A historical perspective of MDR invasive pneumococcal disease in Spanish adults.

OBJECTIVES: To analyse the clonal dynamics and clinical characteristics of adult invasive pneumococcal disease (IPD) caused by MDR and penicillin-non-susceptible (PNS) pneumococci in Spain. METHODS: All adult IPD episodes were prospectively collected (1994-2018). Streptococcus pneumoniae isolates were serotyped, genotyped and tested for antimicrobial susceptibility. Changes in the incidence of IPD were analysed and risk factors contributing to MDR were assessed by logistic regression. RESULTS: Of 2095 IPD episodes, 635 (30.3%) were caused by MDR/PNS isolates. Over the study period, the incidence of MDR/PNS-IPD decreased (IRR 0.70; 95% CI 0.53-0.93) whereas that of susceptible isolates remained stable (IRR 0.96; 95% CI 0.80-1.16). A reduction of resistance rates to penicillin (-19.5%; 95% CI -37% to 2%) and cefotaxime (-44.5%; 95% CI -64% to -15%) was observed. Two clones, Spain9V-ST156 and Denmark14-ST230, accounted for 50% of current resistant disease. Among current MDR/PNS isolates, 45.8% expressed serotypes not covered by the upcoming PCV15/PCV20 vaccines. MDR/PNS episodes were associated with older patients with comorbidities, nosocomial acquisition and higher 30 day mortality. MDR/PNS pneumococci were not independently associated with 30 day mortality in multivariate analysis [OR 0.826 (0.648-1.054)]. CONCLUSIONS: Our study shows an overall reduction of MDR/PNS isolates in adults after the introduction of pneumococcal conjugate vaccines. However, a significant proportion of current resistant isolates are not covered by any of the upcoming PCV15/PCV20 vaccines. The burden of resistant disease is related to older patients with underlying conditions and caused by two major clones. Our data show that MDR is not a statistically significant factor related to increased mortality.

Evolution of the ß-lactam-resistant Streptococcus pneumoniae PMEN3 clone over a 30 year period in Barcelona, Spain.

Objectives: To analyse the epidemiology and genetic evolution of PMEN3 (Spain9V-156), a penicillin-non-susceptible clone of Streptococcus pneumoniae, causing invasive pneumococcal disease (IPD) in Barcelona during 1987-2016. Methods: WGS was performed on 46 representative isolates and the data were used to design additional molecular typing methods including partial MLST, PCR-RFLP and detection of surface-exposed proteins and prophages, to assign the remaining isolates to lineages. The isolates were also subjected to antimicrobial susceptibility testing. Results: Two hundred and twenty-seven adult cases of IPD caused by PMEN3 were identified. PMEN3 caused mainly pneumonia (84%) and the 30 day mortality rate was 23.1%. Evidence of recombination events was found, mostly in three regions, namely the capsular operon (associated with capsular switching) and adjacent regions containing pbp2x and pbp1a, the murM gene and the pbp2b-ddl region. Some of these genetic changes generated successful new variant serotype lineages, including one of serotype 11A that is not included in the current PCV13 vaccine. Other genetic changes led to increased MICs of ß-lactams. Notably, most isolates also harboured prophages coding for PblB-like proteins. Despite these adaptations, the ability of this clone to cause IPD remained unchanged over time, highlighting the importance of its core genetic background. Conclusions: Our study demonstrated successful adaptation of PMEN3 to persist over time despite the introduction of broader antibiotics and conjugate vaccines. In addition to enhancing understanding of the molecular evolution of PMEN3, these findings highlight the need for the development of non-serotype-based vaccines to fight pneumococcal infection.

Endocarditis associated with vertebral osteomyelitis and septic arthritis of the axial skeleton.

