Emergence of cefiderocol resistance during ceftazidime/avibactam treatment caused by a large genomic deletion, including ampD and piuCD genes, in Pseudomonas aeruginosa.

We report the emergence of cefiderocol resistance during the treatment of a ST312 Pseudomonas aeruginosa respiratory infection with ceftazidime/avibactam. whole genome sequencing (WGS) revealed that resistance was caused by a large genomic deletion, including PiuDC (iron transport system) and AmpD (ampC negative regulator), driven by the integration of phage DNA. Thus, our findings alert that this type of deletion could be an efficient (two mechanisms in one step) specific cefiderocol resistance mechanism that might occur nonspecifically upon treatment with ß-lactams that select for AmpC overexpression.

Prevalence of sports supplements consumption and its association with food choices among female elite football players.

OBJECTIVES: The present study aimed to 1) investigate the consumption of Sports Supplements (SSs) among female elite football players, 2) evaluate the influence of age on SS consumption, and 3) determine the relationship between the consumption of SSs and dietary choices among elite football players. METHODS: A total of 126 female football players of Primera Iberdrola and Reto Iberdrola who participated in this descriptive, observational, and cross-sectional study completed a self-administered questionnaire on SSs and the Athletes' Food Choices Questionnaire. RESULTS: Overall, 84.1% of participants consumed supplements, mainly for improved sports performance (68.3%) and health (34.1%). The main sources of purchase were the Internet (34.9%) and specialized shops (23.8%), and players were commonly advised by a dietitian-nutritionist to use SSs (56.3%). The SSs most often consumed included whey protein (30.2%), sports drinks (28.6%), creatine monohydrate (28.6%), sports bars (27.8%), and caffeine (27.8%). Older players consumed more supplements at the time of data compilation. Players predominantly acquired these supplements by using the Internet and reported benefits from their use (all P ≤ 0.036). Additionally, players who consumed SSs conveyed more concern about their food choices. CONCLUSIONS: A high prevalence of female football players consumed SSs, particularly SSs supported by robust scientific evidence. Older players had higher supplement consumption rates. The use of SSs was related to food choices through nutritional characteristics of foods, knowledge about health and nutrition, weight control with the help of food, and the performance benefits players could acquire.

Do Spanish Triathletes Consume Sports Supplements According to Scientific Evidence? An Analysis of the Consumption Pattern According to Sex and Level of Competition.

BACKGROUND: The use of sports supplements (SS) to improve sports performance is very common in athletes. In the case of triathletes, the physiological characteristics of the sport may require the use of certain SS. Although the consumption of SS is widespread in this sport, very few studies have investigated it thus far. The aim is to analyze the pattern of SS consumption by triathletes according to sex and the competitive level. METHODOLOGY: This is a descriptive cross-sectional study on the consumption and habitual use of SS of 232 Spanish-federated triathletes. Data were collected through a validated questionnaire. RESULTS: Overall, 92.2% of the athletes consumed SS, but no significant differences were found in terms of competition level or sex. Yet, significant differences were found regarding the level of competition for total SS (p = 0.021), the total number of Group A supplements from the AIS classification (p = 0.012), and for the ergogenic aids (p = 0.003). The most-consumed SS were bars, sports drinks, sports gels, and caffeine (83.6%, 74.1%, 61.2%, and 46.6%, respectively). CONCLUSIONS: The consumption of SS by triathletes is high, and the number of SS consumed rises from the regional to the national and international levels. The four SS most consumed were included in category A of the AIS (greatest scientific evidence).

Simultaneous and divergent evolution of resistance to cephalosporin/ß-lactamase inhibitor combinations and imipenem/relebactam following ceftazidime/avibactam treatment of MDR Pseudomonas aeruginosa infections.

