Behavior of the renal kallikrein in spontaneously hypertensive rats: Influence of sexual hormones and aldosterone-sensitive distal nephron ion channels.

The renal kallikrein-kinin system (RKKS) has been related to blood pressure control and sodium and water balance. We have previously shown that female spontaneously hypertensive rats (SHR) have high urinary kallikrein activity (UKa) and lower blood pressure (BP) than males whereas ovariectomy stimulates UKa and diminishes BP. We also showed that high K+ intake and prepuberal gonadectomy (Gx) diminish BP with a concomitant increase in UKa and plasma aldosterone levels. Since kallikrein co-localize in the same distal nephron segments of aldosterone effectors, we explored the effect of pharmacological blockage of aldosterone receptor, epithelial Na+ (ENaC) and the rectifying outer medulla K+ (ROMK) channels in different gonad contexts on the gene expression, renal tissue content and urine release of kallikrein. Klk1 gene expression was determined by real-time PCR and enzymatic activity of kallikrein by the amidolytic method. We found that the inhibition of the aldosterone receptor by spironolactone increases kallikrein renal tissue storage and decreases its urinary activity, especially in Gx rats. Moreover, ENaC blockade by benzamil increases the renal content of kallikrein without affecting synthesis or excretion, especially in females and Gx animals, while the inhibition of ROMK by glibenclamide increases the synthesis and renal content of kallikrein only in intact male animals. We concluded that RKKS regulation showed sexual dimorphism and seemed to be modulated by sex hormones throughout a process involving aldosterone and the aldosterone-sensitive ion channels..

Development of an Intelligent System for the Monitoring and Diagnosis of the Well-Being.

Today, society is more aware of their well-being and health, making wearable devices a new and affordable way to track them continuously. Smartwatches allow access to daily vital physiological measurements, which help people to be aware of their health status. Even though these technologies allow the following of different health conditions, their application in health is still limited to the following physical parameters to allow physicians treatment and diagnosis. This paper presents LM Research, a smart monitoring system mainly composed of a web page, REST APIs, machine learning algorithms, psychological questionnaire, and smartwatches. The system introduces the continuous monitoring of the users' physical and mental indicators to prevent a wellness crisis; the mental indicators and the system's continuous feedback to the user could be, in the future, a tool for medical specialists treating well-being. For this purpose, it collects psychological parameters on smartwatches and mental health data using a psychological questionnaire to develop a supervised machine learning wellness model that predicts the wellness of smartwatch users. The full construction of the database and the technology employed for its development is presented. Moreover, six machine learning algorithms (Decision Tree, Random Forest, Naive Bayes, Neural Networks, Support Vector Machine, and K-nearest neighbor) were applied to the database to test which classifies better the information obtained by the proposed system. In order to integrate this algorithm into LM Research, Random Forest being the one with the higher accuracy of 88%.

[Use of aspirin 100 mg / day to prevent Preeclampsia, in high risk pregnancies, in a cohort from Argentina]. / Utilización de aspirina 100 mg/día para prevenir Preeclampsia, en embarazos de alto riego, en una cohorte de Argentina.

Objectives: The objective of the present study was to analyse the use of 100 g aspirin dose as prevention method for preeclampsia in high risk pregnant patients. Methods: A retrospective cohort study was performed in high risk pregnant patients with a blood pressure protocol, and the use of 100 mg of aspirin vs. its non-use was evaluated in the incidence of PREEC. Estimations between the two groups were performed with and without variable adjustment by means of binary logistic regression models. Results: 633 high risk pregnant patients were evaluated. The average age was 30±7 years old, and 25±8 weeks of pregnancy. 281 women (44.3 %) within this group received aspirin. The total prevalence of PREEC in our sample was 151 pregnant women (23.8 %). Pregnant patients under the aspirin treatment developed less PREEC events (19.2% vs 27.5%, p=0.019); with OR not adjusted 0.62 (IC95% 0.43-0.91 p= 0.017). The risk was similar when it was adjusted by age, preeclampsia history, diabetes mellitus and chronic high blood pressure. (OR adjusted 0.63 IC95% 0.43-0.92 p= 0.017). Conclusions: The use of 100 mg of aspirin a day before the 20th week of pregnancy in high risk pregnant patients decreased the risk of developing PREEC, regardless the age and risk factors.

