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Spontaneous bacterial meningitis (BM) is more common among patients with underlying conditions, but its characteristics in previously healthy patients are not well described. We analyzed the time trends of BM in terms of characteristics, and outcomes in patients without comorbidities. Patients and methods: Single-center, prospective observational cohort study of 328 adults with BM hospitalized in a tertiary university hospital in Barcelona (Spain). We compared the features of infections diagnosed in 1982–2000 and 2001–2019. The main outcome measure was in-hospital mortality. Results: The median age of the patients increased from 37 to 45 years. Meningococcal meningitis significantly diminished (56% versus 31%, p < 0.000) whereas listerial meningitis increased (1.2% versus 8%, p = 0.004). Systemic complications were more common in the second period, although mortality did not vary significantly between periods (10.4% versus 9.2%). However, after adjusting for relevant variables, infection in the second period was associated with lower risk death. Conclusions: Adult patients without underlying comorbidities that developed BM in recent years were older and more likely to have pneumococcal or listerial infections and systemic complications. In-hospital death was less likely in the second period, after adjusting for risk factors of mortality.

Disk diffusion is a well standardized method that provides reliable categorical results to guide antimicrobial therapy in numerous types of infections. Based on the guidelines of the European Committee on Antimicrobial Susceptibility Testing (EUCAST), which are widely implemented in Spain, the Spanish Antibiogram Committee (COESANT) has drawn up recommendations for antimicrobial selection by the disk diffusion technique, including selective reporting and its use for the detection of resistance mechanisms. Factors affecting disk diffusion results, along with advantages and shortcomings of the method, are also discussed.

P. aeruginosa bacteremia is a common and severe infection carrying high mortality in older adults. We aimed to evaluate outcomes of P. aeruginosa bacteremia among old adults (≥ 80 years).We included the 464/2394 (19%) older adults from a retrospective multinational (9 countries, 25 centers) cohort study of individuals hospitalized with P. aeruginosa bacteremia. Bivariate and multivariable logistic regression models were used to evaluate risk factors for 30-day mortality among older adults.Among 464 adults aged ≥ 80 years, the mean age was 84.61 (SD 3.98) years, and 274 (59%) were men. Compared to younger patients, ≥ 80 years adults had lower Charlson score; were less likely to have nosocomial acquisition; and more likely to have urinary source. Thirty-day mortality was 30%, versus 27% among patients 65-79 years (n = 894) and 25% among patients 65 years (n = 1036). Multivariate analysis for predictors of mortality among patients ≥ 80 years, demonstrated higher SOFA score (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.23-1.51, p 0.001), corticosteroid therapy (OR 3.15, 95% CI: 1.24-8.01, p = 0.016) and hospital acquired P. aeruginosa bacteremia (OR 2.30, 95% CI: 1.33-3.98, p = 0.003) as predictors. Appropriate empirical therapy within 24 h, type of definitive anti-pseudomonal drug, and type of regimen (monotherapy or combination) were not associated with 30-day mortality.In older adults with P. aeruginosa bacteremia, background conditions, place of acquisition, and disease severity are associated with mortality, rather than the antimicrobial regimen. In this regard, preventive efforts and early diagnosis before organ failure develops might be beneficial for improving outcomes.

Introduction Awareness of the importance of SM among trainees at our IM Training Program (IMTP) has not been documented, despite the high prevalence of Sleep Disordered Breathing (SDB) within our clinical population. Recently, the Indiana University Sleep Questionnaire (IUSQ) was administered to quantify the perception of SM in IM residents. Methods We administered the IUSQ questionnaire through an anonymous computer survey sample of IM residents at our ACGME accredited IMTP. Results A total of 52/61 (85%) residents from the Veterans Administration Caribbean Health Care System (VACHS) IMTP participated. There were 18 PGY-1, 16 PGY-2, 15 PGY-3 and 3 PGY-4 residents whom the majority strongly agreed or agreed that the burden of SDB was large in the general population (63% & 35%), that it is important for their training (48% & 46%) and for their general practice (54% & 38%). They were mostly neutral or disagreed about getting adequate training in SDB during residency (38% & 40%). The majority strongly agreed or agreed that sleep specialist is needed for managing SDB (27% & 48%) and 9.6% disagreed with this. Many do not have interest in pursuing a sleep medicine fellowship answering neutral, disagree and strongly disagree (23%, 38% &23%). The majority strongly agree and agree that a sleep fellowship is important in treating sleep disorders (48% & 33%). The residents are mostly neutral or disagree when it comes to their confidence in treating sleep apnea (40% & 48%) and treating other sleep disorders (46% & 38%). Conclusion Despite the high prevalence of SDB in the population they manage, residents do not feel they are getting enough training in the management of sleep disorders. They acknowledge the importance of SM education for the latter purpose, but the majority does not want to pursue formal subspecialty training in SM. In addition, they do not feel comfortable managing SDB and other sleep disorders. Interestingly this mismatch between burden of disease and the need for disease management proficiency is similar to one found previously in a different resident population to which the same IUSQ was administered. An educational approach toward residents may furtherly change these perceptions. Support (if any)

To evaluate if microbial load from diabetic foot ulcers (DFUs) can help in predicting outcomes.A multicenter prospective cohort study was performed in an outpatient setting (September 1, 2017-January 31, 2019) in diabetic patients with DFU.Quantitative cultures from DFU tissue biopsies at a baseline visit were obtained; high and low microbial loads were defined as ≥6logCFU/mL and6logCFU/mL, respectively. Diagnosis of DFU infection was made and managed according to established guidelines. The outcome was evaluated at 6 month-visit as failure (persistence/new infection/amputation) or cure.Out of 65 patients, 52 (80%) had long-standing DFUs (≥4 weeks), with high microbial load in 19 (29%).DFU infection (n = 24, 37%) was not associated with high microbial load in all patients but those with shorter DFU duration.Treatment failure occurred in 20/57 (35%) patients; high DFU microbial load was associated with worse outcome (n = 9/20, 45% failure rate, adjusted OR4.69; 95% CI, 1.22-18.09; p = 0.03),mainly due to the subgroup of patients with high microbial load and long-stand DFUs.Since patients with high microbial load had a worse outcome, quantitative cultures from DFUs can identify patients who would benefit from antibiotic therapy.

