis. The modified C-index of the prognosis nomogram was 0.873 with bootstrapping and 0.887 with 10-fold cross validation. The decision curve analysis (DCA) for two nomogram models both demonstrated better clinical practicality. For clinicians, nomogram models were effective individualized risk prediction tools to facilitate the early identification of HM patients with GNB BSI at high risk of mortality and carbapenem resistance.

Pcv-aCO2 and procalcitonin levels for the early diagnosis of bloodstream infections caused by gram-negative bacteria.

The central venous-to-arterial carbon dioxide difference (Pcv-aCO2) is a biomarker for tissue perfusion, but the diagnostic value of Pcv-aCO2 in bacteria bloodstream infections (BSI) caused by gram-negative (GN) bacteria remains unclear. This study evaluated the expression levels and diagnostic value of Pcv-aCO2 and procalcitonin (PCT) in the early stages of GN bacteria BSI. Patients with BSI admitted to the intensive care unit at Guangdong Provincial People's Hospital between August 2014 and August 2017 were enrolled. Pcv-aCO2 and PCT levels were evaluated in GN and gram-positive (GP) bacteria BSI patients. A total of 132 patients with BSI were enrolled. The Pcv-aCO2 (8.32 ± 3.59 vs 4.35 ± 2.24 mmHg p=0.001) and PCT (30.62 ± 34.51 vs 4.92 ± 6.13ng/ml p=0.001) levels were significantly higher in the GN group than in the GP group. In the diagnosis of GN bacteria BSI, the area under the receiver operating characteristic curve (AUROC) for Pcv-aCO2 was 0.823 (95% confidence interval (CI): 0.746-0.900). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 71.90%, 88.00%, 74.07% and 78.21%, respectively. The AUROC for PCT was 0.818 (95% CI: 0.745-0.890). The sensitivity, specificity, PPV and NPV were 57.90%, 94.67%, 71.93% and 74.67%, respectively. Pcv-aCO2 and PCT have similar and high diagnostic value for the early diagnosis of BSI caused by GN bacteria.

Prognostic Risk Factors of Carbapenem-Resistant Gram-Negative Bacteria Bloodstream Infection in Immunosuppressed Patients: A 7-Year Retrospective Cohort Study.

Carbapenem-resistant Gram-negative bacteria bloodstream infection (CRGNB-BSI) has gradually become a major threat worldwide due to its treatment difficulty and high mortality. This study aimed to determine the risk factors for CRGNB-BSI in immunosuppressed patients. A total of 427 immunosuppressed patients with CRGNB-BSI were retrospectively investigated from 2015 to 2021. Both univariate and multivariate logistic regression analyses were applied to evaluate independent risk factors for CRGNB-BSI. The most common etiology was Klebsiella Pneumoniae (50.59%; 216/427), while the Acinetobacillus baumannii infection was associated with the highest mortality (58.25%) among all etiologies. The 60-day mortality of immunosuppressed patients with CRGNB-BSI was 52.48% (224/427). Procalcitonin (PCT) > 0.5 μg/L (OR = 2.32, 95% CI: 1.28-4.19, P = 0.005) and age > 55 years (OR = 2.06, 95% CI: 1.17-3.64, P = 0.012) were found to be predictors of 60-day mortality of CRGNB-BSI, and tigecycline regimen (OR = 3.20, 95% CI: 1.81-5.67, P < 0.001) was associated with higher mortality. Multivariate analysis also revealed that patients who developed acute kidney injury (AKI) (OR = 2.19, 95% CI: 1.11-4.30, P = 0.023), gastrointestinal bleeding (OR = 3.18, 95% CI: 1.10-9.16, P = 0.032), multiple organ dysfunction syndrome (MODS) (OR = 12.11, 95% CI: 2.61-56.19, P = 0.001), and septic shock (OR = 3.24, 95% CI: 1.77-5.94, P < 0.001) showed worse outcomes. The risk factors were also significantly associated with mortality in the different subgroups. This study demonstrated that PCT > 0.5 μg/L, age > 55 years, and the tigecycline regimen were significantly associated with higher 60-day mortality among immunosuppressed patients with CRGNB- BSI. Patients developing MODS, septic shock, or AKI had worse clinical outcomes. .

