Gram-negative Bloodstream Infections Research Articles

Epidemiology of Gram-Negative Bloodstream Infections in the United States: Results From a Cohort of 24 Hospitals.

To address knowledge gaps in management of Gram-negative bloodstream infection, the Antibiotic Stewardship Implementation Collaborative was established consisting of programs from 24 academic and community hospitals across the United States. A retrospective cohort study was conducted of unique adult patients with Gram-negative bloodstream infection hospitalized at participating hospitals from January to December 2019. Patient level and microbiologic data were collected via electronic medical record review with a standardized data collection form and data dictionary. Data analysis was largely descriptive. The Pearson χ2 test to compare categorical variables and the Wilcoxon rank sum test for continuous variables were used. In total, 4851 bacterial isolates from 3710 eligible unique patients were included in the cohort. Most common source of infection was the urinary tract (47.9%). Source control was achieved in 84% of cases. Escherichia coli (2471, 51.0%) was the most common Gram-negative organism recovered. Antibiogram combining isolates from all participating centers with species-level susceptibilities and source specific antibiograms for isolates from urinary, respiratory, and intraabdominal source were created. Northeast sites contributed the most extended spectrum beta-lactamase (ESBL) producing organisms (73%), but West sites had the highest percentage of ESBL producers of total isolates (16%). A statistically significant difference in percentage of ESBL-producing organisms in Whites vs. non-Whites (14.6 % and 9.5 %, respectively, P<0.01) was observed. While the present study was conducted pre-pandemic, it highlights the need for stewardship data collaboratives to enhance our understanding of the antimicrobial resistance patterns.

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

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

Levofloxacin prophylaxis vs no prophylaxis in patients with neutropenia within an endemic country for carbapenem-resistant GNB.

Fluoroquinolone prophylaxis's (FQ-P) usefulness in patients with neutropenia is controversial. In recent decades, Italian epidemiological data has shown worrisome rates of FQ resistance. A single-center cohort study on 136 autologous stem cell transplantations (ASCTs) and 223 allogeneic hematopoietic stem cell transplantations (allo-HSCTs) was performed from January 2018 to December 2020. Piperacillin/tazobactam was the first-line therapy for febrile neutropenia (FN). Since February 2019, FQ-P has been omitted. We evaluated the day+30 posttransplant cumulative incidence function (CIF) of gram-negative bacteria pre-engraftment bloodstream infections (PE-BSIs) and any changes in antimicrobial resistance, FN, and infection-related mortality (IRM). In ASCTs, ≥1 FN episode occurred in 74.3% of transplants, without differences among groups (P = .66). CIF of gram-negative bacteria PE-BSI was 10.1%, with a significant difference according to FQ-P (0% [LEVO-group] vs 14.1% [NO-LEVO-group], P = .016). CIF of IRM was 0% in both groups. In allo-HSCTs, ≥1 FN episode occurred in 96.4% of transplants, without differences among groups (P = .72). CIF of gram-negative bacteria PE-BSI was 28%, significantly higher without FQ-P (14.7% [LEVO-group] vs 34.4% [NO-LEVO-group], P = .003). CIF of IRM was 5%, superimposable in both groups (P = .62). Comparing antimicrobial resistance among gram-negative bacteria of allo-HSCT setting, in the group without FQ-P, a significantly higher proportion of pathogens was susceptible to piperacillin/tazobactam (71% vs 30%, P = .026), FQ (49% vs 10%, P = .03), and carbapenems (95% vs 50%, P = .001). FQ-P discontinuation increased gram-negative bacteria PE-BSI but did not impact IRM, both in the ASCT and allo-HSCT settings; importantly, it concurred to significantly decrease antimicrobial resistance in gram-negative bacteria.

