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

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

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

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

Evaluation of a new Rapid Antimicrobial Susceptibility system for Gram-negative and Gram-positive bloodstream infections: speed and accuracy of Alfred 60AST.

BACKGROUND: Blood stream infections (BSIs) are a major cause of morbidity and mortality. The time from taking blood cultures to obtain results of antibiotic sensitivity can be up to five days which impacts patient care. The Alfred 60 AST™ can reduce laboratory time from positive culture bottle to susceptibility results from 16 to 25 h to 5-6 h, transforming patient care. To evaluate the diagnostic accuracy of a rapid antimicrobial susceptibility system, the Alfred 60 AST™, in clinical isolates from patients with BSIs and confirm time to results. 301 Gram-negative and 86 Gram-positive isolates were analysed directly from positive blood culture bottles following Gram staining. Antimicrobial susceptibility results and time-to-results obtained by rapid Alfred 60 AST system and BD Phoenix were compared . RESULTS: A total of 2196 antimicrobial susceptibility test results (AST) were performed: 1863 Gram-negative and 333 Gram-positive. AST categorical agreement (CA) for Alfred 60 AST™ was 95% (1772/1863) for Gram-negative and 89% (295/333) for Gram-positive isolates. Gram-negative CA: ampicillin 96% (290/301); ciprofloxacin 95% (283/297); ceftriaxone 96% (75/78); meropenem 97% (288/297); piperacillin-tazobactam 95% (280/295); gentamicin 94% (279/297) and amikacin 93% (277/298). The median time to susceptibility results from blood culture flagging positive was 6.3 h vs 20 h (p < 0.01) for Alfred system vs BD Phoenix™. CONCLUSION: Alfred 60 AST system greatly reduced time to antimicrobial susceptibility results in Gram-negative and Gram-positive BSIs with good performance and cost, particularly for Gram-negative bacteraemia

The Italian arm of the PREPARE study: an international project to evaluate and license a maternal vaccine against group B streptococcus.

BACKGROUND: Group B streptococcus (GBS) is a leading cause of sepsis, pneumonia and meningitis in infants, with long term neurodevelopmental sequelae. GBS may be associated with poor pregnancy outcomes, including spontaneous abortion, stillbirth and preterm birth. Intrapartum antibiotic prophylaxis (IAP) is currently the only way to prevent early-onset disease (presenting at 0 to 6 days of life), although it has no impact on the disease presenting over 6 days of life and its implementation is challenging in resource poor countries. A maternal vaccine against GBS could reduce all GBS manifestations as well as improve pregnancy outcomes, even in low-income countries. MAIN BODY: The term "PREPARE" designates an international project aimed at developing a maternal vaccination platform to test vaccines against neonatal GBS infections by maternal immunization. It is a non-profit, multi-center, interventional and experimental study (promoted by the St George University of London. [UK]) with the aim of developing a maternal vaccination platform, determining pregnancy outcomes, and defining the extent of GBS infections in children and mothers in Africa. PREPARE also aims to estimate the protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa and to conduct two trials on candidate GBS vaccines. PREPARE consists of 6 work packages. In four European countries (Italy, UK, Netherlands, France) the recruitment of cases and controls will start in 2020 and will end in 2022. The Italian PREPARE network includes 41 centers. The Italian network aims to collect: GBS isolates from infants with invasive disease, maternal and neonatal sera (cases); cord sera and GBS strains from colonized mothers whose infants do not develop GBS infection (controls). SHORT CONCLUSION: PREPARE will contribute information on protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa. The vaccine that will be tested by the PREPARE study could be an effective strategy to prevent GBS disease

Vaccinazioni: stato dell\u2019arte, falsi miti e prospettive. Il ruolo chiave della prevenzione.

La pratica vaccinale in Italia \ue8 organizzativamente incardinata all\u2019interno del Servizio Sanitario Nazionale (SSN) e nei Servizi Sanitari Regionali (SSR). I luoghi \u201cclassici\u201d in cui viene effettuata la procedura/prestazione vaccinale sono i servizi di vaccinazione della Aziende Sanitarie Locali (ASL) o Provinciali (ASP) delle varie Regioni

Adherence to antibiotic treatment guidelines and outcomes in the hospitalized elderly with different types of pneumonia

Background: Few studies evaluated the clinical outcomes of Community Acquired Pneumonia (CAP), Hospital-Acquired Pneumonia (HAP) and Health Care-Associated Pneumonia (HCAP) in relation to the adherence of antibiotic treatment to the guidelines of the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) in hospitalized elderly people (65 years or older). Methods: Data were obtained from REPOSI, a prospective registry held in 87 Italian internal medicine and geriatric wards. Patients with a diagnosis of pneumonia (ICD-9 480-487) or prescribed with an antibiotic for pneumonia as indication were selected. The empirical antibiotic regimen was defined to be adherent to guidelines if concordant with the treatment regimens recommended by IDSA/ATS for CAP, HAP, and HCAP. Outcomes were assessed by logistic regression models. Results: A diagnosis of pneumonia was made in 317 patients. Only 38.8% of them received an empirical antibiotic regimen that was adherent to guidelines. However, no significant association was found between adherence to guidelines and outcomes. Having HAP, older age, and higher CIRS severity index were the main factors associated with in-hospital mortality. Conclusions: The adherence to antibiotic treatment guidelines was poor, particularly for HAP and HCAP, suggesting the need for more adherence to the optimal management of antibiotics in the elderly with pneumonia

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council