COVID-19 in hematopoietic stem cell transplant recipients during three years of the pandemic: a multicenter study in Brazil.

Hematopoietic stem cell transplant (HSCT) recipients are at -increased risk for severe COVID-19. The aim of this study was to evaluate the burden of COVID-19 in a cohort of HSCT recipients. This retrospective study evaluated a cohort of adult hospitalized HSCT recipients diagnosed with COVID-19 in two large hospitals in São Paulo, Brazil post-HSCT, from January 2020 to June 2022. The primary outcome was all-cause mortality. Of 49 cases, 63.2% were male with a median age of 47 years. Allogeneic-HSCT (51.2%) and autologous-HSCT (48.9%) patients were included. The median time from HSCT to COVID-19 diagnosis was 398 days (IQR: 1211-134), with 22 (44.8%) cases occurring within 12 months of transplantation. Most cases occurred during the first year of the pandemic, in non-vaccinated patients (n=35; 71.4%). Most patients developed severe (24.4%) or critical (40.8%) disease; 67.3% received some medication for COVID-19, primarily corticosteroids (53.0%). The probable invasive aspergillosis prevalence was 10.2%. All-cause mortality was 40.8%, 51.4% in non-vaccinated patients and 14.2% in patients who received at least one dose of the vaccine. In the multiple regression analyses, the variables mechanical ventilation (OR: 101.01; 95% CI: 8.205 - 1,242.93; p = 0.003) and chest CT involvement at diagnosis ≥50% (OR: 26.61; 95% CI: 1.06 - 664.26; p = 0.04) remained associated with all-cause mortality. Thus, HSCT recipients with COVID-19 experienced high mortality, highlighting the need for full vaccination and infection prevention measures.

Acquisition of plasmids from Shiga toxin-producing Escherichia coli strains had low or neutral fitness cost on commensal E. coli.

Although it has been hypothesized that the acquisition of plasmids-especially those bearing virulence factors and antimicrobial resistance genes-increases the energetic burden and reduces the fitness of a bacterium in general, some results have challenged this view, showing little or no effect on fitness after plasmid acquisition, which may lead to change in the view that there are evolutionary barriers for a wide spread of such plasmids among bacteria. Here, to evaluate the fitness impact of plasmid-encoded antibiotic resistance and virulence genes, plasmids from O26:H11, O111:H8, and O118:H16 Shiga toxin-producing Escherichia coli (STEC) human and bovine isolates were transferred to the non-virulent E. coli HS and K-12 MG1655 strains. Sequencing and PCR were used to characterize plasmids, and to identify the presence of antimicrobial resistance and/or virulence genes. The fitness impact of plasmids encoding virulence and antimicrobial resistance upon bacterial hosts was determined by pairwise growth competition. Plasmid profile analysis showed that STEC strains carried one or more high and low molecular weight plasmids belonging to the B/O, F, I, K, P, Q, and/or X incompatibility groups encoding virulence genes (SPATE-encoding genes) and/or antimicrobial resistance genes (aadA1, strAB, tetA, and/or tetB). Competition experiments demonstrated that the biological cost of carriage of these plasmids by the commensal E. coli strain HS or the laboratory strain E. coli K-12 MG1655 was low or non-existent, ranging from - 4.7 to 5.2% per generation. This suggests that there are few biological barriers-or, alternatively, it suggests that there are biological barriers that we were not able to measure in this competition model-against the spread of plasmid encoding virulence and resistance genes from STEC to other, less pathogenic E. coli strains. Thus, our results, in opposition to a common view, suggest that the acquisition of plasmids does not significantly affect the bacteria fitness and, therefore, the theorized plasmid burden would not be a significant barrier for plasmid spread.

Carbapenem-resistant Klebsiella pneumoniae bloodstream infections in haematological malignances and hematopoietic stem cell transplantation: Clinical impact of combination therapy in a 10-year Brazilian cohort.

Bacterial bloodstream infections (BSI) are a common threat among patients with haematological malignancies (HM) and hematopoietic stem cell transplant recipients (HSCT). The purpose of this research was to describe clinical and microbiological aspects of BSI caused by carbapenem-resistant Klebsiella pneumoniae (CRKp) and assess risk factors associated with 30-day mortality in a 10-year cohort of haematological patients. A total of 65 CRKp-BSI episodes occurring in HM patients and HSCT recipients and CRKp-BSI between January 2010 and December 2019 were retrospectively studied. Acute leukemias were the most frequently observed underlying disease (87.7%) and 18 patients (27.7%) received HSCT. Mucosal barrier injury in the gastrointestinal tract was the primary cause of bacteremia (86.1%). Also, 14 individuals (21.6%) had an Invasive Fungal Disease (IFD) throughout the episode. Regarding treatment, in 31 patients (47.7%) empirical therapy was deemed appropriate, whereas 33 (50.8%) patients received a combination therapy. Microbiological data revealed that the majority of isolates (53-58%) had the Polymyxin B co-resistance phenotype, while amikacin resistance was less common (16 samples, or 24.7%). The mortality rates at 14 and 30 days were 32.3% and 36.9%, respectively. In a multivariate Cox regression analysis, prompt appropriate antibiotic administration within three days was associated with a better outcome (Adjusted Hazard Ratio [aHR]: 0.33; 95% Confidence Interval [CI]: 0.14-0.76; p = 0.01), whereas hypotension at presentation (aHR: 3.88; 95% CI: 1.40-10.74; p = 0.01) and concurrent IFD (aHR: 2.97; 95% CI: 1.20-7.37; p = 0.02) were independently associated with death within 30 days. Additionally, a favorable correlation between combination therapy and overall survival was found (aHR: 0.18; 95%CI: 0.06-0.56; p = 0.002). In conclusion, 30-day mortality CRKp-BSI was elevated and most of the isolates were polymyxin B resistant. Early appropriate antimicrobial treatment and the use of combination therapy were linked to a better outcome.

