Carbapenem-resistant Enterobacterales sepsis following endoscopic retrograde cholangiopancreatography: risk factors for 30-day all-cause mortality and the development of a nomogram based on a retrospective cohort.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has become a routine endoscopic procedure that is essential for diagnosing and managing various conditions, including gallstone extraction and the treatment of bile duct and pancreatic tumors. Despite its efficacy, post-ERCP infections - particularly those caused by carbapenem-resistant Enterobacterales (CRE) - present significant risks. These risks highlight the need for accurate predictive models to enhance postprocedural care, reduce the mortality risk associated with post-ERCP CRE sepsis, and improve patient outcomes in the context of increasing antibiotic resistance. OBJECTIVE: This study aimed to examine the risk factors for 30-day mortality in patients with CRE sepsis following ERCP and to develop a nomogram for accurately predicting 30-day mortality risk. METHODS: Data from 195 patients who experienced post-ERCP CRE sepsis between January 2010 and December 2022 were analyzed. Variable selection was optimized via the least absolute shrinkage and selection operator (LASSO) regression model. Multivariate logistic regression analysis was then employed to develop a predictive model, which was evaluated in terms of discrimination, calibration, and clinical utility. Internal validation was achieved through bootstrapping. RESULTS: The nomogram included the following predictors: age > 80 years (hazard ratio [HR] 2.61), intensive care unit (ICU) admission within 90 days prior to ERCP (HR 2.64), hypoproteinemia (HR 4.55), quick Pitt bacteremia score ≥ 2 (HR 2.61), post-ERCP pancreatitis (HR 2.52), inappropriate empirical therapy (HR 3.48), delayed definitive therapy (HR 2.64), and short treatment duration (< 10 days) (HR 5.03). The model demonstrated strong discrimination and calibration. CONCLUSIONS: This study identified significant risk factors associated with 30-day mortality in patients with post-ERCP CRE sepsis and developed a nomogram to accurately predict this risk. This tool enables healthcare practitioners to provide personalized risk assessments and promptly administer appropriate therapies against CRE, thereby reducing mortality rates.

Outcomes of inadequate empiric therapy and timing of newer antibacterial therapy in hospitalized adults with culture-positive Enterobacterales and Pseudomonas aeruginosa: a multicenter analysis.

BACKGROUND: Infections caused by multi-drug resistant Gram-negative pathogens are associated with worse clinical outcomes in critically ill patients. We evaluated hospital outcomes based on adequacy of overall and newer antibacterial therapy for Enterobacterales (ENT) and Pseudomonas aeruginosa (PsA) in US patients. METHODS: Hospitalized adults ≥ 18 years old with facility-reported antibiotic susceptibility from 2018-2022 across 161 facilities in the BD Insights Research Database were identified as ENT- or PsA-positive. Generalized linear mixed models were used to evaluate the impact of inadequate empiric therapy (IET) and time to initiate newer antibacterials (ceftazidime-avibactam; ceftolozane-tazobactam; cefiderocol; meropenem-vaborbactam; eravacycline; and imipenem-cilcastatin-relebactam) on hospital mortality and post-culture length of stay (LOS). RESULTS: Among 229,320 ENT and 36,027 PsA susceptibility results, 1.7% and 16.8% were carbapenem non-susceptible (carb-NS), respectively. Median time to first susceptibility result was longer for carb-NS vs. carb susceptible in ENT (64 h vs. 48 h) and PsA (67 h vs. 60 h). For ENT, IET was associated with significantly higher mortality (odds ratio [OR],1.29 [95% CI, 1.16-1.43, P < 0.0001]) and longer hospital LOS (14.8 vs. 13.3, P < 0.0001). Delayed start to newer antibacterial therapy was associated with significantly greater hospital mortality for ENT (P = 0.0182) and PsA (P = 0.0249) and significantly longer post-culture LOS for ENT (P < 0.0001) and PsA (P < 0.0001). CONCLUSIONS: Overall, IET and delayed use of newer antibacterials are associated with significantly worse hospital outcomes. More rapid identification of high-risk patients can facilitate adequate therapy and timely use of newer antibacterials developed for resistant Gram-negative pathogens.

Emergence and expansion of carbapenem resistant enterobacterales in the Western Cape Province, South Africa.