PURPOSE: The relationship between infective endocarditis (IE) and osteoarticular infections (OAIs) are not well known. We aimed to study the characteristics of patients with IE and OAIs, and the interactions between these two infections. METHODS: An observational study (1993-2014) which includes two cohorts: (1) patients with IE (n = 607) and (2) patients with bacteremic OAIs (n = 458; septic arthritis of peripheral and axial skeleton, and vertebral and peripheral osteomyelitis). These two cohorts were prospectively collected, and we retrospectively reviewed the clinical and microbiological variables. RESULTS: There were 70 cases of IE with concomitant OAIs, representing 11.5% of IE cases and 15% of bacteremic OAI cases. Among cases with IE, the associated OAIs mainly involved the axial skeleton (n = 54, 77%): 43 were vertebral osteomyelitis (61%), mainly caused by "less virulent" bacteria (viridans and bovis streptococci, enterococci, and coagulase-negative staphylococci), and 15 were septic arthritis of the axial skeleton (21%), which were mainly caused by Staphylococcus aureus. OAIs with involvement of the axial skeleton were associated with IE (adjusted OR = 2.2; 95% CI 1.1-4.3) independently of age, sex, and microorganisms. CONCLUSIONS: Among patients with IE, the associated OAIs mainly involve the axial skeleton. Transesophageal echocardiography should be carefully considered in patients presenting with these bacteremic OAIs.

Invasive pneumococcal disease rates linked to meteorological factors and respiratory virus circulation (Catalonia, 2006-2012).

BACKGROUND: To study the impact of meteorological data and respiratory viral infections on invasive pneumococcal disease (IPD) rates. METHODS: We analysed all notifications of IPD and respiratory viral infections to the Microbiological Reporting System of Catalonia (2006-2012). Correlations between rates of IPD and viral infections (influenza virus, respiratory syncytial virus [RSV] and adenovirus), and meteorological variables (temperature, humidity, hours of sunshine, wind speed and number of days with rainfall) were assessed using Spearman's correlation coefficient and negative binomial regression models. RESULTS: We found significant correlations between monthly rates of IPD and monthly rates of all respiratory viruses and meteorological factors. However, after multiple regression analysis, associations remained between IPD rates and influenza rates and reductions in temperature in the total population, and between IPD rates and adenovirus rates in children aged <5 years. When models were repeated for the total population using data from the preceding month, IPD rates increased when RSV was circulating and when the temperature was lower. In children aged <5 years, RSV circulation was associated with increased IPD rates. CONCLUSIONS: IPD rates were linked to increased activity of some respiratory viruses and reductions in temperature. Preventive measures, including influenza vaccination, may help reduce IPD.

Evolution of invasive pneumococcal disease by serotype 3 in adults: a Spanish three-decade retrospective study.

Background: Invasive pneumococcal disease due to serotype 3 (S3-IPD) is associated with high mortality rates and long-term adverse effects. The introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into the Spanish paediatric immunisation programme has not led to a decrease in the adult S3-IPD. We aimed to analyse the incidence, clinical characteristics and genomics of S3-IPD in adults in Spain. Methods: Adult IPD episodes hospitalized in a Southern Barcelona hospital were prospectively collected (1994-2020). For genomic comparison, S3-IPD isolates from six Spanish hospitals (2008-2020) and historical isolates (1989-1993) were analysed by WGS (Illumina and/or MinION). Findings: From 1994 to 2020, 270 S3-IPD episodes were detected. When comparing pre-PCV (1994-2001) and late-PCV13 (2016-2020) periods, only modest changes in S3-IPD were observed (from 1.58 to 1.28 episodes per 100,000 inhabitants year). In this period, the incidence of the two main lineages shifted from 0.38 to 0.67 (CC180-GPSC12) and from 1.18 to 0.55 (CC260-GPSC83). The overall 30-day mortality remained high (24.1%), though a decrease was observed between the pre-PCV (32.4%; 95.0% CI, 22.0-45.0) and the late-PCV13 period (16.7%; 95.0% CI, 7.5-32.0) (p = 0.06). At the same time, comorbidities increased from 77.3% (95.0% CI, 65.0-86.0) to 85.7% (95.0% CI, 71.0-94.0) (p = 0.69). There were no differences in clinical characteristics or 30-day mortality between the two S3 lineages. Although both lineages were genetically homogeneous, the CC180-GPSC12 lineage presented a higher SNP density, a more open pan-genome, and a major presence of prophages and mobile genetic elements carrying resistance genes. Interpretation: Adult S3-IPD remained stable in our area over the study period despite PCV13 introduction in children. However, a clonal shift was observed. The decrease in mortality rates and the increase in comorbidities suggest a change in clinical management and overall population characteristics. The low genetic variability and absence of clinical differences between lineages highlight the role of the S3 capsule in the disease severity. Funding: This study has been funded by Instituto de Salud Carlos III (ISCIII) "PI18/00339", "PI21/01000", "INT22/00096", "FI22/00279", CIBER "CIBERES-CB06/06/0037", "CIBERINFEC-CB21/13/00009" and MSD grant "IISP 60168".

