Streptococcus pneumoniae carriage, serotypes, genotypes, and antimicrobial resistance trends among children in Portugal, after introduction of PCV13 in National Immunization Program: A cross-sectional study.

Streptococcus pneumoniae carriage studies are crucial to monitor changes induced by use of pneumococcal conjugate vaccines and inform vaccination policies. In this cross-sectional study, we examined changes within the pneumococcal population following introduction of PCV13 in 2015 in the National Immunization Program (NIP), in Portugal. In 2018-2020 (NIP-PCV13), we obtained 1450 nasopharyngeal samples from children ≤6 years attending day-care. We assessed serotypes, antimicrobial resistance, and genotypes (MLST and GPSC) and compared findings with earlier periods: 2009-2010 (pre-PCV13), 2011-2012 (early-PCV13), and 2015-2016 (late-PCV13). Pneumococcal carriage prevalence remained stable at 60.2 %. Carriage of PCV13 serotypes was 10.7 %, markedly reduced compared to pre-PCV13 period (47.6 %). The most prevalent PCV13 serotypes were 19F, 3, and 19A all showing a significant decreasing trend compared to the pre-PCV13 period (from 7.1 % to 4.7 %, 10.1 % to 1.8 %, and 14.1 % to 1.8 %, respectively), a notable observation given the described limited effectiveness of PCV13 against serotype 3. Non-vaccinated children and children aged 4-6 years were more likely to carry PCV13 serotypes (2.5-fold, 95 %CI [1.1-5.6], and 2.9-fold, 95 %CI [1.3-6.8], respectively). The most prevalent non-PCV13 serotypes were 15B/C, 11A, 23B, 23A, and NT, collectively accounting for 51.9 % of all isolates. In total, 30.5 % of all pneumococci were potentially covered by PCV20. Resistance to penicillin (low-level) and macrolides increased significantly, from 9.3 % and 13.4 %, respectively, in the late-PCV13 period, to approximately 20 % each, mostly due to lineages expressing non-PCV13 serotypes, nearing pre-PCV13 levels. An expansion of lineages traditionally associated with PCV13 serotypes, like CC156-GPSC6 (serotype 14) and CC193-GPSC11 (serotype 19F), but now predominantly expressing non-PCV13 serotypes (11A, 15B/C, and 24F for GPSC6; and 15A and 21 for GPSC11) was noted. These findings indicate that the pneumococcal population is adapting to the pressures conferred by PCV13 and antimicrobial use and indicate the need to maintain close surveillance.

Clonal Changes in the Pneumococcal Population Carried by Portuguese Children during Six Years of Private Use of the 13-Valent Pneumococcal Conjugate Vaccine: the Relative Contribution of Clonal Expansion, Clonal Emergence, and Capsular Switch Events.

In Portugal, the 13-valent pneumococcal conjugate vaccine (PCV13) was available for private use from 2010 to 2015 and it was introduced in the National Immunization Program in 2015. We have reported that private use of PCV13 led to extensive serotype replacement and an increase in antimicrobial susceptibility among pneumococci carried by healthy children. We investigated which clonal changes concurred with these observations. A total of 657 pneumococcal strains, representative of a collection of 2,615 isolates, were genotyped by multilocus sequence typing (MLST). The isolates were recovered in 2009 to 2010 (pre-PCV13), 2011 to 2012 (early PCV13), and 2015 to 2016 (late PCV13) from children attending day care centers in two regions of Portugal (one urban, one rural). One-hundred seventy-one sequence types (STs) were identified, corresponding to 18 clonal complexes (CCs) and 58 singletons. Most CCs (n = 17) and several singletons (n = 16) were found in both regions, indicating that they were geographically disseminated. Clonal complexes expressing PCV13 serotypes in circulation in the late PCV13 period were a subset of the ones identified in the pre-PCV13 period and were often associated with antimicrobial resistance. Among those, the most frequent in both regions was CC179, a multidrug-resistant clone of serotype 19F. Serotype replacement, following PCV13 use, was mainly due to expansion of the susceptible lineages expressing non-PCV13 serotypes already in circulation in the pre-PCV13 period. The emergence of ST53, associated with serotype 8, a major cause of disease in several European countries, was observed in the rural region. Potential capsular switching events, unrelated to PCV13 use, were detected. This study improves our understanding of changes triggered by the private use of PCV13 in Portugal. IMPORTANCE Streptococcus pneumoniae (pneumococcus) is a major human respiratory pathogen linked with high morbidity, mortality, and health care-associated costs worldwide. This bacterium often colonizes asymptomatically healthy children. Colonization is a prerequisite for disease and is also essential for transmission between individuals. The 13-valent pneumococcal conjugate vaccine targets 13 of 101 capsular types of pneumococci described to date. This vaccine not only prevents pneumococcal disease but also impacts colonization by decreasing the carriage of vaccine serotypes. Consequently, serotype replacement occurs. The clonal changes occurring during serotype replacement may be due to various mechanisms, such as clonal expansion, emergence, extinction, or capsular switch (vaccine escape). This study shows that in Portugal, the use of PCV13 has led to significant changes in clonal composition and that these were mainly due to the clonal expansion of lineages expressing serotypes not included in the vaccine.

