Meropenem-Vaborbactam as Salvage Therapy for Ceftazidime-Avibactam-, Cefiderocol-Resistant ST-512 Klebsiella pneumoniae-Producing KPC-31, a D179Y Variant of KPC-3

A 68-year-old man had recurrent bacteremia by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae resistant to ceftazidime-avibactam and cefiderocol. The sequencing of a target region showed that it harbored a KPC-3 variant enzyme (D179Y; KPC-31), which confers resistance to ceftazidime-avibactam and restores meropenem susceptibility. The patient was successfully treated with meropenem-vaborbactam

Feasibility of Using a Commercial Fitness Tracker as an Adjunct to Family-Based Weight Management Treatment: Pilot Randomized Trial.

BACKGROUND: Fitness trackers can engage users through automated self-monitoring of physical activity. Studies evaluating the utility of fitness trackers are limited among adolescents, who are often difficult to engage in weight management treatment and are heavy technology users. OBJECTIVE: We conducted a pilot randomized trial to describe the impact of providing adolescents and caregivers with fitness trackers as an adjunct to treatment in a tertiary care weight management clinic on adolescent fitness tracker satisfaction, fitness tracker utilization patterns, and physical activity levels. METHODS: Adolescents were randomized to 1 of 2 groups (adolescent or dyad) at their initial weight management clinic visit. Adolescents received a fitness tracker and counseling around activity data in addition to standard treatment. A caregiver of adolescents in the dyad group also received a fitness tracker. Satisfaction with the fitness tracker, fitness tracker utilization patterns, and physical activity patterns were evaluated over 3 months. RESULTS: A total of 88 adolescents were enrolled, with 69% (61/88) being female, 36% (32/88) black, 23% (20/88) Hispanic, and 63% (55/88) with severe obesity. Most adolescents reported that the fitness tracker was helping them meet their healthy lifestyle goals (69%) and be more motivated to achieve a healthy weight (66%). Despite this, 68% discontinued use of the fitness tracker by the end of the study. There were no significant differences between the adolescent and the dyad group in outcomes, but adolescents in the dyad group were 12.2 times more likely to discontinue using their fitness tracker if their caregiver also discontinued use of their fitness tracker (95% CI 2.4-61.6). Compared with adolescents who discontinued use of the fitness tracker during the study, adolescents who continued to use the fitness tracker recorded a higher number of daily steps in months 2 and 3 of the study (mean 5760 vs 4148 in month 2, P=.005, and mean 5942 vs 3487 in month 3, P=.002). CONCLUSIONS: Despite high levels of satisfaction with the fitness trackers, fitness tracker discontinuation rates were high, especially among adolescents whose caregivers also discontinued use of their fitness tracker. More studies are needed to determine how to sustain the use of fitness trackers among adolescents with obesity and engage caregivers in adolescent weight management interventions

Time to appropriate antibiotic therapy is a predictor of outcome in patients with bloodstream infection caused by KPC-producing Klebsiella pneumoniae

