[One stage surgical treatment of aortic coarctation associated with bicuspid aortic valve. Report of one case]. / Tratamiento en un tiempo quirúrgico de una coartación aortica asociada a valvulopatía aórtica bicúspide severa. Reporte de un caso.

Percutaneous surgery is the treatment of choice of isolated aortic coarctation in adults However, when there are other heart problems related to aortic coarctation, its surgical management may vary. We report a 41-year-old male presenting with aortic coarctation associated with severe, symptomatic, bicuspid aortic valve lesions and significant left ventricular dysfunction. He underwent open heart surgery for the surgical resolution of these problems. One year after surgery the results are satisfactory with no evidence of postoperative complications and a significant improvement of patient symptoms and left ventricular function.

Exome Sequencing Identifies Genetic Variants Associated with Extreme Manifestations of the Cardiovascular Phenotype in Marfan Syndrome.

Marfan Syndrome (MFS) is an autosomal dominant condition caused by variants in the fibrillin-1 (FBN1) gene. Cardinal features of MFS include ectopia lentis (EL), musculoskeletal features and aortic root aneurysm and dissection. Although dissection of the ascending aorta is the main cause of mortality in MFS, the clinical course differs considerably in age of onset and severity, even among individuals who share the same causative variant, suggesting the existence of additional genetic variants that modify the severity of the cardiovascular phenotype in MFS. We recruited MFS patients and classified them into severe (n = 8) or mild aortic phenotype (n = 14) according to age of presentation of the first aorta-related incident. We used Exome Sequencing to identify the genetic variants associated with the severity of aortic manifestations and we performed linkage analysis where suitable. We found five genes associated with severe aortic phenotype and three genes that could be protective for this phenotype in MFS. These genes regulate components of the extracellular matrix, TGFß pathway and other signaling pathways that are involved in the maintenance of the ECM or angiogenesis. Further studies will be required to understand the functional effect of these variants and explore novel, personalized risk management and, potentially, therapies for these patients.

Tratamiento en un tiempo quirúrgico de una coartación aortica asociada a valvulopatía aórtica bicúspide severa. Reporte de un caso / One stage surgical treatment of aortic coarctation associated with bicuspid aortic valve. Report of one case

Percutaneous surgery is the treatment of choice of isolated aortic coarctation in adults However, when there are other heart problems related to aortic coarctation, its surgical management may vary. We report a 41-year-old male presenting with aortic coarctation associated with severe, symptomatic, bicuspid aortic valve lesions and significant left ventricular dysfunction. He underwent open heart surgery for the surgical resolution of these problems. One year after surgery the results are satisfactory with no evidence of postoperative complications and a significant improvement of patient symptoms and left ventricular function.

Resultados clínicos del reemplazo valvular aórtico percutáneo con dispositivo balón expandible MyVal en estenosis aórtica severa de alto riesgo / Clinical results of percutaneous aortic valve replacement using the MyVal prosthesis in patients with severe aortice stenosis and hisgh surgical risk

INTRODUCCIÓN: El dispositivo MyVal balón-expandible (Meril Life Sciences, India) fue recientemente aprobado en Chile y la Unión Europea para uso comercial. El objetivo del presente estudio fue proveer datos de eficacia y seguridad temprana y de mediano plazo en pacientes portadores de estenosis aórtica (EA) severa de alto riesgo quirúrgico sometidos a reemplazo valvular aórtico percutáneo (RVAP) con dispositivo MyVal. MATERIAL Y MÉTODOS: Se enrolaron retrospectivamente todos los pacientes con EA severa sintomática de alto riesgo según criterio del ´heart team´ local, sometidos a RVAP usando prótesis MyVal en Hospital San Borja Arriarán. RESULTADOS: La población quedó compuesta por 14 sujetos tratados entre Octubre 2018 y Noviembre 2019. La población tuvo una edad media de 82,5±7,8 años y elevado perfil de riesgo (puntaje STS promedio 11,6±5,1% de mortalidad a 30 días). Se logró éxito de dispositivo y procedimiento en 12 pacientes (86%) con caída sustancial de la gradiente aórtica media, persistente a 6 meses de seguimiento sin insuficiencia aórtica más que leve. Ocurrió falla de dispositivo en 2 pacientes, una debida a falla de entrega y otra por embolización a ventrículo, esta última con resultado de muerte. En términos de complicaciones, ocurrió una muerte precoz atribuida a disección/ruptura de aorta y 2 hemorragias mayores. La tasa de marcapasos ascendió a 3 pacientes, 23% considerando todos quienes recibieron implante. CONCLUSIÓN: El presente registro cuestiona la seguridad de MyVal en el tratamiento percutáneo de la EA severa de alto riesgo. Sin embargo, una vez logrado un implante exitoso MyVal muestra adecuados parámetros de funcionamiento, persistentes a un plazo mediano de seguimiento.