Patients' Characterization, Pattern of Medication Use, and Factors Associated with Polypharmacy: A Cross-Sectional Study Focused on Eight Units of the Portuguese National Network for Long-Term Integrated Care.

The Portuguese National Network for Long-term Integrated Care (RNCCI) comprises several Units for Integrated Continuous Care (UCCIs) that provide medical, nursing, and rehabilitation care. This study aimed to evaluate the demographic and medical characteristics of patients admitted to the RNCCI, their patterns of medication use, and factors associated with polypharmacy. An observational, retrospective, cross-sectional, multicenter study was performed. This study population consisted of 180 patients. Polypharmacy status was divided into two groups: non-polypharmacy (taking ≤ 4 drugs) and polypharmacy (taking ≥ 5 drugs). Bivariate analysis and multivariate logistic regression analysis were used to determine the influence of predictor factors such as demographic and medical characteristics on the polypharmacy status during the UCCI stays. This study population (mean age of 78.4 ± 12.3 years, range 23-102 years, 59% female) was prescribed a median of 8 medications. Approximately 89.4% of the patients were taking ≥ 5 drugs, demonstrating that polypharmacy is highly prevalent in Portuguese RNCCI residents of the eight UCCIs studied. A subsequent analysis with multivariate logistic regression found that polypharmacy status was significantly associated with the unit of internment (facility) when compared to facility E with H and with the Charlson Comorbidity Index (CCI). The high prevalence of polypharmacy and the associated factors show that it is urgent to improve pharmacotherapy regimens through periodic monitoring and review of patients' therapeutic lists, an area in which pharmacists play a very important role.

Haemophilus influenzae Carriage among Healthy Children in Portugal, 2015-2019.

Haemophilus influenzae is an important cause of mucosal and invasive infections and a common colonizer of the upper respiratory tract. As there are no recent data on H. influenzae carriage in Portugal, we aimed to characterize carriage samples and investigate possible parallelisms with disease isolates. Between 2016-2019, 1524 nasopharyngeal samples were obtained from children (0-6 years) attending day-care. H. influenzae were serotyped and screened for ß-lactamase production. Strains producing ß-lactamase and/or those that were encapsulated were further characterized by antibiotype; encapsulated strains were also investigated for MLST and the presence of antimicrobial resistance and virulence genes (extracted from whole genome sequencing). The overall carriage rate was 84.1%. Most isolates (96.7%) were nonencapsulated. Encapsulated strains were of serotypes f (1.8%), e (1.1%), a (0.3%), and b (0.1%). MLST showed clonality within serotypes. Although the lineages were the same as those that were described among disease isolates, colonization isolates had fewer virulence determinants. Overall, 7.5% of the isolates were ß-lactamase positive; one isolate had blaTEM-82, which has not been previously described in H. influenzae. A single isolate, which was identified as H. parainfluenzae, had an incomplete f-like cap locus. In conclusion, circulation of serotype b is residual. The few encapsulated strains are genetically related to disease-causing isolates. Thus, surveillance of H. influenzae carriage should be maintained.