OBJECTIVES: To describe and characterize the emergence of resistance to ceftolozane/tazobactam, ceftazidime/avibactam and imipenem/relebactam in a patient receiving ceftazidime/avibactam treatment for an MDR Pseudomonas aeruginosa CNS infection. METHODS: One baseline (PA1) and two post-exposure (PA2 and PA3) isolates obtained before and during treatment of a nosocomial P. aeruginosa meningoventriculitis were evaluated. MICs were determined by broth microdilution. Mutational changes were investigated through WGS. The impact on ß-lactam resistance of mutations in blaPDC and mexR was determined through cloning experiments and complementation assays. RESULTS: Isolate PA1 showed baseline resistance mutations in DacB (I354A) and OprD (N142fs) conferring resistance to conventional antipseudomonals but susceptibility to ceftazidime/avibactam, ceftolozane/tazobactam and imipenem/relebactam. Post-exposure isolates showed two divergent ceftazidime/avibactam-resistant phenotypes associated with distinctive mutations affecting the intrinsic P PDC ß-lactamase (S254Ins) (PA2: ceftolozane/tazobactam and ceftazidime/avibactam-resistant) or MexAB-OprM negative regulator MexR in combination with modification of PBP3 (PA3: ceftazidime/avibactam and imipenem/relebactam-relebactam-resistant). Cloning experiments demonstrated the role of PDC modification in resistance to ceftolozane/tazobactam and ceftazidime/avibactam. Complementation with a functional copy of the mexR gene in isolate PA3 restored imipenem/relebactam susceptibility. CONCLUSIONS: We demonstrated how P. aeruginosa may simultaneously develop resistance and compromise the activity of new ß-lactam/ß-lactamase inhibitor combinations when exposed to ceftazidime/avibactam through selection of mutations leading to PDC modification and up-regulation of MexAB-OprM-mediated efflux.

Are the Consumption Patterns of Sports Supplements Similar among Spanish Mountain Runners?

BACKGROUND: The use of sports supplements (SS) to improve sports performance is widespread in all types of athletes, however, the specific characteristics of mountain races may require the use of certain SS. Despite being a sport where the consumption of SS seems widespread, few studies have been conducted in this regard. The objective of this study is to analyze the pattern of SS consumption of mountain runners in relation to the degree of scientific evidence, sex, and level of competition. METHODS: Descriptive and cross-sectional study on the consumption and habitual use of SS of 357 federated mountain runners in Spain. Data were collected through a validated questionnaire. RESULTS: From the total sample, 93.84% of the athletes stated that they consumed SS, with no differences observed based on the competitive level or in terms of sex; however, there were significant differences according to the competitive level in terms of the number of SS consumed, with consumption being greater at a higher competitive level (p = 0.009). The most consumed SS were sports bars (66.1%), sports drinks (60.5%), sports gels (52.9%), and caffeine (46.2%). CONCLUSIONS: The consumption of SS in mountain races is high, and the number of SS consumed is higher as the competition level increases. The four SS most consumed by the participants in this study were all included in category A in the classification of the Australian Institute of Sport (AIS), this category is the one with the greatest scientific evidence.

Analysis of Sports Supplement Consumption in 1688 Federated Road Cyclists.

The widespread use of sports supplements (SS) to enhance athletic performance extends to cyclists, although little research has been conducted on this subject within this sport. This descriptive and cross-sectional study involved 1688 federated road cyclists, aiming to analyse the pattern of SS consumption concerning the degree of scientific evidence and different categories. This study categorised SS based on the groups and subgroups established by the Australian Sport Institute (AIS, 2023) based on the level of evidence. Our results showed that 62.5% of the sample cyclists used SS, with an average of 12.2 ± 8.6 supplements consumed per participant. Health status (78.2%), pharmacies (62.5%), and medical doctors (45.7%) were the main reasons, purchase sites, and sources of information for SS consumption, respectively. The most prevalent SS consumed were Sports Gels (94%), Sports Bars (89.3%), and Sports Drinks (73.8%). Notably, 80% of the top ten most consumed SS belonged to the group with the highest level of evidence according to the AIS, with an average of 6.9 ± 3.2 supplements per participant. However, 23.3% of the total SS consumers used prohibited substances. In conclusion, while the prevalence of SS consumption among road cyclists is considerable and the primary sources for purchasing SS and obtaining advice are reliable, there is a notable prevalence of prohibited substance use within the sample.

Analysis of the Consumption of Sports Supplements in Open Water Swimmers According to the Competitive Level.