Impact of fluoroquinolone administration and gut mucosal colonization on the risk of pre-engraftment bloodstream infections after allogeneic hematopoietic cell transplantation

Fluoroquinolones (FQ) has been used after allogeneic hematopoietic stem cell transplantation (allo-HCT) for decades. This study on 284 allo-HCT recipients aimed to analyze the impact of FQ on pre-engraftment BSI. A total of 154 patients were colonized with resistant gram-negative bacteria, and 130 patients were not. Colonized patients did not receive FQ (n = 147) except 7 who received FQ as sequential therapy; 98 non-colonized patients received FQ, whereas 32 did not. Gram-negative (p < 0.0001), and ESBL-E BSI (p < 0.0001) were higher in colonized patients receiving FQ. No difference was found in gram-positive BSI (p = 0.452). In multivariate analysis colonized patients with (p < 0.0001) or without FQ (p = 0.007), omission of FQ in non-colonized patients (p = 0.038), and active disease (p = 0.042) were associated with gram-negative BSI, whereas mismatched unrelated donor transplantations - with gram-positive BSI (p = 0.009). Colonized patients with FQ have a higher risk of gram-negative BSI. In non-colonized patients, FQ prophylaxis is effective approach significantly reducing gram-negative BSI risk.

Snapshots of ID Week 2022

Snapshots of ID Week 2022

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.

Risk of bloodstream infections in allogeneic hematopoietic cell transplant recipients according to gut mucosal colonization and fluoroquinolone implementation during neutropenia

Background . Higher rate of gram-negative bloodstream infections (BSI) have been recently documented from transplantation centers providing fluoroquinolone (FQ) prophylaxis. Aim . To define the incidence of BSI during neutropenia according to gut mucosal colonization with resistant gramnegative bacteria and FQ administration. Materials and methods . Of 284 allogeneic hematopoietic cell transplant recipients included in the study, 154 (54.2 %) were identified as colonized with resistant gram-negative bacteria, and 130 (45.8 %) patients as non-colonized. Resistant gram-negative bacteria included Enterobacterales with extended spectrum beta-lactamase production, carbapenem-resistant Enterobacterales, Stenotrophomonas maltophilia , and carbapenem-resistant strains of Pseudomonas aeruginosa . Colonized patients did not receive FQ prophylaxis (n = 147) except 7 patients who received FQ as sequential therapy due to residual inflammatory lung lesions. Among non-colonized patients 98 received FQ prophylaxis, whereas 32 did not. Results . Probability of gram-negative BSI (71.4 %; p &lt;0.0001), and extended spectrum beta-lactamase-producing Enterobacterales BSI (57.1 %; p &lt;0.0001) was significantly higher in colonized patients receiving FQ. No significant difference was found in probability of gram-positive BSI (p = 0.452). In multivariate analysis colonized patients with (hazard ratio (HR) 35.32; 95 % confidence interval (CI) 9.15–136.44; p &lt;0.0001) or without FQ (HR 3.44; 95 % CI 1.15–10.31; p = 0.007), omission of FQ in non-colonized patients (HR 4.03; 95 % CI 1.08–15.00; p = 0.038), and active disease before allogeneic hematopoietic cell transplantation (HR 2.17; 95 % CI 1.03–4.63; p = 0.042) were associated with higher risk of gram-negative BSI, whereas mismatched unrelated donor transplantations were associated with higher gram-positive BSI risk (HR 3.84; 95 % CI 1.63–9.08; p = 0,009). Conclusion . Colonization with multiresistant gram-negative bacteria is a predictor of gram-negative BSI, including multiresistant pathogens, especially when FQ are prescribed during neutropenia, while in non-colonized patients FQ prophylaxis is an effective approach significantly reducing gram-negative BSI.

Evaluation of a rapid combination disc test (RCDT) for direct phenotypic detection of extended-spectrum β-lactamase production in E. coli from positive blood culture bottles.

The spread of multi-resistant bacteria endangers the effectiveness of empirical antimicrobial treatment, particularly in Gram-negative bloodstream infections. Thus, rapid and reliable susceptibility testing has become a key challenge of modern microbiology. Here, we evaluated a combination disc test for rapid detection of ESBL production in Escherichia coli (rapid combination disc test, RCDT) directly from blood cultures. RCDT with discs containing cefotaxime and ceftazidime alone or in combination with clavulanic acid was validated using a cryo-collection of 96 third-generation cephalosporin-resistant (3GCR), whole-genome sequenced E. coli isolates spiked into blood culture bottles. All isolates were subjected to RCDT and rapid antibiotic susceptibility testing (RAST). Zone diameters were assessed after 4, 6 and 8 h of incubation. All isolates also underwent conventional combination disc testing. The real-life performance of RCDT was assessed by analysis of 306 blood cultures growing E. coli. Eighty of 90 (88.9%) ESBL-positive E. coli validation isolates were correctly identified by RCDT after 4 h of incubation. The detection rate increased to 100% after 6 and 8 h. RCDT was negative in six 3GCR E. coli isolates expressing class B or C β-lactamases. RCDT from routine blood cultures correctly classified all 56 ESBL producers and 245/250 ESBL-negative isolates after 4 h, resulting in 100% sensitivity and 98.8% specificity. RCDT is a reliable method for rapid ESBL detection in E. coli directly from positive blood cultures. RCDT might complement RAST to support antibiotic stewardship interventions and treatment decisions.