Background: Staphylococcus epidermidis is a commensal of human skin flora and a frequent causative micro-organism in prosthetic joint infections (PJIs). To date, no single marker has been identified to distinguish infecting strains from commensal S. epidermidis populations. Aim: To find possible genetic markers to distinguish between the two populations. Methods: Fifty S. epidermidis strains from patients with PJIswere analysed, 50 fromthe skin of healthy individuals (commensal strains) and 17 from the surgical field of patients undergoing primary arthroplasty. In these three groups the antimicrobial susceptibility profile, sequence type, biofilm formation, and virulence factors were studied. Strains from the surgical field have not been compared previously with strains from the other two groups. Findings: S. epidermidis strains from PJI patients were significantly more antibiotic resistant than commensal strains and surgical field strains. A wide variety of sequence types was found in commensal and surgical field strains. The predominant sequence type was ST2 and it was only present in PJI strains (44%). Differences in biofilm production did not differ between populations. Virulence genes sdrF and bhp, the complete ica operon, and the insertion sequence IS256 were significantly predominant in PJI strains. By contrast, embp and hld genes and the arginine catabolic mobile element (ACME) were more prevalent in commensal strains. Surgical field strains could be a valid control group to discriminate between infecting and commensal strains. Conclusion: A combination of characteristic features can differentiate between infecting and commensal S. epidermidis strains in PJI, whereas a single marker cannot. (C) 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Fil: Rivera de la Rosa, Alba. Universidad Autónoma de Yucatán; México. Fil: Ortiz Pech, Rafael. Universidad Autónoma de Yucatán; México. Fil: Santoyo Manzanilla, David de Jesús. Universidad Autónoma de Yucatán; México. Rivera de la Rosa, A., Ortiz Pech, R. y Santoyo Manzanilla, D. de J. (2021). Los financiamientos y subsidios a la producción agropecuaria en México y su impacto en la falta de autosuficiencia alimentaria.. Estudios Rurales, 11(24). La política de subsidios y financiamientos a la agricultura mexicana requiere replantearse para generar desarrollo económico. El objetivo de este trabajo es llevar a cabo un comparativo de los porcentajes de subsidios y financiamientos ejercidos por dependencias al campo mexicano en los años 2007 y 2011; tanto en recursos monetarios como en el número de beneficiarios. Con una proyección tendencial de 2003 al 2017 de los montos ejercidos por la SAGARPA y SEDESOL. Los resultados arrojan una proporción desigual en la aplicación de los financiamientos otorgados a grandes productores agropecuarios, con respecto a los subsidios que reciben pequeños y medianos productores, de poco monto y para mitigar su pobreza. Con ello logró reforzarse el área agropecuaria y un superávit en la Balanza Comercial Agroalimentaria a partir de 2015. Sin embargo, con todo y el éxito en las exportaciones, México sigue dependiendo de las importaciones de alimentos como el maíz, con afectaciones en su autosuficiencia alimentaria. A política de subsídios e financiamento para a agricultura mexicana exige repensar para gerar desenvolvimento econômico. O objetivo deste trabalho é realizar uma comparação dos percentuais de subsídios e financiamentos exercidos por agências ao campo mexicano nos anos de 2007 e 2011; tanto em recursos monetários quanto em número de beneficiários. Com projeção de tendência de 2003 a 2017 dos valores exercidos pela SAGARPA e SEDESOL. Os resultados mostram uma proporção desigual na aplicação dos financiamentos concedidos aos grandes produtores agrícolas, no que diz respeito aos subsídios recebidos pelos pequenos e médios produtores, de pouco valor e para aliviar a sua pobreza. Com isso, a área agrícola foi fortalecida e superavitária na Balança Comercial Agroalimentar a partir de 2015. No entanto, apesar do sucesso nas exportações, o México continua a depender de importações de alimentos como o milho, com reflexos em sua autossuficiência alimentar. The policy of subsidies and financing to Mexican agriculture requires rethinking to generate economic development. The objective of this work is to carry out a comparison of the percentages of subsidies and financing exercised by dependencies in the Mexican field in 2007 and 2011; both in monetary resources and in the number of beneficiaries. It includes a trend projection from 2003 to 2017 of the amounts exercised by SAGARPA and SEDESOL. The results show an unequal proportion in the implementation of financing granted to large agricultural producers, with respect to subsidies received by small and medium-sized producers, of little amount and mitigating their poverty. This strengthened the agricultural area and a surplus in the Agri-Food Trade Balance from 2015. However, yet, the success in exports, Mexico remains dependent on imports of food such as maiz, with effects on its food self-sufficiency.

[Background] Pseudomonas aeruginosa bacteraemia is a common and serious infection. No consensus exists regarding whether definitive combination therapy is superior to monotherapy. We aimed to evaluate the impact of combination therapy on mortality., [Methods] This was a multicentre retrospective study (nine countries, 25 centres), including 1277 patients with P. aeruginosa bacteraemia during 2009–15. We evaluated the association between β-lactam plus aminoglycoside or quinolone combination therapy versus β-lactam monotherapy and mortality. The primary outcome was 30 day all-cause mortality. Univariate and multivariate Cox regression analyses were conducted, introducing combination as a time-dependent variable. Propensity score was conducted to adjust for confounding for choosing combination therapy over monotherapy., [Results] Of 1119 patients included, 843 received definitive monotherapy and 276 received combination therapy (59% aminoglycoside and 41% quinolone). Mortality at 30 days was 16.9% (189/1119) and was similar between combination (45/276; 16.3%) and monotherapy (144/843; 17.1%) groups (P = 0.765). In multivariate Cox regression, combination therapy was not associated with reduced mortality (HR 0.98, 95% CI 0.64–1.53). No advantage in terms of clinical failure, microbiological failure or recurrent/persistent bacteraemia was demonstrated using combination therapy. Likewise, adverse events and resistance development were similar for the two regimens., [Conclusions] In this retrospective cohort, no mortality advantage was demonstrated using combination therapy over monotherapy for P. aeruginosa bacteraemia. Combination therapy did not improve clinical or microbiological failure rates, nor affect adverse events or resistance development. Our finding of no benefit with combination therapy needs confirmation in well-designed randomized controlled trials.

