Search

An ease-of-use protocol for the identification of resistance against third-generation cephalosporins in Enterobacteriaceae isolated from blood culture bottles was evaluated using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. A cefotaxime hydrolysis assay from chocolate agar subcultures using antibiotic discs and without inoculum standardization was developed for routine work flow, with minimal hands-on time. This assay showed good performance in distinguishing between cefotaxime-susceptible and cefotaxime-resistant strains, with excellent results for Escherichia coli (sensitivity 94.7%, specificity 100%). However, cefotaxime resistance was not detected reliably in Enterobacteriaceae expressing AmpC genes or carbapenemase-producing Klebsiella pneumoniae. [ABSTRACT FROM AUTHOR]

Candida auris represents a serious global health threat. Cases have been reported from over 40 countries in six continents. In Italy, the 1st case was detected in July 2019, never reported to the Ministry of Health (MoH); 2 cases were notified on January and July 2020; 277 cases occurred between November 2020 and October 2021, notified on November 2021 following specific ministerial request; 32 cases were notified November 2021-July 2022. Here we describe the outbreak to raise awareness on this growing threat. Cases were notified by the local facilities to regional health authorities and/or the MoH. We defined a confirmed case as a subject infected/colonized by C. auris isolated from any type of sample from sterile/non- sterile site. We performed descriptive analysis by R software (version 4.1.1). In 4 regions, 312 cases (66% males, median age 59, range 0-76 years) were detected in 12 healthcare facilities, including 34 (11%) deaths. The minority of patients (22%) were colonised. One had history of travel abroad. Over two third were from reanimation and intensive care units. All the environmental samples tested negative. Weekly screening of contacts and instruction of cases were performed at the facilities. Infection prevention and control (IPC) measures were applied locally. The MoH nominated a National Reference Laboratory. Two messages were posted through the Epidemic Intelligence Information System in 2021. On February 2022, rapid risk assessment declared the risk for further spread high within Italy and low to other countries. Awareness is crucial to identify C. auris colonisation/infection. Appropriate microbiological capacity and ability for patient isolation, prompt case information, strict adherence to IPC measures, periodic screening of contacts, chlorine-based environmental cleaning and reprocessing of medical devices or dedicated equipment, strengthened microbiological and epidemiological surveillance, and prompt notification at both regional and national level are fundamental to stop C. auris spread. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the risk factors for candidaemia in patients with liver cirrhosis. This was a case–control–control (1:2:2) study performed in four Italian tertiary centres from 2006 to 2015. Cases were patients with liver cirrhosis developing candidaemia. For every case of candidaemia we enrolled two additional patients undergoing blood cultures for suspected infection yielding isolation of a bacterial pathogen (control A) and two additional patients undergoing blood cultures for suspected infection yielding negative results (control B). Patients were matched according to age, sex and model for end stage liver disease at hospital admission. During the study period 90 cases, 180 controls A and 180 controls B were included. At multivariate analysis assessed by means of multinomial conditional regression models, factors independently associated with candidaemia were previous (<30 days) acute-on-chronic liver failure (relative risk ratio (RRR) 2.22 (95% confidence interval (CI) 1.09–4.54), p = 0.046), previous(<30 days) gastrointestinal endoscopy (RRR 2.38 (95% CI 1.19–4.78) p = 0.014), previous(<30 days) antibiotic treatment for at least 7 days (RRR 2.74 (95% CI 1.00–7.48), p = 0.049), presence of central venous catheter (RRR 2.77 (95% CI 1.26–6.09, p = 0.011), total parenteral nutrition (RRR 3.90 (95% CI 1.62–9.40), p = 0.002) at infection onset and length of in-hospital stay >15 days (RRR 4.63 (95% CI 2.11–10.18), p <0.001] Conversely, rifaximin treatment was associated with lower rate of candidaemia (RRR 0.38 (95% CI 0.19–0.77), p = 0.007). Multivariable analysis for 30-day mortality showed that patients with isolation of Candida spp. from blood cultures had worse outcome when compared with controls even though the difference did not reach a statistical significance (hazard ratio 1.64 (95% 0.97–2.75) p = 0.06). We identified previous antibiotic use, gastrointestinal endoscopy or acute-on-chronic liver failure and presence of central venous catheter especially for parenteral nutrition as independent factors associated with candidaemia. Surprisingly, chronic rifaximin use was a protective factor. [ABSTRACT FROM AUTHOR]