Prevalence of bloodstream infection pathogens in hemato-oncological patients and predictors of carbapenem-resistant gram-negative bacterial infections during febrile neutropenia.

Carbapenem-Resistant Gram-Negative (CRGN) Bloodstream Infections (BSI) represent a therapeutic challenge, especially in the context of Febrile Neutropenia (FN) in cancer patients. We characterized pathogens causing BSI in patients aged ≥18 years who had undergone systemic chemotherapy for solid or hematological cancers between 2012 and 2021 in Porto Alegre, Brazil. Predictors of CRGN were evaluated through a case-control analysis. Each case was matched to two controls from whom CRGN were not isolated and had the same sex and year of inclusion in the study. From 6094 blood cultures evaluated, 1512 (24.8%) showed positive results. Gram-negative bacteria accounted for 537 (35.5%) of the isolated bacteria, of which 93 (17.3%) were carbapenem-resistant. From 105 patients included in the case-control analysis, all cases had baseline hematological malignancies (60% acute myeloid leukemia). Variables related to CRGN BSI in Cox regression analysis were the first chemotherapy session (p<0.01), chemotherapy performed in the hospital setting (p=0.03), intensive care unit admission (p<0.01), and CRGN isolation in the previous year (p<0.01). Patients with CRGN BSI received 75% less empirical active antibiotics and had 27.2% higher 30-day mortality rates than controls. A CRGN risk-guided approach should be considered for empirical antibiotic therapy in patients with FN.

Levofloxacin Prophylaxis Versus no Prophylaxis in Acute Myeloid Leukemia During Post-Induction Aplasia: a Single Center Study.

Acute myeloid leukemia (AML) patients are at high risk of infections during post-induction neutropenia. Recently, the role of antibacterial prophylaxis has been reconsidered due to concerns about the emergence of multi-resistant pathogens. The aim of the present study was to evaluate the impact of avoiding prophylaxis on the rate of induction death (primary endpoint), neutropenic fevers, bloodstream infections (BSIs), resistant pathogens BSIs and septic shocks (secondary endpoints). We performed a retrospective single-center study including 373 AML patients treated with intensive induction chemotherapy, divided into two groups according to levofloxacin prophylaxis given (group A, gA) or not (group B, gB). Neutropenic fever was observed in 91% of patients in gA and 97% in gB (OR 0.35, IC95% 0.08 - 1.52, p=0162). The rate of BSIs was 27% in gA compared to 34% in gB (OR 0.69, 0.38 - 1.25, p=0.222). The induction death rate was 5% in gA and 3% in gB (OR 1.50, 0.34 - 6.70, p=0.284). Fluoroquinolones (FQ) resistant pathogens were responsible for 59% of total BSIs in gA and 22% in gB (OR 5.07, 1.87 - 13.73, p=0.001); gram-negative BSIs due to multi-drug resistant organisms were 31% in gA and 36% in gB (OR 0.75, 0.15 - 3.70, p=0.727). Despite its limitations (retrospective nature, single-center, different cohort size), the present study showed that avoiding levofloxacin prophylaxis was not associated with an increased risk of induction death. The cumulative incidence of neutropenic fever was higher in non-prophylaxis group, while no difference was observed for BSIs. In the prophylaxis group we observed a higher incidence of FQ-resistant organisms.

