Real-Time TDM-Guided Optimal Joint PK/PD Target Attainment of Continuous Infusion Piperacillin-Tazobactam Monotherapy Is an Effective Carbapenem-Sparing Strategy for Treating Non-Severe ESBL-Producing Enterobacterales Secondary Bloodstream Infections: Findings from a Prospective Pilot Study.

(1) Objectives: To assess the impact of optimal joint pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous infusion (CI) piperacillin-tazobactam monotherapy on the microbiological outcome of documented ESBL-producing Enterobacterlaes secondary bloodstream infections (BSIs). (2) Methods: Patients hospitalized in the period January 2022-October 2023, having a documented secondary BSI caused by ESBL-producing Enterobacterales, and being eligible for definitive targeted CI piperacillin-tazobactam monotherapy according to specific pre-defined inclusion criteria (i.e., absence of septic shock at onset; favorable clinical evolution in the first 48 h after starting treatment; low-intermediate risk primary infection source) were prospectively enrolled. A real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program was adopted for optimizing (PK/PD) target attainment of CI piperacillin-tazobactam monotherapy. Steady-state plasma concentrations (Css) of both piperacillin and tazobactam were measured, and the free fractions (f) were calculated based on theoretical protein binding. The joint PK/PD target attainment was considered optimal whenever the piperacillin fCss/MIC ratio was >4 and the tazobactam fCss/target concentration (CT) ratio was >1 (quasi-optimal or suboptimal if only one or neither of the two thresholds were achieved, respectively). Univariate analysis was carried out for assessing variables potentially associated with failure in achieving the optimal joint PK/PD target of piperacillin-tazobactam and microbiological eradication. (3) Results: Overall, 35 patients (median age 79 years; male 51.4%) were prospectively included. Secondary BSIs resulted from urinary tract infections as a primary source in 77.2% of cases. The joint PK/PD target attainment was optimal in as many as 97.1% of patients (34/35). Microbiological eradication occurred in 91.4% of cases (32/35). Attaining the quasi-optimal/suboptimal joint PK/PD target of CI piperacillin-tazobactam showed a trend toward a higher risk of microbiological failure (33.3% vs. 0.0%; p = 0.08) (4) Conclusions: Real-time TDM-guided optimal joint PK/PD target attainment of CI piperacillin-tazobactam monotherapy may represent a valuable and effective carbapenem-sparing strategy when dealing with non-severe ESBL-producing Enterobacterales secondary BSIs.

Prevalence of and risk factors for intestinal colonisation by multidrug-resistant Gram-negative bacteria in patients with haematological malignancies: A systematic review and meta-analysis.

BACKGROUND: Patients with haematological malignancies (HM patients) are at high risk of infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB). MDR-GNB intestinal colonisation is associated with MDR-GNB infections. The aim of this systematic review and meta-analysis on HM patients was to pool the prevalence of and risk factors for intestinal colonisation by MDR-GNB, including carbapenem-resistant Enterobacterales (CRE) and extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales, reported in previous studies. METHODS: This study was conducted according to the protocol registered in PROSPERO (CRD42022374425). PubMed, Embase, Web of Science, Ovid MEDLINE(R) ALL and Cochrane Library were searched from inception to 25 October 2022. Observational studies reporting CRE and/or ESBL intestinal colonisation in HM patients were included. Subgroup analyses were conducted by study region. RESULTS: A total of 21 402 HM patients from 32 studies were analysed. The pooled CRE and ESBL colonisation rates were 21.7% [95% confidence interval (95%CI) 18.7-24.8] and 19.2% (95%CI 13.9-24.5), respectively. Prior exposure to tigecycline [odds ratio (OR) 3.99, 95%CI 2.08-7.68], carbapenem (OR 1.84, 95%CI 1.13-2.97) or penicillin (OR 1.72, 95%CI 1.05-2.83), as well as chemotherapy (OR 2.45, 95%CI 1.05-5.73), neutropenia (OR 1.88, 95%CI 1.08-3.26) and acute myeloid leukaemia (AML; OR 1.86, 95%CI 1.33-2.61), were risk factors for CRE colonisation in HM patients. Prior antibiotic exposure was a risk factor for ESBL colonisation in HM patients (OR 4.90, 95%CI 2.76-8.70). CONCLUSIONS: This study shows the high prevalence of MDR-GNB (CRE and ESBL) colonisation in HM patients and explains associated factors for the colonisation. The results provide evidence for MDR-GNB infection control in HM management.

