Clinical and cost benefit of rapid molecular screening for carbapenem-resistant organisms: a seven-year analysis in a tertiary hospital.

Cefiderocol versus standard therapy for hospital-acquired and health-care-associated Gram-negative bacterial bloodstream infection (the GAME CHANGER trial): an open-label, parallel-group, randomised trial.

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

BackgroundThe emergence of carbapenem-resistant organisms (CROs) poses a major challenge to clinical infection control in hospitals. Patients undergoing hematopoietic stem cell transplants (HSCTs) infected with CROs are at high risk of mortality. Proactive screening of HSCT patients for CRO colonization may enable early and accurate preemptive anti-CRO therapy, reduce the probability of secondary infections, and contribute to infection prevention and control measures. However, screening CRO colonization with stool/rectal swab culture and sensitivity has a low positivity rate with a long turnaround time, which limits the effectiveness of the interventions. A more rapid and accurate method to detect CRO colonization is urgently needed. Xpert Carba-R assay provides a rapid and accurate detection of carbapenemase types, enabling targeted anti-infective therapy selection based on the identified resistance mechanism.MethodsWe conducted a historically controlled prospective study at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between August 2021 and July 2022. The study population comprised adult HSCT patients (≥18 years old) who received preemptive anti-CRO therapy based on rectal culture and Xpert Carba-R screening during this period. A total of 381 patients who underwent HSCT from August 2020 to July 2022 were included in the study, and CRO colonization screening was performed on admission and weekly thereafter. In the historic control group from August 2020 to July 2021, HSCT patients were screened only by rectal swab traditional CRO culture, and CRO colonization was determined if the rectal culture was positive. In the study group from August 2021 to July 2022, two rectal swab specimens were collected from HSCT patients for both CRO traditional culture (RS-culture) and Xpert Carba-R testing (RS-Carba-R). CRO colonization was determined if either of the screening methods was positive. CRO-active antibiotics were immediately provided on the first febrile episode of neutropenia (FN) in CRO-colonized patients. Clinical outcome data for the CRO monthly colonization rate and anti-infection efficiency were collected and contrasted between the two groups.ResultsIn the historic group, 47 out of 197 patients (23.9%) were identified as colonized with CRO, detected only by RS-culture. In the study group, 41 out of 184 patients (22.3%) were identified as colonized with CRO, detected by either RS-culture or RS-Carba-R; among them, Escherichia coli was the most common CP-CRO strain, and the most prevalent carbapenemase type was NDM. This indicated a slightly lower annual detection rate of CRO gut colonization in the study group compared to the historic group, but no significant difference was observed (22.3% vs. 23.9%, p = 0.715). The incidence of CRO-related bloodstream infections (CRO-BSI) was significantly lower in the study group compared to the historic group (4.8% vs. 25.5%, p = 0.012), and the CRO-related mortality in colonized patients decreased from 19.4% in the historic group to 2.4% in the study group (p = 0.046). The monthly detection rate of CRO gut colonization by RS-culture in the historic group remained steady, with no significant fluctuation (19.7% in the first month and 18.8% in the last month). In contrast, the monthly detection rate of CRO gut colonization by either RS-culture or RS-Carba-R in the study group was higher in the first month compared to the historic group (21.2% in August 2021 vs. 18.8% in July 2021). However, a gradual decline in the monthly detection rates of CRO gut colonization by RS-culture and/or RS-Carba-R was observed in the study group, dropping from 21.2% in the first month to 2.9% in the last month. The univariate and multivariate analyses indicated that the study group had a shorter length of hospitalization (OR = 0.94, 95% CI 0.88–0.99, p = 0.038) and CRO-related mortality (OR = 0.12, 95% CI 0.01–0.75, p = 0.021) than the historic group.ConclusionsOur study showed a positive effect of more rapid CRO colonization screening using rectal swabs with Xpert Carba-R and culture, which can guide potent CRO preemptive therapy for subsequent infections based on the detected carbapenemase mechanism, thereby reducing mortality and the spread of CRO infection in HSCT patients.Clinical Trial Registrationchictr.org, identifier ChiCTR2100041976.