Objetivos: El objetivo de este estudio fue analizar la utilidad de la dosis de 100 mg de aspirina como medida de prevención para preeclampsia en pacientes embarazadas de alto riesgo. Métodos: Se realizó un estudio de cohorte retrospectivo de embarazadas de alto riesgo en seguimiento con un protocolo de tensión arterial y se evaluó la utilización de aspirina 100 mg vs la no utilización de la misma, en la incidencia de PREEC. Se realizó estimaciones de riesgos entre ambos grupos sin y con ajuste de variables con modelos de regresión logística binaria. Resultados: Fueron evaluadas 633 embarazadas de alto riesgo con promedio de 30±7 años y 25±8 semanas de gestación, de las cuales 281 mujeres (44,3%) recibieron aspirina. La prevalencia total de PREEC en nuestra muestra fue de 151 embarazadas (23,8%). Las embarazadas que estaban ingiriendo aspirina, desarrollaron menos eventos de PREEC (19.2% vs 27.5%, p=0.019); con OR no ajustado 0.62 (IC95% 0.43-0.91 p= 0.017). Siendo este riesgo similar cuando fue ajustado por edad, antecedentes de preeclampsia, diabetes mellitus e hipertensión arterial crónica. (OR ajustado 0.63 IC95% 0.43-0.92 p= 0.017). Conclusiones: La utilización de Aspirina 100 mg por día antes de las 20 semanas de gestación en embarazadas de alto riesgo disminuyó el riesgo de desarrollar PREEC, independientemente de la edad y factores de riesgo.

Analysis of Adherence to Antihypertensive Drug Treatment in an Argentinean Cohort

Abstract Background Adherence to antihypertensive medication is a major challenge in the management of hypertension, and non-adherence is an important barrier to effective management of hypertension. Objectives To determine the adherence rate to hypertensive drug treatment and the factors that influence non-adherence in a cohort of the Argentinean population. Methods A multicenter cross-sectional study was conducted in eight cities of Argentina. Consecutive hypertensive patients seen in general practice offices, receiving pharmacological treatment for at least six months were included. Blood pressure measurements were performed by physicians during the patient visit. The level of adherence was assessed using the Morisky questionnaire, and patients were divided into non-adherent and adherent. Continuous variables were compared using independent t-test. Categorical variables were compared using the χ2 test. To identify the variables independently associated with non-adherence, a forward stepwise binary regression logistic model was performed, and the results expressed as odds ratio (OR) with 95% of confidence interval. All tests were two-tailed, and p-values < 0.05 were considered statistically significant. Results A total of 852 individuals (52% women, 62 ± 13 years) were included. The main reason for lack of adherence was forgetfulness of medication intake and errors in the time of intake (~ 40% in both). Individuals with more cardiovascular risk factors (smoking, diabetes, dyslipidemia and previous cardiovascular events) had lower adherence to antihypertensive treatment, and considerably younger (~ five years younger). Conclusions Adherence rate to antihypertensive drug treatment in our study group was higher than the one reported in previous studies, and the main reason for non-adherence was forgetfulness of medication intake. (Int J Cardiovasc Sci. 2020; 33(3):272-277)

Clonal spread of Klebsiella pneumonia producing OXA-1 betalactamase in a Spanish hospital