Extended-spectrum ß-lactamase-producing Enterobacterales in diverse foodstuffs: a prospective, longitudinal study in the city of Basel, Switzerland.

Background: The involvement of non-human-to-human transmission of extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) remains elusive. Foodstuffs may serve as reservoirs for ESBL-PE and contribute to their spread. Aim: We aimed to systematically investigate the presence and spatiotemporal distribution of ESBL-PE in diverse unprocessed foodstuffs of different origin purchased in a central European city. Methods: Chicken and green (herbs, salad, sprouts, vegetables) samples were collected monthly for two consecutive years, from June 2017 to June 2019, from large supermarket chains and small local food retailers, representing all ten postcode areas of the City of Basel (Switzerland), and the kitchen of the University Hospital Basel (Basel, Switzerland). After enrichment, presumptive ESBL-PE were isolated by selective culture methods and identified by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. ESBL production was confirmed by phenotypic testing. Results: Among 947 food samples, 14.8% were positive for ESBL-PE isolate/s belonging to eight different ESBL-producing bacterial species. Escherichia coli and Serratia fonticola were predominant across samples (9 and 2%, respectively). Higher ESBL-PE prevalence was observed in chicken (25.9%) than in green (3.8%) samples (p < 0.001). Among greens, ESBL-PE were most frequently isolated from sprouts (15.2%). High ESBL-PE species diversity was observed among chicken samples, with E. coli as predominant (17.6%). ESBL-producing Enterobacter cloacae was detected among different greens. Yet, ESBL-producing Klebsiella pneumoniae was predominant in sprouts (12.1%). In total, 20.5% of samples from organic farming and 14.2% of samples from conventionally raised animals harbored an ESBL-producing isolate. Detection of ESBL-PE across samples differed between organic and non-organic when stratified by food source (p < 0.001), particularly among greens (12.5% organic, 2.4% conventional). High proportion of organic chicken samples was positive for ESBL-E. coli (33.3%), while the detection of several species characterized the conventional chicken samples. No significant differences in ESBL-PE frequences were detected between national (13.4%) and international samples (8.0%) (p = 0.122). Instead, differences were observed between regions of food production and countries (p < 0.001). No significant differences were found when comparing the proportion of ESBL-PE positive samples across districts, shop sizes and the hospital kitchen. The percentage of ESBL-PE positive samples did not differ monthly across the two-year sampling period (p = 0.107). Conclusion: Our findings indicate moderate dissemination of ESBL-PE in foodstuffs, especially between chicken products and sprouts. Chicken meat represents a source for several ESBL-producing Enterobacterales, especially E. coli, while greens are more prone to carry ESBL-K. pneumoniae and E. cloacae. We disclose the importance of food type, food production system and production origin when assessing the risk of contamination with different ESBL-PE species.

Epidemiology of multidrug-resistant organisms before and during COVID-19 in Hong Kong.

