Cícero Armídio Gomes Dias

Background: Carbapenemase-producing Enterobacterales (CPE) colonization is rising globally, yet data on pediatric patients and the risk of progression to infection remain scarce. This study identified clinical/microbiologic profiles and risk factors for progression to infection in colonized children. Methods: This retrospective cohort study included children colonized by CPE at a tertiary pediatric hospital in Brazil (August 2019–December 2024). Colonization was defined as a CPE-positive rectal swab without clinical signs of infection, while infection was defined as illness caused by the bacteria. Demographic, clinical and microbiologic data were evaluated over a 12-month postcolonization follow-up. Cox proportional hazard models assessed the association between risk factors and the time to CPE infection. Results: We included 521 CPE colonization episodes in 466 patients (82% with comorbidities; median age 8.8 months [interquartile range: 2.6–64.6]). Klebsiella pneumoniae predominated. Isolates produced Klebsiella pneumoniae carbapenemase (KPC) (56.9%), New Delhi metallo-β-lactamase (31.3%) or both (11.6%). Progression to infection by the same carbapenemase type occurred in 55 patients (11.8%). Independent risk factors were age 6 months or under (hazard ratio [HR]: 2.19, 95% confidence interval [CI]: 1.27–3.79), KPC colonization (HR: 2.00, 95% CI: 1.05–3.81), preexisting liver disease (HR: 2.67, 95% CI: 1.03–6.92) and respiratory disease (HR: 1.95, 95% CI: 1.07–3.57) and the presence of invasive devices (HR: 2.15, 95% CI: 1.16–3.98). Infection-related mortality was 10.9%. Conclusions: CPE colonization is an emerging threat in vulnerable pediatric populations. Progression to infection is primarily driven by KPC production, chronic comorbidities and invasive devices.

Background: Mozambique introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in 2013 using a three-dose primary series with no booster dose (3p+0) and later switched to the PCV13 using a schedule of two primary doses with one booster (2p+1). We aimed to describe the burden and serotype distribution of pneumococcal meningitis in children under 5 years of age in Mozambique over an eleven-year period starting with the year of PCV10 introduction, and assess the impact of the PCV vaccine and schedule changes. Methods: We analysed meningitis surveillance data in Mozambique from March 2013 through to December 2023. Cerebrospinal fluid (CSF) samples were collected from eligible children in three referral hospitals (Maputo Central Hospital [south], Beira Central Hospital [central], and Nampula Central Hospital [north]). Culture and polymerase chain reaction assay (qPCR) were performed on each sample. S. pneumoniae-positive samples were subsequently serotyped using multiplex assay. We estimated annual incidence rates for pneumococcal meningitis in children under 5 years old following the PCVs’ introduction (2013–2023). The impact of the product switch and schedule change from PCV10/3p+0 to PCV13/2p+1 on the burden and serotype distribution of pneumococcal meningitis was assessed. Results: Of the 4075 CSF samples tested, 7.4% (301/4075) were positive for S. pneumoniae, 2.5% (103/4075) for H. influenzae, and 1.0% (42/4075) for N. meningitidis. Pneumococcal meningitis incidence in children under five reduced from 44.7 cases per 100,000 in 2013 to 4.6 cases per 100,000 in 2023, an 89.7% reduction. In the PCV13/2p+1 period (2020–2023), pneumococcal meningitis incidence was 51.2% lower than the PCV10/3p+0 period (2013–2017) (IRR 0.49, 95% CI 0.4–0.6; p < 0.001). PCV10-serotype pneumococcal meningitis incidence among children under five decreased by 65.6% in the PCV13/2p+1 period (IRR 0.34, 95% CI 0.2–0.6; p < 0.001). We detected zero cases of pneumococcal meningitis due to the PCV13-serotype in 2020–2023, whereas non-PCV10/13-serotypes increased by 76% (IRR 1.76, 95% CI 1.2–2.6; p = 0.004). The case–fatality proportion decreased by 71.9% (95% CI 62.9–84.8%) in the PCV13/2p+1 period. Conclusions: Since the introduction of PCVs in Mozambique, the burden of pneumococcal meningitis and deaths in children under 5 years of age has substantially decreased, as well as the prevalence of PCV13-serotypes. Higher valency PCVs are needed due to the increased prevalence of non-PCV10/13-serotypes. Funding: Gavi, The Vaccine Alliance, reference number: MOZ-HSS-2-INS; WHO Reference: 2014405143-0, creation DFC to support HIB & Surveillance System.