Serotype 5 pneumococci causing invasive pneumococcal disease outbreaks in Barcelona, Spain (1997 to 2011).

In this study, we analyzed the clinical and molecular epidemiology of invasive serotype 5 (Ser5) pneumococcal isolates in four teaching hospitals in the Barcelona, Spain, area (from 1997 to 2011). Among 5,093 invasive pneumococcal isolates collected, 134 (2.6%) Ser5 isolates were detected. Although the overall incidence of Ser5-related invasive pneumococcal disease (IPD) was low (0.25 cases/100,000 inhabitants), three incidence peaks were detected: 0.63/100,000 in 1999, 1.15/100,000 in 2005, and 0.37/100,000 in 2009. The rates of Ser5 IPD were higher among young adults (18 to 64 years old) and older adults (>64 years old) in the first two peaks, whereas they were higher among children in 2009. The majority (88.8%) of the patients presented with pneumonia. Comorbid conditions were present in young adults (47.6%) and older adults (78.7%), the most common comorbid conditions being chronic obstructive pulmonary disease (20.6% and 38.3%, respectively) and cardiovascular diseases (11.1% and 38.3%, respectively). The mortality rates were higher among older adults (8.5%). All Ser5 pneumococci tested were fully susceptible to penicillin, cefotaxime, erythromycin, and ciprofloxacin. The resistance rates were 48.5% for co-trimoxazole, 6.7% for chloramphenicol, and 6% for tetracycline. Two major related sequence types (STs), ST1223 (n = 65) and ST289 (n = 61), were detected. The Colombia(5)-ST289 clone was responsible for all the cases in the Ser5 outbreak in 1999, whereas the ST1223 clone accounted for 73.8% and 61.5% of the isolates in 2005 and 2009, respectively. Ser5 pneumococci are a frequent cause of IPD outbreaks in the community and involve children and adults with or without comorbidities. The implementation of the new pneumococcal conjugated vaccines (PCV10 and PCV13) might prevent such outbreaks.

Species and biotypes of Streptococcus bovis causing infective endocarditis.

INTRODUCTION: Streptococcus bovis/equinus complex (SBEC) is a major cause of infective endocarditis (IE), although its incidence varies greatly depending on the geographical area. The characteristics of IE caused by Streptococcus gallolyticus susp. gallolyticus are well known; there are hardly any descriptions of IE caused by other species or biotypes. METHODS: Retrospective cohort study, from 1990 to 2019, of all SBEC IE in adults in three Spanish hospitals, Lugo (LH), Barcelona (BH) and Ferrol (FH) where the population is mainly rural, urban and mixed, respectively. The incidence of IE was analyzed in 3 areas. Clinical characteristics of IE (277 cases, 258 biotyped) were compared according to SBEC species and biotypes. RESULTS: There are significant differences between the incidence of SBEC IE in HL (27.9/106) vs. HF and HB (8.8 and 7,1, respectively, p<0.001). We found significant differences (SbI vs. SbII) in mean age (68.5 vs. 73 years; p<0.01), duration of symptoms before diagnosis (46.9±46.5 vs. 30.4±40.9 days; p<0.01), presence of comorbidities: 39.1% (78) vs. 54.2% (32; p<0.04), predisposing heart illness:62.3% (124) vs. 81.3% (48; p<0.006), particularly, prosthetic or intravascular devices IE: 24.6% (49) vs. 52.4% (31; p<0.001), bi-valve involvement:23.6% (47) vs. 11.8% (7; p<0.05) and heart failure: 24.6% (49) vs. 38.9% (23; p<0.03). There were no significant differences in embolic events, need for surgery or mortality. The association with CRC was high in both groups: 77.7% vs. 66.6%. CONCLUSIONS: IE due to SBEC has geographical variations in incidence and different clinical characteristics among biotypes. The association with CRC was high.