Multi-drug resistant Klebsiella pneumoniae isolates are associated with nosocomial infections, in which colonized patients act as a reservoir and source of cross-infection for other patients. In this study, the antimicrobial susceptibility of K. pneumoniae was tested by microdilution using the commercial method MicroScan (Siemens). The genetic relatedness of K. pneumoniae strains was determined by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). PCR experiments were carried out to obtain primer sets and positive PCR products were purified and sequenced. From May 2007 until December 2009, 98 clonally related K. pneumoniae isolates were detected from clinical samples of 38 patients admitted to the University Hospital of Bellvitge, Barcelona, Spain, including 27 admitted to the intensive care unit (ICU). The most important sources of the isolates were: lower respiratory tract (n = 12), urine (n = 12), and blood (n = 11). The strains were resistant to amoxicillin/clavulanic acid, piperacillin/tazobactam, tobramycin, amikacin, and ciprofloxacin, and had diminished susceptibility to cefepime. All the isolates shared a common PFGE pattern related to sequence type 14 after MLST analysis. In K. pneumoniae isolates and their transconjugants, the bla(OXA-1) gene was located in the variable region of a class I integron that also contains the aac(6')Ib-cr gene. Sequencing of the quinolone resistance determinant regions of gyrA and parC revealed a S83F change in GyrA and no changes in ParC (AU)

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Prevalence and molecular characterization of methicillin-resistant Staphylococcus aureus ST398 resistant to tetracycline at a Spanish hospital over 12 years.

Methicillin-resistant Staphylococcus aureus (MRSA) ST398, associated with livestock animals, was described in 2003 as a new lineage infecting or colonizing humans. We evaluated the prevalence and molecular characteristics of MRSA ST398 isolated in the Hospital Universitari de Bellvitge from January 2000 to June 2011. Tetracycline resistant (Tet-R) MRSA isolates from single patients (pts) were screened by SmaI-pulsed field gel electrophoresis (PFGE). Nontypable MRSA strains by SmaI (NT Sma I)-MRSA were further analysed by ApaI-PFGE, spa, SCCmec, agr, MLST typing, and by DNA microarray hybridization. Among 164 pts harboring Tet-R MRSA, NT Sma I-MRSA ST398-agrI was found in 33 pts (20%). Although the first pt was detected in 2003, 22/33 pts (67%) were registered in the 2010-2011 period. Ten pts (30%) were infected and cancer was the most frequent underlying disease. In one case, death was due to MRSA-ST398-related infection. Five pulsotypes (A-E) were detected using ApaI-PFGE, with type A accounting for 76% of the strains. The majority of the studied isolates presented spa type t011 (70%) and SCCmec type V (88%). One strain was spa negative both by PCR and microarray analysis. Forty-nine percent of the studied isolates showed resistance to 3 or more antibiotic classes, in addition to beta-lactams. Ciprofloxacin resistance was 67%. Tet-R was mediated by tet(M) and tet(K) in 26 isolates. All isolates lacked Panton-Valentine Leukocidin production, as well as other significant toxins. This study displays the molecular features of MRSA-ST398 clone and shows the increase in tetracycline resistance together with arise in MRSA-ST398 isolates infecting or colonizing patients in our clinical setting.

Low prevalence of Cfr-mediated linezolid resistance among methicillin-resistant Staphylococcus aureus in a Spanish hospital: case report on linezolid resistance acquired during linezolid therapy.

Linezolid is an effective antimicrobial agent to treat methicillin-resistant Staphylococcus aureus (MRSA). Resistance to linezolid due to the cfr gene is described worldwide. The present study aimed to analyze the prevalence of the cfr-mediated linezolid resistance among MRSA clinical isolates in our area. A very low prevalence of cfr mediated linezolid resistance was found: only one bacteremic isolate out of 2 215 screened isolates. The only linezolid resistant isolate arose in a patient, previously colonized by MRSA, following linezolid therapy. Despite the low rate of resistance in our area, ongoing surveillance is advisable to avoid the spread of linezolid resistance.

Clonal spread of Klebsiella pneumoniae producing OXA-1 betalactamase in a Spanish hospital.