BACKGROUND: Carbapenem resistant Enterobacterales (CRE) have become established as leading pathogens in South African healthcare facilities. The aim of this study is to describe the epidemiology of CRE carriage and clinical infection episodes at healthcare facilities in the Western Cape Province of South Africa (2016-2020), and identify factors associated with mortality in CRE infected patients. METHODOLOGY: We used routine data from the Provincial Health Data Centre to track the emergence of CRE in healthcare facilities in the Western Cape Province of South Africa. We included all CRE episodes (clinical and carriage) at Western Cape hospitals (including day and inpatients) from 2016 to 2020 to determine the distribution of CRE, patient demographics and antibiotic resistance phenotypes. Logistic regression was performed to identify factors associated with mortality from clinical CRE episodes. RESULTS: 2242 CRE episodes (1580 [70.5%] clinical and 662 [29.5%] carriage) were identified. From these, 2281 CRE isolates were identified, with Klebsiella species predominating (1644, 72.1%). Affected patients had a median age of 31 (IQR 0-52) years, and 1167 (52.0%) were male. Most CRE episodes were recorded in central hospitals (70.0%, p < 0.001). Where outcome data was available, crude in-hospital mortality rates were 26.9% (371/1379) for CRE clinical episodes versus 6.4% (41/640) for CRE carriage episodes (p < 0.001). Factors that showed a statistically significant association with in-hospital mortality were female sex [adjusted odd ratio (aOR) 1.40 (95% confidence interval (CI) 1.09-1.560)], adult patients [aOR 1.76 (95% CI 1.20-2.57)], CRE isolation from a sterile specimen [aOR 0.41 (95% CI 0.32-0.53)], and >3 days between hospital admission and specimen collection [aOR 1.56 (95% CI 1.11-2.18)]. CONCLUSIONS: CRE episodes at Western Cape healthcare facilities are concentrated at tertiary hospitals, with high case fatality rates in patients with clinical CRE episodes. Infection control interventions must be strengthened to reduce transmission of CRE, and to reduce infection risks.

Hospital mortality and length of stay associated with Enterobacterales positive blood cultures: a multicenter analysis.

Delayed time to antimicrobial susceptibility results can impact patients' outcomes. Our study evaluated the impact of susceptibility turnaround time (TAT) and inadequate empiric antibacterial therapy (IET) in patients with bloodstream infections (BSI) caused by Enterobacterales (ENT) species on in-hospital mortality and length of stay (LOS). This retrospective, multicenter investigation which included 29,570 blood ENT-positive admissions across 161 US healthcare facilities evaluated the association between antimicrobial susceptibility testing (AST) TAT, carbapenem susceptibility, and empiric therapy on post-BSI in-hospital mortality and LOS following an ENT BSI event in adult patients. After adjusting for outcomes covariates, post-BSI in-hospital mortality was significantly higher for patients in the IET vs adequate empiric therapy (AET) group [odds ratio (OR): 1.61 (95% CI: 1.32, 1.98); P < 0.0001], and when AST TAT was >63 h [OR:1.48 (95% CI: 1.16, 1.90); P = 0.0017]. Patients with carbapenem non-susceptible (carb-NS) ENT BSI had significantly higher LOS (16.6 days, 95% CI: 15.6, 17.8) compared to carbapenem susceptible (carb-S, 12.2 days, 95% CI: 11.8, 12.6), (P < 0.0001). Extended AST TAT was significantly associated with longer LOS for TAT of 57-65 h and >65 h (P = 0.005 and P< 0.0001, respectively) compared to TAT ≤42 h (reference). Inadequate empiric therapy (IET), carb-NS, and delayed AST TAT are significantly associated with adverse hospital outcomes in ENT BSI. Workflows that accelerate AST TAT for ENT BSIs and facilitate timely and adequate therapy may reduce post-BSI in-hospital mortality rate and LOS.IMPORTANCEFor patients diagnosed with bloodstream infections (BSI) caused by Enterobacterales (ENT), delayed time to antimicrobial susceptibility (AST) results can significantly impact in-hospital mortality and hospital length of stay. However, this relationship between time elapsed from blood culture collection to AST results has only been assessed, to date, in a limited number of publications. Our study focuses on this important gap using retrospective data from 29,570 blood ENT-positive admissions across 161 healthcare facilities in the US as we believe that a thorough understanding of the dynamic between AST turnaround time, adequacy of empiric therapy, post-BSI event mortality, and hospital length of stay will help guide effective clinical management and optimize outcomes of patients with ENT infections.

Seven-day antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients: toward a new paradigm.