Which trial do we need? Early oral antibiotic therapy for the treatment of gram-negative bloodstream infections

Which trial do we need? Early oral antibiotic therapy for the treatment of gram-negative bloodstream infections

Persistent bacteremia predicts poor outcomes among neutropenic patients with carbapenem-resistant gram-negative bloodstream infections receiving appropriate therapy

PurposeIdentifying persistent bacteremia early in patients with neutropenia may improve outcome. This study evaluated the role of follow-up blood cultures (FUBC) positivity in predicting outcomes among patients with neutropenia and carbapenem-resistant gram-negative bloodstream infections (CRGNBSI).MethodsThis retrospective cohort study conducted between December 2017 and April 2022 included patients more than 15 years old with neutropenia and CRGNBSI, who survived for ≥ 48 h, receiving appropriate antibiotic therapy and had FUBCs. Patients with polymicrobial bacteremia within 30 days were excluded. The primary outcome was 30 day mortality. Persistent bacteremia, septic shock, recovery from neutropenia, prolonged or profound neutropenia, requirement of intensive care and dialysis, and initiation of appropriate empirical therapy were also studied.ResultsIn our study cohort of 155 patients, the 30 day mortality rate was 47.7%. Persistent bacteremia was common in our patient cohort (43.8%). Carbapenem resistant isolates identified in the study were K.pneumoniae (80%), E.coli (12.26%), P.aeruginosa (5.16%), A.baumanii (1.94%) and E.cloacae (0.65%). The median time for sending a FUBC was 2 days (IQR, 1–3 days). Patients with persistent bacteremia had higher mortality than those without (56.76% versus 32.1%; p < 0.001). Appropriate initial empirical therapy was given to 70.9%. Recovery from neutropenia occurred in 57.4% while 25.8% had prolonged or profound neutropenia. Sixty-nine percent (107/155) had septic shock and needed intensive care; 12.2% of patients required dialysis. Non-recovery from neutropenia (aHR, 4.28; 95% CI 2.53–7.23), presence of septic shock (aHR, 4.42; 95%CI 1.47–13.28), requirement of intensive care (aHR,3.12;95%CI 1.23–7.93), and persistent bacteremia (aHR,1.74; 95%CI 1.05–2.89) significantly predicted poor outcomes in multivariable analysis.ConclusionFUBC showing persistent bacteremia predicted poor outcomes among neutropenic patients with carbapenem-resistant gram-negative bloodstream infections (CRGNBSI) and should be routinely reported.

Clearance of blood stream infections in patients receiving extracorporeal membrane oxygenation: a retrospective single-center cohort study

BackgroundThere are limited data on the treatment of blood stream infections (BSIs) in patients receiving extracorporeal membrane oxygenation (ECMO). Current guidance recommends documenting clearance only in fungal and Gram-positive BSIs. This study investigates the incidence and clinical significance of blood stream infections with positive repeat cultures (BSIPRC) in ECMO as well as clinical factors that may predict positive repeat cultures.MethodsAll BSIs in patients receiving ECMO at Brooke Army Medical Center between September 2012 and October 2021 were included in this study. BSIPRC was defined as re-isolation of the same organism on repeat blood cultures following an initial positive blood culture.ResultsA total of 60 patients developed 87 BSI (38.5 BSI per 1000 ECMO days). Of the 80 (92%) BSIs who had repeat blood cultures drawn, patients had BSIPRC in 35 (44%) of cases. Fever, leukocytosis, and vasopressor requirement on day of repeat culture were not associated with persistent positivity. There was no difference in survival to discharge for patients with BSIPRC as compared to single day BSI (58% vs. 63%, p = 0.78). 19% of patients with Gram-negative bacteremia had BSIPRC, and gram-negative bacteremia in general was associated with an 83% morality.ConclusionsThere were no clinical findings that differentiated patients with BSIPRC from those who had a single day of positivity. BSI was associated with high mortality in patients with Gram-negative bacteremia. Given high incidence of positive repeat cultures being seen in Gram-negative BSIs, repeat blood cultures have utility for all BSIs in patients receiving ECMO.

Increasing Gram-Negative Catheter-Related Bloodstream Infection in Cancer Patients.

