Multidrug-resistant Gram-negative Bacteremia Research Articles

Early bacteremia following allogeneic hematopoietic stem cell transplantation without antibiotic prophylaxis: epidemiology and antimicrobial resistance

ObjectiveBacteremia is a serious complication in patients undergoing allogeneic hematopoietic stem cell transplantation. The aim of this study was to determine the frequency, epidemiological profile, and risk factors of bacteremia early after allogeneic hematopoietic stem cell transplantation. MethodsAn observational descriptive retrospective study was conducted in patients who received transplants between January 2016 and December 2021. Early bacteremia was defined as blood stream infection occurring between Day 0 and Day 100 after transplantation. ResultsForty episodes of early bacteremia occurred in 36/245 transplanted patients. Fifteen episodes (37.5%) were due to gram-positive bacteria and 25 (62.5%) to gram-negative bacteria. The most frequent species isolated were coagulase negative staphylococci (CoNS) in gram-positive bacteremia (n = 8/15), and Klebsiella species (8/25) and Pseudomonas species (8/25) in gram-negative bacteremia. Twenty-nine episodes of bacteremia (72.5%) occurred during the first 30 days after transplantation with a median time of nine days (range: 0-90 days). Coagulase negative staphylococci were methicillin-resistant in 75% of cases, the only Staphylococcus aureus isolated was methicillin-resistant. All gram-positive bacilli were penicillin-resistant. Gram-negative bacilli were multidrug resistant in 61.5% of cases. In multivariate analysis, bone marrow as source of graft (p-value = 0.02) and cytomegalovirus reactivation (p-value = 0.02) were significantly associated with an increased risk of bacteremia. Mortality attributable to bacteremia was 2.8%. The one-year overall survival was not significantly different between those with and without bacteremia. ConclusionsBacteremia was more frequent within the first 30 days after transplantation indicating the crucial role of neutropenia. An increase in multidrug resistant gram-negative bacteremia was noted.

Predictors and outcomes of multi-drug–resistant gram-negative bacteremia in patients with cancer: A retrospective cohort study at a tertiary cancer center in Oman

ObjectivesThis study aimed to delineate the characteristics and outcomes of gram-negative bacteremia (GNB) in oncology patients; analyze the risk factors for multi-drug–resistant (MDR) GNB; and assess its impact on the recurrence of bloodstream infection (BSI), hospital stay, and 30-day mortality. MethodsData, including demographics, clinical features, common cancers, and microbiologic findings, were collected retrospectively from electronic medical records of patients admitted with solid tumors and BSI episodes between January and December 2022. Fisher's exact tests were used to determine the effect of MDR-GNB on 30-day mortality and BSI recurrence. The Wilcoxon rank-sum test assessed the differences in the length of hospital stay. Logistic regression models identified the risk factors for MDR-GNB. ResultsAmong 1074 patients, 77 episodes of GNB bacteremia occurred in 59 individuals (47% male, median age 57.4 years). Of these, 37 (48%) were MDR-GNB. Carbapenem resistance was noted in 9.1% of GNB episodes. Previous antibiotic use was significantly associated with MDR-GNB (odds ratio 7.82; 95% confidence interval 2.52-24). MDR-GNB was linked to longer hospital stays (median 23 vs 10.5 days, P = 0.003) and higher recurrence rates than non-MDR-GNB (35.13% vs 5.0%, P <0.001). However, 30-day mortality did not significantly differ between the groups (35.14% vs 32.5%, P = 0.81). ConclusionPrevious antibiotic use predicted MDR-GNB in patients with solid tumor. MDR-GNB bacteremia increased the length of hospital stay and risk of recurrence compared with non-MDR-GNB bacteremia.

Survivorship Struggles: Navigating Etiologies and Clinical Parameters of Febrile Neutropenia During Induction Chemotherapy in Acute Leukemia Patients.