Multi-drug resistant Klebsiella pneumoniae isolates are associated with nosocomial infections, in which colonized patients act as a reservoir and source of cross-infection for other patients. In this study, the antimicrobial susceptibility of K. pneumoniae was tested by microdilution using the commercial method MicroScan (Siemens). The genetic relatedness of K. pneumoniae strains was determined by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). PCR experiments were carried out to obtain primer sets and positive PCR products were purified and sequenced. From May 2007 until December 2009, 98 clonally related K. pneumoniae isolates were detected from clinical samples of 38 patients admitted to the University Hospital of Bellvitge, Barcelona, Spain, including 27 admitted to the intensive care unit (ICU). The most important sources of the isolates were: lower respiratory tract (n = 12), urine (n = 12), and blood (n = 11). The strains were resistant to amoxicillin/clavulanic acid, piperacillin/tazobactam, tobramycin, amikacin, and ciprofloxacin, and had diminished susceptibility to cefepime. All the isolates shared a common PFGE pattern related to sequence type 14 after MLST analysis. In K. pneumoniae isolates and their transconjugants, the bla(OXA-1) gene was located in the variable region of a class I integron that also contains the aac(6')Ib-cr gene. Sequencing of the quinolone resistance determinant regions of gyrA and parC revealed a S83F change in GyrA and no changes in ParC.

Direct detection of Mycobacterium tuberculosis complex in clinical samples by a molecular method based on GenoQuick technology.

Several molecular systems for direct detection of Mycobacterium tuberculosis complex (MTBC) have recently been developed. The GenoQuick MTB assay (GQ-MTB) used in this study detected 82 of the 96 (85.4%) samples with MTBC, including 50 of 64 (78.1%) samples with negative acid-fast bacillus smears. Fifteen samples containing nontuberculous mycobacteria were also studied: 13 were GQ-MTB negative, one was positive, and one was indeterminate. GQ-MTB showed good effectiveness for the direct detection of MTBC from clinical samples.

Effectiveness of an integrated real-time PCR method for detection of the Mycobacterium tuberculosis complex in smear-negative extrapulmonary samples in an area of low tuberculosis prevalence.

Early extrapulmonary tuberculosis (EPTB) diagnosis is particularly difficult. Among 108 smear-negative extrapulmonary samples showing a positive culture for Mycobacterium tuberculosis complex (43 body fluids and 65 nonliquid specimens), 63 (58.3%) were positive with the Xpert MTB/RIF assay (GX). GX sensitivity was quite low for samples from sterile locations (especially for pleural fluids: 26.9%) but high for some nonliquid samples, like abscess aspirates (76.5%). In summary, GX may be a useful tool to be considered for EPTB diagnosis.

Characterization of invasive Pneumococci of serogroup 6 from adults in Barcelona, Spain, in 1994 to 2008.

A total of 91 of 1,480 invasive isolates (6.1%) collected from adults in Barcelona, Spain, in the period of 1994 to 2008 were of serogroup 6 (6B, 47 isolates; 6A, 28; and 6C, 16). Throughout this period, serotype 6B (Spain(6B)-ST90) decreased, and serotype 6A remained stable. An increase in serotype 6C (ST224) in the 2004-2008 period was observed.

Serotypes and genotypes of Streptococcus pneumoniae causing pneumonia and acute exacerbations in patients with chronic obstructive pulmonary disease.