Potentially Inappropriate Medications and Potential Prescribing Omissions in Elderly Patients Receiving Post-Acute and Long-Term Care: Application of Screening Tool of Older People's Prescriptions/Screening Tool to Alert to Right Treatment Criteria.

Background: Screening Tool of Older People's Prescriptions (STOPP) and Screening Tool to Alert to Right Treatment (START) criteria have been used to detect potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs). These criteria were applied to geriatric Portuguese patients receiving post-acute and long-term care to assess the prevalence and predictors of PIMs and PPOs. Methods: An observational, retrospective, cross-sectional and multicenter study was performed in 161 patients (aged ≥65 years) from eight Units for Integrated Continuous Care. Results: In these studied patients (mean age: 81.6, 64% female, median number of medications: 9) PIMs were detected in 85.1% and PPOs in 81.4% of patients. While PIMs mainly involved the central nervous system and psychotropic drugs (66.5%), PPOs were mostly related to musculoskeletal system (55.3%) and cardiovascular (39.8%) system. A subsequent analysis with logistic regression found the female gender, the hospital provenience, and the number of medications as predictors of PIMs. Predictors of PPOs were the Charlson Comorbidity Index and history of recent fractures. Conclusion: PIMs and PPOs were highly prevalent in the studied patients receiving post-acute and long-term care in Units for Integrated Continuous Care. Therefore, STOPP/START criteria might be an effective tool for improving prescribing quality and clinical outcomes in these frail elderly patients.

Impact of private use of the 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal carriage among Portuguese children living in urban and rural regions.

In Portugal, the 13-valent pneumococcal conjugate vaccine (PCV13) was commercially available between 2010 and 2015, following a decade of private use of PCV7. We evaluated changes on serotype distribution and antimicrobial susceptibility of pneumococci carried by children living in two regions of Portugal (one urban and one rural). Three epidemiological periods were defined: pre-PCV13 (2009-2010), early-PCV13 (2011-2012), and late-PCV13 (2015-2016). Nasopharyngeal samples (n = 4,232) were obtained from children 0-6 years old attending day-care centers. Private use of PCVs was very high in both regions (>75%). Pneumococcal carriage remained stable and high over time (62.1%, 62.4% and 61.6% (p = 0.909) in the urban region; and 59.8%, 62.8%, 59.5% (p = 0.543) in the rural region). Carriage of PCV7 serotypes remained low (5.3%, 7.8% and 4.3% in the urban region; and 2.5%, 3.7% and 4.8% in the rural region). Carriage of PCV13 serotypes not targeted by PCV7 decreased in both the urban (16.4%, 7.3%, and 1.6%; p < 0.001) and rural regions (13.2%, 7.8%, and 1.9%; p < 0.001). This decline was mostly attributable to serotype 19A (14.1%, 4.4% and 1.3% in the urban region; and 11.1%, 3.6% and 0.8% in the rural region, both p < 0.001). Serotype 3 declined over time in the urban region (10.1%, 4.4%, 0.8%; p < 0.001) and had no obvious trend in the rural region (4.2%, 6.7%, 2.4%; p = 0.505). Serotype 6C decreased in both regions while serotypes 11D, 15A/B/C, 16F, 21, 22F, 23A/B, 24F, 35F, and NT were the most prevalent in the late-PCV13 period. Intermediate resistance to penicillin and non-susceptibility to erythromycin decreased significantly in both regions (19.5%, 13.3%, and 9.3%; and 25.4%, 25.9%, and 13.4%; both p < 0.001, respectively in the urban region; and 12.4%, 11.1%, and 2.8% (p < 0.001); and 15.3%, 14.7%, and 9.2% (p = 0.037), respectively, in the rural region). In conclusion, private use of PCV13 led to significant changes on the pneumococcal population carried by children in Portugal.