Serum bactericidal titres (SBTs) were widely used in the 1970s and 1980s to monitor antimicrobial therapy but are now seldom recommended. It is the only laboratory test that integrates drug pharmacodynamics, host pharmacokinetics and synergistic or antagonistic interactions of antimicrobial combinations into a single index of antimicrobial activity. We hypothesized that SBTs could play a renewed role in monitoring antibiotic treatment of multidrug-resistant Gram-negative infections. However, the last critical appraisal of the test was published over 30 years ago. This narrative review provides an updated assessment of the SBT test and its methodological limitations. We performed a diagnostic meta-analysis to estimate the value of SBTs for predicting clinical failure or death during antibiotic treatment. A comprehensive literature search of PubMed including all English publications was performed in December 2019 using the Medical Subject Headings (MeSH search terms "serum", "bactericidal", "inhibitory", "titre", "monitoring", "anti-infective agents" "antimicrobial therapy" and "therapeutic drug monitoring"). Although standardized methods for performing SBTs were approved in 1999, the test remains labour intensive, and results may not be available until 72 hr. However, the use of non-culture-based endpoints (i.e. spectrophotometric or fluorescent) may shorten test time to 24 hr. Despite considerable heterogeneity in published studies, a meta-analysis of 11 evaluable studies published from 1974 to 2007 indicated a critical SBT result (peak SBT ≤1:8 or trough ≤1:2) is associated with a diagnostic odds ratio for clinical failure during antibiotic treatment of 12.27 (95% confidence interval 5.28–28.54) and a 5.32 (95% 1.32–21.42) odds of death. SBTs have prognostic value for identifying patients at high risk for antibiotic treatment failure, but the slow turnaround time of the current test limits its clinical utility. Standardization of a more rapid SBT testing method is needed. Image 1 [ABSTRACT FROM AUTHOR]

We examined factors associated with follow-up blood cultures (FUBCs) in patients with monomicrobial Gram-negative (GN) bloodstream infection (BSI) and investigated the impact of FUBCs on therapeutic management and patient outcome. A retrospective cohort analysis was conducted of adult patients diagnosed with GN-BSI at a tertiary-care university hospital during 2013–2016. FUBCs performed between 24 hours and 7 days after index BCs was the exposure variable. Risk factors for 30-day mortality were analysed by multivariate Cox analysis on the overall cohort, including FUBCs as a time-varying covariate and on 1:1 matched patients according to Sequential Organ Failure Assessment (SOFA) score and time to FUBC. In 278 (17.6%) of 1576 patients, FUBCs were performed within a median of 3 and 2 days after index BCs and active antibiotic therapy initiation. Persistent BSI was found in 107 (38.5%) of 278 patients. FUBCs were performed in more severely ill patients, with nonurinary sources, difficult-to-treat pathogens and receipt of initial inappropriate therapy. Source control and infectious disease consultation rates were higher among patients with preceding FUBCs and was associated with longer treatment duration. Thirty-day mortality was 10.4%. Independent risk factors for mortality were Charlson comorbidity index (hazard ratio (HR) 1.12) SOFA (HR 1.11), septic shock (HR 2.64), urinary source (HR 0.60), central venous catheter source (HR 2.30), complicated BSI (HR 2.10), carbapenem resistance (HR 2.34), active empiric therapy (HR 0.68), source control (HR 0.34) and FUBCs (HR 0.48). Association between FUBCs and lower mortality was confirmed in the 274 matched pairs. FUBCs were performed in more severe GN-BSIs, yielding a high rate of persistent BSI. In this context, FUBCs were associated with lower mortality. [ABSTRACT FROM AUTHOR]