Background: We aimed to assess the incidence, etiology and outcomes of catheter-related bloodstream infection (CRBSI) in onco-hematological patients, to assess the differences between patients with hematological malignancies (HMs) and solid tumors (STs) and to identify the risk factors for Gram-negative (GN) CRBSI. Methods: All consecutive episodes of BSI in adult cancer patients were prospectively collected (2006-2020). The etiology of CRBSI was analyzed in three different 5-year periods. Risk factors for GN CRBSI were assessed in the whole cohort and separately in patients with HMs and STs. Results: Among 467 episodes of monomicrobial CRBSI, 407 were Gram-positive (GP) (87.1%), 49 GN (10.5%) and 11 fungal (2.4%). Hematological patients (369 episodes) were more frequently neutropenic and were more likely to carry central venous catheters and develop GP CRBSI. Patients with STs (98 episodes) had more comorbidities, more frequently carried port reservoirs and commonly presented more GN CRBSI. GN CRBSI significantly increased over the study period, from 5.2% to 23% (p < 0.001), whereas GP CRBSI decreased from 93.4% to 73.3% (p < 0.001). CRBSI episodes involving port reservoirs and peripherally-inserted central catheters were significantly increased (p < 0.001). The most frequent GPs were coagulase-negative staphylococci (CoNS) (57.8%) and Pseudomonas aeruginosa was the most common GN (3%). Multidrug-resistant (MDR) GN represented 32.7% of all GN CRBSIs and increased over time (p = 0.008). The independent risk factors for GN CRBSI in the whole cohort were solid tumor, chronic kidney disease and carrying a port reservoir. Carrying a port reservoir was also a risk factor in patients with STs. Health-care acquisition was identified as a risk factor for GN CRBSI in the whole cohort, as well as in patients with STs and HMs. Inadequate empirical antibiotic treatment (IEAT) occurred regardless of the etiology: 49% for GNs and 48.6% for GPs (p = 0.96). In GP CRBSI, IEAT was mainly due to inadequate coverage against CoNS (87%), whereas in GN CRBSI, IEAT was associated with multidrug resistance (54.2%). Early (48 h and 7-day) and 30-day case-fatality rates were similar when analyzed according to the type of underlying disease and etiology, except for the 30-day case-fatality rate, which was higher in the group of patients with STs compared to those with HMs (21.5% vs. 12.5%, p = 0.027). The 48 h case-fatality rate was significantly higher in patients in whom the catheter had not been removed (5.6% vs. 1%; p = 0.011), and it remained significant for GP CRBSI (6% vs. 1.3%, p = 0.023). Conclusions: GNs are an increasing cause of CRBSI in cancer patients, particularly in solid tumor patients carrying port reservoirs. Multidrug resistance among GNs is also increasing and is associated with higher rates of IEAT. Decreased 48 h survival was associated with the non-removal of the catheter. These findings should be considered when deciding on early therapeutic management for cancer patients with suspected CRBSI.

Multicenter Surveillance of Antimicrobial Resistance among Gram-Negative Bacteria Isolated from Bloodstream Infections in Ghana