BACKGROUND: Bloodstream infections (BSIs) by Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (Kp) are associated with high mortality. The aim of this study is to assess the relationship between time to administration of appropriate antibiotic therapy and the outcome of patients with BSI due to KPC-Kp hospitalized in intensive care unit (ICU). METHODS: An observational study was conducted in the ICUs of two academic centers in Italy. Patients with KPC-Kp bacteremia hospitalized between January 2015 to December 2018 were included. The primary outcome was the relationship between time from blood cultures (BC) collection to appropriate antibiotic therapy and 30-day mortality. The secondary outcome was to evaluate the association of different treatment regimens with 30-day mortality and a composite endpoint (30-day mortality or nephrotoxicity). A Cox regression analysis to identify factors independently associated with 30-day mortality was performed. Hazard ratio (HR) and 95% confidence interval (CI) were calculated. RESULTS: A total of 102 patients with KPC-Kp BSI were included. The most common sources of infection were intra-abdominal (23.5%), urinary tract (20.6%), and skin and skin structure (17.6%). The 30-day mortality was 45%. Median time to appropriate antibiotic therapy was shorter in patients who survived (8.5\u2009h [IQR 1-36]) versus those who died (48\u2009h [IQR 5-108], p\u2009=\u20090.014). A propensity score matching showed that receipt of an in vitro active therapy within 24\u2009h from BC collection was associated with lower 30-day mortality (HR\u2009=\u20090.36, 95% CI: 0.188-0.690, p\u2009=\u20090.0021). At Cox regression analysis, factors associated with 30-day mortality were primary bacteremia (HR 2.662 [95% CI 1.118-6.336], p\u2009=\u20090.027), cardiovascular disease (HR 2.196 [95% CI 1.082-4.457], p\u2009=\u20090.029), time (24-h increments) from BC collection to appropriate therapy (HR 1.382 [95% CI 1.132-1.687], p\u2009=\u20090.001), SOFA score (HR 1.122 [95% CI 1.036-1.216], p\u2009=\u20090.005), and age (HR 1.030 [95% CI 1.006-1.054], p\u2009=\u20090.012). Ceftazidime-avibactam-containing regimens were associated with reduced risk of composite endpoint (30-day mortality OR nephrotoxicity) (HR 0.231 [95% CI 0.071-0.745], p\u2009=\u20090.014) compared to colistin-containing regimens. CONCLUSIONS: Time to appropriate antibiotic therapy is an independent predictor of 30-day mortality in patients with KPC-Kp BSI. Appropriate antibiotic therapy should begin within 24\u2009h from the collection of BC

Increased risk of acquisition of New Delhi metallo-beta-lactamase-producing carbapenem-resistant enterobacterales (Ndm-cre) among a cohort of covid-19 patients in a teaching hospital in Tuscany, Italy

We describe the epidemiology of New Delhi Metallo-Beta-Lactamase-Producing Carbapenem-Resistant Enterobacterales (NDM-CRE) colonization/infection in a cohort of COVID-19 patients in an Italian teaching hospital. These patients had an increased risk of NDM-CRE acquisition versus the usual patients (75.9 vs. 25.3 cases/10,000 patient days). The co-infection significantly increased the duration of hospital stay (32.9 vs. 15.8 days)

Expansion of KPC-producing klebsiella pneumoniae with various mgrB-mutations giving rise to colistin-resistance:the role of ISL3 on plasmids

BACKGROUND: mcr-1 has been reported as first plasmid gene to confer colistin-resistance. In KPC-producing Klebsiella pneumoniae (KPC-KP) isolates, however, colistin resistance is rapidly emerging through other mechanisms. This is frequently the result of disruption of mgrB gene by insertion sequences, for instance ISL3. The aim of this study is to investigate the expansion of mgrB-mutated KPC-KP. In addition, we identify localization and targets of ISL3 sequences within the core and accessory genome of common KPC-KP lineages. METHODS: Twenty-nine clinical isolates of K. pneumoniae collected from Italian patients were randomly selected. Whole genome sequences (WGS) were analysed for resistance genes, plasmids, and insertion sequences. Additionally, 27 colistin-resistant KPC-KP isolates from a previous study from Crete was assessed. FINDINGS: We observed clonal expansion of KPC-KP isolates with various mutations in mgrB among all lineages. In two Italian MLST ST512 isolates, and eight Greek ST258 isolates an identical copy of the ISL3 was inserted in mgrB nucleotide position 133. ISL3s, transposable restriction modification systems of 8154 nucleotides, were positioned on pKpQIL carrying isolates and may transpose into the chromosome. In 4 isolates, chromosomal integration of ISL3 in diverse inner-membrane proteins other than mgrB was identified. INTERPRETATION: Colistin resistance is most often explained by clonal expansion of isolates with mutated mgrB. pKpQIL-like plasmids, which are omnipresent in KPC-KP, carry insertion sequences such as ISL3 that have mgrB as a target hotspot for transposition. Transposition of insertion sequences from plasmids and subsequent clonal expansion may contribute to the emerging colistin resistance in KPC-KP

