ObjectivesCARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.MethodsIn total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC > 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.ResultsIn total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were blaOXA–48 (263/377), blaKPC–3 (62/377), blaVIM–1 (28/377), and blaNDM–1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5).ConclusionThis study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3.

Sepsis is a heterogeneous disease with variable clinical course and several clinical phenotypes. As it is associated with an increased risk of death, patients with this condition are candidates for receipt of a very well-structured and protocolized treatment. All patients should receive the fundamental pillars of sepsis management, which are infection control, initial resuscitation, and multiorgan support. However, specific subgroups of patients may benefit from a personalized approach with interventions targeted towards specific pathophysiological mechanisms. Herein, we will review the framework for identifying subpopulations of patients with sepsis, septic shock, and multiorgan dysfunction who may benefit from specific therapies. Some of these approaches are still in the early stages of research, while others are already in routine use in clinical practice, but together will help in the effective generation and safe implementation of precision medicine in sepsis.

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Two hundred twelve patients with colonization/infection due to amoxicillin-clavulanate (AMC)-resistant Escherichia coli were studied. OXA-1-and inhibitor-resistant TEM (IRT)-producing strains were associated with urinary tract infections, while OXA-1 producers and chromosomal AmpC hyperproducers were associated with bacteremic infections. AMC resistance in E. coli is a complex phenomenon with heterogeneous clinical implications.A moxicillin-clavulanate (AMC) is one of the most frequently used antimicrobials in many countries (1, 2). Over the last years, an increase in the rate of resistance to AMC has been noted among Escherichia coli isolates in several areas (3-5), which has been related to an increase in the consumption of this antibiotic (3). However, to our knowledge, there are no recent clinical studies investigating infections caused by AMC-resistant E. coli. The objective of this study is to analyze the clinical epidemiology and features of infections caused by AMC-resistant E. coli.A cross-sectional multicenter study was performed in 7 Spanish tertiary centers. Each center was committed to include up to 44 patients from whom AMC-resistant E. coli (MIC of Ն32 [amoxicillin]-16 [clavulanate] mg/liter and/or disk inhibition zone of Յ13 mm) were isolated from clinical samples (22 communityonset and 22 nosocomial isolates) from 15 January to 15 May 2010. Overall, 257 AMC-resistant E. coli isolates were collected. A previous publication reported the mechanism of resistance to AMC and clonality for all these isolates (6). For the present analysis, 13 patients harboring isolates with more than one mechanism of resistance to AMC, 3 patients harboring isolates for which the mechanism of resistance was not elucidated, and 37 patients with isolates producing extended-spectrum ␤-lactamases (ESBLs) were excluded; thus, 212 patients are studied here. Epidemiological and clinical data were collected by reviewing the clinical charts and interviewing the patients or their relatives. The study was approved by the ethics committees of the participating centers. Isolates were considered nosocomial if obtained from patients who were hospitalized for Ͼ48 h. Community isolates were classified as health care associated according to previously described criteria (7). CDC criteria (8) were used for establishing whether the patients had an infection and the types of infection.The microbiological methods used were previously reported in detail (6). Briefly, antibiotic susceptibility was confirmed by microdilution according to CLSI recommendations (9). The mechanisms of resistance to AMC of the 212 isolates included here, as determined from the previously reported data (6), were as follows: hyperproduction of TEM-1 or SHV-1 (HPen) (54 isolates . Isolates showing resistance to at least one of the following families/drugs (in addition to AMC and ampicillin) were considered multidrug resistant: aminoglycosides, cephalosporins, carbapenems, piperacillin-tazobactam, ciprofloxacin, and trimethoprim-sulfamethoxazole (10). The number of abov...