BACKGROUND: The recently approved balloon expandable MyVal (Meril Life Sciences, India) transcatheter aortic valve replacement (TAVR) prosthesis is available for commercial use in Chile and the European Union. The aim of this study is to provide early and mid-term data on the safety and efficacy of patients with severe aortic stenosis (AS) at high surgical risk undergoing TAVR using the MyVal device. METHODS: All patients with symptomatic severe AS at high surgical risk undergoing intended TAVR with MyVal prosthesis at San Borja-Arriarán Hospital entered to a retrospective registry. RESULTS: Between October 2018 and November 2019, 14 patients entered to the registry. The mean age was 82.5±7.8 years-old with a high-surgical riskprofile (mean STS score of 11.6±5.1% for 30-day mortality). Device and procedural success were achieved in 12 patients (86%) with substantial decrease in the mean aortic gradient, persistent at 6 months follow-up, all with mild or trace aortic regurgitation. Device failure occurred in 2 patients, one due to failed delivery and other due to device embolization into the left ventricle, which resulted in patient death. There were one death attributed aortic dissection/rupture and two major bleeding episodes. Three patients receiving MyVal implant required the implantation of a permanent pacemaker (23%). CONCLUSION: The present registry rises a question upon the safety of the MyVal TAVR device in high-risk AS. However, once a successfully implant was achieved the MyVal prosthesis showed an adequate performance to mid-term follow-up.

The Respiratory Microbiome in Cystic Fibrosis: Compartment Patterns and Clinical Relationships in Early Stage Disease.

We compared the bacterial microbiomes lodged in the bronchial tree, oropharynx and nose of patients with early stage cystic fibrosis (CF) not using chronic antibiotics, determining their relationships with lung function and exacerbation frequency. CF patients were enrolled in a cohort study during stability and were checked regularly over the following 9 months. Upper respiratory samples (sputum [S], oropharyngeal swab [OP] and nasal washing [N]) were collected at the first visit and every 3 months. 16S rRNA gene amplification and sequencing was performed and analyzed with QIIME. Seventeen CF patients were enrolled (16.6 SD 9.6 years). Alpha-diversity of bacterial communities between samples was significantly higher in S than in OP (Shannon index median 4.6 [IQR: 4.1-4.9] vs. 3.7 [IQR: 3-1-4.1], p = 0.003/Chao 1 richness estimator median 97.75 [IQR: 85.1-110.9] vs. 43.9 [IQR: 31.7-59.9], p = 0.003) and beta-diversity analysis also showed significant differences in the microbial composition of both respiratory compartments (Adonis test of Bray Curtis dissimilarity matrix, p = 0.001). Dominant taxa were found at baseline in five patients (29.4%), who showed lower forced expiratory volume in the first second (FEV1%, mean 74.8 [SD 19] vs. 97.2 [SD 17.8], p = 0.035, Student t test). The Staphylococcus genus had low RAs in most samples (median 0.26% [IQR 0.01-0.69%]), but patients with RA > 0.26% of Staphylococcus in bronchial secretions suffered more exacerbations during follow-up (median 2 [IQR 1-2.25] vs. 0 [0-1], p = 0.026. Mann-Whitney U test), due to S. aureus in more than a half of the cases, microorganism that often persists as bronchial colonized in these patients (9/10 [90%] vs. 2/7 [28.6%], p = 0.034, Fisher's exact test). In conclusion, the bronchial microbiome had significantly higher diversity than the microbial flora lodged in the oropharynx in early stage CF. Although the RA of the Staphylococcus genus was low in bronchial secretions and did not reach a dominance pattern, slight overrepresentations of this genus was associated with higher exacerbation frequencies in these patients.