Background Acute leukemia, characterized by the uncontrolled proliferation of immature white blood cell precursors, poses significant challenges during induction chemotherapy, including the elevated risk of febrile neutropenia and its associated complications. Our study aims to explain the clinical and etiological parameters of these patients in a resource-limited setting. Methods This retrospective study focused on a total of 102 adult patients with acute leukemia who developed febrile neutropenia during the induction chemotherapy phase. Patients with disease relapse, prior bone marrow transplantation, and cases of acute promyelocytic leukemia were excluded from the study. Demographical characteristics, symptoms at presentation, diagnoses, infectious causes, and outcomes were systematically reported. Infectious etiologies and detailed culture reports were meticulously tabulated, and subsequent data were analyzed. Results Of the 102 patients, 43 (42.2%) were males, with a mean age of 31.9 ± 6.5 years. During the induction chemotherapy, a total of 31 patients died of complicated febrile neutropenia. Severe vomiting was the most common symptom present in 37 (36.2%), followed by cough in 35 (34.3%) and loose stools in 28 (27.5%). Community-acquired pneumonia, neutropenic sepsis, and neutropenic colitis were among the most common etiologies of febrile neutropenia. A total of 72 (70.6%) patients had culture-proven multidrug-resistant Gram-negative bacteremia that contributed to poor outcomes. Conclusions Acute leukemia patients undergoing induction chemotherapy face high infection-associated mortality due to their immunocompromised state. Inadequate infection control measures and antimicrobial resistancecontribute to the emergence of multidrug-resistant organisms. Enhanced infection prevention strategies and evidence-based antibiotic prescription guidelines are need of time in resource-limited settings such as Pakistan to address febrile neutropenia complications and bridge the existing care gap in its management.

244. Predictors and Outcomes of Multi-Drug Resistant Gram-Negative Bacteremia in Patients with Solid Tumours

Abstract Background Multi-drug resistant Gram-negative bacteraemia (MDR-GNB) is a major concern in cancer patients. However, predictors and outcomes of MDR-GNB bacteraemia in patients with solid tumours are not well defined. The objective of this study was to identify the predictors and outcomes of MDR-GNB bacteraemia in patients with solid tumours. Methods This retrospective cohort study was conducted on patients with solid tumours admitted to a tertiary care hospital between January 2022 and December 2022. Demographic, clinical, and microbiological data were collected from electronic medical records. Univariate and multivariate analyses were performed to identify the predictors of MDR bacteraemia. The outcomes of interest included in-hospital 30-day mortality, length of hospital stay, and recurrence of bacteraemia. Results Among 1074 patients with solid tumours, a total of 77 episodes of Gram-negative bacteremias occurred in 59 patients (47% male) with a mean age of 57.4 years. Of which 37(48%) had MDR-GNB bacteraemia. The most common source of bacteraemia was biliary (34.2%) followed by central line-associated (21%) and abdomen(21%). Carbapenem resistance was documented in 7(9.1%) of all Gram-negative bacteremias of which 75% were harbouring NDM with or without OXA-48 among enterobacteralis. The predictors of MDR-GNB bacteraemia were prior use of antibiotics (odds ratio [OR] 7.82, 95% [CI] 2.52,24.2) and E.coli bacteremia (OR 6.56, 95% CI 1.26,34.22). The median length of hospital stay was significantly longer in the MDR group compared to the non-MDR group (23 vs. 10.5 days; p= 0.003) and recurrence of bacteremia was significantly more common in the MDR group (35.13% vs. 5.0%; p=&amp;lt; 0.001). The 30-day in-hospital mortality was not significantly different (35.14% vs. 32.5%; p=0.81). Conclusion This study identifies prior use of antibiotics and E.coli bacteremias as predictors of MDR-GNB bacteraemia in patients with solid tumours. Patients with MDR-GNB bacteraemia had longer hospital stays, and higher recurrence rates compared to those with non-MDR-GNB bacteremias. This highlights the importance of the judicious use of antibiotics and infection control measures to prevent MDR-GNB bacteraemia in this population. Disclosures All Authors: No reported disclosures