Evaluation of a modified cleaning procedure in the prevention of carbapenem-resistant Acinetobacter baumannii clonal spread in a burn intensive care unit using a high-sensitivity luminometer

Background: Enhanced environmental cleaning practices are among the most accepted measures for controlling the spread of carbapenem-resistant . Acinetobacter baumannii (CR-Ab). Aim: To evaluate the impact of heightened cleaning on an ongoing CR-Ab outbreak in a burn intensive care unit (BICU) of an Italian teaching hospital, where chlorhexidine-60% isopropyl alcohol was applied as a complementary disinfectant on high-touch surfaces. Methods: Compliance with the microbial limit proposed for the BICU by AFNOR-NF-S90-351 (20 colony-forming units/100cm2) was assessed by plate count, and compared with the results obtained with intracellular adenosine triphosphate (ATP) detection. Genotyping was performed using pulsed-field gel electrophoresis. Findings: During the standard cleaning regimen, three out of 23 samples (13%) gave results over the AFNOR limit and five (21.7%) showed unacceptable ATP levels with 100 relative light units/100cm2 as the benchmark limit (sensibility 86.4%, specificity 92.2%). Following improvement of the cleaning procedure, only two samples out of 50 (4%) did not satisfy the microbiological criteria and seven (14%) exceeded the ATP limit. In a successive phase, eight of 30 samples collected showed unacceptable results (27%). Conclusions: Adding chlorhexidine-60% isopropyl alcohol as complementary disinfectant proved to be effective for reducing environmental microbial contamination, ATP levels and CR-Ab infection/colonization in patients admitted to the BICU. Real-time monitoring by ATP assay was useful for managing the cleaning schedule and reducing hospital infections, although the calculated values must be interpreted as cleanliness indicators rather than risk indicators

Bloodstream infections in patients with rectal colonization by Klebsiella pneumoniae producing different type of carbapenemases: a prospective, cohort study

Objective: To investigate the hypothesis that intestinal colonization by different types of carbapenemase-resistant Klebsiella pneumoniae (CR-Kp) leads to different risks for bloodstream infections (BSI) caused by the same colonizing organism. Methods: Prospective observational study including consecutive CR-Kp rectal carriers admitted to the Pisa University Hospital (December 2018 to December 2019). Patients underwent rectal swabbing with molecular testing for the different carbapenemases at hospital admission and during hospitalization. Rectal carriers were classified as: NDM, KPC, VIM and OXA-48. The primary end point was the rate of BSI by the same colonizing organism in each study group. A multivariate logistic regression analysis was performed to identify factors independently associated with the risk for BSI by the colonizing organism. Results: Of 677 rectal carriers, 382/677 (56.4%) were colonized by NDM, 247/677 (36.5%) by KPC, 39/677 (5.8%) by VIM and 9/677 (1.3%) by OXA-48. Dissemination of NDM-Kp was mostly sustained by ST147, while KPC-Kp belonged to ST512. A higher rate of BSI was documented in NDM rectal carriers compared with KPC rectal carriers (59/382, 15.4% versus 20/247, 8.1%, p 0.004). Incidence rates of BSI per 100 patients/month were significantly higher in the NDM group (22.33, 95% CI 17.26-28.88) than in the KPC group (9.56, 95% CI 6.17-14.82). On multivariate analysis, multi-site extraintestinal colonization, solid organ transplantation, invasive procedures, intravascular device, admission to intensive care unit, cephalosporin, fluoroquinolones and NDM rectal colonization (OR 3.27, 95% CI 1.73-6.18, p < 0.001) were independently associated with BSI. Conclusions: NDM-Kp was associated with increased risk of BSI compared with KPC-Kp. This finding seems to be strongly related to the high-risk clone ST147