Objectives: To assess the effect on the functional ambulatory outcome of postoperative joint infection (PJI) cured at the first treatment attempt versus not developing PJI in patients with hip and knee prostheses. Methods: In a single-hospital retrospectively matched cohort study, each patient with PJI between 2007 and 2016 was matched on age, sex, type of prosthesis and year of implantation with two other patients with uninfected arthroplasties. The definition of a PJI cure included infection eradication, no further surgical procedures, no PJI-related mortality and no suppressive antibiotics. Functional ambulatory status evaluated one year after the last surgery was classified into four simple categories: able to walk without assistance, able to walk with one crutch, able to walk with two crutches, and unable to walk. Patients with total hip arthroplasties (THA), total knee arthroplasties (TKA) and partial hip arthroplasty (PHA) were analysed separately. Results: A total of 109 PJI patients (38 TKA, 41 THA, 30 PHA) and 218 non-PJI patients were included. In a model adjusted for clinically relevant variables, PJI was associated with a higher risk of needing an assistive device for ambulation (vs. walking without aid) among THA (adjusted odds ratio (OR) 3.10, 95% confidence interval (95% CI) 1.26&ndash, 7.57, p = 0.014) and TKA patients (OR 5.40, 95% CI 2.12&ndash, 13.67, p &lt, 0.001), and with requiring two crutches to walk or being unable to walk (vs. walking unaided or with one crutch) among PHA patients (OR 3.05, 95% CI 1.01&ndash, 9.20, p = 0.047). Conclusions: Ambulatory outcome in patients with hip and knee prostheses with postoperative PJI is worse than in patients who do not have PJI.

The aim was to develop and validate a Pseudomonas aeruginosa genotypic resistance score, based on analysis of the whole genome sequence resistome, to predict antimicrobial susceptibility phenotypes.A scoring system based on the analysis of mutation-driven resistance in 40 chromosomal genes and horizontally acquired resistance (Resfinder) was developed for ceftazidime, ceftolozane/tazobactam, meropenem, ciprofloxacin and tobramycin. Resistance genes/mutations were scored from 0 (no effect) to 1 (EUCAST clinical resistance). One hundred wild-type strains obtained from 51 different hospitals during a 2017 multicentre study were fully sequenced and analysed in order to define a catalogue of natural polymorphisms in the 40 chromosomal resistance genes. The capacity of genotypic score to predict the susceptibility phenotype was tested in 204 isolates randomly selected from the 51 hospitals (four from each hospital).The analysis of the 100 wild-type isolates yielded a catalogue of 455 natural polymorphisms in the 40 genes involved in mutational resistance. However, resistance mutations and high-risk clones (such as ST235) were also documented among a few wild-type isolates. Overall, the capacity of the genotypic score (0.5) for predicting phenotypic susceptibility (S + I in the case of meropenem) was very high (95-100%). In contrast, the capacity of the genotypic score to predict resistance (≥1) was far more variable depending on the agent. Prediction of meropenem clinical resistance was particularly low (18/39, 46.1%), whereas it classified clinical ceftolozane/tazobactam resistance in 100% (7/7) of cases.Although a margin for improvement was evidenced in this proof of concept study, an overall good correlation between the genotypic resistance score and the susceptibility profile was documented. Further refining of the scoring system, automatization and testing of large international cohorts should follow.

This study was presented as poster presentation at the European Society of Clinical Microbiology and Infectious Diseases annual conference, Madrid, Spain, 21–24 April 2018., [Background] The optimal antibiotic regimen for Pseudomonas aeruginosa bacteremia is controversial. Although β-lactam monotherapy is common, data to guide the choice between antibiotics are scarce. We aimed to compare ceftazidime, carbapenems, and piperacillin-tazobactam as definitive monotherapy. [Methods] A multinational retrospective study (9 countries, 25 centers) including 767 hospitalized patients with P. aeruginosa bacteremia treated with β-lactam monotherapy during 2009–2015. The primary outcome was 30-day all-cause mortality. Univariate and multivariate, including propensity-adjusted, analyses were conducted introducing monotherapy type as an independent variable. [Results] Thirty-day mortality was 37/213 (17.4%), 42/210 (20%), and 55/344 (16%) in the ceftazidime, carbapenem, and piperacillin-tazobactam groups, respectively. Type of monotherapy was not significantly associated with mortality in either univariate, multivariate, or propensity-adjusted analyses (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.52–2.46, for ceftazidime; OR, 1.3; 95% CI, 0.67–2.51, for piperacillin-tazobactam, with carbapenems as reference in propensity adjusted multivariate analysis; 542 patients). No significant difference between antibiotics was demonstrated for clinical failure, microbiological failure, or adverse events. Isolation of P. aeruginosa with new resistance to antipseudomonal drugs was significantly more frequent with carbapenems (36/206 [17.5%]) versus ceftazidime (25/201 [12.4%]) and piperacillin-tazobactam (28/332 [8.4%] (P = .007). [Conclusions] No significant difference in mortality, clinical, and microbiological outcomes or adverse events was demonstrated between ceftazidime, carbapenems, and piperacillin-tazobactam as definitive treatment of P. aeruginosa bacteremia. Higher rates of resistant P. aeruginosa after patients were treated with carbapenems, along with the general preference for carbapenem-sparing regimens, suggests using ceftazidime or piperacillin-tazobactam for treating susceptible infection., This study was conducted with no external funding. In Sweden only, the research was funded by grants from the Stockholm County Council and Emil and Wera Cornell Foundation.

