Evolution of ceftazidime-avibactam and cefiderocol resistance in ST131-H30R1-Escherichia coli isolates with KPC-3 mutants and application of FTIR biotyping.

Ceftazidime-avibactam and cefiderocol represent two of the few alternatives for infections by KPC-producing Enterobacterales. We reported the emergence of resistance to both ceftazidime-avibactam and cefiderocol in a KPC-producing ST131-Escherichia coli (KPC-ST131-Ec) clinical isolate. Antimicrobial susceptibility testing, Fourier-transform infrared (FTIR) spectroscopy, whole-genome sequencing, and cloning experiments were performed. A KPC-49-Ec isolate resistant to ceftazidime-avibactam (MICCZA > 16/4 mg/L) and susceptible to cefiderocol (MICFDC: 2 mg/L) was recovered in a blood sample from an oncologic patient hospitalized in the medical ICU (June 2019) during ceftazidime-avibactam treatment. After 44 days, a KPC-31-Ec resistant to both ceftazidime-avibactam and cefiderocol (MICCZA > 16/4 mg/L, MICFDC: 8 mg/L) was found in a rectal sample during a second cycle of ceftazidime-avibactam treatment. Both KPC-49 (R163S) and KPC-31 (D179Y) were detected in the epidemic ST131-H30R1-Ec high-risk clone and showed a phenotype resembling that of ESBL producers. FTIR spectroscopy managed to differentiate cefiderocol-susceptible and resistant ST131-Ec isolates, and these from others belonging to different clones. After cloning and transformation experiments, KPC-49 and KPC-31 were responsible for ceftazidime-avibactam resistance (MICCZA > 16/4 mg/L) and decreased carbapenem MICs (MICMER ≤ 0.12 mg/L, MICIMI ≤ 1 mg/L). KPC-31 was also shown to be associated with increased MICs of cefiderocol (twofold and threefold dilutions over KPC-3 and KPC-49, respectively). However, mutations in proteins participating in outer membrane stability and integrity, such as TolR, could have a more relevant role in cefiderocol resistance. The effects of ceftazidime-avibactam and cefiderocol co-resistance in clinical isolates of Enterobacterales producing KPC mutants make their identification challenging for clinical laboratories.IMPORTANCEThroughout four admissions in our hospital of a single patient, different KPC-3 variants (KPC-3, KPC-49, and KPC-31) were found in surveillance and clinical ST131-Escherichia coli isolates, after prolonged therapies with meropenem and ceftazidime-avibactam. Different patterns of resistance to cefiderocol and ceftazidime-avibactam emerged, accompanied by restored carbapenem susceptibility. The inability to detect these variants with some phenotypic methods, especially KPC-31 by immunochromatography, and the expression of a phenotype similar to that of ESBL producers, posed challenge to identify these variants in the clinical microbiology laboratory. Molecular methods and whole-genome sequencing are necessary and new techniques able to cluster or differentiate related isolates could also be helpful; this is the case of Fourier-transform infrared spectroscopy, which managed in our study to discriminate isolates by cefiderocol susceptibility within ST131, and those from the non-ST131 ones.

Cost-effectiveness Analysis of Peripherally Inserted Central Catheters Versus Central Venous Catheters for in-Hospital Parenteral Nutrition.

OBJECTIVE: Our objective was to evaluate the cost-effectiveness of the use of peripherally inserted central venous catheters (PICCs) by a vascular access team (VAT) versus central venous catheters (CVCs) for in-hospital total parenteral nutrition (TPN). METHODS: The study used a cost-effectiveness analysis based on observational data retrospectively obtained from electronic medical records from 2018 to 2019 in a teaching hospital. We included all interventional procedures requiring PICCs or CVCs with the indication of TPN. We recorded the costs of insertion, maintenance, removal, and complications. The main outcome measure was the incidence rate of catheter-associated bacteremia per 1000 catheter days. Cost-effectiveness analysis was performed from the hospital perspective within the context of the publicly funded Spanish health system. Confidence intervals for costs and effectiveness differences were calculated using bootstrap methods. RESULTS: We analyzed 233 CVCs and 292 PICCs from patients receiving TPN. Average duration was longer for PICC (13 versus 9.4 days, P < 0.001). The main reason for complications in both groups was suspected infection (9.77% CVC versus 5.18% PICC). Complication rates due to bacteremia were 2.44% for CVC and 1.15% for PICC. The difference in the incidence of bacteremia per 1000 catheter days was 1.29 (95% confidence interval, -0.89 to 3.90). Overall, costs were lower for PICCs than for CVCs: the difference in mean overall costs was -€559.9 (95% confidence interval, -€919.9 to -€225.4). Uncertainty analysis showed 86.37% of results with lower costs and higher effectiveness for PICC versus CVC. CONCLUSIONS: Placement of PICC by VAT compared with CVC for TPN reduces costs and may decrease the rate of bacteremia.

Translational demand is not a major source of plasmid-associated fitness costs.