BACKGROUND: Sports supplements (SS) are widely consumed by many types of athletes to improve their performance. These SS are classified according to their level of scientific evidence, by the ABCD system from the Australian Institute of Sport (AIS). In open water swimming, their use may be necessary due to the physiological challenges posed by this sport discipline. However, there is currently little literature on the use of SS in open water swimmers. The aim of this work is to analyze the pattern of consumption of SS by open water swimmers, by studying the differences according to the competitive level (regional vs. national). METHODS: Descriptive and cross-sectional study on the consumption and use of SS by federated open water swimmers in Spain in the 2019/2020 and 2020/2021 seasons. The data were collected through a validated questionnaire. RESULTS: 79.5% of the participants consumed SS, with significant differences according to their level, being higher in athletes at the national level. The most-consumed SS by the swimmers studied were sports drinks, energy bars, caffeine, vitamin C, and vitamin D. CONCLUSIONS: It was observed that the consumption of SS in open water swimmers was high, and of the five most-consumed SS, four of them belonged to the category of greatest scientific evidence.

Sports supplements use in mountain runners: differences by sex and competitive level.

Introduction: Introduction: sports supplements (SS) are widely used by all types of athletes to improve their performance. These SS are classified according to the ABCD system of the Australian Institute of Sports (AIS) from higher to lower scientific evidence. In mountain runners, their use could be necessary due to the physiological demands required by this sport. However, the literature on the use of SS by mountain runners is scarce. Objective: to analyze the pattern of SS consumption in mountain runners by studying differences according to sex and competitive level (regional vs national). Methodology: this was a descriptive and cross-sectional study on the consumption and use of SS by mountain runners participating in the Alcoy Solidarity Trail. Data were collected through a validated questionnaire based on content, applicability, structure, and presentation. This questionnaire was completed online by the athletes, who could fill it out voluntarily and at their convenience, as well as anonymously. Results: the results showed that 87.5 % of participants reported consuming SS, with no significant differences observed with respect to competitive level, although differences were found with respect to sex (92.7 % in men vs 70.6 % in women; p = 0.029), with a higher consumption found in men compared to women. The most consumed SS were sports bars (81.9 %), sports drinks (75.0 %), caffeine (48.6 %), magnesium (38.9 %), and electrolytes (27.8 %). Conclusions: among mountain runners consumption of SS is high, and 4 of the 5 most habitually consumed SS belong in the category of greater scientific evidence.

Introducción: Introducción: los suplementos deportivos (SS) son muy utilizados por todo tipo de deportistas para mejorar su rendimiento. Estos SS se clasifican según el sistema ABCD del Australian Institute of Sports (AIS) de mayor a menor evidencia científica. En corredores de montaña, su uso podría ser necesario debido a las exigencias fisiológicas de este deporte. Sin embargo, la literatura sobre el uso de SS por corredores de montaña es escasa. Objetivo: analizar el patrón de consumo de SS en corredores de montaña, estudiando las diferencias según el sexo y el nivel competitivo (autonómico vs. nacional). Metodología: se trata de un estudio descriptivo y transversal sobre el consumo y uso de SS por parte de los corredores de montaña participantes en el Trail Solidario de Alcoy. Los datos fueron recolectados a través de un cuestionario validado en base al contenido, la aplicabilidad, la estructura y la presentación. El cuestionario fue completado de manera online por los atletas que pudieron rellenarlo voluntariamente y a conveniencia, y de manera anónima. Resultados: los resultados mostraron que el 87,5 % de los participantes reportaron consumir SS, no observándose diferencias significativas con respecto al nivel competitivo, aunque sí se encontraron diferencias con respecto al sexo (92,7 % en hombres y 70,6 % en mujeres; p = 0,029), donde los hombres tenían un mayor consumo en comparación con las mujeres. Los SS más consumidos fueron las barritas deportivas (81,9 %), las bebidas deportivas (75,0 %), la cafeína (48,6 %), el magnesio (38,9 %) y los electrólitos (27,8 %). Conclusiones: entre los corredores de montaña, el consumo de SS es alto y 4 de los 5 SS más consumidos pertenecen a la categoría de mayor evidencia científica.

Dietary Supplement Use of Turkish Footballers: Differences by Sex and Competition Level.