Antimicrobial resistance (AMR) in Gram-negative bacteria-causing bloodstream infections (BSIs), such as Klebsiella pneumoniae and non-typhoidal Salmonella (NTS), is a major public health concern. Nonetheless, AMR surveillance remains scarce in sub-Saharan Africa, where BSI treatment is largely empirical. The aim of the study was to determine the distribution and AMR patterns of BSI-causing NTS, K. pneumoniae, and other Gram-negative bacteria in Ghana. A cross-sectional study was conducted between April and December 2021 at eleven sentinel health facilities across Ghana as part of a pilot study on the feasibility and implementation of the human sector AMR surveillance harmonized protocol in sub-Saharan Africa. Gram-negative bacteria recovered from blood specimens of febrile patients were identified using MALDI-TOF and evaluated for antimicrobial resistance using the BD Phoenix M50 analyzer and Kirby-Bauer disc diffusion. The Department of Medical Microbiology at the University of Ghana served as the reference laboratory. Out of 334 Gram-negative blood isolates, there were 18 (5.4%) NTS, 85 (25.5%) K. pneumoniae, 88 (26.4%) Escherichia coli, 40 (12.0%) Acinetobacter baumannii, 25 (7.5%) Pseudomonas aeruginosa, and 77 (23.1%) other Gram-negative bacteria. As a composite, the isolates displayed high resistance to the antibiotics tested-amoxicillin (89.3%), tetracycline (76.1%), trimethoprim-sulfamethoxazole (71.5%), and chloramphenicol (59.7%). Resistance to third-generation cephalosporins [ceftriaxone (73.7%), cefotaxime (77.8%), and ceftazidime (56.3%)] and fluoroquinolones [ciprofloxacin (55.3%)] was also high; 88% of the isolates were multidrug resistant, and the rate of extended-spectrum beta-lactamase (ESBL) production was 44.6%. Antibiotic resistance in K. pneumoniae followed the pattern of all Gram-negative isolates. Antibiotic resistance was lower in NTS blood isolates, ranging between 16.7-38.9% resistance to the tested antibiotics. Resistance rates of 38.9%, 22.2%, and 27.8% were found for cefotaxime, ceftriaxone, and ceftazidime, respectively, and 27.8% and 23.8% for ciprofloxacin and azithromycin, respectively, which are used in the treatment of invasive NTS. The prevalence of multidrug resistance in NTS isolates was 38.9%. Multicenter AMR surveillance of Gram-negative blood isolates from febrile patients was well-received in Ghana, and the implementation of a harmonized protocol was feasible. High resistance and multidrug resistance to first- or second-choice antibiotics, including penicillins, third-generation cephalosporins, and fluoroquinolones, were found, implying that these antibiotics might have limited effectiveness in BSI treatment in the country. Continuation of AMR surveillance in Gram-negative blood isolates is essential for a better understanding of the extent of AMR in these pathogens and to guide clinical practice and policymaking.

Antibiotic appropriateness for Gram-negative bloodstream infections: impact of infectious disease consultation

Background We investigated the role of infectious disease consultation (IDC) on therapeutic appropriateness in Gram-negative bloodstream infections (GNBSIs) in a setting with a high proportion of antibiotic resistance. Secondary outcomes were in-hospital mortality and the impact of rapid diagnostic tests (RDTs). Methods Retrospective study on hospitalised patients with GNBSIs. Therapy was deemed appropriate if it had the narrowest spectrum considering infection and patients’ characteristics. Interventional-IDC (I-IDC) group included patients with IDC-advised first appropriate or last non-appropriate therapy. Time to first appropriate therapy and survival were evaluated by Kaplan-Meier curves. Factors associated with therapy appropriateness were assessed by multivariate Cox proportional-hazard models. Results 471 patients were included. High antibiotic resistance rates were detected: quinolones 45.5%, third-generation cephalosporins 37.4%, carbapenems 7.9%. I-IDC was performed in 31.6% of patients (149/471), RDTs in 70.7% (333/471). The 7-day probability of appropriate treatment was 91.9% (95% confidence interval [95%CI]: 86.4–95.8%) vs. 75.8% (95%CI: 70.9–80.4%) with and without I-IDC, respectively (p-value = 0.0495); 85.5% (95%CI: 81.3–89.1%) vs. 69.4% (95%CI: 61.3–77.2%) with and without RDTs, respectively (p-value = 0.0023). Compared to RDTs alone, the combination with I-IDC was associated with a higher proportion of appropriate therapies at day 7: 81.9% (95%CI: 76.4–86.7%) vs. 92.6% (95%CI: 86.3–96.7%). At multivariate analysis, I-IDC and RDTs were associated with time to first appropriate therapy [adjusted hazard-ratio 1.292 (95%CI: 1.014–1.647) and 1.383 (95%CI: 1.080–1.771), respectively], with no impact on mortality. Conclusions In a setting with a high proportion of antibiotic resistance, IDC and RDTs were associated with earlier prescription of appropriate therapy in GNBSIs, without impact on mortality.

Benefits and Safety of Empiric Antibiotic Treatment Active Against KPC-K. pneumoniae in Febrile Neutropenic Patients with Acute Leukemia Who are Colonized with KPC-K. pneumoniae. A 7-Years Retrospective Observational Cohort Study.