PURPOSE: Data on short courses of antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients are limited. The aim of the study was to describe and compare the frequency of bacteremia relapse, 30-day overall and infection-related mortality, Clostridiodes difficile infection and length of hospital stay since bacteremia among those who received antibiotic therapy for 7 or 14 days. METHODS: This is a multicenter, prospective, observational cohort study in adult high-risk neutropenic patients with hematologic malignancies or hematopoietic stem cell transplant and monomicrobial Enterobacterales bacteremia. They received appropriate empirical antibiotic therapy, had a clinical response within 7 days, and infection source control. Clinical, epidemiological and outcomes variables were compared based on 7 or 14 days of AT. RESULTS: Two hundred patients were included (100, 7-day antibiotic therapy; 100, 14-day antibiotic therapy). Escherichia coli was the pathogen most frequently isolated (47.5%), followed by Klebsiella sp. (40.5%). Among those patients that received 7-day vs. 14-day antibiotic course, a clinical source of bacteremia was found in 54% vs. 57% (p = 0.66), multidrug-resistant Enterobacterales isolates in 28% vs. 30% (p = 0.75), and 40% vs. 47% (p = 0.31) received combined empirical antibiotic therapy. Overall mortality was 3% vs. 1% (p = 0.62), in no case related to infection; bacteremia relapse was 7% vs. 2% (p = 0.17), and length of hospital stay since bacteremia had a median of 9 days (IQR: 7-15) vs. 14 days (IQR: 13-22) (p = < 0.001). CONCLUSIONS: These data suggest that seven-day antibiotic therapy might be adequate for patients with high-risk neutropenia and Enterobacterales bacteremia, who receive appropriate empirical therapy, with clinical response and infection source control.

Mortality factors and antibiotic options in carbapenem-resistant Enterobacterales bloodstream infections: Insights from a high-prevalence setting with co-occurring NDM-1 and OXA-48.

Bloodstream infections (BSI) caused by carbapenem-resistant Enterobacterales (CRE) are associated with a high mortality rate. This study aimed to investigate factors associated with 14-day mortality and identify a potential treatment option. A retrospective cohort study was conducted on patients with CRE-BSI in Thailand from 2015 to 2020. The multivariate Cox proportional-hazards model was employed to identify factors influencing 14-day mortality. Out of 134 diagnosed cases of CRE-BSI, the all-cause 14-day mortality rate was 35.1%. The most prevalent organism isolated was Klebsiella pneumoniae (85.8%), followed by Escherichia coli (11.9%). Among the 60 isolates tested for carbapenemase genes, the majority exhibited co-occurring blaNDM-1 and blaOXA-48 (51.7%), followed by blaOXA-48 (31.7%) and blaNDM-1 (15.0%). In the multivariate analysis, neutropenia (adjusted hazard ratio [aHR] 2.55; 95% confidence interval [95%CI] 1.28-5.06; p = 0.008), sepsis/septic shock (aHR 3.02; 95%CI 1.33-6.86; p = 0.008), and previous metronidazole exposures (aHR 3.58; 95%CI 1.89-6.71; p < 0.001) were identified as independent factors for 14-day mortality. The fosfomycin-based regimen was found to be protective (aHR 0.37; 95%CI 0.15-0.92; p = 0.032). In patients with CRE-BSI, particularly in regions with a high occurrence of co-occurring blaNDM-1 and blaOXA-48, neutropenia, sepsis/septic shock, and previous metronidazole exposures emerged as independent risk factors for mortality. Moreover, the fosfomycin-based regimen showed an improvement in the survival rate.

Clinical outcomes in patients infected with ertapenem-only-resistant Enterobacterales versus multi-carbapenem-resistant Enterobacterales.