216. A Comparison of Multidrug-Resistant Gram-negative Bacteremia in Cancer and Non-Cancer Patients

Abstract Background Multidrug-resistant gram-negative bacteremia (MDR-GNB) is a growing threat worldwide as it is associated with increased morbidity and mortality. We sought to describe the clinical features of MDR-GNB and outcomes in cancer and non-cancer Pts. Methods We performed a retrospective study of adult patients with MDR-GNB at the Ochsner LSU Health Shreveport between January 2018 and July 2022. We collected patients' demographics, medical comorbidities, cancer diagnosis, causative bacteria (MDROs), source of bacteremia, antibiotics therapy, and clinical outcomes. Results We identified 112 Pts with MDR-GNB. Pts were divided into 2 groups: cancer group (n=33, 29%) and non-cancer group (n=79, 71%). In the cancer group, the majority of Pts had solid tumors (n=20, 61%) vs liquid tumors (n=13, 39%). Mean age was 69 y in cancer compared to 57 y in the non-cancer group. Enterobacteriaceae were isolated in 28 cancer Pts (85%) including ESBL E. coli in 20 Pts (61%), Klebsiella s.p (CRE/ESBL) in 5 Pts (15%), and ESBL P. mirabilis in 3 Pts (9%). Pseudomonas aeruginosa CRO in 3 Pts (9%) and A. baumannii in 2 Pts (6%). In non-cancer Pts, Enterobacteriaceae were isolated in 65 Pts (82%) including ESBL E. coli in 40 Pts (51%), Klebsiella s.p (CRE/ESBL) in 18 Pts (23%) and ESBL P. mirabilis in 6 Pts (8%). P. aeruginosa CRO found in 6 Pts (8%) and A. baumannii in 8 Pts (10%). The sources of bacteremia in cancer group were UTI in 14 Pts (42.4%), osteoarticular infection (OAI) in 5 Pts (15%), pneumonia in 3 Pts (9%), CLABSI in 2 Pts (6%), endovascular in 1 Pt (3%) and unknown in 8 Pts (24%), whereas in non-cancer group, UTI was reported in 40 Pts (68%), pneumonia in 9 (27%), OAI in 1 (1.3%), endocarditis in 1 Pt (1.3%), and unknown in 20 Pts (25.3%). Mean duration of targeted antibiotics was 9 days in cancer vs 13.3 days in non-cancer group (p-value=0.4). Mean length of hospital stay was comparable, 34 d in cancer vs 31 d in non-cancer(p-value= 0.87). 9 Pts were admitted to ICU in cancer group (27%) vs 39 Pts (49%). Mortality rate was 39% in cancer (8 pts went to hospice) vs 16.4% in non-cancer. Conclusion Our data showed that the common source of MDR-GNB remains urinary tract infection in both groups and the bacterial epidemiology is comparable between the two groups. Further studies are warranted to assess the impact of resistant organisms on cancer Pts. Disclosures All Authors: No reported disclosures

Mortality due to Multidrug-Resistant Gram-Negative Bacteremia in an Endemic Region: No Better than a Toss of a Coin.

The incidence of multidrug-resistant (MDR) bloodstream infections (BSIs) is associated with high morbidity and mortality. Little evidence exists regarding the epidemiology of BSIs and the use of appropriate empirical antimicrobial therapy in endemic regions. Novel diagnostic tests (RDTs) may facilitate and improve patient management. Data were assessed from patients with MDR Gram-negative bacteremia at a university tertiary hospital over a 12-month period. In total, 157 episodes of MDR Gram-negative BSI were included in the study. The overall mortality rate was 50.3%. Rapid molecular diagnostic tests were used in 94% of BSI episodes. In univariate analysis, age (OR 1.05 (95% CI 1.03, 1.08) p < 0.001), Charlson Comorbidity Index (OR 1.51 (95% CI 1.25, 1.83) p < 0.001), procalcitonin ≥ 1(OR 3.67 (CI 95% 1.73, 7.79) p < 0.001), and monotherapy with tigecycline (OR 3.64 (95% CI 1.13, 11.73) p = 0.030) were the only factors associated with increased overall mortality. Surprisingly, time to appropriate antimicrobial treatment had no impact on mortality. MDR pathogen isolation, other than Klebsiella pneumoniae and Acinetobacter baumanii, was associated with decreased mortality (OR 0.35 (95% CI 0.16, 0.79) p = 0.011). In multivariate analysis, the only significant factor for mortality was procalcitonin ≥ 1 (OR 2.84 (95% CI 1.13, 7.11) p = 0.025). In conclusion, in an endemic area, mortality rates in MDR BSI remain notable. High procalcitonin was the only variable that predicted death. The use of rapid diagnostics did not improve mortality rate.

Impact of Persistent Multidrug-Resistant Gram-Negative Bacteremia on Clinical Outcome and Mortality

The clinical aspects of persistent bacteremia (PB) caused by gram-negative rods (GNRs) in terms of antimicrobial resistance (AMR) and PB clearance status are unclear. This secondary analysis of a retrospective cohort study investigated differences in PB caused by Enterobacterales and glucose non-fermentative GNRs (NF-GNRs) based on AMR and PB clearance. We retrospectively surveyed medical records at Tohoku University Hospital. Patients for whom blood cultures were performed between January 2012 and December 2021 were recruited. PB cases were grouped based on AMR and PB clearance; the characteristics of PB due to each bacterial pathogen were examined. The main outcome variable was mortality. The late (30-90-day) mortality rate was significantly higher in the multidrug-resistant (MDR) group than in the non-MDR group for Enterobacterales. However, no significant difference was noted in mortality rates between NF-GNRs with and without AMR. Mortality rates tended to be higher in the non-PB-clearance group than in the clearance group for both Enterobacterales and NF-GNRs. Since the mortality rate was higher in the MDR group in the case of Enterobacterales PB, more careful management is necessary for this condition. Follow-up blood cultures and confirming the clearance of PB are useful for improving the survival rate.