Combination therapy is an attractive therapeutic option for extensively drug-resistant (XDR) Pseudomonas aeruginosa infections. Colistin has been the only treatment available for these infections for many years, but its results are suboptimal. Ceftolozane-tazobactam (C/T) is a newly available therapeutic option that has shown good antipseudomonal activity, even against a number of XDR P. aeruginosa strains. However, data about combinations containing C/T are scarce. The aim of this study was to analyze the activity of C/T and colistin alone and in combination against a collection of XDR P. aeruginosa strains containing 24 representative clinical isolates from a multicentre Spanish study. Twenty-four time-kill experiments performed over 24 h were conducted in duplicate to determine the effects of colistin and C/T alone and combined. An in vitro pharmacodynamic chemostat model then was used to validate this combination against three selected XDR P. aeruginosa ST175 isolates with different susceptibility levels to C/T. Static time-kill assays demonstrated superior synergistic or additive effect for C/T plus colistin against 21 of the 24 isolates studied. In the in vitro dynamic pharmacokinetic/pharmacodynamic (PK/PD) model, the C/T regimen of 2/1 g every 8 h with a steady-state concentration of 2 mg/liter colistin effectively suppressed the bacterial growth at 24 h. Additive or synergistic interactions were observed for C/T plus colistin against XDR P. aeruginosa strains and particularly against C/T-resistant strains. C/T plus colistin may be a useful treatment for XDR P. aeruginosa infections, including those caused by high risk-clones resistant to C/T.

This study aimed to evaluate risk factors for 30-day mortality among hospitalised patients with Pseudomonas aeruginosa bacteraemia, a highly fatal condition. A retrospective study was conducted between 1 January 2009 and 31 October 2015 in 25 centres (9 countries) including 2396 patients. Univariable and multivariable analyses of risk factors were conducted for the entire cohort and for patients surviving >= 48 h. A propensity score for predictors of appropriate empirical therapy was introduced into the analysis. Of the 2396 patients, 636 (26.5%) died within 30 days. Significant predictors (odds ratio and 95% confidence interval) of mortality in the multivariable analysis included patient-related factors: age (1.02, 1.01-1.03); female sex (1.34, 1.03-1.77); bedridden functional capacity (1.99, 1.24-3.21); recent hospitalisation (1.43, 1.07-1.92); concomitant corticosteroids (1.33, 1.02-1.73); and Charlson comorbidity index (1.05, 1.01-1.93). Infection-related factors were multidrug-resistant Pseudomonas (1.52, 1.15-2.1), nonurinary source (2.44, 1.54-3.85) and Sequential Organ Failure Assessment (SOFA) score (1.27, 1.18-1.36). Inappropriate empirical therapy was not associated with increased mortality (0.81, 0.49-1.33). Among 2135 patients surviving >= 48 h, hospital-acquired infection (1.59, 1.21-2.09), baseline endotracheal tube (1.63, 1.13-2.36) and ICU admission (1.53, 1.02-2.28) were additional risk factors. Risk factors for mortality among patients with P. aeruginosa were mostly irreversible. Early appropriate empirical therapy was not associated with reduced mortality. Further research should be conducted to explore subgroups that may not benefit from broad-spectrum antipseudomonal empirical therapy. Efforts should focus on prevention of infection, mainly hospital-acquired infection and multidrug-resistant pseudomonal infection. (C) 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Summary Background Staphylococcus aureus persistent bacteraemia is only vaguely defined and the effect of different durations of bacteraemia on mortality is not well established. Our primary aim was to analyse mortality according to duration of bacteraemia and to derive a clinically relevant definition for persistent bacteraemia. Methods We did a secondary analysis of a prospective observational cohort study at 17 European centres (nine in the UK, six in Spain, and two in Germany), with recruitment between Jan 1, 2013, and April 30, 2015. Adult patients who were consecutively hospitalised with monomicrobial S aureus bacteraemia were included. Patients were excluded if no follow-up blood culture was taken, if the first follow-up blood-culture was after 7 days, or if active antibiotic therapy was started more than 3 days after first blood culture. The primary outcome was 90-day mortality. Univariable and time-dependent multivariable Cox regression analysis were used to assess predictors of mortality. Duration of bacteraemia was defined as bacteraemic days under active antibiotic therapy counting the first day as day 1. Findings Of 1588 individuals assessed for eligibility, 987 were included (median age 65 years [IQR 51–75]; 625 [63%] male). Death within 90 days occurred in 273 (28%) patients. Patients with more than 1 day of bacteraemia (315 [32%]) had higher Charlson comorbidity index and sequential organ failure assessment scores and a longer interval from first symptom to first blood culture. Crude 90-day mortality increased from 22% (148 of 672) with 1 day of bacteraemia, to 39% (85 of 218) with 2–4 days, 43% (30 of 69) with 5–7 days, and 36% (10 of 28) with more than 7 days of bacteraemia. Metastatic infections developed in 39 (6%) of 672 patients with 1 day of bacteraemia versus 40 (13%) of 315 patients if bacteraemia lasted for at least 2 days. The second day of bacteraemia had the highest HR and earliest cutoff significantly associated with mortality (adjusted hazard ratio 1·93, 95% CI 1·51–2·46; p Interpretation We suggest redefining the cutoff duration for persistent bacteraemia as 2 days or more despite active antibiotic therapy. Our results favour follow-up blood cultures after 24 h for early identification of all patients with increased risk of death and metastatic infection. Funding None.