OBJECTIVES: This study aimed to compare the antibiotic susceptibilities, serotypes and genotypes of pneumococci causing pneumonia or acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in patients with COPD. METHODS: A total of 611 pneumococci collected from 487 COPD patients with pneumonia (n = 255, 94 bacteraemic pneumonia) or AECOPD episodes (n = 356), from 2001 to 2008, were analysed. Antibiotic susceptibility was studied by microdilution. Serotypes (PCR or Quellung) and genotypes (PFGE and multilocus sequence typing) were determined. RESULTS: Pneumococci isolated from AECOPD episodes were significantly more resistant to co-trimoxazole and chloramphenicol than those isolated from pneumonia episodes (39.0% versus 29.7% and 13.8% versus 8.2%, respectively, P < 0.05). Comparing serotypes of isolates causing bacteraemic pneumonia, non-bacteraemic pneumonia and AECOPD, serotypes 4, 5 and 8 were associated with bacteraemic pneumonia (P < 0.05), serotypes 1 and 3 were associated with bacteraemic and non-bacteraemic pneumonia (P < 0.05) and serotypes 16F and 11A and non-typeable pneumococci were associated with AECOPD episodes (P < 0.05). The genotypes related to serotypes 3 (Netherlands(3)-ST180 and ST260(3)), 1 (Sweden(1)-ST306), 5 (Colombia(5)-ST289) and 8 (Netherlands(8)-ST53) were isolated more frequently in pneumonia episodes (P < 0.05), whereas genotype ST30(16F) (serotype 16F) was more frequently recovered from AECOPD episodes. CONCLUSIONS: In our experience, serotype 3 pneumococci (Netherlands(3)-ST180 and ST260(3) genotypes) commonly cause pneumonia and acute exacerbations in COPD patients. Pneumococci of serotypes 1 (Sweden(1)-ST306), 4 (ST247(4)), 5 (Colombia(5)-ST289) and 8 (Netherlands(8)-ST53) were more often associated with pneumonia. Non-typeable pneumococci may play an important role in acute exacerbations.

Rapid detection of Mycobacterium tuberculosis complex and rifampin resistance in smear-negative clinical samples by use of an integrated real-time PCR method.

Sixty-four of 85 (75.3%) smear-negative respiratory (n = 78) and nonrespiratory (n = 7) samples with positive cultures of Mycobacterium tuberculosis complex (MTC) were detected by the GeneXpert system using the Xpert MTB/RIF assay (GX). In addition, GX found rpoB mutations in all six of the rifampin-resistant strains detected. The test was negative in 20 culture-negative and 20 nontuberculous culture-positive samples (100% specificity). GX offers high potential for the diagnosis of tuberculosis due to its capacity for direct detection of MTC, its rapidity, and its simplicity.

Molecular characterization of resistance to Rifampicin in an emerging hospital-associated Methicillin-resistant Staphylococcus aureus clone ST228, Spain.

BACKGROUND: Methicillin-resistant S. aureus (MRSA) has been endemic in Hospital Universitari de Bellvitge, Barcelona, since 1990. During the 1990-95 period the Iberian clone (ST-247; SCCmec-I) was dominant. Isolates of clonal complex 5 (ST-125; SCCmec-IV) gradually replaced the Iberian clone from 1996 to 2003. A new multiresistant MRSA phenotype showing rifampicin resistance emerged in 2004 and rapidly increased from 25% in 2004 to 45% in 2006. The aims of this study were i) the molecular characterisation of rifampicin resistant MRSA isolates, ii) the study of the rifampicin resistance expression by disk diffusion, microdilution and E-test, and iii) the analysis of the rpoB gene mutations involved in rifampicin resistance. RESULTS: A sample of representative 108 rifampicin-resistant MRSA isolates belonged to a single PFGE genotype, ST-228, SCCmec type I and spa type t041. Of 108 isolates, 104 (96%) had a low-level rifampicin resistance (MICs, 2 to 4 mg/L) and 4 a high-level rifampicin resistance (MICs, 128 - > or = 256 mg/L). Disk diffusion and E-test methods failed to identify a low-level rifampicin resistance in 20 and 12 isolates, respectively. A low-level rifampicin resistance was associated with amino acid substitution 481His/Asn in the beta-subunit of RNA polymerase. Isolates with a high-level rifampicin resistance carried additional mutations in the rpoB gene. CONCLUSIONS: The emergence of MRSA clone ST228-SCCmecI, related to the Southern Germany clone, involved a therapeutical challenge for treating serious MRSA infections. Decreased susceptibility to rifampicin in MRSA strains of ST228-SCCmecI was associated with one or two specific mutations in the rpoB gene. One fifth of isolates with low-level rifampicin-resistance were missed by the diffusion methods.