This study aimed to evaluate the consumption of dietary supplements (DS) and to determine related topics in Turkish football players of different sexes and competition levels. A total of 117 footballers (79 males and 38 females) completed a specific survey regarding DS consumption in athletes. The type of DS ingested was classified based on the level of scientific evidence by the Australian Institute of Sport (AIS): group A (high level of scientific evidence), group B (DS that could have a positive effect, but require more evidence), group C (evidence is against their use), and group D (prohibited substances). After a Kolmogorov−Smirnov test, a t-test or Mann−Whitney U test was performed for quantitative variables, while Pearson's chi-square and odds ratio (with the confidence interval) were performed for qualitative variables. Of the sample, 87.2% reported having consumed DS, with a higher consumption rate in males (males: 93.7%, females: 73.7%; p = 0.006; OR = 5.3 [1.7−16.8]) and professional players (professional: 98.2%, non-professional: 77.4%; p < 0.001; OR = 7.9 [1.2−52.3]). Males and professional players consume more sports foods (p < 0.001), performance supplements (p < 0.001), and total group A supplements (p < 0.001) compared to females and non-professionals. In addition, males consume more medical supplements (p = 0.012) and total group C supplements (p < 0.001) than female footballers. The most consumed DS were sports drinks (63.2%), magnesium (52.1%), vitamin C (51.3%), vitamin D (46.2%), caffeine (38.5%), sports bars (37.6%), whey protein (28.2%), meat protein (25.6%), vitamin E (24.8%), and omega-3 fatty acids (24.8%). The supplement consumption was higher in male and professional footballers. According to the AIS classification, there were significant differences in the consumption of sports foods, medical supplements, performance supplements, and the total number of group A and group C supplements according to sex, and there were significant differences in the consumption of sports foods, performance supplements, and the total number of group A supplements according to competition level.

Analysis of Sport Supplement Consumption by Competitive Swimmers According to Sex and Competitive Level.

Sports supplements (SS) are commonly used by athletes to improve their performance. SS use by competitive swimmers is reported to be prevalent but there is no evidence of such use by elite swimmers, either male or female. The objective of this research was to study the patterns of SS use by competitive swimmers based on sex and competitive levels (national and international); Methods: Using the categories of the Australian Institute of Sport (AIS), a total of 102 competitive swimmers (59 men and 43 women) completed a validated self-administered questionnaire on the use of SS; (3) Results: Overall, 86.9% of swimmers had consumed SSs with no differences observed between males and females (p = 0.247) or between competitive levels (p = 0.597). The SS that were most consumed by swimmers were caffeine (53.5%), sport drinks (52.5%), sport bars (51.5%), and vitamin C (43.4%). SSs categorized as medical supplements were consumed significantly more frequently by international swimmers (p = 0.012), with significant differences also found in the level-sex interaction (p = 0.049); (4) Conclusions: Compared to other sports disciplines, the prevalence of SS consumption is high in competitive swimmers regardless of performance level or gender. However, the consumption of medical supplements was greater in swimmers at a higher performance level.

Effects of ß-Hydroxy ß-Methylbutyric Supplementation in Combination with Conservative Non-Invasive Treatments in Athletes with Patellar Tendinopathy: A Pilot Study.

The aim of the present study was to analyze the effect of conservative non-invasive treatments based on eccentric training, stretching and extracorporeal shock wave therapy (ESWT) supplemented with ß-Hydroxy ß-methylbutyric (HMB) or placebo (PLAC) on body composition, pain and muscular function (jump ability, muscular power and muscular strength) in athletes with patellar tendinopathy (PT). In a double-blind randomized trial, 8 athletes (4 males and 4 females) performed a physical rehabilitation for 4 weeks. They were randomly divided into two experimental groups (two males and two females in each one) that ingested HMB (HMBG) or PLAC (PLACG). In pre- and post-intervention were assessed body composition, pain, countermovement jump (CMJ), back-squat (BS) for analyzing peak power (W) (PPPP), load (kg) associated to PPPP (PPKG) and mean velocity (m/s) (PPMV) in addition to a 5-RM leg extension tests. An interaction intervention·supplementation (p = 0.049; È 2p = 0.774) was observed in the height reached in the CMJ as an intervention effect in PPPP detected for the HMBG (p = 0.049). In addition, an enhancement in PPKG (p = 0.028; È 2p = 0.842) was detected in the intervention, but not in PPMV, as an increase in the intervention in the 5-RM test (p = 0.001; È 2p = 0.981) was observed. No changes were noted on body composition or pain (p > 0.05). The combination of eccentric training with stretching and ESWT increased concentric muscular power and strength after 4 weeks without changes in body lean mass or pain. In addition, HMB supplementation could enhance the power muscular performance in athletes with PT, optimizing the intervention adaptions.