BACKGROUND: Use of anti-carbapenem-resistant Enterobacterales (anti-CRE) agents such as ceftazidime/avibactam has been associated with improved clinical outcome in cohorts that primarily include patients infected with CRE that are resistant to meropenem (MCRE). OBJECTIVES: To clarify whether patients with CRE resistant to ertapenem but susceptible to meropenem (ertapenem-only-resistant Enterobacterales; EORE) benefit from therapy with anti-CRE agents. METHODS: Patients treated for CRE infection in hospitals in the USA between 2016 and 2019 and enrolled in the CRACKLE-2 study were included. The primary outcome was the desirability of outcome ranking (DOOR) assessed at 30 days after index cultures. RESULTS: The EORE group included 213 patients and the MCRE group included 643. The demographics were similar between the groups except for the patients' race and origin before admission. The MCRE group received anti-CRE agents for definitive therapy significantly more frequently compared with the EORE group (30% versus 5% for ceftazidime/avibactam). We did not observe a significant difference between the groups in the adjusted DOOR probability of a more desirable outcome for a randomly selected patient in the EORE group compared with the MCRE group (52.5%; 95% CI, 48.3%-56.7%). The MCRE group had a similar proportion of patients who died at 30 days (26% versus 21%) and who were discharged to home (29% versus 40%), compared with the EORE group. CONCLUSIONS: Patients with clinical EORE infection rarely received anti-CRE agents, but attained similar outcomes compared with patients with MCRE infection. The findings support current IDSA treatment guidance for meropenem- or imipenem-based therapy for treatment of EORE infections.

The impact of colistin-based regimens on mortality compared to other antimicrobials in patients with carbapenem-resistant Enterobacterales bacteremia in South African hospitals: a cross-sectional study.

BACKGROUND: Treatment of carbapenem-resistant Enterobacterales (CRE) infections in low-resource settings is challenging particularly due to limited treatment options. Colistin is the mainstay drug for treatment; however, nephrotoxicity and neurotoxicity make this drug less desirable. Thus, mortality may be higher among patients treated with alternative antimicrobials that are potentially less efficacious than colistin. We assessed mortality in patients with CRE bacteremia treated with colistin-based therapy compared to colistin-sparing therapy. METHODS: We conducted a cross-sectional study using secondary data from a South African national laboratory-based CRE bacteremia surveillance system from January 2015 to December 2020. Patients hospitalized at surveillance sentinel sites with CRE isolated from blood cultures were included. Multivariable logistic regression modeling, with multiple imputations to account for missing data, was conducted to determine the association between in-hospital mortality and colistin-based therapy versus colistin-sparing therapy. RESULTS: We included 1 607 case-patients with a median age of 29 years (interquartile range [IQR], 0-52 years) and 53% (857/1 607) male. Klebsiella pneumoniae caused most of the infections (82%, n=1 247), and the most common carbapenemase genes detected were blaOXA-48-like (61%, n=551), and blaNDM (37%, n=333). The overall in-hospital mortality was 31% (504/1 607). Patients treated with colistin-based combination therapy had a lower case fatality ratio (29% [152/521]) compared to those treated with colistin-sparing therapy 32% [352/1 086]) (p=0.18). In our imputed model, compared to colistin-sparing therapy, colistin-based therapy was associated with similar odds of mortality (adjusted odds ratio [aOR] 1.02; 95% confidence interval [CI] 0.78-1.33, p=0.873). CONCLUSION: In our resource-limited setting, the mortality risk in patients treated with colistin-based therapy was comparable to that of patients treated with colistin-sparing therapy. Given the challenges with colistin treatment and the increasing resistance to alternative agents, further investigations into the benefit of newer antimicrobials for managing CRE infections are needed.

Differences in clinical outcomes of bloodstream infections caused by Klebsiella aerogenes, Klebsiella pneumoniae and Enterobacter cloacae: a multicentre cohort study.

BACKGROUND: Klebsiella aerogenes has been reclassified from Enterobacter to Klebsiella genus due to its phenotypic and genotypic similarities with Klebsiella pneumoniae. It is unclear if clinical outcomes are also more similar. This study aims to assess clinical outcomes of bloodstreams infections (BSI) caused by K. aerogenes, K. pneumoniae and Enterobacter cloacae, through secondary data analysis, nested in PRO-BAC cohort study. METHODS: Hospitalized patients between October 2016 and March 2017 with monomicrobial BSI due to K. aerogenes, K. pneumoniae or E. cloacae were included. Primary outcome was a composite clinical outcome including all-cause mortality or recurrence until 30 days follow-up. Secondary outcomes were fever ≥ 72 h, persistent bacteraemia, and secondary device infection. Multilevel mixed-effect Poisson regression was used to estimate the association between microorganisms and outcome. RESULTS: Overall, 29 K. aerogenes, 77 E. cloacae and 337 K. pneumoniae BSI episodes were included. Mortality or recurrence was less frequent in K. aerogenes (6.9%) than in E. cloacae (20.8%) or K. pneumoniae (19.0%), but statistical difference was not observed (rate ratio (RR) 0.35, 95% CI 0.08 to 1.55; RR 0.42, 95% CI 0.10 to 1.71, respectively). Fever ≥ 72 h and device infection were more common in K. aerogenes group. In the multivariate analysis, adjusted for confounders (age, sex, BSI source, hospital ward, Charlson score and active antibiotic therapy), the estimates and direction of effect were similar to crude results. CONCLUSIONS: Results suggest that BSI caused by K. aerogenes may have a better prognosis than E. cloacae or K. pneumoniae BSI.