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.

DNA bacterial load in children and adolescents with pneumococcal pneumonia and empyema.

The purpose of this investigation was to evaluate a rapid quantitative real-time polymerase chain reaction (PCR) for the direct detection and quantification of pneumococcal DNA bacterial load (DBL) in patients with pneumonia and empyema. DBL and molecular serotype detection was determined by DNA quantification of the pneumolysin (ply) gene and an additional capsular gene by real-time PCR. Plasma or pleural fluid samples from children and adolescents with confirmed pneumococcal pneumonia were analyzed. DBL was correlated with clinical parameters and outcomes. One hundred and sixty-nine patients with pneumococcal pneumonia (145 empyema) had bacterial cultures and real-time PCR assays performed. Among them, 41 (24.3%) had positive results for both, 4 (2.4%) had positive culture alone, and 124 (73.3%) had positive real-time PCR alone. The pleural fluid DBL was lower in patients with prior antibiotics (p = 0.01) and higher in patients with positive culture (p < 0.001). The pleural fluid DBL was positively correlated with serum C-reactive protein (p = 0.009), pleural fluid neutrophils (p < 0.001), and pleural fluid glucose (p < 0.001). The plasma and pleural fluid DBL were higher in patients with ≥8 days of hospital stay (p = 0.002), and the pleural fluid DBL was positively correlated with the number of hours of pleural drainage (p < 0.001). Quantification of pneumococcal DBL by real-time PCR may be helpful for the diagnosis and clinical management of pediatric patients with pneumonia and empyema.

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.

Influence of pneumococcal vaccine on the incidence of empyema.

PURPOSE OF REVIEW: The aim of this review is to highlight recent reports (2009) concerning empyema and the heptavalent pneumococcal conjugate vaccine. RECENT FINDINGS: Streptococcus pneumoniae remains the most common cause of complicated pneumonia worldwide. Moreover, the incidence of empyema is increasing in many parts of the world and nonvaccine pneumococcal serotypes have been related with this increase. The introduction of heptavalent pneumococcal conjugate vaccine has been associated with the replacement phenomenon in the nasopharynx. Replacement implies that nonvaccine serotypes acquire an ecological advantage for colonizing the nasopharynx and, consequently, increase the carriage status and, in a second step, the disease. Pneumonia with or without empyema has been the main clinical presentation related with the emergence of nonvaccine serotypes. The replacement phenomenon could be multifactorial because other factors apart from heptavalent pneumococcal conjugate vaccine can also contribute to this event. SUMMARY: A new generation of conjugate vaccines that include new serotypes and a wider spectrum of coverage, and the protein-based vaccines that may prevent invasion and preserve colonization, should help us to achieve a positive long-term impact of pneumococcal vaccination.

Prevalence and prognostic implications of dysphagia in elderly patients with pneumonia.