Selection of AmpC ß-Lactamase Variants and Metallo-ß-Lactamases Leading to Ceftolozane/Tazobactam and Ceftazidime/Avibactam Resistance during Treatment of MDR/XDR Pseudomonas aeruginosa Infections.

Infections caused by ceftolozane-tazobactam and ceftazidime-avibactam-resistant P. aeruginosa infections are an emerging concern. We aimed to analyze the underlying ceftolozane-tazobactam and ceftazidime-avibactam resistance mechanisms in all multidrug-resistant or extensively drug-resistant (MDR/XDR) P. aeruginosa isolates recovered during 1 year (2020) from patients with a documented P. aeruginosa infection. Fifteen isolates showing ceftolozane-tazobactam and ceftazidime-avibactam resistance were evaluated. Clinical conditions, previous positive cultures, and ß-lactams received in the previous month were reviewed for each patient. MICs were determined by broth microdilution. Multilocus sequence types (MLSTs) and resistance mechanisms were determined using short- and long-read whole-genome sequencing (WGS). The impact of Pseudomonas-derived cephalosporinases (PDCs) on ß-lactam resistance was demonstrated by cloning into an ampC-deficient PAO1 derivative (PAOΔC) and construction of 3D models. Genetic support of acquired ß-lactamases was determined in silico from high-quality hybrid assemblies. In most cases, the isolates were recovered after treatment with ceftolozane-tazobactam or ceftazidime-avibactam. Seven isolates from different sequence types (STs) owed their ß-lactam resistance to chromosomal mutations and all displayed specific substitutions in PDC: Phe121Leu and Gly222Ser, Pro154Leu, Ala201Thr, Gly214Arg, ΔGly203-Glu219, and Glu219Lys. In the other eight isolates, the ST175 clone was overrepresented (6 isolates) and associated with IMP-28 and IMP-13, whereas two ST1284 isolates produced VIM-2. The cloned PDCs conferred enhanced cephalosporin resistance. The 3D PDC models revealed rearrangements affecting residues involved in cephalosporin hydrolysis. Carbapenemases were chromosomal (VIM-2) or plasmid-borne (IMP-28, IMP-13) and associated with class-1 integrons located in Tn402-like transposition modules. Our findings highlighted that cephalosporin/ß-lactamase inhibitors are potential selectors of MDR/XDR P. aeruginosa strains producing PDC variants or metallo-ß-lactamases. Judicious use of these agents is encouraged.

In Vivo Evolution of GES ß-Lactamases Driven by Ceftazidime/Avibactam Treatment of Pseudomonas aeruginosa Infections.

The mechanisms underlying an in vivo switch in the resistance phenotype of P. aeruginosa after ceftazidime-avibactam treatment was investigated. The initial isolate (a blood culture) was resistant to meropenem but remained susceptible to antipseudomonal cephalosporins and combinations with ß-lactamase inhibitors. One week after ceftazidime-avibactam therapy, a subsequent isolate (a rectal swab) recovered from the same patient showed the opposite phenotype. Whole-genome sequence analysis revealed a single SNP difference between both (ST235) isolates, leading to a P162S change in blaGES-5, creating blaGES-15. Thus, blaGES-1, blaGES-5, and blaGES-15 were cloned and expressed in the wild-type strain PAO1. Susceptibility profiles confirmed the P162S substitution reverted the carbapenemase phenotype determined by the G170S change of GES-5 back into the ESBL phenotype of GES-1.

[Fraud in nutritional supplements for athletes: a narrative review]. / Fraude en suplementos nutricionales para deportistas: revisión narrativa.