Virulent and Multi-drug-Resistant Edwardsiella tarda Infection in Oscar Fish: Unveiling the Threat of Mass Mortality and AMR Dissemination.

The Oscar fish (Astronotus ocellatus) is among the most commonly domesticated and exported ornamental fish species from Kerala. The ornamental fish industry faces a significant challenge with the emergence of diseases caused by multi-drug-resistant bacteria. In the present study, six isolates were resolved from the diseased Oscar fish showing haemorrhages, necrosis, and loss of pigmentation. After phenotypic and genotypic characterization, the bacteria were identified as Edwardsiella tarda, Klebsiella pneumoniae, Enterococcus faecalis, Escherichia coli, Brevibacillus borstelensis, and Staphylococcus hominis. Experimental challenge studies in healthy Oscar fish showed that E. tarda caused 100% mortality within 240 h with 6.99 × 106 CFU/fish as LD50 and histopathology revealed the typical signs of infection. The pathogen was re-recovered from the moribund fish thereby confirming Koch's postulates. E. tarda was confirmed through the positive amplification of tarda-specific gene and virulence genes viz., etfD and escB were also detected using PCR. Antibiotic susceptibility tests using disc diffusion displayed that the pathogen is multi-drug-resistant towards antibiotics belonging to aminoglycosides, tetracyclines, and quinolones categories with a MAR index of 0.32, which implicated the antibiotic pressure in the farm. Plasmid curing studies showed a paradigm shift in the resistance pattern with MAR index of 0.04, highlighting the resistance genes are plasmid-borne except for the chromosome-borne tetracycline resistance gene (tetA). This study is the first of its kind in detecting mass mortality caused by E. tarda in Oscar fish. Vigilant surveillance and strategic actions are crucial for the precise detection of pathogens and AMR in aquaculture.

Clinical characteristics and risk factors for neonatal bloodstream infection due to carbapenem-resistant Enterobacteriaceae: A single-centre Chinese retrospective study.

OBJECTIVES: To analyse the clinical characteristics and risk factors for bloodstream infections (BSIs) caused by carbapenem-resistant Enterobacteriaceae (CRE) in neonates. METHODS: This single-centre, retrospective study included all patients with BSIs admitted to a neonatal intensive care unit between 1 January 2015 and 30 April 2022. The clinical and microbiological data of patients were collected; predictors of 30-day mortality in patients with CRE BSIs were also identified in this study. RESULTS: Among the 224 neonates with Enterobacteriaceae BSIs, 39.29% (88/224) of the patients developed CRE BSIs. The 30-day mortality rate reached up to 21.59% (19/88). The Quick Sequential Organ Failure Assessment score > 2 (odds ratio [OR] and 95% credibility interval [CI]: 3.852 [1.111-13.356], P < 0.05), prior to more than two kinds of antibiotics use (OR and 95% CI: 9.433 [1.562-56.973], P < 0.05), pneumonia (OR and 95% CI: 3.847 [1.133-13.061], P < 0.05), and caesarean section (OR and 95% CI: 2.678 [1.225-5.857], P < 0.05) were independent risk factors associated with CRE BSIs. Moreover, the risk factors for mortality in neonates with CRE BSIs were significantly associated with neonatal Sequential Organ Failure Assessment score > 6 (OR and 95% CI: 16.335 [1.446-184.517], P < 0.05). CONCLUSION: Prior to more than two kinds of antibiotics use, Quick Sequential Organ Failure Assessment score > 2, pneumonia and caesarean section were independent risk factors for CRE BSIs. The Neonatal Sequential Organ Failure Assessment score > 6 was a risk factor for mortality associated with CRE BSIs.