299. Paediatric Collaborative Network on Infections in Canada (PICNIC) Study of the Current Landscape of Gram Negative Bacteremias

BackgroundAntimicrobial resistance is a public health threat, invasive infection from multi-drug resistant gram-negative (MDRGN) pathogens is associated with significant morbidity and mortality. The incidence of MDRGN bacteremia in Canada is rising, and pediatric data is limited.MethodsThis retrospective chart review of paediatric patients with gram negative bacteremia in a multicenter PICNIC database (n=7 centers) from 2013 to 2017. MDRGN was defined as enterobacteriaceae that were resistant to third generation cephalosporins (including ESBL, CPE). Ethics approval was obtained at all sites, and data was entered into a secure REDCAP database, descriptive statistics are described herein.ResultsOf the 676 bacteremia patients in the database, 214 (31.7%) were gram negative pathogens. E. coli was the most frequent pathogen (59.8%, of which 22 of 128 were MDR), followed by Klebsiella (31.8%, of which 9 of 68 were MDR). Of the 31 MDRGNs, 19 were ESBL, 1 was a CPE, and 11 were nonspecific mechanisms of resistance. There were no multidrug resistant Pseudomonas, Stenotrophomonas, or Acinetobacter. The majority of patient were less than 3 months of age (59.3%) and were male (58.8%). The majority had an underlying comorbid condition; hematoncologic diagnosis accounting for 14.5%. Length of stay varied from 1 to 742 days (mean 72, standard deviation 88). 11% required admission to ICU, 10% required removal of a intravascular catheter, 7% required a change in ventilation status, 2% requiring procedural source control, and there was an 8% mortality rate. Treatment duration greater than 14 days occurred in 123 patients (61% of patients). ConclusionThis preliminary analysis of a multicenter review of pediatric gram negative bacteremias demonstrates a higher risk in neonates with comorbid conditions. A surprisingly prolonged treatment duration of greater than 14 days occurred in the majority of patients. Further analysis to assess factors associated with prolonged treatment durations, MDR infection, and complications is required. Gram negative bacteremia remains a significant cause of morbidity and mortality in pediatric patients.Disclosures All Authors: No reported disclosures

Pediatric Febrile Neutropenia: Change in Etiology of Bacteremia, Empiric Choice of Therapy and Clinical Outcomes.

The optimal choice of initial antibiotic therapy for patients with high-risk febrile neutropenia (FN) in children is unclear and varies by the institution on the basis of local antibiograms and epidemiology of specific pathogens. The authors evaluated the appropriateness of antibiotics for the empiric treatment of FN in pediatric patients with cancer in our institution on the basis of changes in the epidemiology of organisms isolated from blood cultures (BCx). The authors conducted a retrospective medical record review of pediatric patients who received any oncology care (including patients with cancer and patients who had stem cell transplant) at University of Chicago Medicine Comer Children's Hospitals (March 2009 to December 2016) with a diagnosis of FN who had at least 1 BCx obtained. They reviewed pathogens isolated from BCx and determined whether they were pathogens or contaminants using the Infectious Diseases Society of America (IDSA) guidelines and the team's decision to treat. They investigated the microbiologic spectrum and susceptibility patterns of pathogens causing bacteremia in pediatric FN and whether the empiric therapy chosen may have affected clinical outcomes. A total of 667 FN episodes were identified in 268 patients. BCx were negative in 497 (74.5%) and were determined to be contaminants in 27 (4%). In 143 episodes (21.5%), the BCx were positive for a pathogenic species. Polymicrobial bacteremia was identified in 25 episodes; a total of 176 pathogens were isolated. The majority of pathogens (95/176, 54%) were Gram-positive (GP), whereas 64 of 162 (36%) were Gram-negative (GN), 5 were fungal, and 4 were mycobacterial. The most common GP pathogens were viridans group streptococci (VGS) (n=34, 19.3%), coagulase-negative staphylococci (n=25, 14%), and methicillin-susceptible Staphylococcus aureus (n=12, 6.8%). Of aerobic GN bacilli, 15 (8.5%) were AmpC producers and 3 (1.7%) carried extended-spectrum beta-lactamases. There was no increase in the prevalence of multidrug-resistant GN isolates during the study period. Patients with VGS and multidrug-resistant GN bacteremia were more likely to be admitted to the pediatric intensive care unit [odds ratio (OR), 3.24; P=0.017; and OR, 2.8; P=0.07, respectively]. There were trends toward a higher prevalence of GP pathogens causing bacteremia and the emergence of VGS with decreased penicillin sensitivity. The prevalence of bacteremia with VGS was higher in acute myelogenous leukemia and neuroblastoma (OR, 2.3; P<0.01) than in patients with other solid tumors. Empiric antibiotic treatment should be tailored to patients' risk for VGS and multidrug-resistant organisms. Individual hospitals should monitor the pathogens causing FN among patients with cancer to guide choice of empiric therapy.