INTRODUCTION: The use of nutritional supplements (NSs) is a widespread practice in both professional and amateur athletes. Their choice must be based on criteria of safety, legality, and effectiveness. There are several risks that some of these products can trigger, this being a reason for fraud to the consumer. By way of example, the presence of a legal substance in doses higher than its recommendation may cause unwanted side effects; on the other hand, its presence in quantities lower than necessary (effective threshold) may not have the effect expected or announced by the product. Therefore, the objective of this review was to describe the existence of fraud in relation to nutritional labeling and/or to the content of NSs intended for athletes. A narrative review was conducted through PubMed in which 16 studies met the inclusion criteria. The results show that nutritional labeling differs from the actual amounts of ingredients. This type of fraud has been found in protein powder supplements, pre-workout mixtures, creatine, and beverages containing vitamins and minerals, among others. Fraud due to errors in the labeling by omission of substances present in the product or by errors in the analysis or declaration of quantities, is high. This lack of transparency in the actual composition of labels can contribute to sports performance and/or health problems in the athlete. Therefore, an improvement of the legislation on NS is necessary to ensure their safety, effectiveness, and legality.

INTRODUCCIÓN: El uso de suplementos nutricionales (SN) es una práctica muy extendida tanto entre los deportistas profesionales como entre los amateurs. Su elección debe realizarse basándose en criterios de seguridad, legalidad y eficacia. Son varios los riesgos que algunos de estos productos pueden desencadenar, siendo motivo de fraude para el consumidor. A modo de ejemplo, la presencia de una sustancia legal en dosis superiores a sus recomendaciones puede ocasionar efectos secundarios indeseados; por el contrario, su presencia en cantidades inferiores a las necesarias (umbral efectivo) puede no provocar el efecto esperado o anunciado por el producto. Por ello, el objetivo de la presente revisión es describir la existencia de fraude en relación con el etiquetado nutricional y/o el contenido de los SN destinados a deportistas. Se realizó una revisión narrativa a través de Pubmed en la que 16 estudios cumplieron los criterios de inclusión. Los resultados muestran que el etiquetado nutricional difiere de la cantidad real de ingredientes. Este tipo de fraude se ha encontrado en suplementos de proteína en polvo, mezclas preentrenamiento, creatina y bebidas que contienen vitaminas y minerales, entre otros. El fraude debido a errores en el etiquetado, por omisión de sustancias presentes en el producto o por errores en el análisis o declaración de las cantidades, es alto. Esta falta de transparencia en la composición real del etiquetado puede contribuir a problemas de rendimiento deportivo y/o de salud en el deportista. Por lo tanto, es necesaria una mejora de la legislación de los SN para garantizar su seguridad, eficacia y legalidad.

Analysis of the consumption of sports supplements in elite fencers according to sex and competitive level.

BACKGROUND: The aim of this study was to analyze the consumption of sports supplements (SS) in competitive level fencers and compare differences based on sex and competitive level (international and national). METHODS: A total of 49 fencers (18 men and 31 women) of national (n = 16) and international (n = 33) level completed a questionnaire with questions about SS consumption and the possible repercussions on health and / or sports performance. The results were analyzed based on the different categorizations established by the Australian Institute of Sport (AIS), as well as by sex and level of competence to which the participants belonged to. RESULTS: 46.9% of fencers have consumed SS with the main motivation being performance improvement (34.2%). Medical doctors were the individuals who were more likely to advise men to consume SS (50.0% vs 5.6%; OR = 3.29 [1.50-7.20]). Friends were most likely to advise women (38.9% vs 8.3%; OR = 1.75 [1.05-2.93]). The most consumed SS were sport drinks (44.9%), vitamin C (43.4%), sport bars (38.8%), and caffeine (28.6%). In regards to the SS categories, it was observed differences in the interaction level·sex in medical supplements (p = 0.017). In addition, there was a higher prevalence of whey protein consumption in women (25.8% vs 0%; p = 0.020) and iron consumption in men (33% vs 6.5%; p = 0.039). CONCLUSIONS: The prevalence of SS use in fencers is within the values previously reported in athletes of the same competitive level. There were no differences by sex and competitive level in the total consumption of SS, nor in each of the groups of level of evidence, being sport drinks, bars and caffeine the most consumed SS.

Rapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection.