Carbapenem-resistant organisms (CROs) are an urgent health threat. Since 2017, Alameda County Health Public Health Department (ACPHD) mandates reporting of carbapenem-resistant Enterobacterales (CRE) and encourages voluntary reporting of non-CRE CROs including carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA). Surveillance data from ACPHD were analyzed to describe the epidemiology of CROs and target public health interventions. Healthcare facilities in Alameda County reported CRO cases and submitted isolates to ACPHD to characterize carbapenemase genes; deaths were identified via the California Electronic Death Registration System. CRO cases with isolates resistant to one or more carbapenems were analyzed from surveillance data from July 2019 to June 2021. Four hundred and forty-two cases of CROs were reported to Alameda County from 408 patients. The county case rate for CROs was 29 cases per 100,000 population, and cases significantly increased over the 2-year period. CRPA was most commonly reported (157 cases, 36%), and cases of CRAB increased 1.83-fold. One-hundred eighty-six (42%) cases were identified among residents of long-term care facilities; 152 (37%) patients had died by January 2022. One hundred and seven (24%) cases produced carbapenemases. The high burden of CROs in Alameda County highlights the need for continued partnership on reporting, testing, and infection prevention to limit the spread of resistant organisms. A large proportion of cases were identified in vulnerable long-term care residents, and CRAB was an emerging CRO among this population. Screening for CROs and surveillance at the local level are important to understand epidemiology and implement public health interventions.

The spread of carbapenem-resistant organisms (CROs) is an increasingly serious threat globally, especially in vulnerable populations, such as intensive care unit (ICU) patients. Currently, the antibiotic options for CROs are very limited, particularly in pediatric settings. We describe a cohort of pediatric patients affected by CRO infections, highlighting the important changes in carbapenemase production in recent years and comparing the treatment with novel cephalosporins (N-CEFs) to Colistin-based regimens (COLI). All patients admitted to the cardiac ICU of the Bambino Gesù Children's Hospital in Rome during the 2016-2022 period with an invasive infection caused by a CRO were enrolled. The data were collected from 42 patients. The most frequently detected pathogens were Pseudomonas aeruginosa (64%), Klebsiella pneumoniae (14%) and Enterobacter spp. (14%). Thirty-three percent of the isolated microorganisms were carbapenemase producers, with a majority of VIM (71%), followed by KPC (22%) and OXA-48 (7%). A total of 67% of patients in the N-CEF group and 29% of patients in the comparative group achieved clinical remission (p = 0.04). The increase over the years of MBL-producing pathogens in our hospital is challenging in terms of therapeutic options. According to the present study, N-CEFs are a safe and effective option in pediatric patients affected by CRO infections.

Modelling interventions and contact networks to reduce the spread of carbapenem-resistant organisms between individuals in the ICU

Background Antimicrobial resistance (AMR) is the global leading cause of death from infections, particularly affecting low- and middle-income countries. Colonization with carbapenem-resistant organisms (CRO) increases the risk of infections with CRO. In an interim analysis of a prospective cohort study, we found 77% (141/182) of neonates in a neonatal intensive care unit (NICU) of a tertiary-care hospital in Bangladesh were colonized with carbapenem-resistant Klebsiella pneumoniae (CR-Kpn), with 63% (89/141) acquiring colonization >48 hours after hospitalization. We aimed to assess the impact of infection control (IC) interventions on CRO colonization among neonates admitted to the NICU. Methods From July 2023 to April 2024, we enrolled 604 neonates: 358 before the intervention and 246 after. Neonates were assessed for CRO colonization using rectal swabs collected on admission, days 3 and 7, and weekly thereafter. Swabs were plated on selective agar mSuperCARBA followed by confirmatory identification and susceptibility testing using VITEK® 2. Positive blood cultures collected from patients with suspected sepsis underwent testing using VITEK® 2. Our IC interventions targeted hand hygiene (HH) and environmental cleaning (EC), including staff training on proper HH techniques and more frequent cleaning of high-touch surfaces, as well as regular audits to measure compliance with HH and EC. We conducted descriptive analyses using Pearson’s Chi-square test. Results Compliance with HH improved from 13% to 28% following the interventions, while environmental cleaning improved from 9% to 43% based on fluorescent markers. Over the same time, CRO colonization decreased from 74% (265/358) to 63% (153/246) (p=0.002) and CR-Kpn colonization decreased from 65% (232/358) to 54% (134/246) (p=0.011). Overall bacterial blood culture positivity [54% (51/95) vs. 57% (30/53), (p=0.87)] and CRO rates [13% (12/95) vs. 21% (11/53), p=0.19] remained stable at pre and post intervention respectively. Conclusion After implementing IC interventions, we observed a decrease in CRO colonization among NICU patients, though blood culture positivity was unchanged. Results suggest that even modest improvements in IC practices may have a role in curbing CRO transmission in high-risk settings. Disclosures All Authors: No reported disclosures