A microfluidic platform combined with bacteriophage receptor binding proteins for multiplex detection of Escherichia coli and Pseudomonas aeruginosa in blood

Bloodstream infections (BSIs) are triggered by the existence of pathogens in blood and are considered a major health burden worldwide, especially when they result in sepsis and septic shock. Common diagnostic methods are time-consuming, present low specificity, or suffer from interference of blood components, which hampers a timely and effective treatment of BSIs. In this work, a novel microfluidic assay was developed combining a bead-based chip and bacteriophage receptor binding proteins (RBPs) as extremely specific and sensitive recognition molecules for the multiplex concentration and detection of Escherichia coli and Pseudomonas aeruginosa, which are highly prevalent bacteria in BSIs. The device comprises a microcolumn in which antibody-functionalized agarose beads were packed allowing the entrapment of the target bacterium from blood, providing its concentration and separation. For bacterial detection, two recombinant RBPs (Gp54 and Gp17) were fused with different fluorescent proteins and used for the identification of P. aeruginosa and E. coli by the measurement of the distinct fluorescent signals obtained. The developed microfluidic-based assay enabled a fast (70 min) and highly specific multiplex detection of both pathogens in whole blood, achieving a detection limit of around 103 CFU, without requiring any time-consuming bacterial pre-enrichment step. Furthermore, it provided a quantitative assessment of bacterial loads present in blood. Noteworthy, this miniaturized and inexpensive device presents simple fabrication and operation, showing great potential to be fully automated, demonstrating to be ideal in point-of-care settings.

Antimicrobial susceptibility to polymyxin B and other comparators against Gram-negative bacteria isolated from bloodstream infections in China: Results from CARVIS-NET program.

ObjectiveTo investigate the bacterial distribution and antimicrobial resistance profile of clinical isolates from Gram-negative bacteria bloodstream infections (GNBSI) in China.MethodsThe clinical bacterial strains isolated from blood culture were collected during April 2019 to December 2021 in 21 member hospitals of China Bloodstream Gram-negative Pathogens Antimicrobial Resistance and Virulence Surveillance Network (CARVIS-NET). Antibiotic susceptibility test was conducted by broth microdilution method recommended by Clinical and Laboratory Standards Institute (CLSI, United States). WHONET 2021 and SPSS 22.0 were used to analyze data.ResultsDuring the study period, 1939 Gram-negative bacteria were collected from 21 hospitals, among which 1,724 (88.9%) were Enterobacteriaceae, 207 (10.7%) were non-fermenting Gram-negative bacteria and 8 (0.4%) were others. The top five bacterial species were Escherichia coli (46.2%), Klebsiella pneumoniae (31.6%), Pseudomonas aeruginosa (4.9%), Acinetobacter baumannii (4.2%) and Enterobacter cloacae (3.0%). For K. pneumoniae, antibiotic resistance was mainly prevalent in hospital-associated bloodstream infections, while for A. baumannii, antibiotic resistance was mainly prevalent in community-associated bloodstream infections. It is worth mentioning that 94.1% of the 1939 Gram-negative isolates were susceptible to polymyxin B. The sensitivity of the strains involved in our investigation to polymyxin B is highly correlated with their sensitivity to colistin.ConclusionThe surveillance results in CARVIS-NET-2021 showed that the main pathogens of GNBSI in China were Enterobacteriaceae, while E. coli was the most common pathogen. The resistance rates of K. pneumonia, P. aeruginosa, A. baumannii, and E. cloacae to multiple antibiotics kept on a high level. In many cases, polymyxin B and colistin has become the last-resort agents to combat bloodstream infections caused by multidrug-resistant (MDR) Gram-negative bacteria.

Diagnostic Value and Prognostic Significance of Procalcitonin Combined with C-Reactive Protein in Patients with Bacterial Bloodstream Infection.