Novel transcatheter therapies for treating tricuspid regurgitation.

Until recently, tricuspid valve (TV) disease has been relatively neglected for a long time, but recently tricuspid regurgitation (TR) has attracted attention. Although the prognosis of patients with these disorders is poor, the high mortality and morbidity associated with TV surgery have resulted in many patients not receiving surgical therapy. Current guidelines recommend that TV surgery should be considered in patients with severe TR who are symptomatic or have progressive right ventricle (RV) dilatation or dysfunction. In the absence of severe RV or left ventricle dysfunction, surgery should be considered in cases of severe pulmonary vascular disease or hypertension; however, it is difficult to assess RV dysfunction. Symptoms of right heart failure are more nonspecific and difficult to diagnose than those of left heart failure. Furthermore, the severity of TR is easily influenced by the use of diuretics. These factors lead to difficulties in patient selection and in determination of optimal timing for surgery. Transcatheter therapies for TR have begun to emerge as an alternative for patients with severe symptomatic TR who are at high-risk for standard surgery. Although initial results from a recent international multicenter registry have demonstrated that transcatheter TV therapy is feasible and safe, its clinical experience is still under development. In the present review, we describe the currently available techniques of transcatheter TV intervention and preliminary clinical results.

Cardioband system as a treatment for functional mitral regurgitation.

INTRODUCTION: Are the current data on the Cardioband in the clinical area enough to consider it a tool for mitral regurgitation treatment? Severe secondary mitral valve insufficiency frequently affects high-risk surgical patients. The Cardioband system is a novel percutaneous surgical-like device for direct annuloplasty. It is implanted into the beating heart by transvenous femoral access, with minimal impact on hemodynamic and cardiac function during implantation. So far, it has demonstrated safety and feasibility in high-risk patients with functional mitral regurgitation; it has imparted significant annular reduction and regurgitation improvements. In well-selected patients, it could be an option for mitral valve repair. AREAS COVERED: This is a bibliographic review based on scientific publications and medical congress reports. It includes the most current information related to Cardioband in mitral regurgitation. EXPERT COMMENTARY: This novel, less-invasive and effective tool is an option for the open repair or replacement of the mitral valve in high-risk surgical patients. Although the current results of Cardioband are promising, more data and longer follow-up times are necessary to confirm its safety and efficacy and to evaluate the durability of the results.

Clinical and Safety Outcomes of Long-Term Azithromycin Therapy in Severe COPD Beyond the First Year of Treatment.

BACKGROUND: Exacerbations of COPD (ECOPD) are a major cause of mortality and morbidity. Continuous cyclic azithromycin (CC-A) reduces the exacerbation rate, but it is unknown whether it remains effective and safe beyond the first year. METHODS: This study was a retrospective analysis of patients with severe COPD (Global Initiative for Chronic Obstructive Lung Disease grade D) with ≥ 4 moderate to severe ECOPD who received CC-A (500 mg three times per week) as add-on therapy. Patients treated over 24 months were considered long-term continuous cyclic azithromycin (LT-CC-A) users, and ECOPD, hospitalizations, and length of hospital stays during the first, second, and third years were compared with the previous 12 months. Microbiologic monitoring, assessment of macrolide resistance, and analysis of side effects were maintained throughout the study period. RESULTS: A total of 109 patients with severe COPD treated with CC-A (39 for ≥ 24 months) comprised the LT-CC-A group (35.8%). This group presented average reductions in ECOPD from baseline of 56.2% at 12 months, 70% at 24 months, and 41% at 36 months, paralleled by respective reductions in hospitalizations of 62.6%, 75.8%, and 39.8%. ECOPD due to common microorganisms fell by 12.5% and 17.3% at 12 and 24 months of LT-CC-A, respectively, with a 50% increase in macrolide resistance. Pseudomonas aeruginosa ECOPD rose by 7.2% and 13.1% at these two time points. CC-A therapy was well tolerated with few side effects: digestive disorders in the short term (7.1%) and hearing loss in the long term (5.1%). CONCLUSIONS: LT-CC-A therapy over a 24- to 36-month period in patients with COPD (Global Initiative for Chronic Obstructive Lung Disease grade D) achieved sustained reductions in ECOPD and hospitalizations of > 50% with few adverse events, although macrolide resistance increased.