Molecular characterization of macrolide- and multidrug-resistant Streptococcus pyogenes isolated from adult patients in Barcelona, Spain (1993-2008).

OBJECTIVES: The increase in erythromycin resistance among Streptococcus pyogenes isolates is a cause for concern. We analysed trends in macrolide resistance, phenotypes, genotypes, resistance determinants and transposons among erythromycin-resistant S. pyogenes isolates collected from adults in a Barcelona hospital (1993-2008). METHODS: Antibiotic susceptibility was studied by microdilution. Molecular typing was performed by PFGE, emm typing and multilocus sequence typing (MLST). Macrolide resistance genes and those related to the Tn916 family of transposons were detected by PCR. RESULTS: Ninety-nine (18.3%) of 541 isolates were erythromycin resistant. Erythromycin resistance rates progressively increased from 0% (0/24) in 1993-1994 to 34.2% (50/146, P < 0.001) in 2001-2004, then falling to 7.4% (8/108, P = 0.02) in 2007-2008. Sixty-six erythromycin-resistant isolates were available for molecular studies. Of these, 26 had an M phenotype [mef(A)] and 40 had an MLS(B) phenotype [erm(B), n = 33; and erm(TR), n = 7]. Among M-phenotype isolates, the most frequent genotypes (88.5%) were emm4-ST39, emm6-ST382 and emm75-ST49, whereas genotypes emm11-ST403, emm28-ST52 and emm25-ST350 accounted for 72.5% of MLS(B)-phenotype isolates. Twenty-five isolates harboured both erm(B) and tet(M) genes related to the Tn916 family of transposons, Tn6002 being the most frequent. Ten isolates (10.1%) were ciprofloxacin non-susceptible, related to the emm6-ST382 clone with a ParC S79A change. CONCLUSIONS: The peak of macrolide resistance rates among S. pyogenes observed in the 2001-2004 period was associated with an increase in the MLS(B) phenotype caused by the spread of emm11-ST403 and emm28-ST52 clones harbouring transposons of the Tn916 family. However, erythromycin resistance rates decreased significantly in the 2007-2008 period.

Serotype and genotype replacement among macrolide-resistant invasive Pneumococci in adults: mechanisms of resistance and association with different transposons.

The aim of this study was to analyze trends in adult invasive pneumococcal disease (IPD) due to macrolide-resistant strains and to study the evolution of serotypes, genotypes, and macrolide-resistant determinants of strains collected in a prospective study between 1999 and 2007 in Barcelona, Spain. IPD due to macrolide-resistant strains of serotypes included in the 7-valent conjugate vaccine (PCV7) decreased from 2.16/100,000 (pre-PCV7 period, 1999 to 2001) to 0.80/100,000 (late-PCV7 period, 2005 to 2007) (P = 0.001), whereas IPD due to macrolide-resistant strains of non-PCV7 serotypes increased from 1.08/100,000 to 2.83/100,000 (P < 0.001). These changes were related to a fall of clones of PCV7 serotypes (ST81 [P < 0.05], ST90, ST315, and ST17) and an increase in new clones of serotypes 19A and 24F (ST230) and 33F (ST717) in the late-PCV7 period. The most common phenotype was MLS(B) (90.9%), related to the erm(B) gene. The frequent association between MLS(B) phenotype and tetracycline resistance [tet(M) gene], was related to transposons of the Tn916-family such as Tn6002 or Tn3872. In conclusion, overall adult IPD rates due to macrolide-resistant pneumococci stabilized between 1999 and 2007 in Barcelona. The decrease in macrolide-resistant PCV7 pneumococci was balanced by the increase in macrolide-resistant non-PCV7 pneumococci.

Diversity of pneumococcal surface protein A (PspA) among prevalent clones in Spain.