2679. Factors Associated with Multidrug-resistant Gram-Negative Bacteremia in Acute Leukemia Patients with Neutropenic Fever, a Retrospective Study

BackgroundGram--negative bacteremia in acute leukemia patients with neutropenia is associated with high morbidity and mortality rate. Appropriate antibiotic for empirical treatment is crucial; however, antibiotic selection is challenging especially in setting with high prevalence of infections with multidrug-resistant (MDR) organisms. Data on associated factors of MDR Gram-negative bacteremia in this population is limited.MethodsA retrospective study was conducted in King Chulalongkorn Hospital, Bangkok, Thailand. Medical records of patients aged ≥15 years with acute leukemia who were hospitalized in our institute and had neutropenic fever between 1 January 2001 and 31 December 2016 were reviewed. Demographic data, causative organisms, treatment and outcomes were documented. Episodes of MDR Gram-negative bacteremia were compared with non-MDR group. Associated risk factor was assessed by multivariate logistic regressionResultsFrom total 405 admission records of 227 acute leukemia patients, 587 episodes of neutropenic fever occurred with 131 episodes of Gram-negative bacteremia. Majority (81.68%) were bacteremia without source of infection. Most common causative pathogens were E. coli, P. aeruginosa and K. pneumoniae, respectively. Sixty episodes of Gram-negative bacteremia (53.57%) were caused by MDR pathogen. Associated factor for MDR Gram-negative bacteremia was prior colonization or infection with MDR Gram-negative bacteria within 3 months (P = 0.049). Subgroup analysis in patients with non-lactose fermenter bacteremia showed higher rate of intensive care unit (ICU) admission and in-hospital death in MDR group (P = 0.03 and P = 0.004).ConclusionPrior colonization or infection by MDR Gram-negative bacteria within 3 months was associated with MDR Gram-negative bacteremia in acute leukemia patients with neutropenic fever. Thoroughly review of previous culture data and active screening for colonization may increase chance of appropriate empirical antibiotics. Disclosures All authors: No reported disclosures.

519. Multidrug-resistant Gram-Negative Bacteremia in Pediatric Patients: Is It Time to Change to Empiric Meropenem?

BackgroundThe rise of antimicrobial resistance among gram-negative (GN) pathogens has been dramatic nationally. Delayed initiation of active antimicrobial agents has been associated with poor outcomes. We aimed at evaluating the prevalence and treatment of multi-drug-resistant gram-negative (MDR-GN) bacteremia in our pediatric patients.MethodsAll episodes of GN bacteremia from 2017–2018 at our institution were retrospectively reviewed. GN defined as MDR in our study were carbapenem-resistant organisms (CRO), extended-spectrum β-lactamase (ESBL) producers, and GN that were resistant to cefepime and ≥2 classes of non-cephalosporin antimicrobial agents. Stenotrophomonas maltophilia was excluded. Ineffective empirical treatment (IET) is defined as an initial antibiotic regimen that is not active against the identified pathogen[s] based on in vitro susceptibility testing results.ResultsA total of 292 episodes of GN bacteremia were identified and 6 S. maltophilia were excluded. Of these, 29 bacteremic episodes in 26 patients were caused by MDR-GN organisms including 18 ESBL, 7 CRO, 1 ESBL and CRO, 3 non-ESBL/non-CRO cefepime-resistant MDR-GN. None of the CRO had carbapenemase genes detected. However, there was a patient with multiple sites of infection simultaneously with non-NDM CR Acinetobacter bacteremia and NDM-mediated CR-Klebsiella ventriculitis. The annual rate of MDR-GN bacteremia increased from 8% in 2017 to 12% in 2018. Almost half (48%) of episodes were community onset. Among these, all but one had underlying medical conditions with hospital exposure and most patients had central venous devices at the time of infection. 52% (15/29) episodes of MDR-GN bacteremia had IET. Despite IET, 47% (7/15) had negative blood cultures prior to initiation of effective therapy (6 ESBL and 1 P. aeruginosa). Various antibiotic regimens were used for CRO therapy as shown in Table 1.ConclusionIn our institution, MDR-GN infection is increasing. As such, empiric meropenem is currently recommended in BMT or neutropenic patients with suspected sepsis. However, empiric meropenem must be used judiciously as its widely use will lead to more selection of MDR pathogens. It is essential to continue monitoring of these MDR-GN to guide appropriate empiric regimens. Disclosures All authors: No reported disclosures.