It is well established that antibiotic treatment selects for resistance, but the dynamics of this process during infections are poorly understood. Here we map the responses of Pseudomonas aeruginosa to treatment in high definition during a lung infection of a single ICU patient. Host immunity and antibiotic therapy with meropenem suppressed P. aeruginosa, but a second wave of infection emerged due to the growth of oprD and wbpM meropenem resistant mutants that evolved in situ. Selection then led to a loss of resistance by decreasing the prevalence of low fitness oprD mutants, increasing the frequency of high fitness mutants lacking the MexAB-OprM efflux pump, and decreasing the copy number of a multidrug resistance plasmid. Ultimately, host immunity suppressed wbpM mutants with high meropenem resistance and fitness. Our study highlights how natural selection and host immunity interact to drive both the rapid rise, and fall, of resistance during infection.

Molecular mechanisms driving the in vivo development of OXA-10-mediated resistance to ceftolozane/tazobactam and ceftazidime/avibactam during treatment of XDR Pseudomonas aeruginosa infections.

BACKGROUND: The development of resistance to ceftolozane/tazobactam and ceftazidime/avibactam during treatment of Pseudomonas aeruginosa infections is concerning. OBJECTIVES: Characterization of the mechanisms leading to the development of OXA-10-mediated resistance to ceftolozane/tazobactam and ceftazidime/avibactam during treatment of XDR P. aeruginosa infections. METHODS: Four paired ceftolozane/tazobactam- and ceftazidime/avibactam-susceptible/resistant isolates were evaluated. MICs were determined by broth microdilution. STs, resistance mechanisms and genetic context of ß-lactamases were determined by genotypic methods, including WGS. The OXA-10 variants were cloned in PAO1 to assess their impact on resistance. Models for the OXA-10 derivatives were constructed to evaluate the structural impact of the amino acid changes. RESULTS: The same XDR ST253 P. aeruginosa clone was detected in all four cases evaluated. All initial isolates showed OprD deficiency, produced an OXA-10 enzyme and were susceptible to ceftazidime, ceftolozane/tazobactam, ceftazidime/avibactam and colistin. During treatment, the isolates developed resistance to all cephalosporins. Comparative genomic analysis revealed that the evolved resistant isolates had acquired mutations in the OXA-10 enzyme: OXA-14 (Gly157Asp), OXA-794 (Trp154Cys), OXA-795 (ΔPhe153-Trp154) and OXA-824 (Asn143Lys). PAO1 transformants producing the evolved OXA-10 derivatives showed enhanced ceftolozane/tazobactam and ceftazidime/avibactam resistance but decreased meropenem MICs in a PAO1 background. Imipenem/relebactam retained activity against all strains. Homology models revealed important changes in regions adjacent to the active site of the OXA-10 enzyme. The blaOXA-10 gene was plasmid borne and acquired due to transposition of Tn6746 in the pHUPM plasmid scaffold. CONCLUSIONS: Modification of OXA-10 is a mechanism involved in the in vivo acquisition of resistance to cephalosporin/ß-lactamase inhibitor combinations in P. aeruginosa.

Analysis of Sport Supplement Consumption and Body Composition in Spanish Elite Rowers.

The aim of this study was to analyze the anthropometric characteristics and sport supplement (SS) consumption patterns of heavyweight and lightweight international rowers. Methods: The 13 heavyweights (11 males) and seven lightweights (five males) of the Spanish National Rowing Team were recruited for the study. Body composition was measured by bio-impedance analysis, and the questionnaire used in this investigation was previously validated to assess SS consumption. According to anthropometrics parameters, it was reported that male heavyweight rowers were heavier (p < 0.001) and taller (p < 0.001), but no statistical differences were reported for % body fat (p = 0.104) or % lean body mass (p = 0.161). All rowers reported consumption of at least one SS. Based on the Australian Institute of Sport's classification, higher medical supplement consumption was observed when comparing heavyweight rowers to lightweight rowers (2.5 ± 1.1 vs. 1.7 ± 0.5, p = 0.040). There were no differences in the totals of group A (strong scientific evidence for sports scenarios, p = 0.069), group B (emerging scientific support, deserving of further research, p = 0.776), or group C (scientific evidence not supportive of benefit and/or security amongst athletes, p = 0.484). The six most consumed SSs were iron (85%), caffeine (85%), ß-alanine (85%), energy bars (85%), vitamin supplements (80%), and isotonic drinks (80%), with no statistical differences between heavyweight and lightweight rowers (p > 0.05). These results suggest that the absence of differences in body composition (expressed as a percentage) do not represent anthropometric disadvantages for heavyweight rowers. In addition, SS consumption was similar between rowers, reporting only higher medical supplement consumption in heavyweight rowers.