Combination therapy is an attractive therapeutic option for extensively drug-resistant (XDR) Pseudomonas aeruginosa infections. Colistin has been the only treatment available for these infections for many years, but its results are suboptimal. Ceftolozane-tazobactam (C/T) is a newly available therapeutic option that has shown good antipseudomonal activity, even against a number of XDR P. aeruginosa strains. However, data about combinations containing C/T are scarce. The aim of this study was to analyze the activity of C/T and colistin alone and in combination against a collection of XDR P. aeruginosa strains containing 24 representative clinical isolates from a multicentre Spanish study. Twenty-four time-kill experiments performed over 24 h were conducted in duplicate to determine the effects of colistin and C/T alone and combined. An in vitro pharmacodynamic chemostat model then was used to validate this combination against three selected XDR P. aeruginosa ST175 isolates with different susceptibility levels to C/T. Static time-kill assays demonstrated superior synergistic or additive effect for C/T plus colistin against 21 of the 24 isolates studied. In the in vitro dynamic pharmacokinetic/pharmacodynamic (PK/PD) model, the C/T regimen of 2/1 g every 8 h with a steady-state concentration of 2 mg/liter colistin effectively suppressed the bacterial growth at 24 h. Additive or synergistic interactions were observed for C/T plus colistin against XDR P. aeruginosa strains and particularly against C/T-resistant strains. C/T plus colistin may be a useful treatment for XDR P. aeruginosa infections, including those caused by high risk-clones resistant to C/T.

Objectives: The objectives were to determine the prevalence of colistin resistance in clinical isolates of Enterobacteriaceae, and to gain knowledge on the epidemiological and clinical features of the patients. Methods: All colistin-resistant Enterobacteriaceae consecutively isolated from clinical samples in our institution from 2012 to 2015, were included in this cross-sectional study. Intrinsic-resistant species were excluded. Minimum inhibitory concentration was performed by gradient diffusion. Detection of plasmid-encoded colistin resistance genes mcr-1 and mcr-2 was performed by amplification. Epidemiological and clinical features were reviewed. Results: Of 13579 Enterobacteriaceae isolates, 91 were colistin-resistant. The overall prevalence of colistin resistance was 0.67%. The rates were higher in Enterobacter cloacae (4.2%) than Escherichia coli (0.5%) and Klebsiella pneumoniae (0.4%). One third of the isolates were multidrug resistant (MDR). While mcr-2 was not detected, mcr-1 was detected only in E. coli. Regarding these infections, 23% were community-acquired. 89% of the patients had not received colistin previously. There were no significant differences between infections caused by mcr-1 and non-mcr-1-carrying isolates. Conclusions: Colistin resistance was not restricted to MDR isolates and to clinical settings. Most patients had no record of previous administration of colistin. (C) 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Proteus mirabilis is the second most common cause of urinary tract infections and is also an important cause of nosocomial infections. TEM-type and CTX-M-type extended-spectrum β-lactamases (ESBLs) are the most widely distributed in this bacterial species, but minor ESBLs such as the VEB-type have also been identified. The aim of this study was to analyze the genetic environment of the blaVEB-4 gene found in a P. mirabilis clinical isolate recovered in Spain. P. mirabilis N2231 showed resistance to penicillins, cephalosporins, and aminoglycosides, remaining susceptible to imipenem, cefoxitin, β-lactamases inhibitors, and quinolones. Southern blot analysis revealed that blaVEB-4 was located in the chromosome. Analysis of the blaVEB-4 genetic context revealed a 15 kb segment 98% identical to the multidrug resistance (MDR) region of a Salmonella genomic island 1 (SGI1), which included a class 1 integron belonging to the In104 family, previously described in blaVEB-6-producing P. mirabilis VB1248. blaVEB-4 wa...

Background: Extensively drug-resistant (XDR) Pseudomonas aeruginosa (P. aeruginosa) and particularly P. aeruginosa high-risk clones, are of growing concern because treatment options are limited. For years, colistin monotherapy has been the only available treatment, but is well known that is not an optimal treatment. A combination of colistin with another antibiotic could be a possible therapeutic option. Objectives: This study aimed to investigate effective antibiotic combinations against 20 XDR P. aeruginosa isolates obtained in a Spanish multicentre study (2015). Methods: Forty-five checkerboards with six antipseudomonal antibiotics (amikacin, aztreonam, ceftazidime, meropenem, colistin, and ceftolozane/tazobactam) were performed to determine whether combinations were synergic or additive by fractional inhibitory concentration indices. On average, 15 different regimens were evaluated in duplicate against the three most prevalent high-risk clones (ST175, ST235, ST111) by time-kill analyses over 24 h. The combination showing synergism in the three high-risk clones was validated in all studied XDR isolates. Results: In time-kill curves, the untreated control failed, as did each study regimen when administered alone. Two combinations were synergistic in the three high-risk clones that were initially studied: amikacin plus ceftazidime and colistin plus meropenem, with the second being the most effective combination. The efficacy of colistin plus meropenem was then tested in all 20 isolates. A synergistic bacterial density reduction for the duration of the study occurred in 80% of the entire XDR collection. Conclusions: These data suggest that colistin plus meropenem may be a useful combination for the treatment of infections due to XDR P. aeruginosa, including high-risk clones, which warrants evaluation in a clinical trial. (C) 2019 International Society for Antimicrobial Chemotherapy. Published by Elsevier Ltd. All rights reserved.

The aim of the study was to investigate the epidemiology and clinical features of bloodstream infections due to Escherichia coli producing AmpC β-lactamases (AmpC-Ec-BSI). In a multi-centre case–control study, all third-generation-cephalosporin-resistant Escherichia coli BSI (3GC-Ec-BSI) isolates were analysed. Acquired bla AmpC (bla ac-AmpC) detection was done by polymerase chain reaction (PCR) and sequencing. Chromosomal bla AmpC (bla c-AmpC) expression was quantified by real-time PCR. Cases were patients with AmpC-Ec-BSI. Controls were patients with cephalosporin-susceptible E. coli BSI, matched 1:1 by sex and age. Demographics, comorbidities, intrinsic and extrinsic risk factors for antimicrobial resistance, clinical presentation and outcomes were investigated. Among 841 E. coli BSI, 17 were caused by AmpC-Ec (2 %). Eleven isolates (58.8 %) had bla ac-AmpC and six were bla c-AmpC overproducers. The mean age of cases was 66.2 years and 71 % were men. Cases were more frequently healthcare-related (82 vs. 52 % controls, p