Mycobacterium tuberculosis Acquires Limited Genetic Diversity in Prolonged Infections, Reactivations and Transmissions Involving Multiple Hosts.

Background:Mycobacterium tuberculosis (MTB) has limited ability to acquire variability. Analysis of its microevolution might help us to evaluate the pathways followed to acquire greater infective success. Whole-genome sequencing (WGS) in the analysis of the transmission of MTB has elucidated the magnitude of variability in MTB. Analysis of transmission currently depends on the identification of clusters, according to the threshold of variability (<5 SNPs) between isolates. Objective: We evaluated whether the acquisition of variability in MTB, was more frequent in situations which could favor it, namely intrapatient, prolonged infections or reactivations and interpatient transmissions involving multiple sequential hosts. Methods: We used WGS to analyze the accumulation of variability in sequential isolates from prolonged infections or translations from latency to reactivation. We then measured microevolution in transmission clusters with prolonged transmission time, high number of involved cases, simultaneous involvement of latency and active transmission. Results: Intrapatient and interpatient acquisition of variability was limited, within the ranges expected according to the thresholds of variability proposed, even though bursts of variability were observed. Conclusions: The thresholds of variability proposed for MTB seem to be valid in most circumstances, including those theoretically favoring acquisition of variability. Our data point to multifactorial modulation of microevolution, although further studies are necessary to elucidate the factors underlying this modulation.

Molecular epidemiology of community-associated methicillin-resistant Staphylococcus aureus in Spain: 2004-12.

OBJECTIVES: In Spain, despite the high rates of healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA), the incidence of community-associated (CA) MRSA seems to be low on the basis of a small number of studies. We analysed the evolution of CA-MRSA in Spain from 2004 to 2012, and identified the clonal lineages and population structure. METHODS: The study included 8326 MRSA strains. Susceptibility to 18 antimicrobials was determined. Isolates were tested for the presence of mecA, Panton-Valentine leucocidin (PVL) and the arginine catabolic mobile element (ACME) by PCR, and typed by staphylococcal cassette chromosome mec, PFGE, spa, multilocus sequence typing and agr. RESULTS: Among the 8326 isolates, 246 (2.9%) were CA-MRSA. We identified genotypically 226 PVL-positive CA-MRSA isolates (88% agr type I, 10.2% agr type III and 1.8% agr type II) and 20 PVL-negative CA-MRSA isolates (all agr type I) from children and adults (82.1% from wounds) from 13 different geographical areas. A significant increase in the rates of CA-MRSA was observed when comparing 2004-07 (0.43%) with 2008-12 (5.44%). Resistance rates were as follows: only ß-lactams, 84.5%; erythromycin, 12.8%; tetracycline, 8.8%; clindamycin, 4.9%; ciprofloxacin, 3.1%; fusidic acid, 2.0%; others, 0.4%; and multiresistant, 6.2% (six isolates USA300). The strains belonged to the PVL-positive clones ST8-IVc (69.9%), ST8-IVa-ACME-positive (USA300, 8.9%), ST8-IVa-ACME-negative (0.8%), ST30-IVc (4.5%), ST80-IVc (2.0%), ST5-IVc (1.2%) and others (ST59, ST72, ST88, ST642, ST1472 and ST1829; 4.5%) and to the PVL-negative ST398-V (8.1%). CONCLUSIONS: We confirm an increase in CA-MRSA in Spain, the predominance of the ST8-IVc clone, the emergence of the USA300 clone, a high genetic diversity among PVL-positive CA-MRSA isolates and the recent emergence of the pig-associated ST398-V clone.