Epidemiological changes, clinical characteristics and outcome of febrile neutropenia episodes in a university hospital over two decades

Background: Epidemiology and antibiotic resistance pattern of bacterial infections in neutropenic patients have changed over time around the world. Multidrug-resistant gram-negative bacteremia (MDR-GNB) has become a major concern in recent years. Methods & Materials: Prospective, observational study. All patients admitted for febrile neutropenia (FN) from February 1997 to October 2017 were enrolled. This period was divided: P1 (1997 to 2002), P2 (2003 to 2008), P3 (2009 to 2014), and P4 (2015 to Oct 2017). Microbiology, clinical characteristics and outcomes of the first infectious event during FN were compared among the four periods. Chi-square analysis and Kruskal-Wallis test were used for categorical and for continuous variables, respectively. Results: 1169 episodes were included. In the last 3 periods there were more high-risk FN episodes (P1 81.3%, P2 88.9%, P3 90.7%, P4 92.6%, p = 0.0001). Quinolones prophylaxis were more used in P2 and P3 (3.6%, 17.8%, 61.1%, 6.6%, p = 0.0001). In P4 there were more severe infections: severe mucositis (7.2%, 6.4%, 3.4%, 14.8% p = 0.0001); abdominal source (16.1%, 11.8%, 15.6%, 21.8%, p = 0.018); catheter related source (10.5%, 8.9%, 15.6%, 19.7%, p = 0.001) and bacteremias (27.2%, 27.1%, 22.1%, 36.7%, p = 0.002). In P4 broad-spectrum antimicrobials were more used: carbapenems (1.3%, 3.2%, 17.4%, 36.2%, p = 0.0001); colistin (0, 0,3%, 4%, 12.7%, p = 0.0001); and vancomycin (5.2%, 3.2%, 24.3%, 40.2%, p = 0.0001); as well as more combination therapy was prescribed (6.2%, 1.6%, 8.1%, 19.7%, 0.0001). Furthermore, in the last 2 periods a rise in MDR-GNB was recorded (6%, 3.5%, 22.5%, 21.4%, p = 0.0001) and carbapenem-resistant bacteremias (9.3%, 2.1%, 9.5%, 24.5%, p = 0.005). Finally, at the end of FN episode there was a trend toward higher mortality (7.2%, 5.4%, 5%, 10.5%, p = 0.054) and bacteremia related mortality (9.6%, 7.05%, 9.85%, 17.8%, p = 0.07) in the last period. Conclusion: The characteristics of infections in patients with FN have changed since the last two periods in our hospital. A rise in MDR-GNB was recorded, as well as a trend toward higher mortality. Knowing the local epidemiology, identifying patients at risk for MDR-GNB and treat them appropriately must be part of the approach of high-risk FN episodes.

Factors influencing mortality in abdominal solid organ transplant recipients with multidrug-resistant gram-negative bacteremia

BackgroundAlthough multidrug-resistant (MDR) gram-negative bacteremia (GNB) has been recognized as an important cause of morbidity and mortality among abdominal solid organ transplant (ASOT) recipients, there are no data on its prognostic factors after an interim standard definition of MDR was proposed in 2012. The objective of this study was to describe the epidemiology, microbiology, and predictors of infection-related 30-day mortality in ASOT recipients with MDR GNB.MethodsWe performed a retrospective, double-center analysis of ASOT patients with MDR GNB over a 13-year study period. Univariate and multivariate analyses were performed to identify the risk factors for mortality.ResultsDuring the observational period, 2169 subjects underwent ASOT. Ninety-nine episodes of MDR GNB were diagnosed in 91 (4.6%) ASOT recipients, with a predominance of E.coli (29 isolates, 29.3%) and A.baumanii (24 isolates, 24.2%). The median age of these 91 recipients was 45 years (interquartile range 35–54). Mortality after the first episode of MDR GNB was 39.6% (36 deaths). The univariate analysis identified the following variables as predictors of MDR GNB-related mortality: lung focus (P = 0.001),nosocomial origin (P = 0.002), graft from donation after cardiac death or deceased donors (P = 0.023), presence of other concomitant bloodstream infection (P < 0.001), temperature of 40 °C or greater at the onset of MDR GNB (P = 0.039), creatinine > 1.5 mg/dl (P = 0.006), albumin < 30 g/L (P = 0.009), platelet count < 50,000/mm3 (P < 0.001), and septic shock (P < 0.001). In the multivariate logistic regression analysis, septic shock (odds ratio (OR) = 160.463, 95% confidence interval (CI) = 19.377–1328.832, P < .001), as well as creatinine > 1.5 mg/dl (OR = 24.498, 95% CI = 3.449–173.998, P = 0.001), nosocomial origin (OR = 23.963, 95% CI = 1.285–46.991, P = 0.033), and presence of other concomitant bloodstream infections (OR = 27.074, 95% CI = 3.937–186.210, P = 0.001) were the variables associated with MDR GNB-related 30-day mortality.ConclusionsMDR GNB was associated with high morbidity and mortality in ASOT recipients, with a predominant causative organisms being E.coli and A.baumanii. Nosocomial origin, as well as presence of other concomitant bloodstream infections, increased creatinine level and septic shock were the main predictors of MDR GNB-related 30-day mortality.