This study assessed the molecular epidemiology, resistance mechanisms, and susceptibility profiles of a collection of 150 extensively drug-resistant (XDR) Pseudomonas aeruginosa clinical isolates obtained from a 2015 Spanish multicenter study, with a particular focus on resistome analysis in relation to ceftolozane-tazobactam susceptibility. Broth microdilution MICs revealed that nearly all (>95%) of the isolates were nonsusceptible to piperacillin-tazobactam, ceftazidime, cefepime, aztreonam, imipenem, meropenem, and ciprofloxacin. Most of them were also resistant to tobramycin (77%), whereas nonsusceptibility rates were lower for ceftolozane-tazobactam (31%), amikacin (7%), and colistin (2%). Pulsed-field gel electrophoresis–multilocus sequence typing (PFGE-MLST) analysis revealed that nearly all of the isolates belonged to previously described high-risk clones. Sequence type 175 (ST175) was detected in all 9 participating hospitals and accounted for 68% (n = 101) of the XDR isolates, distantly followed by ST244 (n = 16), ST253 (n = 12), ST235 (n = 8), and ST111 (n = 2), which were detected only in 1 to 2 hospitals. Through phenotypic and molecular methods, the presence of horizontally acquired carbapenemases was detected in 21% of the isolates, mostly VIM (17%) and GES enzymes (4%). At least two representative isolates from each clone and hospital (n = 44) were fully sequenced on an Illumina MiSeq. Classical mutational mechanisms, such as those leading to the overexpression of the β-lactamase AmpC or efflux pumps, OprD inactivation, and/or quinolone resistance-determining regions (QRDR) mutations, were confirmed in most isolates and correlated well with the resistance phenotypes in the absence of horizontally acquired determinants. Ceftolozane-tazobactam resistance was not detected in carbapenemase-negative isolates, in agreement with sequencing data showing the absence of ampC mutations. The unique set of mutations responsible for the XDR phenotype of ST175 clone documented 7 years earlier were found to be conserved, denoting the long-term persistence of this specific XDR lineage in Spanish hospitals. Finally, other potentially relevant mutations were evidenced, including those in penicillin-binding protein 3 (PBP3), which is involved in β-lactam (including ceftolozane-tazobactam) resistance, and FusA1, which is linked to aminoglycoside resistance.

OBJECTIVES To describe the prevalence and risk factors for infection due to AmpC β-lactamase-producing Escherichia coli (AmpC-EC). METHODS For the prevalence study, all clinical isolates of E. coli with reduced susceptibility to third-generation cephalosporins were prospectively included from June 2010 to November 2011. For risk factor analysis, a case-control study was conducted. Cases were patients with an infection due to AmpC-EC. Controls were patients infected with cephalosporin-susceptible E. coli, matched 1 : 2. Detection of blaAmpC genes was done with a multiplex AmpC-PCR, and hyperproduction of E. coli chromosomal blaAmpC by quantitative RT-PCR. Alteration of the blaAmpC promoter was studied by PCR and sequencing. RESULTS We identified 243 (1.1%) AmpC-EC strains out of 21 563 clinical isolates. Three cases with strains carrying ESBLs, 18 strains that were considered due to colonization and 8 cases lost to clinical follow-up were excluded. Finally, 214 cases were included in the analysis. Ninety-one cases (42.5%) and 269 (62.8%) controls were strictly community acquired (P

This study assessed the molecular epidemiology, resistance mechanisms, and susceptibility profiles of a collection of 150 extensively drug-resistant (XDR) Pseudomonas aeruginosa clinical isolates obtained from a 2015 Spanish multicenter study, with a particular focus on resistome analysis in relation to ceftolozane-tazobactam susceptibility. Broth microdilution MICs revealed that nearly all (>95%) of the isolates were nonsusceptible to piperacillin-tazobactam, ceftazidime, cefepime, aztreonam, imipenem, meropenem, and ciprofloxacin. Most of them were also resistant to tobramycin (77%), whereas nonsusceptibility rates were lower for ceftolozane-tazobactam (31%), amikacin (7%), and colistin (2%). Pulsed-field gel electrophoresis–multilocus sequence typing (PFGE-MLST) analysis revealed that nearly all of the isolates belonged to previously described high-risk clones. Sequence type 175 (ST175) was detected in all 9 participating hospitals and accounted for 68% ( n = 101) of the XDR isolates, distantly followed by ST244 ( n = 16), ST253 ( n = 12), ST235 ( n = 8), and ST111 ( n = 2), which were detected only in 1 to 2 hospitals. Through phenotypic and molecular methods, the presence of horizontally acquired carbapenemases was detected in 21% of the isolates, mostly VIM (17%) and GES enzymes (4%). At least two representative isolates from each clone and hospital ( n = 44) were fully sequenced on an Illumina MiSeq. Classical mutational mechanisms, such as those leading to the overexpression of the β-lactamase AmpC or efflux pumps, OprD inactivation, and/or quinolone resistance-determining regions (QRDR) mutations, were confirmed in most isolates and correlated well with the resistance phenotypes in the absence of horizontally acquired determinants. Ceftolozane-tazobactam resistance was not detected in carbapenemase-negative isolates, in agreement with sequencing data showing the absence of ampC mutations. The unique set of mutations responsible for the XDR phenotype of ST175 clone documented 7 years earlier were found to be conserved, denoting the long-term persistence of this specific XDR lineage in Spanish hospitals. Finally, other potentially relevant mutations were evidenced, including those in penicillin-binding protein 3 (PBP3), which is involved in β-lactam (including ceftolozane-tazobactam) resistance, and FusA1, which is linked to aminoglycoside resistance.