Abdominal abscess due to NDM-1-producing Klebsiella pneumoniae in Spain.

We describe a clinical case of an abdominal abscess due to NDM-1-producing Klebsiella pneumoniae in a 35-year-old Spanish patient after hospitalization in India for perforated appendicitis and peritonitis. The strain belonged to the MLST type 231 and had multiple additional antibiotic resistance genes such as bla(CTX-M-15), armA methylase, aac(6')-Ib-cr, dfrA12, sul1 and qnrB and lack of porin genes ompK35 and ompK36. The patient was cured after abscess drainage.

Nosocomial outbreak of VIM-1-producing Klebsiella pneumoniae isolates of multilocus sequence type 15: molecular basis, clinical risk factors, and outcome.

We study the epidemiology, molecular basis, clinical risk factors, and outcome involved in the clonal dissemination of VIM-1-producing Klebsiella pneumoniae isolates in the hospital setting. All patients infected/colonized by carbapenem-nonsusceptible K. pneumoniae (CNSKP) in 2009 were included. Molecular epidemiology was studied by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Antibiotic resistance genes were analyzed by PCR and sequencing. Plasmids were studied by PFGE with S1 nuclease digestion and for incompatibility group by a PCR-based replicon typing scheme. Risk factors associated with CNSKP colonization/infection were assessed by an observational case-control study. All 55 patients studied were infected (n = 28) or colonized (n = 27) by VIM-1-producing K. pneumoniae. All but one acquired isolates of a single clone (PFGE cluster 1 [C1], sequence type 15 [ST15]), while another clone (PFGE C2, ST340) was detected in four patients. C1 isolates also produced the new extended-spectrum ß-lactamase SHV-134. bla(VIM-1) was carried in a class 1 integron and an untypeable plasmid of ∼50 bp. The number of days that the patient received mechanical ventilation, the use of parenteral nutrition, previous treatment with linezolid, and treatment with extended-spectrum cephalosporins for more than 7 days were detected to be independent risk factors for CNSKP acquisition. The VIM-1-producing K. pneumoniae ST15 clone has a high capacity to spread among intensive care unit patients with severe underlying conditions. A high rate of associated mortality and great difficulty in controlling the spread of this clone, without permanent behavioral changes in the personnel, were observed.

Extended-spectrum-ß-lactamase-producing Escherichia coli as a cause of pediatric infections: report of a neonatal intensive care unit outbreak due to a CTX-M-14-producing strain.

Little information is available about pediatric infections caused by extended-spectrum-ß-lactamase (ESBL)-producing Escherichia coli. We characterized an outbreak caused by a CTX-M-14-producing E. coli isolate in a neonatal intensive care unit (NICU) and studied other infections caused by ESBL-producing E. coli in non-NICU pediatric units. All children ≤4 years old who were infected or colonized by ESBL-producing E. coli isolates between January 2009 and September 2010 were included. Molecular epidemiology was studied by phylogroup analysis, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing. Antibiotic resistance genes were analyzed by PCR and sequencing. Plasmids were studied by PFGE with S1 nuclease digestion and by incompatibility group analysis using a PCR-based replicon-typing scheme. Of the ESBL-producing E. coli isolates colonizing or infecting the 30 newborns, identical PFGE results were observed for 21 (70%) isolates, which were classified as CTX-M-14-producing E. coli of ST23 phylogroup A. bla(CTX-M-14a) was linked to ISEcp1 and was carried on an ∼80-bp IncK plasmid. A smaller ongoing outbreak due to SHV-12-producing ST131 E. coli was also identified in the same NICU. Fifteen additional infections with ESBL-producing E. coli were identified in non-NICU pediatric units, but none was caused by the CTX-M-14-producing E. coli epidemic clone. Overall, CTX-M-14 (71.1%), CTX-M-15 (13.3%), and SHV-12 (13.3%) were the most important ESBLs causing pediatric infections in this study. Infections of newborns with CTX-M-14-producing E. coli were caused by both clonal and nonclonal isolates.