Ceftazidima/avibactam frente a otros antimicrobianos para el tratamiento de bacteriemias por Enterobacterales productores de carbapenemasa KPC: datos de la vida real en un hospital universitario de Argentina / Ceftazidime/avibactam versus other antibiotics for the treatment of KPC carbapenemase-producing Enterobacterales bacteremia: real-life data from a university hospital in Argentina

INTRODUCCIÓN: Las bacteriemias por Enterobacterales productores de carbapenemasa KPC (EPC-KPC) presentan una mortalidad elevada y opciones terapéuticas limitadas. OBJETIVOS: Describir y comparar la evolución de los pacientes con bacteriemia por EPC-KPC tratados con ceftazidima/avibactam (CA) frente a otros antimicrobianos (OA). PACIENTES Y MÉTODOS: Estudio prospectivo y retrospectivo de casos y controles. Se incluyeron pacientes adultos con bacteriemia por EPC-KPC, con una proporción entre casos tratados con CA y controles tratados con OA. de 1:2. Se analizaron variables clínicas, epidemiológicas y de evolución. RESULTADOS: Se incluyeron 48 pacientes (16 CA y 32 OA). Los casos se encontraban más frecuentemente neutropénicos (50 vs.16%, p = 0,012); asimismo, presentaron medianas de score de APACHE II más altas y de score de Pitt más bajas. El 65% de la cohorte total presentó un foco clínico y Klebsiellapneumoniae fue el microorganismo más frecuentemente aislado. Los casos recibieron una mayor proporción de tratamiento antimicrobiano empírico adecuado (81 vs. 53%, p = 0,05). La antibioterapia dirigida en casos y controles fue combinada en 38 y 91%, p = 0,009. Los casos presentaron menor mortalidad al día 7 y al día 30 relacionada a infección (0 vs. 22%, p = 0,04 y 0 vs. 34%, p = 0,008). Solo los controles desarrollaron shock, ingresaron a la unidad de cuidados intensivos y presentaron bacteriemia de brecha. CONCLUSIÓN: CA mostró beneficio clínico frente a OA para el tratamiento de pacientes con bacteriemia por EPC-KPC.

BACKGROUND: KPC-producing Enterobacterales bacteremia (KPCCPE) is associated with a high mortality rate and limited therapeutic options. AIM: To describe and compare the outcome of patients with KPC-CPE bacteremia treated with ceftazidime/avibactam (CA) versus other antibiotics (OA). METHODS: Prospective and retrospective cases and control study performed in adult patients with KPC-CPE bacteremia, with a 1:2 ratio between cases treated with CA. and controls treated with OA. Clinical, epidemiological, and outcome variables were analyzed. RESULTS: Forty-eight patients (16 CA and 32 OA) were included. Cases were more frequently neutropenic (50 vs. 16%, p = 0.012), presented higher median APACHE II score and lower Pitt score. Of the total cohort, 65% had a clinical source, and Klebsiella pneumoniae was the most frequently isolated microorganism. Cases received more adequate empirical antibiotic treatment (81 vs. 53%, p = 0.05). Targeted antibiotic therapy in cases and controls was combined in 38 and 91%, p = 0.009. Cases had a lower 7-day mortality and 30-day infection-related mortality (0 vs. 22%, p = 0.04 and 0 vs. 34%, p = 0.008). Only controls developed shock, were admitted to the intensive care unit, and had breakthrough bacteremia. CONCLUSION: CA. showed clinical benefit over OA in the treatment of patients with EPC-KPC bacteremia.

Validation of the Giannella Risk Score for the Prediction of Infection by Carbapenemase-producing Enterobacteriaceae in the Pediatric Population.

BACKGROUND: Despite efforts made to prevent the spread of multi-drug-resistant bacteria, carbapenemase-producing Enterobacteriaceae (CPE) has become one of the most dangerous threat worldwide. However, data on the epidemiology of CPE and on the correlation between CPE colonization and infection are scanty. The objectives of this study were first to describe the epidemiologic characteristics of colonizations and invasive CPE infections in the pediatric population, and second, to apply the Giannella Risk Score (GRS) to the pediatric population for the assessment of the risk of invasive CPE infection in patients with already known colonization. METHODS: Pediatric patients with evidence of colonization by CPE were retrospectively enrolled. For each colonized patient, the subsequent development of an infection by CPE was then assessed for a 90-day period after the first CPE isolation; GRSs were compared between patients who had developed any type of CPE infection and those without infection. RESULTS: A total of 215 patients (113 males and 102 females) with at least 1 isolation of CPE during hospitalization were analyzed. Median age was 5.6 years [interquartile range (IQR), 1.89-12.2 years]. Overall, 28 CPE infections (13%) were documented: 23 blood stream infections and 5 complicated urinary tract infections. The 30-day mortality of invasive CPE infections was 34.8%. The GRS values in patients with any CPE infection were statistically higher than in noninfected patients: median GRS 9 (IQR, 4-12.5) versus 4 (IQR, 2-4), respectively; P < 0.0001. The analysis of the receiver operating characteristic curves identified a GRS cut-off value ≥8 as the best predictor of CPE infection. The likelihood ratio of the results was <2 and the informedness of the test had a value <0.50. CONCLUSIONS: Our study confirms that the spread of CPE is an impelling problem also in the pediatric population, with a high mortality rate of invasive infections. However, the application of the GRS appears to be poorly informative in the pediatric setting; it might sometimes help to identify patients at very low-risk of CPE infection, in whom it is reasonable to spare targeted antimicrobial treatments.

