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Antibiotic Susceptibility, Virulome, and Clinical Outcomes in European Infants with Bloodstream Infections Caused by Enterobacterales.

ABSTRACT: Mortality in neonates with Gram-negative bloodstream infections has remained unacceptably high. Very few data are available on the impact of resistance profiles, virulence factors, appropriateness of empirical treatment and clinical characteristics on patients' mortality. A survival analysis to investigate 28-day mortality probability and predictors was performed including (I) infants <90 days (II) with an available Enterobacterales blood isolate with (III) clinical, treatment and 28-day outcome data. Eighty-seven patients were included. Overall, 299 virulence genes were identified among all the pathogens. Escherichia coli had significantly more virulence genes identified compared with other species. A strong positive correlation between the number of resistance and virulence genes carried by each isolate was found. The cumulative probability of death obtained by the Kaplan-Meier survival analysis was 19.5%. In the descriptive analysis, early age at onset, gestational age at onset, culture positive for E. coli and number of classes of virulence genes carried by each isolate were significantly associated with mortality. By Cox multivariate regression, none of the investigated variables was significant. This pilot study has demonstrated the feasibility of investigating the association between neonatal sepsis mortality and the causative Enterobacterales isolates virulome. This relationship needs further exploration in larger studies, ideally including host immunopathological response, in order to develop a tailor-made therapeutic strategy.

SUBMITTER: Folgori L

PROVIDER: S-EPMC8230887 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Comparative effectiveness of antibiotic therapy for carbapenem-resistant Enterobacterales (CRE) bloodstream infections in hospitalized US veterans

Project description:Abstract Background Carbapenem-resistant Enterobacterales bloodstream infections (CRE-BSI) increase mortality three-fold compared with carbapenem-susceptible bloodstream infections. Because these infections are rare, there is a paucity of information on mortality associated with different treatment regimens. This study examines treatment regimens and association with in-hospital, 30 day and 1 year mortality risk for patients with CRE-BSI. Methods This retrospective cohort study identified hospitalized patients within the Veteran Affairs (VA) from 2013 to 2018 with a positive CRE blood culture and started antibiotic treatment within 5 days of culture. Primary outcomes were in-hospital, 30 day and 1 year all-cause mortality. Secondary outcomes were healthcare costs at 30 days and 1 year and Clostridioides difficile infection 6 weeks post culture date. The propensity for receiving each treatment regimen was determined. Multivariable regression assessed the association between treatment and outcomes. Results There were 393 hospitalized patients from 2013 to 2018 included in the study. The cohort was male (97%) and elderly (mean age 71.0 years). Carbapenems were the most prescribed antibiotics (47%). In unadjusted analysis, ceftazidime/avibactam was associated with a lower likelihood of 30 day and 1 year mortality. After adjusting, ceftazidime/avibactam had a 30 day mortality OR of 0.42 (95% CI 0.17–1.02). No difference was found in C. difficile incidence at 6 weeks post-infection or total costs at 30 days or 1 year post culture date by any treatments. Conclusions In hospitalized veterans with CRE-BSI, none of the treatments were shown to be associated with all-cause mortality. Ceftazidime/avibactam trended towards protectiveness against 30 day and 1 year all-cause mortality. Use of ceftazidime/avibactam should be encouraged for treatment of CRE-BSI.

| S-EPMC9596539 | biostudies-literature

Early Treatment Outcomes for Bloodstream Infections Caused by Potential AmpC Beta-Lactamase-Producing Enterobacterales with Focus on Piperacillin/Tazobactam: A Retrospective Cohort Study.