Background: The coronavirus disease 2019 (COVID-19) has influenced antimicrobial consumption and incidence of multidrug-resistant organisms (MDROs). We aimed to study the epidemiology of MDROs before and during the COVID-19 pandemic in Hong Kong. Methods: With the maintenance of infection control measures, we described the trend of MDRO infections, including methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Acinetobacter species (CRA), and extended-spectrum-beta-lactamase-(ESBL)-producing Enterobacterales, in a healthcare region with 3100-bed before (1 January 2016 to 31 December 2019, period 1) and during COVID-19 (1 January 2020 to 30 September 2022, period 2), together with the antimicrobial consumption using piecewise Poisson regression. The epidemiological characteristics of newly diagnosed COVID-19 patients with or without MDRO infections were analyzed. Results: Between period 1 and 2, we observed a significant increase in the trend of CRA infections (P<0.001), while there was no significant increase in the trend of MRSA (P=0.742) and ESBL-producing Enterobacterales (P=0.061) infections. Meanwhile, a significant increase in the trend of carbapenems (P<0.001), extended-spectrum beta-lactam-beta-lactamase inhibitor combinations (BLBI) (P=0.045), and fluoroquinolones (P=0.009) consumption was observed. The observed opportunity (23,540 ± 3703 vs 26,145 ± 2838, p=0.359) and compliance (81.6% ± 0.5% vs 80.1% ± 0.8%, P=0.209) of hand hygiene per year was maintained. In a multivariable model, older age, male sex, referral from residential care home for the elderly, presence of indwelling device, presence of endotracheal tube, and use of carbapenems, use of BLBI, use of proton pump inhibitors and history of hospitalization in the past 3 months were associated with higher risks of infections by MDROs among COVID-19 patients. Conclusion: Infection control measures may control the surge of MDROs despite an increasing trend of antimicrobial consumption.

Spatiotemporal dissemination of ESBL-producing Enterobacterales in municipal sewer systems: a prospective, longitudinal study in the city of Basel, Switzerland.

Background: The contribution of community and hospital sources to the transmission of extended-spectrum ß-lactamase producing Enterobacterales (ESBL-PE) remains elusive. Aim: To investigate the extent of community dissemination and the contribution of hospitals to the spread of ESBL-PE by exploring their spatiotemporal distribution in municipal wastewater of the central European city of Basel. Methods: Wastewater samples were collected monthly for two consecutive years throughout Basel, Switzerland, including 21 sites across 10 postcode areas of the city collecting either community wastewater (urban sites, n = 17) or community and hospital wastewater (mixed sites, n = 4). Presumptive ESBL-PE were recovered by selective culture methods. Standard methodologies were applied for species identification, ESBL-confirmation, and quantification. Results: Ninety-five percent (477/504) of samples were positive for ESBL-PE. Among these isolates, Escherichia coli (85%, 1,140/1,334) and Klebsiella pneumoniae (11%, 153/1,334) were most common. They were recovered throughout the sampling period from all postcodes, with E. coli consistently predominating. The proportion of K. pneumoniae isolates was higher in wastewater samples from mixed sites as compared to samples from urban sites, while the proportion of E. coli was higher in samples from urban sites (p = 0.003). Higher numbers of colony forming units (CFUs) were recovered from mixed as compared to urban sites (median 3.2 × 102 vs. 1.6 × 102 CFU/mL). E. coli-counts showed moderate correlation with population size (rho = 0.44), while this correlation was weak for other ESBL-PE (rho = 0.21). Conclusion: ESBL-PE are widely spread in municipal wastewater supporting that community sources are important reservoirs entertaining the spread of ESBL-PE. Hospital-influenced abundance of ESBL-PE appears to be species dependent.

Implementation of contact isolation strategy for the containment of extended-spectrum ß-lactamase carriers in a University Hospital positively affects the epidemiology of carbapenemase-producing Enterobacterales.

INTRODUCTION: The lack of consensus of control measures to prevent extended-spectrum ß-lactamase producing Enterobacterales (ESBL-E) transmission in the hospital setting is of great concern. We describe the prevalence and species distribution of ESBL-E and carbapenemase producing Enterobacterales (CPE) in patients admitted in a tertiary Hospital during an active surveillance screening program for detecting ESBL-E carriers and reducing the ESBL-E transmission (R-GNOSIS Project). METHODS: From March-2014 to March-2016, 15,556 rectal swabs were collected from 8209 patients admitted in two medical (Gastroenterology, Pneumology) and two surgical (Neurosurgery, Urology) wards. Swabs were seeded onto ChromoID-ESBL and -CARB/OXA-48 agar plates. Growing colonies were identified by MALDI-TOF MS. ESBL and carbapenemases were phenotypically detected. Changes in species diversity (SDI) and distribution over time were analyzed. RESULTS: ESBL-E incidence (8.4%) tended to decrease over time (p=0.003) and CPE carrier prevalence remained unchanged during the study (2%). The contact isolation strategy targeted to reduce ESBL-E transmission was ineffective in reducing ESBL-E carriers but significant differences were observed with CPE (p=0.017). SDI did not change among ESBL-E and E. coli was predominant (78.5%) during the study. K. pneumoniae (54%) was the most frequent CPE species, followed by E. coli (19%). SDI decreased among the CPE population over time mainly due to K. pneumoniae dominance and increased E. coli prevalence in the last part of the study. CONCLUSIONS: During the R-GNOSIS project, contact precautions were not effective in reducing the ESBL-E transmission but may have had a positive collateral effect on the CPE containment.