Significant ecological impact on the progression of fluoroquinolone resistance in Escherichia coli with increased community use of moxifloxacin, levofloxacin and amoxicillin/clavulanic acid.

OBJECTIVES: To determine trends in ciprofloxacin resistance and co-resistance to other antibiotic classes in blood isolates of Escherichia coli, and to investigate if there is an ecological relationship to the community use of fluoroquinolones and other antibiotics. METHODS: Forty-two Spanish hospitals of the European Antimicrobial Resistance Surveillance Network collected ciprofloxacin and other antibiotic susceptibility data for non-duplicate consecutive E. coli isolates from patients with bacteraemia between 2001 and 2009. The nationwide ambulatory use of antibiotics between 1997 and 2008 was determined by WHO methods, and the co-evolution of both parameters was further analysed. RESULTS: Of the 28 307 E. coli blood isolates, 27.9% were ciprofloxacin non-susceptible (CIPNS), increasing from 17.6% in 2001 to 32.7% in 2009. A continuous increase was observed between CIPNS and other resistances, including cephalosporin resistance due to the production of extended-spectrum ß-lactamases (ESBLs) and non-susceptibility to both amoxicillin/clavulanic acid and tobramycin. Although the total use of antibiotics did not increase, community use of levofloxacin, moxifloxacin and amoxicillin/clavulanic acid increased by 307.2%, 62.6% and 70.1%, respectively. Yearly rates of CIPNS E. coli strongly correlated with the use of levofloxacin, moxifloxacin and amoxicillin/clavulanic acid (r(2 )> 0.80; P < 0.005 in all cases). CONCLUSIONS: The rapid increase in CIPNS E. coli causing bacteraemia was closely related to the increase in resistance to amoxicillin/clavulanic acid, production of ESBLs and resistance to aminoglycosides. Community use of fluoroquinolones (mainly moxifloxacin and levofloxacin) and of amoxicillin/clavulanic acid represents a significant driver in the progression of fluoroquinolone resistance in bacteraemic E. coli.

Parallel increase in community use of fosfomycin and resistance to fosfomycin in extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli.

OBJECTIVES: To document fosfomycin susceptibility of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC), analyse trends in fosfomycin use and investigate fosfomycin resistance in ESBL-EC isolated from urinary tract infections (UTIs). METHODS: Twenty-seven Spanish hospitals participating in the European Antimicrobial Resistance Surveillance Network were requested to collect up to 10 sequential ESBL-EC for centralized susceptibility testing and typing. EUCAST guidelines were followed for antibiotic susceptibility testing, and bla(ESBL) type, phylogroups and O25b serotype were determined by PCR and sequencing. In addition, the trend in fosfomycin resistance among ESBL-EC causing UTIs was determined in 9 of the 27 hospitals. Total fosfomycin use for ambulatory care was established by WHO-recommended methods. RESULTS: A total of 231 ESBL-EC (42.4% CTX-M-15, 34.2% SHV-12 and 23.4% CTX-M-14) were collected. The overall rate of fosfomycin resistance was 9.1%, but varied according to ESBL type (5.6% of CTX-M-14 isolates, 5.1% of SHV-12 and 15.3% of CTX-M-15). Of 67 O25b/B2 isolates, 11 (16.4%) were fosfomycin resistant. Predictors of infection with fosfomycin-resistant ESBL-EC were O25b/phylogroup B2 isolates, female gender and nursing home residence. Among 114 197 UTIs caused by E. coli 4740 (4.2%) were due to ESBL-EC. Fosfomycin resistance increased in these isolates from 4.4% (2005) to 11.4% (2009). The use of fosfomycin grew from 0.05 defined daily doses per 1000 inhabitants per day (1997) to 0.22 (2008), a 340% increase. CONCLUSIONS: Key factors related to increased fosfomycin resistance in ESBL-EC causing UTIs could be the rapid growth in community use of fosfomycin, the widespread distribution of the 025b/B2 E. coli clone and the existence of a susceptible population comprising women residing in nursing home facilities.