Genetic characterization of heterologous Edwardsiella piscicida isolates from diverse fish hosts and virulence assessment in a Chinook salmon Oncorhynchus tshawytscha model.

Edwardsiella piscicida is an emergent global fish pathogen with a wide host range, although host associations driving genetic diversity remain unclear. This study investigated the genetic and virulence diversity of 37 E. piscicida isolates recovered from 10 fish species in North America. Multilocus sequence analysis (MLSA) was conducted using concatenated alignments of the gyrB, pgi and phoU sequences. MLSA clustered the tested isolates into six discrete clades. In light of recent disease outbreaks in cultured salmonids, the virulence of each clade was evaluated in Chinook salmon Oncorhynchus tshawytscha fingerlings following intracoelomic challenge of ~106  CFU/fish. Challenged and control fish were monitored for 21d, and microbiological and histological examination was performed on dead and surviving fish. Peak mortality occurred 3-5 days post-challenge (dpc) regardless of isolate or genetic group. Edwardsiella piscicida was recovered from all moribund and dead animals. At 21 dpc, fish challenged with isolates from clades II, III and IV presented cumulative mortality ≥83.3%, whereas isolates from clade I, V and VI resulted in cumulative mortality ≤71.4%. This study suggests an underlying genetic basis for strain virulence and potential host associations. Further investigations using other fish models and variable challenge conditions are warranted.

Association between mortality and highly antimicrobial-resistant bacteria in intensive care unit-acquired pneumonia.

Data on the relationship between antimicrobial resistance and mortality remain scarce, and this relationship needs to be investigated in intensive care units (ICUs). The aim of this study was to compare the ICU mortality rates between patients with ICU-acquired pneumonia due to highly antimicrobial-resistant (HAMR) bacteria and those with ICU-acquired pneumonia due to non-HAMR bacteria. We conducted a multicenter, retrospective cohort study using the French National Surveillance Network for Healthcare Associated Infection in ICUs ("REA-Raisin") database, gathering data from 200 ICUs from January 2007 to December 2016. We assessed all adult patients who were hospitalized for at least 48 h and presented with ICU-acquired pneumonia caused by S. aureus, Enterobacteriaceae, P. aeruginosa, or A. baumannii. The association between pneumonia caused by HAMR bacteria and ICU mortality was analyzed using the whole sample and using a 1:2 matched sample. Among the 18,497 patients with at least one documented case of ICU-acquired pneumonia caused by S. aureus, Enterobacteriaceae, P. aeruginosa, or A. baumannii, 3081 (16.4%) had HAMR bacteria. The HAMR group was associated with increased ICU mortality (40.3% vs. 30%, odds ratio (OR) 95%, CI 1.57 [1.45-1.70], P < 0.001). This association was confirmed in the matched sample (3006 HAMR and 5640 non-HAMR, OR 95%, CI 1.39 [1.27-1.52], P < 0.001) and after adjusting for confounding factors (OR ranged from 1.34 to 1.39, all P < 0.001). Our findings suggest that ICU-acquired pneumonia due to HAMR bacteria is associated with an increased ICU mortality rate, ICU length of stay, and mechanical ventilation duration.

Comparing mortality in patients with carbapenemase-producing carbapenem resistant Enterobacterales and non-carbapenemase-producing carbapenem resistant Enterobacterales bacteremia.