Objective: This study aimed to analyze the homology between carbapenem-resistant organisms (CRO) intestinal colonization strains and bloodstream infection (BSI) strains in patients undergoing hematopoietic stem cell transplantation (HSCT), confirming the clinical use of the real-time rectal swab Xpert Carba-R assay, and investigate its feasibility in early warning of BSI. Methods: Drug-resistant strains obtained from rectal swabs and blood culture samples of patients undergoing the same HSCT from January 2021 to December 2021 were collected and analyzed. The homology of the CRO intestinal colonization and BSI strains was confirmed using strain identification, antimicrobial resistance phenotyping, whole genome sequencing (WGS), multilocus sequence typing (MLST), and carbapenemase type identification. Rectal swab cultures and the real-time rectal swab Xpert Carba-R assay were conducted concurrently on patients with HSCT from August 2021 to August 2022. The accuracy of the real-time rectal swab Xpert Carba-R assay was confirmed with the sequencing results of polymerase chain reaction amplification products of the carbapenemase gene from purified colonies as a reference standard. Results: This study included 24 CRO strains from 10 patients undergoing HSCT, including 14 intestinal colonizers and 10 CRO-BSI strains. The results revealed that the CRO intestinal colonization strains and CRO-BSI strains from the same patient and their carbapenemase genes were almost identical. Additionally, WGS revealed that CRO intestinal colonization and CRO-BSI strains from the same patient were more closely related than strains from different patients. Additionally, this study included 488 rectal swab specimens from 184 patients undergoing HSCT, with CRO detection rates of 16.4% for rectal swab culture and 18.4% for the real-time rectal swab Xpert Carba-R assay. The overall sensitivity, specificity, and positive and negative predictive values of the real-time rectal swab Xpert Carba-R assay were 96.6%, 72.8%, 90.6%, and 88.9%, respectively. Conclusions: A high degree of homology was found between the CRO intestinal colonization strains and the CRO-BSI strains in patients undergoing HSCT. The real-time rectal swab Xpert Carba-R assay is a reliable and convenient method for detecting common carbapenemase genes, serving as an alternative to rectal swab culture for early warning of CRO-BSI.

Carbapenem-resistant (CR) infections cause major morbidity and mortality. Data on CR infections in children with cancer are scarce, especially from the developing world. The aim of this study was to evaluate the characteristics and outcomes of bacteremia with CR organisms (CRO) compared with bacteremia with Carbapenem-sensitive organisms in children with cancer. This retrospective observational study was conducted in a tertiary pediatric oncology center in South India. Data on all bloodstream infections with Gram-negative organisms (CRO and Carbapenem sensitive-organisms) in children with malignancy ≤14 years of age from August 2017 to July 2021 were retrieved. The outcome was determined as survival and all-cause death 28 days after the date of Bloodstream infection (BSI) onset. Sixty-four Gram-negative BSI were identified, with 24% (n=15) in the Carbapenem-Resistant Bloodstream Infection (CR-BSI) group and 76% (n=49) in the Carbapenem-sensitive-Bloodstream Infection group. The patients included 35 males (64%) and 20 females (36%), with ages ranging from 1 year to 14 years (median age: 6.2 y). The most common underlying disease was hematologic malignancy (92.2%, n=59). Children with CR-BSI had a higher incidence of prolonged neutropenia, septic shock, pneumoniae, enterocolitis, altered consciousness, and acute renal failure and were associated with 28-day mortality in univariate analysis. The most common carbapenem-resistant Gram-negative bacilli isolates were Klebsiella species (47%) and Escherichia coli (33%). All carbapenem-resistant isolates were sensitive to colistin, and 33% were sensitive to Tigecycline. The case-fatality rate was 14% (9/64) in our cohort. The overall 28 days mortality was significantly higher in patients with CR-BSI than in those with Carbapenem-sensitive Bloodstream Infection (28-day mortality: 43.8% vs. 4.2%, P =0.001). Bacteremia with CRO has higher mortality in children with cancer. Prolonged neutropenia, pneumoniae, septic shock, enterocolitis, acute renal failure, and altered consciousness were predictors of 28-day mortality in carbapenem-resistant septicemia.