Background In Mozambique, the introduction of a 13-valent pneumococcal conjugate vaccine (PCV13) using a two plus one schedule began in September 2019. However, the replacement of serotypes with non-PCV types remains a concern worldwide following widespread vaccination. We aim to describe the epidemiology of non-PCV13 types among children under 5 years of age with pneumococcal meningitis four years after PCV13 introduction in Mozambique. Methods Between January 2020 and December 2023, a total of 2,014 cerebrospinal fluid (CSF) samples were collected from eligible children as part of the meningitis surveillance system in Mozambique, 103 (5.1%) of which tested positive for S. pneumoniae after triplex qPCR. Among these, 86 (83.5%) samples met the quality criteria for serotyping and were subsequently analysed using sequential quadriplex qPCR. Results Among children under 2 years of age, 84.8% of the S. pneumoniae- positive samples belonged to non-PCV13 serotypes, with serotype 15B/C (31.0%) being the most prevalent, followed by 12F/12A/12B/44/46 (12.1%), 38B (10.6%), and 8 (7.6%). Serotypes 15B/C, 12F/12A/12B/44/46, 38, 8, and 1 were predominant in the northern region of the country (Nampula), whereas serotypes 15B/C and 12F/12A/12B/44/46 were most common in the central region (Sofala). The serotypes coverage of the PCV13, PCV15 and PCV20 vaccine formulations were 20.0%, 26.3% and 75.8%, respectively. Conclusion PCV13 vaccines save many lives in Mozambique. However, they do not seem to be adequate in addresing some of the highly prevailing non-PCV13 serotypes (15B/C and 12F/12A/12B/44/46). Therefore, we suggest that the country's National Immunization Technical Advisory Group (NITAG) review new data and advice on switching to extended valency vaccines such as PCV20.

Background: Streptococcus pneumoniae is considered one of the main agents for pneumonia, meningitis, bacteremia, sinusitis, and acute otitis media (AOM)especially in children under 5 years, and a cause for morbidity and mortality due to respiratory infections worldwide. Our aim was to investigate the influence of Streptococcus pneumoniae colonization in vaccinated children regarding infections in a one-year follow-up. Methods: A double-blind, observational, prospective cohort study was conducted on children aged 18–59 months, vaccinated with pneumococcal conjugate vaccine 10 (PCV10) or pneumococcal conjugate vaccine 13 (PCV13). A total of 225 children were monitored, with different dates of entry into the study, which occurred between March 2018 and October 2019 (zero time). At the end of one year, counting from the date of entry, interviews and data collection took place in medical records (end of follow-up). The Poisson regression with robust variance and Chi-squared or Fisher’s exact tests were used for qualitative analyses; Mann-Whitney or Friedman tests for quantitative analyses. Results: A high colonization rate (64.4%) was observed, with only 2.8% of carriers having a PCV10 vaccine serotype, specifically 6B, as expected. Being male showed association to colonization (p = 0.05). We found that children colonized by pneumococcus do not have an increased risk for respiratory diseases or antimicrobial use. Exception was only observed in cases of serotype 6B colonization, showing association with pneumonia in children under 2 years (p = 0.016). Conclusion: Our study reveals that the carriage of Streptococcus pneumoniae does not appear to significantly impact the incidence of respiratory diseases in a fully-vaccinated children population. However, it is noteworthy that a correlation was observed in the occurrence of pneumonia in children under the age of 2 when colonized by serotype 6B.

Introduction: Colonization and infections caused by Carbapenemase Producing Enterobacteria (CPE) are a global problem, being associated with an increase in hospitalization time, costs for health services, and morbidity and mortality rates. Oncologic patients represent a group of special interest and there are few studies involving CPE colonization among these patients. Aim: to investigate factors associated with colonization in cancer patients. Outlining: Case-control study developed in a tertiary reference hospital in cancer treatment in Porto Alegre, Brazil, from January to December 2017. The population consisted of patients diagnosed with cancer in clinical or surgical hospitalization. Results: The univariate analysis showed that variables associated with colonization by CPE were age, male sex, tumors with bone type of surgical hospitalization, number of intra-hospital transfers since hospitalization, hospitalization time >30 days, ICU hospitalization in the last 30 days, ICU time more than 15 days, surgical procedure in the last 30 days, use of antibiotics in the last 30 days, presence of tumor wound, and KPC infection. After multivariate analysis, male sex, external hospital as origin, hospital stay longer than 30 days, antibiotic use in the last 30 days, and presence of tumor wound, remained associated with EPC colonization. Use of aminoglycosides, and linezolide were associated with CPE colonization. Implications: We identified variables associated with CPE colonization in oncologic patients. Our results may indicate actions to prevent CPE colonization and consequent development of infections.

This study aimed to evaluate the epidemiology and 30-day mortality of adult patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. We retrospectively reviewed the demographic and clinical data of adult patients with S. aureus bloodstream infections (BSI), admitted to a tertiary public teaching medical center in Porto Alegre, Southern Brazil, from January 2014 to December 2019. A total of 928 patients with S. aureus BSI were identified in the study period (68.5 per 100,000 patient-years), and the proportion of MRSA isolates was 22% (19–27%). Thus, 199 patients were included in the analyses. The median age was 62 (IQR: 51–74) years, Charlson Comorbidity Index (CCI) median was 5 (IQR: 3–6), the Pitt bacteremia score (PBS) median was 1 (IQR: 1–4), and the most common site of infection was skin and soft tissue (26%). Most infections were hospital-acquired (54%), empirical anti-MRSA treatment was initiated in 34% of the cases, and in 44% vancomycin minimum inhibitory concentration was 1.5mg/L or above. Sixty-two (31.2%) patients died up to 30 days after the bacteremia episode. Patients with more comorbid conditions (higher CCI; aOR 1.222, p = 0.006) and a more severe presentation (higher PBS; aOR 1.726, pS. aureus bacteremia. Empiric treatment with an anti-MRSA drug was a protective factor. No significant variation in the incidence of S. aureus BSI was recorded throughout the period.