Carbapenem-resistant Enterobacterales (CRE) are classified as either carbapenemase-producing CRE (CP-CRE) or non-carbapenemase-producing CRE (non-CP-CRE) based on their mechanism of carbapenem resistance. Few studies have compared outcomes associated with each type of infection. We attempted to determine if either CRE subset is associated with increased mortality. We performed a retrospective observational study to collect demographic, clinical and outcomes data to compare patients with CP-CRE and non-CP-CRE bacteremia. Of 146 cases analyzed, 88/146 (60%) were CP-CRE and 58/146 (40%) were non-CP-CRE. Patients with CP-CRE bacteremia were less likely to receive active empiric or targeted antibiotic therapy. Non-CP-CRE bacteremia was associated with a 2.4 times higher hazard of death at 30 days after bacteremia onset compared to CP-CRE (HR, 2.4; 95% CI, 1.2, 4.6). Patients with non-CP-CRE bacteremia had a higher hazard of death at 30 days after bacteremia onset compared to those with CP-CRE bacteremia.

Pan-drug resistant Providencia rettgeri contributing to a fatal case of COVID-19.

Following prolonged hospitalization that included broad-spectrum antibiotic exposure, a strain of Providencia rettgeri was cultured from the blood of a patient undergoing extracorporeal membrane oxygenation treatment for hypoxic respiratory failure due to COVID-19. The strain was resistant to all antimicrobials tested including the novel siderophore cephalosporin, cefiderocol. Whole genome sequencing detected ten antimicrobial resistance genes, including the metallo-ß-lactamase bla NDM-1, the extended-spectrum ß-lactamase bla PER-1, and the rare 16S methyltransferase rmtB2.

Comparison of outcomes in urinary tract infections caused by AmpC-harboring organisms treated with AmpC stable versus AmpC susceptible agents.

There is minimal data on the optimal treatment of lower inoculum infections such as urinary tract infections (UTIs) caused by SPICE organisms which encode the betalactamase enzyme, AmpC. This single-center, retrospective review of adult hospitalized patients with UTIs caused by a SPICE organism compared outcomes amongst patients treated with drugs susceptible to AmpC hydrolysis versus drugs stable against AmpC. Of 156 patients, similar rates of clinical response, 30-day infection related readmission, 30-day infection recurrence, 30-day mortality rates, and median length of hospital stay were found between the two groups. Notably, 44% of patients with ceftriaxone resistance reported had recent ß-lactam exposure versus only 11% of patients without ceftriaxone resistance (P = 0.002). Based on our data, there does not appear to be a difference in clinical response or any of the secondary outcomes in patients with UTIs treated with AmpC stable and AmpC susceptible agents.

Klebsiella spp. cause severe and fatal disease in Mozambican children: antimicrobial resistance profile and molecular characterization.

BACKGROUND: Klebsiella spp. are important pathogens associated with bacteremia among admitted children and is among the leading cause of death in children < 5 years in postmortem studies, supporting a larger role than previously considered in childhood mortality. Herein, we compared the antimicrobial susceptibility, mechanisms of resistance, and the virulence profile of Klebsiella spp. from admitted and postmortem children. METHODS: Antimicrobial susceptibility and virulence factors of Klebsiella spp. recovered from blood samples collected upon admission to the hospital (n = 88) and postmortem blood (n = 23) from children < 5 years were assessed by disk diffusion and multiplex PCR. RESULTS: Klebsiella isolates from postmortem blood were likely to be ceftriaxone resistant (69.6%, 16/23 vs. 48.9%, 43/88, p = 0.045) or extended-spectrum ß-lactamase (ESBL) producers (60.9%, 14/23 vs. 25%, 22/88, p = 0.001) compared to those from admitted children. blaCTX-M-15 was the most frequent ESBL gene: 65.3%, 9/14 in postmortem isolates and 22.7% (5/22) from admitted children. We found higher frequency of genes associated with hypermucoviscosity phenotype and invasin in postmortem isolates than those from admitted children: rmpA (30.4%; 7/23 vs. 9.1%, 8/88, p = 0.011), wzi-K1 (34.7%; 8/23 vs. 8%; 7/88, p = 0.002) and traT (60.8%; 14/23 vs. 10.2%; 9/88, p < 0.0001), respectively. Additionally, serine protease auto-transporters of Enterobacteriaceae were detected from 1.8% (pic) to 12.6% (pet) among all isolates. Klebsiella case fatality rate was 30.7% (23/75). CONCLUSION: Multidrug resistant Klebsiella spp. harboring genes associated with hypermucoviscosity phenotype has emerged in Mozambique causing invasive fatal disease in children; highlighting the urgent need for prompt diagnosis, appropriate treatment and effective preventive measures for infection control.