Project description:The Gram-negative bacilli Serratia spp., Providencia spp., Morganella morganii, Citrobacter freundii complex, Enterobacter spp. and Klebsiella aerogenes are common Enterobacterales that may harbor inducible chromosomal AmpC beta-lactamase genes. The purpose of the present study was to evaluate treatment outcomes and identify predictors of early treatment response in patients with bloodstream infection caused by potential AmpC beta-lactamase-producing Enterobacterales (SPICE-BSI). This cohort study included adult patients with SPICE-BSI hospitalized between 01/2011 and 02/2019. The primary outcome was early treatment response 72 h after the start of active treatment, defined as survival, hemodynamic stability, improved or stable SOFA score, resolution of fever and leukocytosis and microbiologic resolution. Among 295 included patients, the most common focus was the lower respiratory tract (27.8%), and Enterobacter spp. (n = 155) was the main pathogen. The early treatment response rate was significantly lower (p = 0.006) in the piperacillin/tazobactam group (17/81 patients, 21.0%) than in the carbapenem group (40/82 patients, 48.8%). Independent negative predictors of early treatment response (p < 0.02) included initial SOFA score, liver comorbidity and empiric piperacillin/tazobactam treatment. In vitro piperacillin/tazobactam resistance was detected in three patients with relapsed Enterobacter-BSI and initial treatment with piperacillin/tazobactam. In conclusion, our findings show that piperacillin/tazobactam might be associated with early treatment failure in patients with SPICE-BSI.

| S-EPMC8229083 | biostudies-literature

Central Venous Catheter-related Bloodstream Infections Caused by Enterobacterales in Pediatric Oncology Patients: Catheter Salvage or Removal.

Project description:BackgroundThe aim was to determine whether salvage treatment with systemic antibiotics is a safe and effective strategy for Enterobacterales bloodstream infections (BSI) in pediatric oncology patients with a central venous catheter (CVC).MethodsA retrospective study was performed on oncology and stem cell recipient patients with a CVC and blood culture with Enterobacterales, at the Princess Máxima Centre for Pediatric Oncology, Utrecht, the Netherlands. Analyses were performed for all BSI and for episodes meeting central line-associated bloodstream infection (CLABSI) criteria. The cumulative incidence of an event (ie, removal, intensive care admission or death) was estimated after blood culture collection for episodes primarily treated with antibiotics. The effect of prognostic factors on the hazard of the event of interest was assessed by estimating a Cox proportional hazard regression model.ResultsIn total, 95 CVC-related Enterobacterales BSIs in 82 patients were included; 12 (13%) BSIs required immediate CVC removal and for 83 (87%) BSIs CVC salvage was attempted. The cumulative incidence of events at 60 days was 53.0% [95% confidence interval (CI): 41.7-63.1] for BSIs (n = 83), and 64.4% (95% CI: 48.3-76.7) for CLABSIs (n = 45). The events occurred after a median of 6 (Q1-Q3: 2-15) and 6 (Q1-Q3: 2-20) days for BSIs and CLABSIs, respectively. Intensive care admission after salvage treatment was required in 16% of the BSIs and CLABSIs, resulting in death in 5% and 2% of cases, respectively. No significant association between risk factors and events was found.ConclusionsThe cumulative incidence of an event at 60 days after salvage treatment for Enterobacterales CLABSIs and BSIs in pediatric oncology patients is high. Immediate CVC removal appears recommendable for this patient group.

| S-EPMC10723766 | biostudies-literature

Vancomycin Heteroresistance and Clinical Outcomes in Bloodstream Infections Caused by Coagulase-Negative Staphylococci.

Project description:Coagulase-negative staphylococci (CoNS) are a common etiology of serious and recurrent infections in immunocompromised patients. Although most isolates appear susceptible to vancomycin, a single strain might have a subpopulation of resistant bacteria. This phenomenon is termed heteroresistance and may adversely affect the response to treatment. A retrospective cohort study was performed of pediatric patients with leukemia treated at St. Jude Children's Research Hospital who developed CoNS central line-associated bloodstream infection (CLABSI). Available isolates were sequenced and tested for vancomycin heteroresistance by population analysis profiling. Risk factors for heteroresistance and the association of heteroresistance with treatment failure (death or relapse of infection) or poor clinical response to vancomycin therapy (treatment failure or persistent bacteremia after vancomycin initiation) were evaluated. For 65 participants with CoNS CLABSI, 62 initial isolates were evaluable, of which 24 (39%) were vancomycin heteroresistant. All heteroresistant isolates were of Staphylococcus epidermidis and comprised multiple sequence types. Participants with heteroresistant bacteria had more exposure to vancomycin prophylaxis (P = 0.026) during the 60 days prior to infection. Of the 40 participants evaluable for clinical outcomes, heteroresistance increased the risk of treatment failure (P = 0.012) and poor clinical response (P = 0.001). This effect persisted after controlling for identified confounders. These data indicate that vancomycin heteroresistance is common in CoNS isolates from CLABSIs in pediatric patients with leukemia and is associated with poor clinical outcomes. Validation of these findings in an independent cohort and evaluation of alternative antibiotic therapy in patients with heteroresistant infections have the potential to improve care for serious CoNS infections.