Objective To study the clinical values and implications for the prognosis of procalcitonin (PCT) combined with C-reactive protein (hs-CRP) in patients with bacterial bloodstream infection. Methods One hundred and twenty patients with infection hospitalized from Mar. 2020 to Jun. 2021 were chosen as subjects. All participants were tested for serum PCT, hs-CRP, and blood culture. According to the types of pathogenic bacteria, they were divided into the gram-negative bacteria bloodstream infection group (n = 53) and the gram-positive bacteria bloodstream infection group (n = 31). Depending on the prognostic outcome of the participants after 28 days, they were categorized into survival and fatality cohorts. The PCT and hs-CRP levels were compared to explore diagnostic value implications for the prognosis of the cases with bacterial bloodstream infection. Results Serum PCT and hs-CRP values in the positive cohort were higher than those in the negative cohort. The levels of serum PCT and hs-CRP in pulmonary infection were higher than those in the group with negative cases, and the difference was statistically significant (P < 0.05). There were 27 gram-positive participants and 9 gram-negative cases in the positive cohort. The serum PCT value of gram-negative bacterial infection was greater than that of gram-positive bacterial infection. The value of serum PCT in the gram-negative bacterial infection group was higher than that in the gram-positive bacterial infection group, and the difference was statistically significant (P < 0.05). The areas under the curve (AUCs) of PCT, combination of hs-CRP and PCT, and hs-CRP were 0.946, 0.783, and 0.991, respectively. The combined examination of PCT and hs-CRP was the largest, PCT was the second, and hs-CRP was the lowest. These results indicated that the accuracy of combined detection of PCT and hs-CRP in the diagnostic bloodstream infection was the highest (0.991), followed by PCT (0.946) and the lowest (0.783). The PCT and hs-CRP levels of the survival cohort were lower than those in the death cohort. AUCs of PCT, hs-CRP and PCT, and hs-CRP were 0.848, 0.826, and 0.934, respectively. The combined examination of PCT and hs-CRP was the largest, followed by PCT and hs-CRP. The accuracy of the combination of PCT and hs-CRP was the highest (0.934), followed by PCT (0.848), and the diagnostic accuracy of hs-CRP was the lowest (0.826). Conclusion There were significant differences in the levels of PCT and CRP between the gram-positive bacteria group and the gram-positive bacteria group. PCT and CRP have high diagnostic values in predicting the short-term prognosis of patients. PCT and CRP assist clinical diagnosis and guide treatment and play a positive role in early treatment and prognosis evaluation of patients.

Clinical Impact of COVID-19 on Multi-Drug-Resistant Gram-Negative Bacilli Bloodstream Infections in an Intensive Care Unit Setting: Two Pandemics Compared.

Two mutually related pandemics are ongoing worldwide: the COVID-19 and antimicrobial resistance pandemics. This study aims to evaluate the impact of COVID-19 on multi-drug-resistant Gram-negative bacteria (MDR-GN) bloodstream infections (BSIs) in a single intensive care unit (ICU). We conducted a retrospective study including patients admitted to the ICU, reorganized for COVID-19 patients’ healthcare, with at least one confirmed MDR-GN BSI during 2019–2020. We compared clinical and microbiological features, incidence density, antibiotic therapy and mortality rate in pre- and during-COVID-19 pandemic periods. We estimated the impact of COVID-19 on mortality by means of univariate Cox regression analyses. A total of 46 patients were included in the study (28 non-COVID-19/18 COVID-19). Overall, 63 BSI episodes occurred (44/19), and non-COVID-19 patients had a higher incidence of MDR-GN BSIs and were more likely to present K. pneumoniae BSIs, while the COVID-19 group showed more A. baumannii BSIs with higher per pathogen incidence. COVID-19 patients presented more critical conditions at the BSI onset, a shorter hospitalization time from BSI to death and higher 30-day mortality rate from BSI onset. COVID-19 and septic shock were associated with 30-day mortality from MDR-GN BSIs, while early active therapy was a protective factor. In conclusion, COVID-19 showed a negative impact on patients with MDR-GN BSIs admitted to the ICU.

Bloodstream Infections Caused by Carbapenem-Resistant Pathogens in Intensive Care Units: Risk Factors Analysis and Proposal of a Prognostic Score.

Considering the growing prevalence of carbapenem-resistant Gram-negative bacteria (CR-GNB) bloodstream infection (BSI) in intensive care units (ICUs), the identification of specific risk factors and the development of a predictive model allowing for the early identification of patients at risk for CR-Klebsiella pneumoniae, Acinetobacter baumannii or Pseudomonas aeruginosa are essential. In this retrospective case–control study including all consecutive patients showing an episode of BSI in the ICUs of a university hospital in Italy in the period January–December 2016, patients with blood culture positive for CR-GNB pathogens and for any other bacteria were compared. A total of 106 patients and 158 episodes of BSI were identified. CR-GNBs induced BSI in 49 patients (46%) and 58 episodes (37%). Prognosis score and disease severity at admission, parenteral nutrition, cardiovascular surgery prior to admission to ICU, the presence of sepsis and septic shock, ventilation-associated pneumonia and colonization of the urinary or intestinal tract were statistically significant in the univariate analysis. The duration of ventilation and mortality at 28 days were significantly higher among CR-GNB cases. The prognostic model based on age, presence of sepsis, previous cardiovascular surgery, SAPS II, rectal colonization and invasive respiratory infection from the same pathogen showed a C-index of 89.6%. The identified risk factors are in line with the international literature. The proposal prognostic model seems easy to use and shows excellent performance but requires further studies to be validated.