To evaluate the benefits and safety of the empiric antibiotic treatment (EAT) active against KPC-K. pneumoniae in febrile neutropenic patients with acute leukaemia (AL) who are colonised by KPC-K. pneumoniae. A 7-year (2013-2019) retrospective observational cohort study was conducted at the Haematology, Sapienza Rome University (Italy) on 94 febrile neutropenia episodes (FNE) in AL patients KPC-K. pneumoniae carriers treated with active EAT. Eighty-two (87%) FNE were empirically treated with antibiotic combinations [38 colistin-based and 44 ceftazidime-avibactam (CAZAVI)-based], 12 with CAZAVI monotherapy. Successful outcomes were observed in 88/94 (94%) FNE, 46/49 (94%) microbiologically documented infections, and 24/27 (89%) gram-negative bloodstream infections (GNB-BSI). Mortality due to infective causes was 4.2% (2.1% within 1 week). KPC-K. pneumoniae infections caused 28/94 FNE (30%) and KPC-K. pneumoniae-BSI was documented in 22 FNE (23.4%) (85% of GNB-BSI), in all cases patients received active EAT, and 21 survived. KPC-K.pneumoniae-BSI mortality rate was 4.5%. CAZAVI-based EAT showed better results than colistin-based EAT (55/56 vs 33/38, p = 0.037), overall and without EAT modification (41/56 vs 20/38, p = 0.02). Empirical combinations including CAZAVI were successful in 98% of cases (43/44 vs 33/38 for colistin-based EAT, p = 0.01), without modifications in 82% (36/44 vs 20/28, p = 0.02). All deaths occurred in patients treated with colistin-based EAT (4/38 vs 0/56, p = 0.02). CAZAVI-containing EAT was the only independent factor for an overall successful response (HR 0.058, CI 0.013-1.072, p = 0.058). Nephrotoxicity occurred in 3(8%) patients undergoing colistin-based EAT (none in those undergoing CAZAVI-based EAT, p = 0.02). KPC-K. pneumoniae infections are frequent in colonised AL patients with FNE. EAT with active antibiotics, mainly CAZAVI-based combinations, was effective, safe, and associated with low overall and KPC-K. pneumoniae-BSI-related mortality.

Post-engraftment Bloodstream Infections After Allogeneic Hematopoietic Cell Transplantation: Risk Factors and Association with Mortality.

Bloodstream infections (BSIs) are major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (allo-HCT). This study aimed to analyze the incidence, etiology, risk factors and outcomes of post-engraftment BSI in allo-HCT recipients. The retrospective study included 261 patients with documented engraftment after first allo-HCT performed from January 2018 till September 2021. Of 261 patients 29 (11.1%) developed at least one post-engraftment BSIs episode with a median time to post-engraftment BSI of 49 days (range, 1 - 158 days from the engraftment). A total of 45 pathogens were isolated from blood - 64.4% (n = 29) were represented by Gram-negative bacteria, and 35.6% (n = 16) - by Gram-positive bacteria. Secondary graft failure (hazard ratio [HR]: 39.93; 95% confidence interval [CI]: 7.64-208.74; P <0.001), secondary poor graft function (HR: 18.07; 95% CI: 3.53 - 92.44; P <0.001), and acute gut graft-versus-host-disease (GvHD) grade II-IV (HR: 29.86; 95% CI: 10.53 - 84.68; P <0.001) were associated with the higher risk of Gram-negative post-engraftment BSIs. Overall 30-day survival after post-engraftment BSIs was 71.4%. By multivariate analysis post-engraftment BSIs (HR: 3.09; 95% CI: 1.29 - 7.38; P = 0.011), and acute gut GvHD grade II-IV (HR: 6.60; 95% CI: 2.78 - 15.68; P <0.001) were associated with the higher 180-day non-relapse mortality risk. Gram-negative bacteria prevailed in the etiology of post-engraftment BSIs with secondary graft failure. secondary poor graft function. and acute gut GvHD being the main predisposing factors for their development. Post-engraftment BSIs were associated with the higher risk of non-relapse mortality after allo-HCT.

The relationship between minimum inhibitory concentration and 28 day mortality in patients with a Gram-negative bloodstream infection: an analysis of data from a cohort study (BSI-FOO).