Outcomes of Rapid Identification of Multi-Drug Resistant Gram-Negative Organisms Causing Bacteremia in Combination with Antimicrobial Stewardship in a Community Health System.

BackgroundRapid initiation of effective antibiotic therapy has been strongly associated with a decrease in mortality in gram-negative (GN) bacteremia. In an effort to improve time to effective antibiotic therapy in the treatment of multi-drug resistant (MDR) GN bacteremia, we implemented Verigene GN Blood Culture (BC-GN) assay, which can rapidly identify GN bacteria at the genus/species level and specific resistance markers from blood cultures within 2 hours of positivity.MethodsThe objective of this multi-center, pre-post quasi-experimental study was to assess outcomes of Verigene BC-GN in combination with antibiotic stewardship in treatment of MDR GN bacteremia. A retrospective chart review was performed one year prior and four months post-implementation of Verigene BC-GN. Patients > 18 years old with MDR GN bacteremia identified by Verigene BC-GN within 5 days of admission were included. The primary endpoint was time to effective antibiotic therapy for MDR GN bacteremia. Secondary outcomes included overall and ICU length of stay (LOS) and 30-day mortality. Education regarding interpretation of resistance markers and selection of optimal antibiotic therapy was provided to pharmacists and physicians prior to implementation.ResultsA total of 110 patients were included, 86 in the pre-intervention group and 24 in the post-intervention group. Mean time to effective antibiotic therapy decreased significantly from 47.6 ± 23.1 vs. 18.8 ± 9.1 hours, respectively (P < 0.0001). Median overall LOS was 6.0 vs 5.5 days (P = 0.88), ICU LOS was 3.0 vs 4.0 days (P = 0.57), and 30-day mortality was 4.7% vs 4.2% (P = 1) pre and post-implementation, respectively.ConclusionVerigene BC-GN, in combination with antibiotic stewardship, successfully improved time to effective antibiotic therapy among MDR GN organisms causing bacteremia.Disclosures All authors: No reported disclosures.

Multidrug-resistant Gram-negative Bacteremia in Cancer Patients: Development of a Clinical Score for Risk Assessment

Multidrug-resistant Gram-negative Bacteremia in Cancer Patients: Development of a Clinical Score for Risk Assessment

Epidemiology and Clinical Outcomes of Multidrug-resistant, Gram-negative Bloodstream Infections in a European Tertiary Pediatric Hospital During a 12-month Period

Bloodstream infections caused by multidrug-resistant, Gram-negative (MDRGN) bacteria represent a significant cause of morbidity and mortality. Prompt diagnosis and appropriate empiric treatment are the most important determinants of patient outcome. The objective of our study was to assess the epidemiology and clinical outcome of MDRGN sepsis in a tertiary-care pediatric hospital during a 12-month period. It was a retrospective, observational study of MDRGN bacteremia including all patients <18 years of age, hospitalized during 2011, with documented bacteremia caused by Enterobacteriaceae or non-fermentative bacteria. Overall, 136 blood cultures in 119 patients were included. The median age of patients was 1.1 years; 86.3% of patients had an underlying disease. The cumulative incidence of Gram-negative bloodstream infections was 5.4/1000 hospital admissions and the infection rate was 0.65/1000 hospital days. Most frequently isolated strains were Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa; 67.6% of infections were hospital acquired. The percentage of multidrug-resistant (MDR) organisms among isolated species was 39%. The crude rate of mortality was 16% and sepsis-related mortality was 9.2%. The mortality rate among patients with an antibiotic-resistant isolate was 22.6%. Factors significantly associated with sepsis-related mortality were antibiotic resistance (odds ratio: 4.26, 95% confidence interval: 1.07-16.9) and hospital acquisition of infection (odds ratio: 1.13, 95% confidence interval: 1.05-1.22). This study demonstrates the high mortality of hospital-acquired MDRGN bacteremia in children. International networks focusing on clinical management and outcomes of MDRGN in children are required. Study of novel antibiotics active against Gram-negative bacteria should include children early in the clinical trial development programs.