Implementation of contact isolation strategy for the containment of extended - spectrum beta lactamase carriers in a University Hospital positively affects the epidemiology of carbapenemase-producing Enterobacterales / La implementación de la estrategia de aislamiento de contacto para la contención de portadores de beta lactamasas de espectro extendido en un hospital universitario afecta positivamente a la epidemiología de las enterobacterias productoras de carbapenemasas

Introduction: The lack of consensus of control measures to prevent extended-spectrum β-lactamase producing Enterobacterales (ESBL-E) transmission in the hospital setting is of great concern. We describe the prevalence and species distribution of ESBL-E and carbapenemase producing Enterobacterales (CPE) in patients admitted in a tertiary Hospital during an active surveillance screening program for detecting ESBL-E carriers and reducing the ESBL-E transmission (R-GNOSIS Project). Methods: From March-2014 to March-2016, 15,556 rectal swabs were collected from 8209 patients admitted in two medical (Gastroenterology, Pneumology) and two surgical (Neurosurgery, Urology) wards. Swabs were seeded onto ChromoID-ESBL and -CARB/OXA-48 agar plates. Growing colonies were identified by MALDI-TOF MS. ESBL and carbapenemases were phenotypically detected. Changes in species diversity (SDI) and distribution over time were analyzed. Results: ESBL-E incidence (8.4%) tended to decrease over time (p=0.003) and CPE carrier prevalence remained unchanged during the study (2%). The contact isolation strategy targeted to reduce ESBL-E transmission was ineffective in reducing ESBL-E carriers but significant differences were observed with CPE (p=0.017). SDI did not change among ESBL-E and E. coli was predominant (78.5%) during the study. K. pneumoniae (54%) was the most frequent CPE species, followed by E. coli (19%). SDI decreased among the CPE population over time mainly due to K. pneumoniae dominance and increased E. coli prevalence in the last part of the study. Conclusions: During the R-GNOSIS project, contact precautions were not effective in reducing the ESBL-E transmission but may have had a positive collateral effect on the CPE containment.(AU)

Introducción: La falta de consenso en las medidas de control necesarias para prevenir la transmisión de enterobacterias productoras de β-lactamasas de espectro extendido (BLEE-E) en el entorno hospitalario es muy preocupante. En este trabajo describimos la prevalencia y la distribución de especies de BLEE-E y las enterobacterias productoras de carbapenemasas (EPC) en pacientes ingresados en un hospital terciario durante un programa de vigilancia activa para detectar portadores de BLEE-E y reducir su transmisión (Proyecto R-GNOSIS). Métodos: Entre marzo-2014 y marzo-2016 se recogieron 15.556 hisopos rectales de 8.209 pacientes ingresados en 2 servicios médicos (Gastroenterología, Neumología) y 2 quirúrgicos (Neurocirugía, Urología). Los hisopos se sembraron en las placas de agar ChromoID-ESBL y CARB/OXA-48. Las colonias crecidas fueron identificadas por MALDI-TOF MS. La producción de BLEE y carbapenemasas se confirmó fenotípicamente. Se analizaron los cambios en la diversidad de especies (SDI) y su distribución en el tiempo. Resultados: La incidencia de BLEE-E (8,4%) tendió a disminuir (p=0,003) y la prevalencia de portadores de CPE permaneció sin cambios durante el estudio (2%). La estrategia de aislamiento de contacto dirigida a reducir la transmisión de BLEE-E fue ineficaz, pero se observaron diferencias significativas en las EPC (p=0,017). La SDI de las BLEE-E no cambió durante el estudio y E. coli fue la especie predominante (78,5%). K. pneumoniae (54%) fue la especie de EPC más frecuente, seguida de E. coli (19%). El SDI disminuyó entre la población de EPC, principalmente debido al dominio de K. pneumoniae y al aumento de la prevalencia de E. coli en la última parte del estudio. Conclusiones: Durante el proyecto R-GNOSIS, las precauciones de contacto no fueron efectivas para reducir la transmisión de BLEE-E, pero pudo haber tenido un efecto colateral positivo en la contención de EPC.(AU)