BACKGROUND: oropharyngeal dysphagia is a common condition among the elderly but not systematically explored. OBJECTIVE: to assess the prevalence and the prognostic significance of oropharyngeal dysphagia among elderly patients with pneumonia. DESIGN: a prospective cohort study. SETTING: an acute geriatric unit in a general hospital. SUBJECTS: a total of 134 elderly patients (>70 years) consecutively admitted with pneumonia. METHODS: clinical bedside assessment of oropharyngeal dysphagia and aspiration with the water swallow test were performed. Demographic and clinical data, Barthel Index, Mini Nutritional Assessment, Charlson Comorbidity Index, Fine's Pneumonia Severity Index and mortality at 30 days and 1 year after admission were registered. RESULTS: of the 134 patients, 53% were over 84 years and 55% presented clinical signs of oropharyngeal dysphagia; the mean Barthel score was 61 points indicating a frail population. Patients with dysphagia were older, showed lower functional status, higher prevalence of malnutrition and comorbidities and higher Fine's pneumonia severity scores. They had a higher mortality at 30 days (22.9% vs. 8.3%, P = 0.033) and at 1 year of follow-up (55.4% vs. 26.7%, P = 0.001). CONCLUSIONS: oropharyngeal dysphagia is a highly prevalent clinical finding in elderly patients with pneumonia and is an indicator of disease severity in older patients with pneumonia.

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.

Trends in mortality and antibiotic resistance among HIV-infected patients with invasive pneumococcal disease.

OBJECTIVES: The aim of the study was to describe trends and risk factors for mortality and changes in antibiotic resistance, serotypes and clones among HIV-infected patients with invasive pneumococcal disease (IPD). METHODS: A prospective study of 199 episodes of IPD occurring in a cohort of 4011 HIV-infected patients was carried out. Predictors of mortality included clinical and microbiological data. The 7-valent pneumococcal conjugate vaccine (PCV7) for children was introduced in late 2001. Time periods were classified for mortality studies as pre- (1986-1996), early (1997-2001) and late (2002-2007) highly active antiretroviral therapy (HAART) era, and for serotype studies as pre-PCV7 (1986-2001) and PCV7 (2002-2007) era. RESULTS: Of 199 IPD episodes, 71 (36%) occurred in HIV-infected patients with associated comorbidities (mainly liver cirrhosis; 52 of 71), which increased in recent years. The incidence of IPD decreased from the pre-HAART era to the early HAART era and then remained stable in the late HAART era (24.1, 8.4 and 7.4 episodes per 1000 patient-years, respectively). Rates of 30-day mortality have risen over the three periods (8, 19 and 25%, respectively; P = 0.017). In multiple logistic regression analysis, predictors of mortality were shock at presentation [odds ratio (OR) 7.01; 95% confidence interval (CI) 2.05-23.87] and associated comorbidities (OR 4.27; 95% CI 1.53-11.92). In the PCV7 era, IPD caused by non-PCV7 serotypes increased, and resistance to betalactams decreased. The most frequent genotypes were Spain(9V)-ST156, Spain(23F)-ST81, ST88(19F), Sweden(1)-ST304 and Spain(6B)-ST90. CONCLUSIONS: In the late HAART era, the incidence of IPD has not significantly decreased. Mortality from IPD has risen in association with an increase in comorbidities such as liver cirrhosis. New vaccination strategies are needed to diminish the burden of IPD in the HIV-infected population.

Indirect effects of paediatric conjugate vaccines on invasive pneumococcal disease in older adults.

OBJECTIVES: The aim of this study was to assess the indirect effect of paediatric 13-valent pneumococcal conjugate vaccine (PCV13) vaccination on people ≥65 years of age with invasive pneumococcal disease (IPD) in Catalonia and to determine factors predictive of mortality. METHODS: During 2014-2016, 1285 IPD cases were reported to the Public Health Agency of Catalonia. The indirect effect of paediatric PCV13 vaccination was calculated by comparing the incidence rate (IR) in 2016 (PCV13 year) with that in 2009 (pre-PCV13). Predictors of mortality were determined using multivariate logistic regression. RESULTS: Comparing 2016 and 2009, IPD decreased by 19% (IR 40.1 and 32.5 per 100 000 person-years, respectively). PCV13 serotypes decreased by 57% (IR 23.7 and 10.1), while non-PCV13 serotypes increased by 36% (IR 16.4 and 22.4). During 2014-2016, the mortality rate was 17.5%, and mortality was associated with age ≥85 years (adjusted odds ratio (aOR) 2.91, 95% confidence interval (CI) 1.89, 4.48), meningitis (aOR 2.29, 95% CI 1.25, 4.19), non-focal bacteraemia (aOR 3.73, 95% CI 2.00, 6.94), and ≥1 high-risk condition (aOR 1.89, 95% CI 1.08, 3.32). PPV23non13 serotypes were associated with lower mortality than PCV13 serotypes (aOR 0.54, 95% CI 0.34, 0.86). CONCLUSIONS: The incidence of IPD in people ≥65 years of age decreased after the introduction of paediatric PCV13, and this was due to a reduction in PCV13 serotypes, although an increase in non-PCV13 serotypes was observed. Mortality was associated with age, meningitis, non-focal bacteraemia, ≥1 high-risk condition, and PCV13 serotypes.