Comparing ceftazidime/avibactam and polymyxin B for treating carbapenem-resistant organisms infections: A propensity score-matched retrospective cohort study.

Objectives: The aim of this work was to investigate the activity of ceftazidime-avibactam (CZA) and aztreonam-avibactam (AZA) against bloodstream infections caused by caused by carbapenem-resistant organisms (CROs). Methods: Nonduplicate CROs, including 56 carbapenem-resistant Escherichia coli (CR-Eco), 318 carbapenem-resistant Klebsiella pneumoniae (CR-Kpn), and 65 carbapenem-resistant Pseudomonas aeruginosa (CR-Pae), were collected by Blood Bacterial Resistant Investigation Collaborative System (BRICS) program in China. The minimum inhibitory concentration (MIC) of 24 antibiotics were tested. Carbapenemase genes were amplified for CZA-resistant CROs by PCR. MIC of CZA and AZA were further determined with avibactam at 8 mg/L and 16 mg/L. Results: The resistant rate of polymyxin B against CROs was less 5%. Only one CR-Kpn was resistant to tigecycline. The resistant rates of CZA against CR-Eco, CR-Kpn and CR-Pae were 75.0%, 12.6%, and 18.5%, respectively. MIC90 of AZA against CR-Eco, CR-Kpn and CR-Pae were 2/4 mg/L, 0.5/4 mg/L and 64/4 mg/L. Among CZA-resistant CROs, 42 (100%) CR-Eco, 24 (60%) CR-Kpn and 1 (8.3%) CR-Pae isolates harboured metallo-β-lactamases genes. Increase of avibactam concentration enhanced the susceptibility of CZA and AZA against CROs, especially for CR-Eco and CR-Kpn. Conclusions: In vitro activity of AZA was superior to that of CZA against CR-Eco and CR-Kpn, whereas CZA showed better effect against CR-Pae.

ObjectivesThe aim of this work was to investigate the activity of ceftazidime–avibactam (CZA) and aztreonam–avibactam (AZA) against bloodstream infections caused by carbapenem-resistant organisms (CROs).MethodsNon-duplicate CROs, including 56 carbapenem-resistant Escherichia coli (CR-Eco), 318 carbapenem-resistant Klebsiella pneumoniae (CR-Kpn), and 65 carbapenem-resistant Pseudomonas aeruginosa (CR-Pae), were collected using the Blood Bacterial Resistant Investigation Collaborative System (BRICS) program in China. The minimum inhibitory concentrations (MICs) of 24 antibiotics were tested. Carbapenemase genes were amplified for CZA-resistant CROs by PCR. The MICs of CZA and AZA were further determined with avibactam at 8 and 16 mg/L, respectively.ResultsThe resistance rate of polymyxin B against CROs was less than 5%. Only one CR-Kpn was resistant to tigecycline. The resistance rates of CZA against CR-Eco, CR-Kpn, and CR-Pae were 75.0%, 12.6%, and 18.5%, respectively. The MIC90 values of AZA against CR-Eco, CR-Kpn, and CR-Pae were 2/4, 1/4, and 64/4 mg/L, respectively. Among the CZA-resistant CROs, 42 (100%) CR-Eco, 24 (60%) CR-Kpn, and 1 (8.3%) CR-Pae isolates harbored metallo-β-lactamase genes. The increase of avibactam concentration enhanced the susceptibility of CZA and AZA against CROs, especially for CR-Eco and CR-Kpn.ConclusionsThe in vitro activity of AZA was superior to that of CZA against CR-Eco and CR-Kpn, whereas CZA showed better effect against CR-Pae.