| S-EPMC7577166 | biostudies-literature

Carbapenem alternatives for treatment of bloodstream infections due to AmpC producing enterobacterales.

Project description:IntroductionCarbapenems (CR) have traditionally been the first line treatment for bacteremia caused by AmpC-producing Enterobacterales. However, CR have a high ecological impact, and carbapenem-resistant strains continue rising. Thus, other treatment alternatives like Piperacillin-Tazobactam (P-T) or Cefepime (CEF) and oral sequential therapy (OST) are being evaluated.MethodsWe conducted a retrospective, single-centre observational study. All adult patients with AmpC-producing Enterobacterales bacteremia were included. The primary endpoint was clinical success defined as a composite of clinical cure, 14-day survival, and no adverse events. We evaluated the evolution of patients in whom OST was performed.ResultsSeventy-seven patients were included, 22 patients in the CR group and 55 in the P-T/CEF group (37 patients received CEF and 18 P-T). The mean age of the patients was higher in the P-T/CEF group (71 years in CR group vs. 76 years in P-T/CEF group, p = 0.053). In the multivariate analysis, age ≥ 70 years (OR 0.08, 95% CI [0.007-0.966], p = 0.047) and a Charlson index ≥ 3 (OR 0.16, 95% CI [0.026-0.984], p = 0.048), were associated with a lower clinical success. Treatment with P-T/CEF was associated with higher clinical success (OR 7.75, 95% CI [1.273-47.223], p = 0.026). OST was performed in 47% of patients. This was related with a shorter in-hospital stay (OST 14 days [7-22] vs. non-OST 18 days [13-38], p = 0.005) without difference in recurrence (OST 3% vs. non-OST 5%, p = 0.999).ConclusionsTargeted treatment with P-T/CEF and OST could be safe and effective treatments for patients with AmpC-producing Enterobacterales bacteremia.

| S-EPMC10436381 | biostudies-literature

Clinical Features, Antibiotic Susceptibility Profiles, and Outcomes of Infectious Keratitis Caused by Achromobacter xylosoxidans.

Project description:Reports on Achromobacter xylosoxidans ocular infections are increasing, drawing attention to its emerging role in infectious keratitis. The purpose of this study is to report the clinical features, antibiotic sensitivities, and visual outcomes of infectious keratitis secondary to Achromobacter xylosoxidans.A microbiology database and clinical chart review was performed in all patients diagnosed with A. xylosoxidans keratitis at the Bascom Palmer Eye Institute between the years 1987 and 2014. Initial presentation, antimicrobial susceptibilities, minimum inhibitory concentrations (MICs), treatment course, and outcomes were recorded.Twenty-eight patients were identified. The main risk factors were corneal graft (n = 8, 28.6%) and contact lens wear (n = 8, 28.6%). On presentation, visual acuity was 20/100 or worse in 20 (71.2%) patients. Hypopyon was present in 7 (25.0%) patients. In most cases, topical fluoroquinolones or tobramycin were the initial treatment, often accompanied by vancomycin. High susceptibility rates were found for piperacillin [100%, minimum inhibitory concentration for 90% of isolates (MIC90) = 8] and ticarcillin (100%, MIC90 = 16). Low susceptibility rates were documented for ciprofloxacin (46.7%, MIC90 = 8), tobramycin (26.7%, MIC90 = 16), and gentamicin (20%, MIC90 = 16). One (3.6%) patient suffered endophthalmitis. Six (21.4%) patients underwent therapeutic penetrating keratoplasty, and 2 (7.1%) patients had conjunctival flap surgery. Visual acuity at final follow-up was 20/100 or worse in 16 (57.1%) patients.Infectious keratitis caused by A. xylosoxidans is associated with poor visual outcomes. Fluoroquinolones and aminoglycosides are not appropriate treatments for these ocular infections. Further studies are needed to define the clinical application of compound piperacillin and ticarcillin eye drops.