Emergence of invasive pneumococcal disease caused by nonvaccine serotypes in the era of 7-valent conjugate vaccine.

BACKGROUND: Little is known about the epidemiology of invasive pneumococcal disease (IPD) after the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in Spain and other European countries. METHODS: We performed a 10-year prospective study including all children with culture-proven IPD admitted to Sant Joan de Deu Hospital, a children's center in the southern area of Barcelona, Catalonia, Spain. PCV7 was introduced in June 2001, and the current estimate of PCV7 coverage is 45%-50%. RESULTS: Comparing the prevaccine period (1997-2001) with the vaccine period (2002-2006), among children aged <2 years, the rate of IPD increased from 32.4 episodes per 100,000 population to 51.3 episodes per 100,000 population (an increase of 58%; 95% confidence interval, 2%-145%), and among children aged 2-4 years, the rate increased from 11.3 episodes per 100,000 population to 26.5 episodes per 100,000 population (an increase of 135%; 95% confidence interval, 31%-320%). At clinical presentation, the rate of pneumonia and/or empyema among children aged <5 years increased from 3.6 episodes per 100,000 population to 15.1 episodes per 100,000 population (an increase of 320%; 95% confidence interval, 98%-790%). These increased rates of IPD were caused by non-PCV7 serotypes, which represented 38% and 72% of infecting serotypes in the prevaccine and vaccine periods, respectively (P=.001). Penicillin resistance decreased from 48% in the prevaccine period to 27% in the vaccine period (P=.005). In the vaccine period, there was an emergence of previously established virulent clones of non-PCV7 serotypes 1 and 5. There was also an increase in the prevalence of serotypes 19A and 6A expressed with different clonal types, including Spain(23F)-1 and Spain(6B)-2. CONCLUSIONS: Since the introduction of PCV7 for children, there has been an emergence of IPD caused by virulent clones of non-PCV7 serotypes that has been associated with significant clinical changes and a decrease in antibiotic resistance.

Functional status as a risk factor for mortality in very elderly patients with pneumonia.

BACKGROUND AND OBJECTIVE: The most commonly used prognostic mortality indexes for pneumonia take into account several variables including comorbidities, physical examination results, and laboratory test results, as well as age. Other factors such as functional status are not included. The objective of this study was to know whether the preadmission functional status was related to 30-day mortality in old or very old patients who were hospitalized for pneumonia. PATIENTS AND METHOD: This was a prospective study including all patients who were hospitalized for pneumonia in the Acute Geriatric Unit of Hospital de Mataró, Barcelona. We calculated the Pneumonia Severity Index (PSI), preadmission and admission Barthel Index (BI), Charlson Comorbidity Index and Mini Nutritional Assessment (MNA). Patients were assessed during hospitalisation and until death or 30 days after admission. RESULTS: We studied 117 patients, 69 (59%) were men. The mean age (standard deviation) was 84.7 (6.5) years. The 30-day mortality was 16.2%. The PSI score was 134.2 (31.8) on admission, and the BI scores on preadmission and admission were 60.3 (35.8) and 37.1 (33.5), respectively. In a multiple logistic regression model, using all variables statistically significant in the univariate analysis, those independently associated with 30-day mortality were: preadmission BI lower than 60 points (odds ratio = 4.89; 95% confidence interval, 1.27-18.9) and lymphopenia (odds ratio = 7.11; 95% confidence interval, 1.7-30.2). CONCLUSIONS: In very old patients who were hospitalized for pneumonia, preadmission functional status was an independent predictor of mortality. Functional status should be included in the severity indices of pneumonia in this population.