To investigate the impact of colonization with carbapenemase-producing Enterobacteriaceae (CPE) on the CPE infection risk after liver transplantation (LT). Prospective cohort study of all adult patients undergoing LT at our centre over an 8-year period (2010–2017). Individuals were screened for CPE colonization by rectal swabs at inclusion onto the waiting list, immediately before LT and weekly after LT until hospital discharge. Asymptomatic carriers did not receive decolonization, anti-CPE prophylaxis or pre-emptive antibiotic therapy. Participants were followed up for 1 year after LT. We analysed 553 individuals who underwent a first LT, 38 were colonized with CPE at LT and 104 acquired colonization after LT. CPE colonization rates at LT and acquired after LT increased significantly over the study period: incidence rate ratios (IRR) 1.21 (95% CI 1.05–1.39) and 1.17 (95% CI 1.07–1.27), respectively. Overall, 57 patients developed CPE infection within a median of 31 (interquartile range 11–115) days after LT, with an incidence of 3.05 cases per 10 000 LT-recipient-days and a non-significant increase over the study period (IRR 1.11, 95% CI 0.98–1.26). In multivariable analysis, CPE colonization at LT (hazard ratio (HR) 18.50, 95% CI 6.76–50.54) and CPE colonization acquired after LT (HR 16.89, 95% CI 6.95–41.00) were the strongest risk factors for CPE infection, along with combined transplant (HR 2.60, 95% CI 1.20–5.59), higher Model for End-Stage Liver Disease at the time of LT (HR 1.03, 95% CI 1.00–1.07), prolonged mechanical ventilation (HR 2.63, 95% CI 1.48–4.67), re-intervention (HR 2.16, 95% CI 1.21–3.84) and rejection (HR 2.81, 95% CI 1.52–5.21). CPE colonization at LT or acquired after LT were the strongest predictors of CPE infection. Prevention strategies focused on LT candidates and recipients colonized with CPE should be investigated. [ABSTRACT FROM AUTHOR]

Abstract Objectives A prospective cohort study was conducted in Italy in order to describe the microbiologic aspects of colonization/infection by carbapenemase-producing Enterobacteriaceae (CPE) in donors and recipients of lung and liver transplants and the possible CPE transmission from donors to recipients. Methods Between 15 January 2014 and 14 January 2015, all recipients of solid organ transplants (SOT) at ten lung and eight liver transplantation centres and the corresponding donors were enrolled. Screening cultures to detect CPE were performed in donors, and screening and clinical cultures in recipients with a 28-day microbiologic follow-up after receipt of SOT. Detection of carbapenemase genes by PCR, genotyping by multilocus sequence typing, and pulsed-field gel electrophoresis and whole-genome sequencing were performed. Results Of 588 screened donors, 3.4% were colonized with CPE. Of the liver first transplant recipients (n = 521), 2.5% were colonized before receipt of SOT and 5% acquired CPE during follow-up. CPE colonization was higher in lung first transplant recipients (n = 111, 2.7% before SOT and 14.4% after SOT). CPE infections occurred in 1.9% and 5.3% of liver or lung recipients, respectively. CPE isolates were mostly Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae belonging to CG258. Three events of donor–recipient CPE transmission, confirmed by whole-genome sequencing and/or pulsed-field gel electrophoresis, occurred in lung recipients: two involving K. pneumoniae sequence type 512 and one Verona integron-encoded metallo-β-lactamase (VIM)-producing Enterobacter aerogenes. Conclusions This study showed a low risk of donor–recipient CPE transmission, indicating that donor CPE colonization does not necessarily represent a contraindication for donation unless colonization regards the organ to be transplanted. Donor and recipient screening remains essential to prevent CPE transmission and cross-infection in transplantation centres. [ABSTRACT FROM AUTHOR]