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.

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)

The value of dynamic monitoring of procalcitonin in the early identification of pathogens and prognosis of bloodstream infections in the ICU

To explore the value of dynamic monitoring of procalcitonin (PCT) for early identification of pathogens and prognosis of bloodstream infections (BSI) in the intensive care unit (ICU). A retrospective analysis was performed on 84 patients with positive blood cultures. Patients were divided into the survival group and death group according to prognosis. Dynamic changes of PCT before and after treatment in the two groups were compared, as well as the relationship between such changes and prognosis. Among the 84 patients with bloodstream infections, 41 cases of Gram-negative (G-) bacteria, 40 cases of Gram-positive (G+) bacteria, and 3 cases of fungi were detected. PCT value in the G- bacteria group was significantly higher than that in the G+ bacteria group and fungus group, and the difference was statistically significant (P<0.05). PCT values on the first day of the G- bacteria group and the non-G- bacteria group were analyzed by a receiver operating characteristic (ROC) curve. When the threshold value was 3.84 ng/mL, the sensitivity, specificity, and area under the ROC curve for predicting G- bacteria bloodstream infection were 61%, 92.5%, and 0.841, respectively. The Kruskal-Wallis test (K-W test) was performed on PCT levels of each G- bacteria on the first day of bloodstream infection, and the difference was not statistically significant (P>0.05). Logistic binary regression analysis showed that the reduction rate of PCT after 5 days of treatment was an independent protective factor for patient survival. ROC curves showed that the sensitivity and specificity for predicting patient survival were 88% and 68.7%, respectively, when the PCT reduction rate (PCT(D1-D5)/D1) reached 36.02% or more. PCT can be used as an adjunctive method to quickly diagnose pathogenic microorganisms of bloodstream infections, and the anti-infection treatment scheme has certain guiding value. The dynamic changes in PCT have a certain role in predicting the therapeutic effect and prognosis of anti-infection treatment.

Clinical characteristics and risk factors of blood stream infections after orthopedic surgery

To analyze the clinical characteristics, risk factors, and drug resistance of pathogenic bacteria in patients with blood stream infections (BSI) after orthopedic surgery, so as to provide reference and basis for clinical diagnosis and treatment. A retrospective analysis was made on the clinical data of 6 348 orthopedic patients admitted for surgery between January 2017 and December 2019. There were 3 598 males and 2 750 females. Their age ranged from 18 to 98 years, with an average of 66 years. The data of patients were collected, and the risk factors of BSI were analyzed by univariate analysis and logistic regression analysis. The distribution of BSI pathogenic bacteria, the results of drug sensitivity test, the incidence of BSI in patients after orthopedic surgery in different years, and the common sites of BSI secondary infection were summarized. BSI occurred in 106 (1.67%) of 6 348 patients after orthopedic surgery. There were 71 cases (66.98%) of secondary infection. The mortality of postoperative BSI patients was 1.89%, and the difference was significant when compared with that of non-postoperative BSI patients (0.24%) ( χ 2=5.313, P=0.021). The incidences of BSI in 2017, 2018, and 2019 were 1.18%, 1.53%, and 2.17%, respectively, showing an increasing trend year by year (trend χ 2=6.610, P=0.037). Statistical analysis showed that the independent risk factors for BSI after orthopedic surgery ( P<0.05) included the trauma, length of hospital stay≥14 days, emergency surgery, postoperative leukocyte counting<4×10 9/L, level of hemoglobin≤90 g/L, albumin≤30 g/L, the time of indwelling ureter>24 hours, use of deep vein catheter insertion, and merging other site infection. Blood culture showed 56 strains (52.83%) of Gram-positive bacteria, 47 strains (44.34%) of Gram-negative bacteria, and 3 strains (2.83%) of fungi. The top three pathogenic bacteria were coagulase negative Staphylococci (CNS; 36 strains, 33.96%), Escherichia coli (16 strains, 15.09%), and Staphylococcus aureus (15 strains, 14.15%). The detection rates of extended-spectum β-lactamases producing strains of Escherichia coli and Klebsiella pneumoniae were 56.25% (9/16) and 44.44% (4/9), respectively. The detection rates of methicillin-resistant strains in Staphylococcus aureus and CNS were 46.67% (7/15) and 72.22% (26/36), respectively. Postoperative BSI in orthopedic patients is caused by multiple factors. Preventive measures should be taken according to related risk factors and perioperative risk assessment should be strengthened. Staphylococcus and Escherichia coli are the most common pathogenic bacteria in BSI after orthopedic surgery. The infection rate and drug-resistant bacteria are increasing year by year. Therefore, drug resistance monitoring should be strengthened.