Analysis of mortality in a cohort of 650 cases of bacteremic osteoarticular infections.

OBJECTIVES: The mortality of patients with bacteremic osteoarticular infections (B-OAIs) is poorly understood. Whether certain types of OAIs carry higher mortality or interventions like surgical debridement can improve prognosis, are unclarified questions. METHODS: Retrospective analysis of a prospective cohort of patients with B-OAIs treated at a teaching hospital in Barcelona (1985-2014), analyzing mortality (30-day case-fatality rate). B-OAIs were categorized as peripheral septic arthritis or other OAIs. Factors influencing mortality were analyzed using logistic regression models. The association of surgical debridement with mortality in patients with peripheral septic arthritis was evaluated with a multivariate logistic regression model and a propensity score matching analysis. RESULTS: Among 650 cases of B-OAIs, mortality was 12.2% (41.8% of deaths within 7 days). Compared with other B-OAI, cases of peripheral septic arthritis were associated with higher mortality (18.6% vs 8.3%, p < 0.001). In a multiple logistic regression model, peripheral septic arthritis was an independent predictor of mortality (adjusted odds ratio [OR] 2.12; 95% CI: 1.22-3.69; p = 0.008). Cases with peripheral septic arthritis managed with surgical debridement had lower mortality than those managed without surgery (14.7% vs 33.3%; p = 0.003). Surgical debridement was associated with reduced mortality after adjusting for covariates (adjusted OR 0.23; 95% CI: 0.09-0.57; p = 0.002) and in the propensity score matching analysis (OR 0.81; 95% CI: 0.68-0.96; p = 0.014). CONCLUSIONS: Among patients with B-OAIs, mortality was greater in those with peripheral septic arthritis. Surgical debridement was associated with decreased mortality in cases of peripheral septic arthritis.

The changing epidemiology of invasive pneumococcal disease after PCV13 vaccination in a country with intermediate vaccination coverage.

BACKGROUND: We studied the impact of 13-valent pneumococcal conjugate vaccine (PCV13) on the incidence of invasive pneumococcal disease (IPD) and serotype distribution in a region with intermediate levels of vaccination (around 64% in children aged <2 years). METHODS: Surveillance data on IPD cases reported by microbiologists participating in the Microbiological Reporting System of Catalonia during 2006-2014 were analysed. We compared estimated incidence rate (IR) ratios for serotypes included in PCV7, PCV10non7, PCV13non10 and non-PCV13 between the PCV7 (2006-2009) and PCV13 periods (2010-2014). IR were corrected for missing serotypes according to year and age groups: <2 years, 2-4 years, 5-64 years and ≥65 years. RESULTS: A total of 9338 IPD cases were reported. Overall IPD incidence declined by 26.2% (from 16.4 to 12.1) in the PCV13 period. The largest decrease was observed in children aged 2-4 years (44.5%, from 37.4 to 20.8). Pneumonia fell in all age groups with the largest reduction in children aged 2-4 years (49.3%) and <2 years (42%). PCV13 serotypes decreased significantly in all age groups, from 52% (31.6 to 15.1) in children aged 2-4 years to 35% (22.8 to 14.8) in adults aged ≥65 years. Non-PCV13 serotypes rose by 13% (14.8 to 16.8) in people aged ≥65 years. CONCLUSIONS: In a region with intermediate vaccination coverage, the introduction of PCV13 has reduced the overall incidence of IPD, mainly due to the decrease in PCV13 serotypes in all age groups, suggesting herd immunity. Non-PCV13 serotypes have increased in adults aged ≥65 years, suggesting serotype replacement. Higher PCV13 vaccination coverage in children will further reduce IPD incidence in all age groups.