Sickle cell disease children's gut colonization by extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales: an antibiotic prophylaxis effect?

Introduction. Sickle cell disease (SCD) children have a high susceptibility to pneumococcal infection. For this reason, they are routinely immunized with pneumococcal vaccines and use antibiotic prophylaxis (AP).Hypothesis/Gap Statement. Yet, little is known about SCD children's gut microbiota. If antibiotic-resistant Enterobacterales may colonize people on AP, we hypothesized that SCD children on AP are colonized by resistant enterobacteria species.Objective. To evaluate the effect of continuous AP on Enterobacterales gut colonization from children with SCD.Methodology. We analysed 30 faecal swabs from SCD children on AP and 21 swabs from children without the same condition. Enterobacterales was isolated on MacConkey agar plates and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) (bioMérieux, Marcy l'Etoile, France). We performed the antibiogram by Vitek 2 system (bioMérieux, Marcy l'Etoile, France), and the resistance genes were identified by multiplex PCR.Results. We found four different species with resistance to one or more different antibiotic types in the AP-SCD children's group: Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, and Citrobacter farmeri. Colonization by resistant E. coli was associated with AP (prevalence ratio 2.69, 95 % confidence interval [CI], 1.98-3.67, P<0.001). Strains producing extended-spectrum ß-lactamases (ESBL) were identified only in SCD children, E. coli, 4/30 (13 %), and K. pneumoniae, 2/30 (7 %). The ESBL-producing Enterobacterales were associated with penicillin G benzathine use (95 % CI, 22.91-86.71, P<0.001). CTX-M-1 was the most prevalent among ESBL-producers (3/6, 50 %), followed by CTX-M-9 (2/6, 33 %), and CTX-M-2 (1/6, 17 %).Conclusion. Resistant enterobacteria colonize SCD children on AP, and this therapy raises the chance of ESBL-producing Enterobacterales colonization. Future studies should focus on prophylactic vaccines as exclusive therapy against pneumococcal infections.

Risk factors for methicillin-resistant Staphylococcus aureus and extended-spectrum ß-lactamase producing Enterobacterales in patients with diabetic foot infections requiring hospital admission.

OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) may complicate the treatment of diabetic foot infections (DFIs). The aim of this study was to determine the risk factors for these pathogens in DFIs. METHODS: This was a prospective observational study of 167 consecutive adult patients with DFIs. The diagnosis and severity of DFIs were based on the Infectious Disease Society of America (IDSA) classification system. Multivariate analyses were performed in order to identify risk factors for MRSA and ESBL-E infections. RESULTS: S. aureus was the most isolated pathogen (n=82, 37.9 %) followed by Escherichia coli (n= 40, 18.5%). MRSA accounted for 57.3% of all S. aureus and 70% of Klebsiella pneumoniae and 25% of E. coli were ESBL producers, respectively. Deep ulcer [OR 8,563; 95% CI (1,068-4,727)], previous use of fluoroquinolones [OR 2,78; 95% CI (1,156-6,685)] and peripheral vasculopathy [OR 2,47; 95% CI (1.068-4.727)] were the independent predictors for MRSA infections; and osteomyelitis [OR 6,351; 95% CI (1,609-25,068)] and previous use of cephalosporins [OR 5,824; 95% CI (1,517-22,361)] for ESBL-E infections. CONCLUSIONS: MRSA and ESBL-E have adquired a great clinical relevance in DFIs. The availability of their risk factors is very convenient to choose the empirical treatment in severe forms.