Risk Factors and Outcomes for Multidrug-Resistant Gram-Negative Bacteremia in the NICU

To assess the risk factors antibiotic therapy and outcomes of multidrug-resistant (MDR) Gram-negative bacilli (GNB) bacteremia in NICU patients. Episodes of MDR GNB bacteremia were compared with a non-MDR GNB bacteremia group in an 8-year cohort study. Of 1106 bacteremias, 393 (35.5%) were caused by GNB. Seventy (18.6%) were caused by an MDR strain. The most frequent mechanism of resistance was extended-spectrum β-lactamase production (67.1%), mainly by Klebsiella pneumoniae (59.6%). Previous antibiotic exposure to third-generation cephalosporin (odds ratio [OR]: 5.97; 95% confidence interval [CI]: 2.37-15.08; P < .001) and carbapenem (OR: 3.60; 95% CI: 1.26-10.29; P = .017) and underlying renal disease (OR: 7.08; 95% CI: 1.74-28.83; P = .006) were identified as independent risk factors for MDR GNB acquisition. Patients with MDR GNB bacteremia more likely received inadequate initial antibiotic therapy (72.9% vs 7.8%; P < .001) had higher rates of infectious complication (21.4% vs 10.5%; P = .011) and overall case fatality +rate (28.6% vs 10.5%; P < .001). Independent risk factors for overall mortality were presence of infectious complications after bacteremia (OR: 3.16; 95% CI: 1.41-7.08; P = .005) and underlying secondary pulmonary hypertension with or without cor pulmonale (OR: 6.19; 95% CI: 1.88-20.31; P = .003). MDR GNB accounted for 18.6% of all neonatal GNB bacteremia in the NICU, especially in those with previous broad-spectrum antibiotic therapy and underlying renal disease. The most frequent mechanism of resistance was extended-spectrum β-lactamase (ESBL) production. Neonates with MDR GNB were more likely to develop infectious complications, which were independently associated with a higher overall case-fatality rate.

Risk Factors and Outcomes for Multidrug-Resistant Gram-Negative Bacteremia in the NICU

Risk Factors and Outcomes for Multidrug-Resistant Gram-Negative Bacteremia in the NICU

Risk factors for multidrug-resistant bacteremia in hospitalized cancer patients with febrile neutropenia: A cohort study

We conducted a prospective cohort study in a single tertiary hospital with the aim of assessing predictors of multidrug-resistant bacteremia in 307 cases of febrile neutropenia in adult patients with cancer. On multivariate analysis using stepwise logistic regression, age (P = .009), duration of neutropenia (P = .022), and presence of an indwelling central venous catheter (P = .022) were associated with bloodstream infection by multidrug-resistant bacteria.

Multidrug resistant gram‐negative bacilli as predominant bacteremic pathogens in liver transplant recipients

Bacteremias, which are often caused by gram-negative bacteria, are the most frequently occurring infectious complications after liver transplantation (LT). The aim of this study was to investigate bacteremic incidence, pathogenic spectrum, risk factors for bacteremia due to multidrug resistant (MDR) gram-negative bacilli, and its impact on mortality after LT. A cohort analysis of prospectively recorded data was done in 475 LT recipients, who were divided into 3 categories: cases with gram-negative bacteremia, cases with MDR gram-negative bacteremia, and cases without bacteremia as controls. In 475 LT recipients, there were 152 (32.0%) patients with gram-negative bacillus bacteremia in the first 6 months after LT. Out of 152 patients, there were 225 bacteremic episodes, which accounted for 69.7% in a total 323 bacteremic episodes. A total of 190 bacteremic episodes were caused by Stenotrophomonas maltophilia, Enterobacteriaceae, Ochrobactrum anthropi, Pseudomonas, and Acinetobacter baumanii, all of which were the most frequent gram-negative isolates in this study, and MDR bacilli constituted 56.3%. The most frequent source was intravascular catheters. There were 70 patients with MDR gram-negative bacillus bacteremia. Independent risk factors for bacteremia due to MDR gram-negative bacillus were as follows: post-LT abdominal infection (P<0.0001, odds ratio [OR] 0.066, 95% confidence interval [CI] 0.019-0.226), post-LT reoperative episodes (P<0.0001, OR 10.505, 95% CI 3.055-36.121), or one or more episodes of acute rejection (P=0.042, OR 4.457, 95% CI 0.988-20.103). In the first 6 months after LT, MDR gram-negative bacillus bacteremia-related mortality was significantly higher than that due to antibiotic-susceptible bacillus (38.6% vs. 14.6%, P<0.001). Post-LT bacteremias caused by MDR gram-negative bacilli are common, and associated with allograft acute rejection, post-LT reoperation, and abdominal infection. The increasing isolates of MDR gram-negative bacilli pose a great challenge for clinical treatment.