To explore the association between MIC/EUCAST breakpoint ratio and 28 day mortality in patients with a Gram-negative bloodstream infection (BSI). Using data from the Bloodstream Infection-Focus on Outcomes (BSI-FOO) observational study, we defined an average MIC/EUCAST breakpoint ratio that was updated daily to reflect changes in treatment in the first 7 days after blood culture. Cox regression analysis was performed to estimate the association between MIC/EUCAST breakpoint ratio and mortality, adjusting for organism and a risk score calculated using potential confounding variables. The primary outcome was 28 day all-cause mortality from the date of blood culture. Of the 1903 study participants, 514 met the eligibility criteria and were included in the analysis (n = 357 Escherichia coli, n = 6 Klebsiella and n = 151 Pseudomonas aeruginosa). The average age was 74.0 years (IQR 60.0-82.0). The mortality rate varied from 11.1% (in patients treated with an average MIC/EUCAST breakpoint ratio of 1) to 27.6% (in patients treated with antibiotics with an average MIC/EUCAST breakpoint ratio >1). After adjusting for risk score and organism, MIC/EUCAST breakpoint ratio was not associated with 28 day mortality (P = 0.148). In an adjusted model controlling for potential confounding variables, there was no evidence to suggest a relationship between MIC/EUCAST breakpoint ratio and 28 day mortality in patients with a Gram-negative BSI.

1841. Incidence and Predictors of Complications in Gram Negative Bloodstream Infection

Abstract Background The incidence of complications in Gram negative bloodstream infection (GN-BSI) is not clearly defined. This retrospective cohort study evaluates the incidence of complications within 90 days of GN-BSI and examines the predictors for these complications. Methods Hospitalized adult patients with monomicrobial GN-BSI at Prisma Health-Midlands hospitals in South Carolina between 1/1/2012 and 6/30/2015 were evaluated. Complications of GN-BSI were defined as endocarditis, septic arthritis, osteomyelitis, spinal infections, deep seated abscesses, and recurrent GN-BSI within 90 days of the initial episode. Clinical and microbiological variables were assessed as potential risk factors for complications, including initial response to antimicrobial therapy within the first 72-96 hours of GN-BSI using the early clinical failure criteria. Kaplan-Meier analysis and multivariate Cox proportional hazards regression were used to examine the incidence and risk factors of complicated GN-BSI, respectively. Results A total 752 patients with GN-BSI were included in the study. The median age was 66 years and 380 (50.6%) were women. The urinary tract was the most common source of GN-BSI (378; 50.2%) and Escherichia coli was the most common bacteria (375; 49.9%). Overall, 13.9% developed complications within 90 days of GN-BSI. The median time to identification of these complications was 5.2 days from the index GN-BSI (interquartile range 1-28 days). The incidence of complications was notably higher in BSI due to Serratia species (39.7%), Proteus mirabilis (35.7%), and Pseudomonas aeruginosa (21.5%) than other bacteria (11.1%; log-rank p&amp;lt; 0.001). Independent risk factors for complications included early clinical failure criteria, non-urinary source, presence of indwelling prosthetic devices, BSI due to Serratia species, P. mirabilis or P. aeruginosa, and persistent GN-BSI (Table). Conclusion At least 13.9% of patients developed complications within 90 days of GN-BSI. Risk of development of complications may be predicted by specific host and microbiological factors. Stratification of patients based on these risk factors may aid in identifying patients requiring further diagnostic work up for early detection of complications. Disclosures Julie Ann Justo, PharmD, MS, FIDSA, BCPS-AQ ID, bioMerieux: Honoraria|bioMerieux: Honoraria|Entasis Therapeutics: Advisor/Consultant|Entasis Therapeutics: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Merck &amp; Co: Advisor/Consultant|Merck &amp; Co: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi Inc.: Advisor/Consultant|Spero Therapeutics: Honoraria|Spero Therapeutics: Honoraria|Vaxart: Stocks/Bonds Julie Ann Justo, PharmD, MS, FIDSA, BCPS-AQ ID, bioMerieux: Honoraria|bioMerieux: Honoraria|Entasis Therapeutics: Advisor/Consultant|Entasis Therapeutics: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Merck &amp; Co: Advisor/Consultant|Merck &amp; Co: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi Inc.: Advisor/Consultant|Spero Therapeutics: Honoraria|Spero Therapeutics: Honoraria|Vaxart: Stocks/Bonds P. Brandon Bookstaver, PharmD, Spero Therapeutics: Advisor/Consultant.