Plasmids are key drivers of bacterial evolution because they are crucial agents for the horizontal transfer of adaptive traits, such as antibiotic resistance. Most plasmids entail a metabolic burden that reduces the fitness of their host if there is no selection for plasmid-encoded genes. It has been hypothesized that the translational demand imposed by plasmid-encoded genes is a major mechanism driving the fitness cost of plasmids. Plasmid-encoded genes typically present a different codon usage from host chromosomal genes. As a consequence, the translation of plasmid-encoded genes might sequestrate ribosomes on plasmid transcripts, overwhelming the translation machinery of the cell. However, the pervasiveness and origins of the translation-derived costs of plasmids are yet to be assessed. Here, we systematically altered translation efficiency in the host cell to disentangle the fitness effects produced by six natural antibiotic resistance plasmids. We show that limiting translation efficiency either by reducing the number of available ribosomes or their processivity does not increase plasmid costs. Overall, our results suggest that ribosomal paucity is not a major contributor to plasmid fitness costs. This article is part of the theme issue 'The secret lives of microbial mobile genetic elements'.

Pervasive transmission of a carbapenem resistance plasmid in the gut microbiota of hospitalized patients.

Infections caused by carbapenemase-producing enterobacteria (CPE) are a major concern in clinical settings worldwide. Two fundamentally different processes shape the epidemiology of CPE in hospitals: the dissemination of CPE clones from patient to patient (between-patient transfer), and the transfer of carbapenemase-encoding plasmids between enterobacteria in the gut microbiota of individual patients (within-patient transfer). The relative contribution of each process to the overall dissemination of carbapenem resistance in hospitals remains poorly understood. Here, we used mechanistic models combining epidemiological data from more than 9,000 patients with whole genome sequence information from 250 enterobacteria clones to characterize the dissemination routes of a pOXA-48-like carbapenemase-encoding plasmid in a hospital setting over a 2-yr period. Our results revealed frequent between-patient transmission of high-risk pOXA-48-carrying clones, mostly of Klebsiella pneumoniae and sporadically Escherichia coli. The results also identified pOXA-48 dissemination hotspots within the hospital, such as specific wards and individual rooms within wards. Using high-resolution plasmid sequence analysis, we uncovered the pervasive within-patient transfer of pOXA-48, suggesting that horizontal plasmid transfer occurs in the gut of virtually every colonized patient. The complex and multifaceted epidemiological scenario exposed by this study provides insights for the development of intervention strategies to control the in-hospital spread of CPE.

Genetic dominance governs the evolution and spread of mobile genetic elements in bacteria.

Mobile genetic elements (MGEs), such as plasmids, promote bacterial evolution through horizontal gene transfer (HGT). However, the rules governing the repertoire of traits encoded on MGEs remain unclear. In this study, we uncovered the central role of genetic dominance shaping genetic cargo in MGEs, using antibiotic resistance as a model system. MGEs are typically present in more than one copy per host bacterium, and as a consequence, genetic dominance favors the fixation of dominant mutations over recessive ones. In addition, genetic dominance also determines the phenotypic effects of horizontally acquired MGE-encoded genes, silencing recessive alleles if the recipient bacterium already carries a wild-type copy of the gene. The combination of these two effects governs the catalog of genes encoded on MGEs. Our results help to understand how MGEs evolve and spread, uncovering the neglected influence of genetic dominance on bacterial evolution. Moreover, our findings offer a framework to forecast the spread and evolvability of MGE-encoded genes, which encode traits of key human interest, such as virulence or antibiotic resistance.

Terapia endoscópica endoluminal con sistema Endo-Sponge(R) en el manejo de dehiscencia de anastomosis tras cirugía colorrectal / Endoluminal endoscopic therapy with Endo-Sponge(R) system in the management of anastomotic dehiscence after colorectal surgery

No disponible

Hiperesplenismo secundario a compresión del eje esplenoportal por quiste hepático gigante / Hypersplenism secondary to splenoportal axis compression by a giant hepatic cyst

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Hypersplenism secondary to splenoportal axis compression by a giant hepatic cyst.

Simple hepatic cysts (SHCs) are formations that contain serous fluid surrounded by normal hepatic parenchyma with no communication with intrahepatic bile ducts. Symptoms develop as a result of their size or complications such as bleeding, rupture, intracystic infection or compression of adjacent structures.

Consumo de carne por niños preescolares adscritos a guardería / Meat consumption by preschoolers assisting to a daycare center

Se determina el consumo de carne en niños sanos adscritos a guardería por medio de un estudio tipo encuesta. Se pesaron las raciones de carne que se incluyen en la dieta habitual de 76 niños preescolares, clínicamente sanos, adscritos a la guardería 201 del IMSS en Culiacán, Sinaloa. El grupo estudiado se clasificó en niños de peso normal, subnormal o con sobrepeso, de acuerdo al índice de masa corporal (IMC). Al término del lapso usual para toma de alimentos, se pesó la carne no consumida. El consumo de carne fue 59 por ciento del total de las raciones otorgadas; dicho consumo no mostró diferencias estadísticamente significativas entre los niños según su IMC (p=0.06). Concluimos que existe baja predilección por la carne en niños preescolares que se encuentran al cuidado de los servicios de guardería y que su consumo es aparentemente independiente de sus condiciones ponderales