Use of Sports Supplements in Competitive Handball Players: Sex and Competitive Level Differences.

Sports supplements are commonly used by elite athletes with the main goal of enhancing sport performance. Supplements use might be substantially different depending on the sport discipline, sex, and competitive level. To date, data about prevalence and the most-commonly used supplements in handball are scarce. Thus, the aim of this investigation was to determine the patterns of supplements use by handball players of both sexes and with different competitive levels: One hundred and eighty-seven handball players (112 men and 75 women) of different competitive levels (106 professional and 81 amateur) completed a validated self-administered questionnaire about supplements use. Supplements were classified according to the categorization of the Australian Institute of Sport (AIS). Overall, 59.9% of the handball players (n = 112) declared the use of at least one supplement and there were no significant differences between men and women (58.9% vs. 61.3%, p = 0.762) nor between professional vs. amateur handball players (67.1% vs. 53.8%, p = 0.074). The most prevalent supplements were sports drinks (42.2%), followed by energy bars (35.3%) and caffeine-containing products (31.6%). However, a greater consumption of group A supplements (those with strong scientific evidence; p = 0.029) and group B supplements (those with emerging scientific support, p = 0.012) was observed in male compared to female handball players. Supplements categorized as medical supplements were more commonly consumed in professional vs. amateur players (0.48 ± 0.80 vs. 0.21 ± 0.44, supplements p < 0.006). Additionally, a higher consumption of group B supplements was observed in professional compared to amateur players (0.58 ± 0.88 vs. 0.33 ± 0.72 supplements, p = 0.015). Handball players revealed a moderate use of supplements while sex and competitive level slighted changed the pattern of supplements use. A high portion of handball players use supplements as fuel during exercise and reported the use of caffeine-containing supplements to enhance performance.

Molecular and biochemical insights into the in vivo evolution of AmpC-mediated resistance to ceftolozane/tazobactam during treatment of an MDR Pseudomonas aeruginosa infection.

BACKGROUND: Pseudomonas aeruginosa may develop resistance to novel cephalosporin/ß-lactamase inhibitor combinations during therapy through the acquisition of structural mutations in AmpC. OBJECTIVES: To describe the molecular and biochemical mechanisms involved in the development of resistance to ceftolozane/tazobactam in vivo through the selection and overproduction of a novel AmpC variant, designated PDC-315. METHODS: Paired susceptible/resistant isolates obtained before and during ceftolozane/tazobactam treatment were evaluated. MICs were determined by broth microdilution. Mutational changes were investigated through WGS. Characterization of the novel PDC-315 variant was performed through genotypic and biochemical studies. The effects at the molecular level of the Asp245Asn change were analysed by molecular dynamics simulations using Amber. RESULTS: WGS identified mutations leading to modification (Asp245Asn) and overproduction of AmpC. Susceptibility testing revealed that PAOΔC producing PDC-315 displayed increased MICs of ceftolozane/tazobactam, decreased MICs of piperacillin/tazobactam and imipenem and similar susceptibility to ceftazidime/avibactam compared with WT PDCs. The catalytic efficiency of PDC-315 for ceftolozane was 10-fold higher in relation to the WT PDCs, but 3.5- and 5-fold lower for piperacillin and imipenem. IC50 values indicated strong inhibition of PDC-315 by avibactam, but resistance to cloxacillin inhibition. Analysis at the atomic level explained that the particular behaviour of PDC-315 is linked to conformational changes in the H10 helix that favour the approximation of key catalytic residues to the active site. CONCLUSIONS: We deciphered the precise mechanisms that led to the in vivo emergence of resistance to ceftolozane/tazobactam in P. aeruginosa through the selection of the novel PDC-315 enzyme. The characterization of this new variant expands our knowledge about AmpC-mediated resistance to cephalosporin/ß-lactamase inhibitors in P. aeruginosa.