Introduction: To characterize OXA-48 carbapenemase-producing Kiebsiella pneumoniae strains isolated after an increase in carbapenem resistance in Catalonia. Methodology: K. pneumoniae identification, antimicrobial susceptibility studies, the Modified Hodge Test method, amplification of antimicrobial resistance genes (against beta-lactamases, quinolones and aminogly-cosides), molecular typing (by PFGE and MLST), conjugation assays, plasmid characterization (PBRT-PCR and Southern blot), a description of mobile genetic elements and statistical analysis were done. Results: OXA-48 was the only carbapenemase detected, with a prevalence of 1.9%. The bla(OXA-48) gene was located in an IncL conjugative plasmid of 62 kb and integrated into the transposons Tn19992 (91.7%) or Tn1999.1. Five PFGE profiles (A to E) were found, which exactly matched the MLST: ST101, ST17, ST1233, ST14 and ST405, respectively. ST1233 is described here for the first time. K. pneumoniae OXA48-producing strains were also CTX-M-15 carriers, some producing OXA-1 and TEM-1 penicillinases. The acquired qnrB66 and qnrB1 and aac(3')-IIa, aac(6')-Ib genes were also identified. Conclusion: The K. pneumoniae ST405 clone has played an important role in the growing prevalence of OXA-48 in Catalonia. All clones described preserved the bla(OXA-48) genetic environment and mobile genetic elements (Tn1999). Notably, the three strains with minor sequence types in this study are not multiresistant strains. These strains are expanding in elderly patients (average age of 76 years) with serious underlying diseases, mainly women (61.2%). (C) 2018 Elsevier Espana, S.L.U. and Sociedad Espanola de Enfermedades lnfecciosas y Microbiologia Clinica. All rights reserved.

Proteus mirabilis is the second most common cause of urinary tract infections and is also an important cause of nosocomial infections. TEM-type and CTX-M-type extended-spectrum β-lactamases (ESBLs) are the most widely distributed in this bacterial species, but minor ESBLs such as the VEB-type have also been identified. The aim of this study was to analyze the genetic environment of the bla

Resumen Los β-lactamicos son los antimicrobianos mas utilizados para el tratamiento de las infecciones producidas por enterobacterias, y el principal mecanismo de resistencia frente a ellos es la produccion de β-lactamasas. Las β-lactamasas de mayor relevancia clinica, debido a su perfil de sustrato y a sus repercusiones epidemiologicas, son las de espectro extendido, las de clase C y las carbapenemasas. La deteccion fenotipica de estas β-lactamasas puede ser complicada y se basa, generalmente, en la utilizacion de inhibidores especificos y en la demostracion de la perdida de actividad frente a β-lactamicos indicadores. A pesar de que diferentes comites internacionales no consideran necesaria la determinacion del mecanismo de resistencia ni la interpretacion del antibiograma, son varias las voces criticas que estiman imprescindible esta deteccion y alertan de la conveniencia de interpretar el antibiograma mientras no se disponga de mas datos sobre la eficacia clinica de los β-lactamicos en estos casos. Por estas dificultades metodologicas y los constantes cambios de criterios de interpretacion, consideramos imprescindibles las labores de docencia en este campo. En este sentido, los controles de calidad externos son de gran relevancia para la continua actualizacion en esta area. Cualquiera de estos programas debe ir siempre acompanado de una revision de los resultados, de la metodologia y de las causas de los posibles errores, para poder realizar una actividad docente completa. En el presente trabajo se repasan y contextualizan todos los aspectos relacionados con la deteccion e interpretacion de estas β-lactamasas.

Colistin resistance was detected in 53 of 10,011 Escherichia coli (0.5%) by prospective phenotypic testing of consecutive clinical isolates in a single hospital in Barcelona, Spain (2012–15). The mcr-1 gene was retrospectively identified by PCR and sequencing in 15 of 50 available isolates. Each isolate had a unique PFGE pattern except for two. This clonal diversity supports the hypothesis of horizontal dissemination of the mcr-1 gene in the local study population.

Summary Background Most available information on carbapenemase-producing Enterobacteriaceae (CPE) is usually associated with specific types of infection or patient or with descriptions of outbreaks. The aim of this study was to comprehensively analyse the clinical epidemiology, clinical features and outcomes of colonisation and infections due to CPE in Spain. Methods A multicentre prospective cohort study was carried out in 34 Spanish hospitals from February to May 2013. All new patients testing positive for CPE in clinical samples were included. Logistic regression was used to identify predictors of mortality. Results Overall, 245 cases were included. The most frequent organism was Klebsiella pneumoniae (74%) and the carbapenemases belonged to the OXA-48 (74%), metallo-β-lactamase (MBL) (24%) and KPC (2%) groups. Acquisition was nosocomial in 145 cases (60%) and healthcare-associated (HCA) in 91 (37%); 42% of the latter were nursing home residents, in whom OXA-48-producing K. pneumoniae ST405 predominated. MBLs and OXA-48 predominated in ICU and medical patients, respectively. Overall, 67% of patients had infections. The most frequent infections identified in this study were urinary tract (43%) and skin structure (21%) infections, and 10% of infections were bacteraemic. Crude mortality was 20%. Inappropriate antibiotic therapy was independently associated with an increased risk of death (OR = 3.30; 95% CI: 1.34–8.11). Conclusions We found some differences in the epidemiology of CPE depending on the type of carbapenemase produced. Although a low proportion of CPE infections were bacteraemic, active antibiotic therapy was a protective factor for reducing mortality.