Objectives: The aim of this work was to investigate the activity of ceftazidime-avibactam (CZA) and aztreonam-avibactam (AZA) against bloodstream infections caused by caused by carbapenem-resistant organisms (CROs). Methods: Nonduplicate CROs, including 56 carbapenem-resistant Escherichia coli (CR-Eco), 318 carbapenem-resistant Klebsiella pneumoniae (CR-Kpn), and 65 carbapenem-resistant Pseudomonas aeruginosa (CR-Pae), were collected by Blood Bacterial Resistant Investigation Collaborative System (BRICS) program in China. The minimum inhibitory concentration (MIC) of 24 antibiotics were tested. Carbapenemase genes were amplified for CZA-resistant CROs by PCR. MIC of CZA and AZA were further determined with avibactam at 8 mg/L and 16 mg/L. Results: The resistant rate of polymyxin B against CROs was less 5%. Only one CR-Kpn was resistant to tigecycline. The resistant rates of CZA against CR-Eco, CR-Kpn and CR-Pae were 75.0%, 12.6%, and 18.5%, respectively. MIC90 of AZA against CR-Eco, CR-Kpn and CR-Pae were 2/4 mg/L, 0.5/4 mg/L and 64/4 mg/L. Among CZA-resistant CROs, 42 (100%) CR-Eco, 24 (60%) CR-Kpn and 1 (8.3%) CR-Pae isolates harboured metallo-β-lactamases genes. Increase of avibactam concentration enhanced the susceptibility of CZA and AZA against CROs, especially for CR-Eco and CR-Kpn. Conclusions: In vitro activity of AZA was superior to that of CZA against CR-Eco and CR-Kpn, whereas CZA showed better effect against CR-Pae.

To determine the relative risk of invasive methicillin-resistant Staphylococcus aureus (MRSA) infection among non-colonized (NC) patients, intermittently colonized (IC) patients, and persistently colonized (PC) patients. Observational cohort study of patient data collected longitudinally over a 41-month period. Department of Veterans Affairs Eastern Colorado Healthcare System, a tertiary care medical center. Any patient who received ≥5 MRSA nasal swab tests between February 20, 2010, and July 26, 2013. In total, 3,872 patients met these criteria, 0 were excluded, 95% were male, 71% were white, and the mean age was 62.9 years on the date of study entry. Patients were divided into cohorts based on MRSA colonization status. Physicians reviewed medical records to identify invasive infection and were blinded to colonization status. Cox and Kaplan-Meier analyses were used to assess the relationship between colonization status and invasive infection. In total, 102 patients developed invasive MRSA infections, 16.3% of these were PC patients, 11.2% of these were IC patients, and 0.5% of these were NC patients. PC patients were at higher risk of invasive infection than NC patients (hazard ratio [HR] 36.8; 95% CI, 18.4-73.6; P<.001). IC patients were also at higher risk than NC patients (HR, 22.8; 95% CI, 13.3-39.3; P<.001). The difference in risk between PC and IC patients was not statistically significant (HR, 1.61; 95% CI, 0.94-2.78, P=.084). Alternate analysis methods confirmed these results. The risk of invasive MRSA infection is much higher among PC and IC patients, supporting routine clinical testing for colonization. However, this risk is similar among PC and IC patients, suggesting that distinguishing between the 2 colonization states may not be clinically important.

e19020 Background: The prevalence of carbapenem resistant organisms (CRO) are increasing worldwide and associated with grave implications in patients with hematological malignancies. Data on such infections in patients with acute leukemia are scarce, especially from the developing world. The aim of this study was to evaluate characteristics and outcomes of bacteremia with CRO in patients treated for acute leukemia with aggressive chemotherapy regimens. Methods: This prospective observational study was conducted in a tertiary oncology centre in South India. Data on Carbapenem resistant bloodstream infection (CRBSI) in patients with acute leukemia (ALL and AML) aged 14-60 years, from March 2017 to February 2018 were prospectively collected. The final outcome was determined as survival and all-cause death due to CRBSI. Results: Out of 334 patients treated for acute leukemia, 49 patients developed infections with CRO (14.6%). The patients included 27 males (55%) and 22 females (45%), with age ranging from 14 year to 58 years (median age: 42 years). The most common isolates were Klebsiella species (63%) and E.coli (25%). All carbapenem resistant isolates were sensitive to Colistin and 74% were sensitive to Tigecycline. The case-fatality rate was 69% (34/49) in our cohort. Acute kidney injury, shock, septicemia and an initial procalcitonin value &gt; 1mcg/L were predictor of mortality. Disease in remission and neutrophil count recovery post chemotherapy were favorable factors associated with the outcome. There was no statistically significant difference in mortality in patients treated with single agent antibiotics versus combination antibiotics sensitive against CRO. Conclusions: Carbapenem resistant infections in patients with acute leukaemia are associated with a high mortality rate. The factors associated with improved outcome were disease in remission and neutrophil count recovery, post chemotherapy. The presence of acute kidney injury, shock, sepsis and a procalcitonin value more than 1 mcg/L were significant predictor of mortality.