Abstract Objectives To investigate the impact of treatment duration on mortality and on relapse in patients with Escherichia coli bloodstream infection (BSI). Methods Retrospective single-centre study of patients diagnosed with E. coli BSI at our centre over a 4-year period. Exclusion criteria: age <18 years, clinical data not available, polymicrobial BSI, failure to receive in vitro active therapy, and death while receiving antibiotic therapy. Exposure variable was treatment duration dichotomized into short (≤10 days) and long (>10 days) therapy. Primary end point was all-cause mortality within 90 days after index BSI. Secondary end point was relapse, defined as repeat isolation of E. coli from blood cultures within 90 days after index BSI, in patients with documented clinical cure and completion of therapy for the initial episode. Results Of the 856 analysed patients: 426 received short and 430 received long therapy. All-cause mortality at day 90 occurred in 47 patients; on multivariate analysis, short therapy was not associated with a higher risk of mortality, also after adjusting the model for the propensity score of receiving short therapy. Relapse occurred in 42 patients. Independent risk factors for relapse using death as competing risk were immunosuppression (subhazard ratio 4.67, p < 0.001), and end-stage liver disease (subhazard ratio 2.58, p 0.013). The propensity-weighted estimation of the average treatment effect for relapse reduction with long therapy (>10 days) was –1.6% (p 0.26) in the total population, and –7.1% (p 0.18) in immunocompromised patients. Conclusions We could not identify shorter treatment duration as a risk factor for mortality and for relapse in patients with E. coli BSI. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the incidence of ceftazidime/avibactam resistance among Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) strains isolated from patients with bloodstream infection. We collected 120 carbapenemase producing Enterobacteriaceae (CPE) strains from unique patients hospitalized in two Italian hospitals between January 2018 to February 2019. Strains were phenotypically characterized for the type of carbapenemase production and susceptibility to ceftazidime/avibactam. Ceftazidime/avibactam-resistant strains were characterized by whole-genome sequencing. During the study period, we characterized 105 (87.5%) KPC producers among a total of 120 CPE strains. Ceftazidime/avibactam resistance was found in three KPC-Kp strains isolated from patients with no history of previous ceftazidime/avibactam-based treatment. Of note, two out of three ceftazidime–avibactam-resistant KPC-Kp were also resistant to meropenem/vaborbactam. Genomic characterization showed that a ceftazidime/avibactam-resistant KPC-Kp harboured a mixed population with D179Y mutated KPC-2, while the other two ceftazidime–avibactam-resistant KPC-Kp possessed non-functional ompK35-ompK37 and mutated ompK36 porins associated with higher copy number of bla KPC gene. Our results showed that incidence of ceftazidime/avibactam resistance emerged in KCP-Kp strains independently from previous antimicrobial exposure. Resistance to ceftazidime/avibactam was associated with mutations within the bla KPC gene or porin deficiency associated with higher bla KPC copy number and is also related to the meropenem/vaborbactam resistance. [ABSTRACT FROM AUTHOR]

Methylobacterium radiotolerans is a fastidious, pink-pigmented, obligate aerobic Gram-negative bacillus commonly isolated from various environmental sources, and only occasionally from clinical samples, mostly in immunocompromised patients or associated with intravascular devices and haemodialysis. It grows poorly on commonly used culture media and its identification is time-consuming by conventional means. In this study, we present a case of M. radiotolerans bacteraemia in an individual affected by end-stage renal failure, identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The species identification was further confirmed by biochemical and molecular methods. The susceptibility to various antimicrobial agents is also presented and discussed. [ABSTRACT FROM AUTHOR]

The increasing prevalence of colistin resistance (ColR) Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (Kp) is a matter of concern because of its unfavourable impact on mortality of KPC-Kp bloodstream infections (BSI) and the shortage of alternative therapeutic options. A matched case–control–control analysis was conducted. The primary study end point was to assess risk factors for ColR KPC-Kp BSI. The secondary end point was to describe mortality and clinical characteristics of these infections. To assess risk factors for ColR, 142 patients with ColR KPC-Kp BSI were compared to two controls groups: 284 controls without infections caused by KPC-Kp (control group A) and 284 controls with colistin-susceptible (ColS) KPC-Kp BSI (control group B). In the first multivariate analysis (cases vs. group A), previous colistin therapy, previous KPC-Kp colonization, ≥3 previous hospitalizations, Charlson score ≥3 and neutropenia were found to be associated with the development of ColR KPC-Kp BSI. In the second multivariate analysis (cases vs. group B), only previous colistin therapy, previous KPC-Kp colonization and Charlson score ≥3 were associated with ColR. Overall, ColR among KPC-Kp blood isolates increased more than threefold during the 4.5-year study period, and 30-day mortality of ColR KPC-Kp BSI was as high as 51%. Strict rules for the use of colistin are mandatory to staunch the dissemination of ColR in KPC-Kp-endemic hospitals. [ABSTRACT FROM AUTHOR]