BACKGROUND: PspA is recognized as a major pneumococcal virulence factor and a possible vaccine candidate. The aim of this study was to analyze the PspA family and clade distribution among 112 Spanish pneumococci representatives of dominant clones among patients with invasive disease (n = 66) and nasopharyngeal healthy carriage in children (n = 46). RESULTS: PspA family 2 was predominant among invasive (63.6%) and carriage (54.3%) pneumococcal isolates. No PspA family 3 isolates were detected and only one strain was PspA negative. Although four clonal complexes contained strains of different clades, a clear association between clade and multi locus sequence typing results was found. Clades 1, 3 and 4 were associated with a wide variety of sequence types (ST) related to multiresistant and antibiotic-susceptible worldwide-disseminated clones. Clade 1 was associated with Spain 6B-ST90, Spain 14-ST18, Colombia 5-ST289, Sweden 1-ST306, Denmark 14-ST230 and Sweden 1-ST304 clones. Clade 3 was associated with Spain 23F-ST81, Spain 9V-ST156, Tennessee 14-ST67, Netherlands 3-ST180 and Netherlands 7F-ST191 clones. Clade 4 was related to Sweden 15A-ST63, Netherlands 18C-ST113 and Greece 21-ST193 clones. In contrast, PspA clade was not related to serotype, age or clinical origin of the isolates. CONCLUSION: PspA clades were associated with genotypes. PspA family 2 and family 1 were dominant among major Spanish pneumococcal clones isolated from patients with invasive disease and nasopharyngeal carriage in children.

Epidemiology of invasive pneumococcal disease among adult patients in barcelona before and after pediatric 7-valent pneumococcal conjugate vaccine introduction, 1997-2007.

BACKGROUND: A dramatic decrease in the incidence of invasive pneumococcal disease (IPD) was observed among children and adults in the United States after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). Little is known about the incidence of IPD after PCV7 licensure in Europe. The objective of this study was to examine changes in the prevalence of IPD among adults in the PCV7 era. METHODS: We undertook a prospective study involving adults with IPD who required hospital admission in the southern area of Barcelona, Spain. Three periods were studied: the pre-PCV7 period (1997-2001), the early PCV7 period (2002-2004), and the late PCV7 period (2005-2007). RESULTS: A total of 1007 episodes of IPD were observed. Rates of IPD among adults increased from 13.9 to 14.6 episodes per 100,000 population between the pre-PCV7 period and the early PCV7 period (P = .6) and then to 19.55 episodes per 100,000 population in the late PCV7 period (P < .001). The rates of IPD among adults due to non-PCV7 serotypes increased from 8.4 to 9.7 episodes per 100,000 population between the pre-PCV7 period and the early PCV7 period (P = .15) and then to 15.3 episodes per 100,000 population in the late PCV7 period (P < .001); IPD due to PCV7 serotypes decreased from 5.6 to 4.9 episodes per 100,000 population between the pre-PCV7 period and the early PCV7 period (P = .3), then to 4.3 episodes per 100,000 population in the late PCV7 period (P = .056). Among people aged > or = 65 years, IPD due to PCV7 serotypes decreased from 19.5 to 14.6 episodes per 100,000 population between the pre-PCV7 period and the early PCV7 period (P = .13), then to 12.3 episodes per 100,000 population in the late PCV7 period (P = .02). A decrease in the prevalence of antibioticresistant pneumococci in the late PCV7 period was associated with a decrease in the prevalence of multidrugresistant PCV7 clones (Spain(23F)-ST81, Spain(6B)-ST90, and ST88(19F)) and an increase in the prevalence of non-PCV7 antibiotic-susceptible clones (ST306(1), ST191(7F), ST989(12F), and ST433(22F)). CONCLUSIONS: Rates of IPD among adults increased in Barcelona in the late PCV7 period, coinciding with a clonal expansion of non-PCV7 serotypes. In contrast, rates of IPD caused by PCV7 serotypes decreased among people aged > or = 65 years, which suggests the development of a herd immunity.