Escherichia coli recovered from three hospitals in Barcelona (Spain) were studied to determine the prevalence of isolates with acquired AmpC (ac-AmpC) and/or overproduced chromosomal AmpC (c-AmpC). Mechanisms involved in blac-AmpC overexpression, blaac-AmpC and the plasmids associated with their distribution as well as the prevalence of plasmid-mediated quinolone resistance (PMQR) in AmpC-producing isolates were also determined. Isolates were selected according to their resistance phenotype. blaac-AmpC, alterations in the blac-AmpC promoter/attenuator, and PMQR genes [qnrA, qnrB, qnrS, aac(6')-Ib-cr and qepA] were characterised by PCR and sequencing. blac-AmpC expression was determined by qRT-PCR. Population structure analysis was performed using PFGE, MLST and phylogenetic group PCR. Plasmids carrying blaac-AmpC were characterised by PCR-based replicon typing and S1-PFGE. IncI1 and IncF plasmids were also analysed by plasmid MLST and replicon sequence typing, respectively. Among 21563 E. coli isolates, 240 (1.1%) overproduced AmpC β-lactamases, including 180 (75.0%) harbouring ac-AmpC (132 CMY-2 variants and 48 DHA-1) and 60 (25.0%) c-AmpC enzymes. Three mutation profiles in the blac-AmpC promoter/attenuator were associated with a 72.5-, 19.9- and 5.8-fold increased expression, respectively. Moreover, 63.3% of ac-AmpC and 43.3% of c-AmpC isolates belonged to B2, D, E or F phylogenetic groups. PMQR was found in 31% of ac-AmpC isolates [38 qnrB4, 8 aac(6')-Ib-cr, 6 qnrS1 and 3 qnrB19] and in 10% of c-AmpC isolates [5 aac(6')-Ib-cr and 1 qnrS1]. IncI1-ST12 and IncF were associated with blaCMY-2 and blaDHA-1, respectively. These results suggest that ac-AmpC β-lactamases were the main mechanism of AmpC production. Isolates and plasmids both showed high genetic diversity.

Group A streptococcus (GAS) has been described as an emerging cause of severe invasive infections. A retrospective hospital-based study was conducted, including GAS isolates causing invasive or non-invasive infections from January 1999 to June 2003 in Barcelona. Demographic and clinical information on the invasive cases was obtained from medical files. GAS isolates collected from 27 patients with invasive infections and 99 patients with non-invasive infections were characterized by emm type and subtype, superantigen (SAg) gene profile (speA–C, speF–J, speL, speM, ssa and smeZ), allelic variants of speA and smeZ genes, antibiotic susceptibility and genetic resistance determinants. The most prevalent emm type was emm1 (17.5 %), followed by emm3 (8.7 %), emm4 (8.7 %), emm12 (7.1 %) and emm28 (7.1 %). The smeZ allele and SAg gene profiles were closely associated with the emm type. The speA2, speA3 and speA4 alleles were found in emm1, emm3 and emm6 isolates, respectively. Overall, 27.8, 25.4 and 11.9 % of isolates were resistant to erythromycin, tetracycline or both agents, respectively. Reduced susceptibility to ciprofloxacin and levofloxacin (MIC 2–4 μg ml−1) was found in 3.2 % of isolates. mef(A)-positive emm types 4, 12 and 75, and erm(B)-positive emm types 11 and 25 were responsible for up to 80 % of the erythromycin-resistant isolates. No significant differences in emm-type distribution, SAg gene profile or resistance rates were found between invasive and non-invasive isolates. The SAg and antibiotic resistance genes appeared to be associated with the emm type and were independent of the disease type.

Objectives The aim of the present study was to characterize and compare the extended-spectrum beta-lactamase (ESBL)-producing organisms isolated from clinical samples and faecal carriers in 2001 and 2002. Methods A total of 5251 Enterobacteriaceae isolated from clinical samples and 1321 stool samples were evaluated for the presence of ESBLs. The stool samples were spread onto plates of MacConkey agar containing 2 mg/L cefotaxime for selection of ESBL-producing strains. These strains were defined as those showing synergism between amoxicillin/clavulanic acid and third-generation cephalosporins. The beta-lactamases involved were characterized by isoelectric focusing, PCR assays and DNA sequencing. Results The prevalence of ESBL-producing strains among clinical Enterobacteriaceae was 1.7%. Of these, 87.6% produced CTX-M, 25.8% produced SHV and 2.2% were TEM-type-producing strains. All clinical ESBL-producing strains were Escherichia coli, with the exception of four Klebsiella pneumoniae and one Citrobacter freundii. The prevalence of faecal carriage of ESBL-producing organisms was 3.3%. Of these, 75% produced CTX-M-type enzymes followed by 22.7% SHV-producing strains. All faecal ESBL-producing strains were E. coli except for one Enterobacter cloacae and one Proteus mirabilis. This latter strain produced the PER-1 enzyme reported for the first time in Spain. Conclusions The prevalence of ESBL-producing strains in stool samples was higher than that observed in clinical samples from the same period. The different types of ESBLs found were similar in both contexts. The most prevalent ESBLs were the CTX-M-related enzymes, with nine different types, followed by SHV-12.

About 7% of 7,252 nonduplicated clinical Escherichia coli strains from a Spanish hospital showed reduced susceptibility to amoxicillin-clavulanate. Of these, 0.37% produced the IRTs TEM-30, TEM-31, TEM-33, TEM-34, TEM-37, TEM-40, TEM-51, and TEM-54; 5.3% were probable class C β-lactamase overproducers; 0.8% were probable TEM-1 hyperproducers; 0.18% produced OXA-30; 0.15% overexpressed SHV-1; and 0.03% produced a PSE-1 enzyme.

Brachyspira pilosicoli is an etiological agent of human intestinal spirochetosis. Bloodstream infection due to this microorganism is rare. We report a case of B. pilosicoli bacteremia in a 70-year-old patient who presented with multiorgan failure.

β-lactam antimicrobial agents are frequently used to treat infections caused by Enterobacteriaceae. The main mechanism of resistance to these antibiotics is the production of certain enzymes, collectively named β-lactamases. Due to their substrate profile and their epidemiological implications, the most clinically important β-lactamases are extended-spectrum β-lactamases, class C β-lactamases and carbapenemases. Phenotypic detection of these enzymes may be complicated and is based on the use of specific inhibitors of each β-lactamase and on the loss of activity on some β-lactam indicators. Various international committees postulate that it is no longer necessary to interpret the susceptibility results or determine the mechanism of resistance. Several critics disagree, however, and consider that susceptibility results should be interpreted until more data are available on the clinical efficacy of treatment with β-lactams. Given these methodological difficulties and constant changes in the interpretation criteria, we consider that training and external quality controls are essential to keep updated in this field. For learning purposes, these external quality controls should always be accompanied by a review of the results and methodology used, and the analysis of errors. In this paper we review and contextualize all the aspects related to the detection and interpretation of these β-lactamases.