| S-EPMC5545926 | biostudies-other

Cefepime versus carbapenems for treatment of AmpC beta-lactamase-producing Enterobacterales bloodstream infections.

Project description:PurposeCefepime is recommended for treating infections caused by AmpC beta-lactamase-producing Enterobacterales (AmpC-PE), though supporting evidence is limited. Therefore, this study compared outcomes associated with cefepime versus carbapenem therapy for bloodstream infections (BSIs) caused by AmpC-PE after phenotypic exclusion of ESBL-co-producing isolates.MethodsThis retrospective cohort study compared definite cefepime versus carbapenem treatment for AmpC-PE BSI in hospitalized patients of the University Hospital Basel, Switzerland, between 01/2015 and 07/2020. Primary outcomes included in-hospital death, renal impairment and neurologic adverse events; secondary outcomes included length of hospital stay and recurrent infection.ResultsTwo hundred and seventy episodes of AmpC-PE BSI were included, 162, 77 and 31 were treated with a carbapenem, cefepime and other antibiotics, respectively. Patients treated with carbapenems were more likely to be transferred to the ICU on admission and more frequently had central venous catheter as a source of infection. In uni- and multivariable analyses, primary and secondary outcomes did not differ between the two treatment groups, except for more frequent occurrence of neurological adverse events among patients treated with carbapenems and shorter length of hospital stay among survivors treated with cefepime.ConclusionAfter excluding isolates with phenotypic ESBL-co-production, cefepime was not associated with adverse outcomes compared to carbapenems when used to treat BSIs caused by AmpC-PE. Our study provides evidence to support the use of cefepime as a safe treatment strategy for AmpC-PE BSI, particularly in clinically stable patients without initial renal impairment or increased susceptibility to neurological adverse events.

| S-EPMC10821988 | biostudies-literature

Empiric Antibiotic Use and Susceptibility in Infants With Bacterial Infections: A Multicenter Retrospective Cohort Study.

Project description:To assess hospital differences in empirical antibiotic use, bacterial epidemiology, and antimicrobial susceptibility for common antibiotic regimens among young infants with urinary tract infection (UTI), bacteremia, or bacterial meningitis. We reviewed medical records from infants <90 days old presenting to 8 US children's hospitals with UTI, bacteremia, or meningitis. We used the Pediatric Health Information System database to identify cases and empirical antibiotic use and medical record review to determine infection, pathogen, and antimicrobial susceptibility patterns. We compared hospital-level differences in antimicrobial use, pathogen, infection site, and antimicrobial susceptibility. We identified 470 infants with bacterial infections: 362 (77%) with UTI alone and 108 (23%) with meningitis or bacteremia. Infection type did not differ across hospitals (P = .85). Empirical antibiotic use varied across hospitals (P < .01), although antimicrobial susceptibility patterns for common empirical regimens were similar. A third-generation cephalosporin would have empirically treated 90% of all ages, 89% in 7- to 28-day-olds, and 91% in 29- to 89-day-olds. The addition of ampicillin would have improved coverage in only 4 cases of bacteremia and meningitis. Ampicillin plus gentamicin would have treated 95%, 89%, and 97% in these age groups, respectively. Empirical antibiotic use differed across regionally diverse US children's hospitals in infants <90 days old with UTI, bacteremia, or meningitis. Antimicrobial susceptibility to common antibiotic regimens was similar across hospitals, and adding ampicillin to a third-generation cephalosporin minimally improves coverage. Our findings support incorporating empirical antibiotic recommendations into national guidelines for infants with suspected bacterial infection.

| S-EPMC5525435 | biostudies-literature

Clinical Features, Antibiotic Susceptibility Profile, and Outcomes of Infectious Keratitis Caused by Stenotrophomonas maltophilia.