Correlation between Multidrug-Resistant Bacteria Colonization and Bloodstream Infections in Children with Hematolymphoid Malignancies at a Tertiary Cancer Center in India

Abstract Background Bloodstream infections with drug-resistant bacteria are associated with a higher morbidity and mortality. Based on previous studies in our institution demonstrating a rising incidence of multidrug resistant organism (MDR) bacteria in bloodstream infections (BSI) and high prevalence of enteric colonization with MDR, the “de-escalation” strategy for empirical antibiotics was adopted in the management of febrile neutropenia in children with hematolymphoid malignancies and MDR colonization. An audit was carried out to determine whether surveillance rectal swabs correlated with blood cultures in febrile neutropenia. Methods Patient data from January 2015 to July 2016 was examined. Rectal swabs of children with hematolymphoid malignancies were obtained at presentation. Blood cultures were taken during febrile neutropenia. Data were analyzed using SPSS version 24.0. The significance level was set at p &lt; 0.05. Results Most patients (62.1%) with confirmed BSI were colonized with either extended-spectrum β-lactamase producing organisms (ESBLO) (31.9%) or MDR (30.2%). Majority 116 (62.7%) developed BSI caused by either MDR or ESBLO. In contrast, only 12 (10.6%) patients colonized by sensitive bacteria, developed BSI caused by either MDR or ESBLO. These differences were statistically significant (p &lt; 0.001). Thus, the baseline rectal swab had a sensitivity and a specificity of 90.6% and 59.4%, respectively, in predicting BSI with either MDR or ESBLO. Conclusions We conclude that high prevalence of MDR colonization at presentation significantly results in MDR BSI, which further results in a significant increase in intensive care unit admissions and mortality. This would justify the use of a “de-escalation” antibiotic policy. Whether such a strategy has been successful in impacting outcomes, would need further study.

Nosocomial Non-fermentative gram negative bacteria bloodstream infections in children; Risk factors and clinical outcomes of carbapenem resistance

IntroductionNon-fermentative Gram-negative bacterias (NFGNBs) are a major cause of life threatening infections in hospitalized children. In this study, we aimed to evaluate the demographic and clinical characteristics of NFGNBs infections and identify the risk factors and outcomes of bloodstream infections (BSIs) caused by carbapenem-resistant (CR) NFGNBs infections. MethodsA retrospective cohort was designed to evaluate the patients with a BSI caused by NFGNBs between in January 2014 and December 2017. ResultsA total of 131 episodes from 115 patients were evaluated. The mean age of the patients was 4.79±(4.74) year. The most commonly isolated NFGNBs species was Acinetobacter spp. (35.9%), Pseudomonas spp. (34.4%), and Stenotrophomonas maltophilia (13%). The rate of carbapenem-resistance was 38.2% in Acinetobacter spp. and 26.6% in Pseudomonas spp. The comparison of CR group with carbapenem-susceptible (CS) group showed statistical significance for the length of hospital stay prior to onset of infection and total hospital stay (P values were 0.001, 0.008). Based on the univariate analysis, requirement of mechanical ventilation, central venous catheter, nasogastric tube, Foley catheter, severe neutropenia (<100/mm3), prolonged neutropenia (≥14 days), prior intensive care unit admission and prior antimicrobial treatment (carbapenems, colistin, glycopeptide) were more common in carbapenem-resistant NFGNBs infections (P values are 0.001, 0.012, 0.000, 0.005, 0.042, 0.027, 0.007, 0.007). In patients with NFGNBs infections 14-day and 30-day mortality rates were %16.8 and 21.4%. ConclusionCR infections were more common in children with prolonged and severe neutropenia. Prior antimicrobial use and intensive care unit admission were more common in CR infections.