Comparative in vitro activity of cefditoren and other antimicrobials against Enterobacteriaceae causing community-acquired uncomplicated urinary tract infections in women: a Spanish nationwide multicenter study.

Cefditoren is a third-generation orally administered cephalosporin with a broad spectrum of activity against Gram-positive and Gram-negative bacterial species. After an oral 400-mg single dose, the mean concentrations in urine are 186.5 mg/L at 2 to 4 h and 12.7 mg/L at 8 to 12 h, and it is a potential drug to be used in the treatment of urinary tract infection (UTI). We performed a multicenter nationwide study in Spain in order to determine the in vitro activity of cefditoren and other comparative agents against Enterobacteriaceae causing community-acquired uncomplicated UTI in women. From June 2008 to March 2009, 89 institutions participated in the study. A total of 2152 Enterobacteriaceae were collected and sent to a coordinating laboratory where identification and antimicrobial susceptibility testing was performed against 20 antimicrobials using an automated microdilution method (MicroScan; Siemens, Sacramento, CA). Cefditoren MICs were determined by the broth microdilution method (Clinical and Laboratory Standards Institute guidelines) using the same inoculum. Microorganisms isolated were Escherichia coli (81.8%), Klebsiella pneumoniae (7.9%), Proteus mirabilis (5.2%), and others (5.1%). A total of 51 isolates (2.4%) were extended-spectrum beta-lactamase (ESBL) producers, 3 (0.1%) produced plasmidic AmpC enzymes, and 64 (2.9%) produced chromosomal AmpC. The MIC(50)/MIC(90) (mg/L) of cefditoren against all isolates was 0.12/0.5. Cefditoren inhibited 96.5% of isolates at 1 mg/L and was uniformly active against all isolates with the exception of strains producing ESBLs or AmpC enzymes. The MIC(50)/MIC(90) of other antimicrobials were ampicillin (AMP) >16/>16, amoxicillin/clavulanic acid (A/C) 2, trimethoprim/sulfamethoxazole (SxT) 4/76, and fosfomycin (FOS)

AmpC beta-lactamases in Escherichia coli: emergence of CMY-2-producing virulent phylogroup D isolates belonging mainly to STs 57, 115, 354, 393, and 420, and phylogroup B2 isolates belonging to the international clone O25b-ST131.

Cephalosporins resistance is increasing in Escherichia coli in Spain. We characterize infections by E. coli with reduced susceptibility to third-generation cephalosporins (3GCs) with the AmpC phenotype. Between January 2004 and March 2007, 121 E. coli isolates with the AmpC phenotype were collected (4.8% of all the 2538 E. coli isolates with reduced susceptibility to 3GCs). These isolates were further characterized by clinical and molecular analysis. Plasmid-encoded ampC genes were detected in 46 (38%) isolates (43 CMY-2); 75 isolates (62%) had modifications in the chromosomal ampC promoter region (c-AmpC). CMY-2 producers belonged primarily to the more virulent phylogroup D (48.4%), whereas most isolates of c-AmpC belonged to phylogroup A (56.4%). Bacteremia and infections in children were more frequently produced by CMY-2 producers. CMY-2-producing phylogroup D E. coli belonged to 8 multilocus sequence typing types. Three CMY-2 producers belonged to O25b/ST131/B2 clone. Infections caused by E. coli with the AmpC phenotype may be spreading primarily because of CMY-2-producing phylogroup D isolates, although this enzyme was also detected in the O25b/ST131/B2 clone.