Ceftolozane/Tazobactam and Ceftazidime/Avibactam for Multidrug-Resistant Gram-Negative Infections in Immunocompetent Patients: A Single-Center Retrospective Study.

Complicated infections from multidrug-resistant Gram-negative bacteria (MDR-GNB) represent a serious problem presenting many challenges. Resistance to many classes of antibiotics reduces the probability of an adequate empirical treatment, with unfavorable consequences, increasing morbidity and mortality. Readily available patient medical history and updated information about the local microbiological epidemiology remain critical for defining the baseline risk of MDR-GNB infections and guiding empirical treatment choices, with the aim of avoiding both undertreatment and overtreatment. There are few literature data that report real-life experiences in the use of ceftolozane/tazobactam and ceftazidime/avibactam, with particular reference to microbiological cure. Some studies reported experiences for the treatment of MDR-GNB infections in patients with hematological malignancies or specifically in Pseudomonas aeruginosa infections. We report our clinical single-center experience regarding the real-life use of ceftolozane/tazobactam and ceftazidime/avibactam to treat serious and complicated infections due to MDR-GNB and carbapenem-resistant Enterobacterales (CRE), with particular regard given to intra-abdominal and urinary tract infections and sepsis.

Multiple Plasmid Vectors Mediate the Spread of fosA3 in Extended-Spectrum-ß-Lactamase-Producing Enterobacterales Isolates from Retail Vegetables in China.

The plasmid-mediated fosfomycin resistance gene fosA3 has been detected in Enterobacterales from various sources but has rarely been reported in vegetables. In this study, the aim was to investigate the prevalence of and, subsequently, to characterize fosA3-positive Enterobacterales isolates from retail vegetables. Seventeen (7.3%) fosA3-carrying strains were identified from 233 extended-spectrum-ß-lactamase-producing Enterobacterales isolates from vegetables. All 17 isolates, including six Escherichia coli, seven Klebsiella pneumoniae, two Raoultella ornithinolytica, and two Citrobacter freundii isolates, carried blaCTX-M S1-nuclease pulsed-field gel electrophoresis (S1-PFGE) and hybridization confirmed that the fosA3 genes in 16 isolates were located on plasmids ranging in size from ∼40 kb to ∼250 kb, except one located on chromosome of C. freundii All the fosA3-carrying plasmids from 16 fosA3-positive isolates were successfully transferred into the recipient bacteria by transformation or conjugation. In agreement with data determined with isolates from food animals, the IncHI2/ST3 and IncN-F33:A-:B-/F33:A-:B plasmids were the main vectors of fosA3 in E. coli Additionally, F24:A-:B1, IncFIIK-IncR, IncFIIS, IncR, and two untypeable plasmids were found for the first time to be vectors for fosA3 in Enterobacterales The genetic contexts of fosA3 in 15 Enterobacterales isolates differed due to insertion and/or loss of molecular modules mediated by mobile elements. However, all fosA3 genes were flanked by IS26, as commonly observed in other fosA3-carrying plasmids. Here, we report a high rate of detection of fosA3 genes, mediated by multiple plasmid vectors, in ESBL-producing Enterobacterales from retail vegetables. FosA3-producing Enterobacterales could be transmitted to the human body by direct contact or consumption of vegetables, which might pose a potential threat to public health.IMPORTANCE This report provides important information on the transmission and epidemiology of fosA3 among Enterobacterales isolates from vegetables. The rate of occurrence of fosA3 in ESBL-producing Enterobacterales from retail vegetables is high, and fosA3 was found to be carried by diverse plasmids. Some novel genetic contexts of fosA3 and novel fosA3-carrying plasmids, including several plasmid types common in K. pneumoniae, were identified, increasing the number of known transfer vectors for the fosA3 gene and reflecting the complexity of fosA3 transmission in Enterobacterales The capture of fosA3 by the resident plasmid of K. pneumoniae will accelerate the spread of fosA3 in K. pneumoniae, one of the most pathogenic species in clinical medicine. Considering the clinical importance of fosfomycin, and the fact that vegetables are directly consumed, the fosfomycin resistance genes present a risk of transmission to the human body through the food chain and thus pose a threat to public health.