In methicillin-resistant Staphylococcus aureus (MRSA) treatment, the vancomycin minimum inhibitory concentration (MIC) increase, vancomycin heteroresistance (hVISA) presence, and accessory gene regulator (agr) dysfunction are predictors of vancomycin therapy failure. This study evaluated the association between vancomycin MIC (≥ 1.0 μg/mL) and agr dysfunction in invasive MRSA isolates. Vancomycin MIC, hVISA phenotype, agr group, and function were determined in 171 MRSA isolates obtained between 2014 and 2019 from hospitals in Porto Alegre, Brazil. All MRSA were susceptible to vancomycin; 16.4% of these had MIC ≥ 1.0 μg/mL. Seventeen MRSA isolates expressed the hVISA phenotype; 35.3% of them had MIC of 1.5 μg/mL. agr groups I (40.9%) and II (47.1%) were the most found groups for MRSA and hVISA isolates, respectively. The proportion of MRSA with vancomycin MIC ≥ 1.0 μg/mL in agr group II was significantly higher than in agr groups I and III (p = 0.002). agr dysfunction was observed in 4.7% (8/171) of MRSA, especially those with vancomycin MIC ≥ 1.0 μg/mL (p < 0.001). In addition, six isolates (35.3%; 6/17) with hVISA phenotype presented agr dysfunction, which was significantly higher than that in non-hVISA phenotype (p < 0.001). In conclusion, agr dysfunction in MRSA is associated with vancomycin MIC ≥ 1.0 μg/mL and hVISA phenotype, which suggests that agr dysfunction might confer potential advantages on MRSA to survive in invasive infections.

Objetivo: Avaliar a redução microbiana após antissepsia cirúrgica das mãos dos cirurgiões, realizada com preparação alcoólica, em diferentestempos. Método: Estudo de prevalência, pragmático, de campo, realizado em hospital terciário do Brasil. Coletaram-se amostras microbiológicas dasmãos de 54 cirurgiões após lavagem simples, para determinar a flora microbiana basal e, após a antissepsia cirúrgica alcoólica, para avaliar a reduçãomicrobiana imediata. Categorizaram-se os resultados da redução microbiana em redução leve (até 50% de redução da flora bacteriana), moderada (de51 a 80%) e alta (acima de 80%). A pesquisa foi submetida e aprovada pelo Comitê de Ética e Pesquisa da instituição hospitalar privada, sede do estudo, eda instituição de ensino superior federal. Resultados: Nas técnicas realizadas em menos de 90 segundos, houve 80% de redução severa, 6,7% de reduçãomoderada e 13,3% de redução leve. Nas técnicas desempenhadas em mais de 180 segundos, todas as amostras apresentaram redução de contagem bacteriana,o que não ocorreu em tempos menores de antissepsia. Conclusão: Quando a técnica e o tempo recomendados são seguidos, maior é a reduçãobacteriana, em comparação aos tempos menores.

Objective: To evaluate culture‐independent procedures (immunochromatography and quantitative polymerase chain reaction [qPCR]) in the detection and susceptibility of Streptococcus pneumoniae directly from culture‐negative pleural fluid (PF) in children.Method: Detection of S. pneumoniae in PF of children with parapneumonic effusion and/or empyema by using two culture‐independent methods: an immunochromatographic membrane test (IMT) which identifies the pneumococcal C antigen, and a real‐time PCR test to detect pneumococcal genes lytA and pbp2b, a marker of susceptibility of β‐lactam agents, in PF samples.Results: We tested 36 PF specimens and recorded the previous use of antimicrobials. In the final analysis, 34 samples were included. IMT and qPCR presented positive results in 23 (67.6%) and 24 (70.6%) of the samples, respectively, showing a moderate agreement (k = 0.518) between the two methods.From the 36 children included, 34 (94.4%) had antibiotic data available by the time when PFs were collected. Thirty‐four (100%) children had been given treatment before PF sampling, with 33 (97%) receiving β‐lactam antibiotics administered empirically. Of the 24 lytA real‐time positive samples, 21 (87.5%) were also positive for pbp2b, a marker of β‐lactam susceptibility.Conclusion: The reduced sensitivity of culture for pneumococcal detection can be improved through the addition of IMT and qPCR analysis. The utility of qPCR combining detection of lytA and a marker of β‐lactam susceptibility should be explored further.