Project description:PURPOSE:Stenotrophomonas maltophilia, an uncommon cause of infectious keratitis, is difficult to treat because of its resistance to multiple antibiotics. The purpose of this study is to describe the clinical features, antibiotic susceptibility profile, and outcomes of S. maltophilia keratitis. METHODS:A retrospective review of records from 1987 to 2016 identified 26 eyes of 26 patients who were treated at the Bascom Palmer Eye Institute for an S. maltophilia corneal ulcer. Clinical data were analyzed as to predisposing factors, clinical presentation, antibiotic susceptibility, treatment selection, and clinical outcomes. RESULTS:Median age at presentation was 65 years (range, 16-98). Twelve patients were using topical corticosteroids, 8 patients had a history of penetrating keratoplasty, and 9 were contact lens wearers. All patients received topical antibiotics, 2 required therapeutic penetrating keratoplasty, and 1 was enucleated. At presentation, 57.7% (15/26) of the patients had visual acuity of 20/400 or worse. At the final visit, only 30.4% (7/23) of the patients had visual acuity worse than 20/400, whereas 65.2% (15/23) of the patients had 20/100 or better. Almost all isolates (25/26, 96.2%) were susceptible to fluoroquinolones and 77.3% (17/22) of them to polymyxin B/trimethoprim. Only 33.3% (5/15) of the tested isolates were susceptible to aminoglycosides and 58.3% (7/12) to cephalosporins. CONCLUSIONS:Infectious keratitis due to S. maltophilia presents a treatment challenge because of its resistance to aminoglycosides and cephalosporins, which are typically used for empiric broad-spectrum gram-negative coverage as fortified solutions. Fluoroquinolones and polymyxin B/trimethoprim should be considered instead in cases of S. maltophilia infection.

| S-EPMC5806132 | biostudies-literature

Clinical Outcomes of Third-Generation Cephalosporin Definitive Therapy for Bloodstream Infections Due to Enterobacterales with Potential AmpC Induction: A Single-Center Retrospective Study.

Project description:The recommended therapy for severe infections caused by AmpC-inducible Enterobacterales (AmpC-E) typically involves cefepime or carbapenems. In an era of emerging resistance to these antimicrobials, we aim to assess the impact of third-generation cephalosporins (3GCs) vs. alternative antibiotics on clinical outcomes in bloodstream infections (BSIs) due to AmpC-E. We retrospectively included hospitalized adult patients with BSIs caused by 3GC-susceptible AmpC-E between 2012 and 2022, comparing the outcomes of 3GC and non-3GC definitive therapies. The primary outcome was overall treatment failure (OTF), encompassing 90-day all-cause mortality, 90-day reinfection, and 90-day readmission. Secondary outcomes comprised components of the OTF, in-hospital all-cause mortality, and length-of-stay. Within a total cohort of 353 patients, OTF occurred in 46.5% and 41.5% in the 3GC- and non-3GC-therapy groups, respectively (p = 0.36). The 3GC-therapy group exhibited a longer length-of-stay (38 vs. 21 days, p = 0.0003) and higher in-hospital mortality (23.3% vs. 13.4%, p = 0.019). However, the 90-day mortality, 90-day reinfection, and 90-day readmission were comparable between the therapy groups. Subgroup analyses involving high-risk AmpC-E and 3GC vs. standard-of-care yielded similar conclusions. Overall, our findings suggest that 3GC definitive therapy may not result in poorer clinical outcomes for the treatment of BSIs caused by AmpC-E.

| S-EPMC10537439 | biostudies-literature

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