Implementation of contact isolation strategy for the containment of extended-spectrum ß-lactamase carriers in a University Hospital positively affects the epidemiology of carbapenemase-producing Enterobacterales.

INTRODUCTION: The lack of consensus of control measures to prevent extended-spectrum ß-lactamase producing Enterobacterales (ESBL-E) transmission in the hospital setting is of great concern. We describe the prevalence and species distribution of ESBL-E and carbapenemase producing Enterobacterales (CPE) in patients admitted in a tertiary Hospital during an active surveillance screening program for detecting ESBL-E carriers and reducing the ESBL-E transmission (R-GNOSIS Project). METHODS: From March-2014 to March-2016, 15,556 rectal swabs were collected from 8209 patients admitted in two medical (Gastroenterology, Pneumology) and two surgical (Neurosurgery, Urology) wards. Swabs were seeded onto ChromoID-ESBL and -CARB/OXA-48 agar plates. Growing colonies were identified by MALDI-TOF MS. ESBL and carbapenemases were phenotypically detected. Changes in species diversity (SDI) and distribution over time were analyzed. RESULTS: ESBL-E incidence (8.4%) tended to decrease over time (p=0.003) and CPE carrier prevalence remained unchanged during the study (2%). The contact isolation strategy targeted to reduce ESBL-E transmission was ineffective in reducing ESBL-E carriers but significant differences were observed with CPE (p=0.017). SDI did not change among ESBL-E and E. coli was predominant (78.5%) during the study. K. pneumoniae (54%) was the most frequent CPE species, followed by E. coli (19%). SDI decreased among the CPE population over time mainly due to K. pneumoniae dominance and increased E. coli prevalence in the last part of the study. CONCLUSIONS: During the R-GNOSIS project, contact precautions were not effective in reducing the ESBL-E transmission but may have had a positive collateral effect on the CPE containment.

Clinical Experience with Ceftazidime-Avibactam for the Treatment of Infections due to Multidrug-Resistant Gram-Negative Bacteria Other than Carbapenem-Resistant Enterobacterales.

BACKGROUND: Experience in real clinical practice with ceftazidime-avibactam for the treatment of serious infections due to gram-negative bacteria (GNB) other than carbapenem-resistant Enterobacterales (CRE) is very limited. METHODS: We carried out a retrospective multicenter study of patients hospitalized in 13 Italian hospitals who received ≤72 h of ceftazidime-avibactam for GNB other than CRE to assess the rates of clinical success, resistance development, and occurrence of adverse events. RESULTS: Ceftazidime-avibactam was used to treat 41 patients with GNB infections other than CRE. Median age was 62 years and 68% of them were male. The main causative agents were P.aeruginosa (33/41; 80.5%) and extended spectrum beta lactamase (ESBL)-producing Enterobacterales (4/41, 9.8%). Four patients had polymicrobial infections. All strains were susceptible to ceftazidime-avibactam. The most common primary infection was nosocomial pneumonia (n = 20; 48.8%), primary bacteremia (n = 7; 17.1%), intra-abdominal infection (n = 4; 9.8%), and bone infection (n = 4; 9.8%). Ceftazidime-avibactam was mainly administered as a combination treatment (n = 33; 80.5%) and the median length of therapy was 13 days. Clinical success at the end of the follow-up period was 90.5%, and the only risk factor for treatment failure at multivariate analysis was receiving continuous renal replacement therapy during ceftazidime-avibactam. There was no association between clinical failures and type of primary infection, microbiological isolates, and monotherapy with ceftazidime-avibactam. Only one patient experienced recurrent infection 5 days after the end of treatment. Development of resistance to ceftazidime-avibactam was not detected in any case during the whole follow-up period. No adverse events related to ceftazidime-avibactam were observed in the study population. CONCLUSIONS: Ceftazidime-avibactam may be a valuable therapeutic option for serious infections due to GNB other than CRE.