Acquisition of plasmids from Shiga toxin-producing Escherichia coli strains had low or neutral fitness cost on commensal E. coli

Although it has been hypothesized that the acquisition of plasmids—especially those bearing virulence factors and antimicrobial resistance genes—increases the energetic burden and reduces the fitness of a bacterium in general, some results have challenged this view, showing little or no effect on fitness after plasmid acquisition, which may lead to change in the view that there are evolutionary barriers for a wide spread of such plasmids among bacteria. Here, to evaluate the fitness impact of plasmid-encoded antibiotic resistance and virulence genes, plasmids from O26:H11, O111:H8, and O118:H16 Shiga toxin-producing Escherichia coli (STEC) human and bovine isolates were transferred to the non-virulent E. coli HS and K-12 MG1655 strains. Sequencing and PCR were used to characterize plasmids, and to identify the presence of antimicrobial resistance and/or virulence genes. The fitness impact of plasmids encoding virulence and antimicrobial resistance upon bacterial hosts was determined by pairwise growth competition. Plasmid profile analysis showed that STEC strains carried one or more high and low molecular weight plasmids belonging to the B/O, F, I, K, P, Q, and/or X incompatibility groups encoding virulence genes (SPATE-encoding genes) and/or antimicrobial resistance genes (aadA1, strAB, tetA, and/or tetB). Competition experiments demonstrated that the biological cost of carriage of these plasmids by the commensal E. coli strain HS or the laboratory strain E. coli K-12 MG1655 was low or non-existent, ranging from − 4.7 to 5.2% per generation. This suggests that there are few biological barriers—or, alternatively, it suggests that there are biological barriers that we were not able to measure in this competition model—against the spread of plasmid encoding virulence and resistance genes from STEC to other, less pathogenic E. coli strains. Thus, our results, in opposition to a common view, suggest that the acquisition of plasmids does not significantly affect the bacteria fitness and, therefore, the theorized plasmid burden would not be a significant barrier for plasmid spread.

COVID-19 in hematopoietic stem cell transplant recipients during three years of the pandemic: a multicenter study in Brazil

ABSTRACT Hematopoietic stem cell transplant (HSCT) recipients are at -increased risk for severe COVID-19. The aim of this study was to evaluate the burden of COVID-19 in a cohort of HSCT recipients. This retrospective study evaluated a cohort of adult hospitalized HSCT recipients diagnosed with COVID-19 in two large hospitals in São Paulo, Brazil post-HSCT, from January 2020 to June 2022. The primary outcome was all-cause mortality. Of 49 cases, 63.2% were male with a median age of 47 years. Allogeneic-HSCT (51.2%) and autologous-HSCT (48.9%) patients were included. The median time from HSCT to COVID-19 diagnosis was 398 days (IQR: 1211-134), with 22 (44.8%) cases occurring within 12 months of transplantation. Most cases occurred during the first year of the pandemic, in non-vaccinated patients (n=35; 71.4%). Most patients developed severe (24.4%) or critical (40.8%) disease; 67.3% received some medication for COVID-19, primarily corticosteroids (53.0%). The probable invasive aspergillosis prevalence was 10.2%. All-cause mortality was 40.8%, 51.4% in non-vaccinated patients and 14.2% in patients who received at least one dose of the vaccine. In the multiple regression analyses, the variables mechanical ventilation (OR: 101.01; 95% CI: 8.205 - 1,242.93; p = 0.003) and chest CT involvement at diagnosis ≥50% (OR: 26.61; 95% CI: 1.06 - 664.26; p = 0.04) remained associated with all-cause mortality. Thus, HSCT recipients with COVID-19 experienced high mortality, highlighting the need for full vaccination and infection prevention measures.

Phenotypic and Genotypic Characterization of Cutibacterium acnes Isolated from Shoulder Surgery Reveals Insights into Genetic Diversity.

Specific virulence factors that likely influence C. acnes invasion into deep tissues remain to be elucidated. Herein, we describe the frequency of C. acnes identification in deep tissue specimens of patients undergoing clean shoulder surgery and assess its phenotypic and genetic traits associated with virulence and antibiotic resistance patterns, compared with isolates from the skin of healthy volunteers. Multiple deep tissue specimens from the bone fragments, tendons, and bursa of 84 otherwise healthy patients undergoing primary clean-open and arthroscopic shoulder surgeries were aseptically collected. The overall yield of tissue sample cultures was 21.5% (55/255), with 11.8% (30/255) identified as C. acnes in 27.3% (23/84) of patients. Antibiotic resistance rates were low, with most strains expressing susceptibility to first-line antibiotics, while a few were resistant to penicillin and rifampicin. Phylotypes IB (73.3%) and II (23.3%) were predominant in deep tissue samples. Genomic analysis demonstrated differences in the pangenome of the isolates from the same clade. Even though strains displayed a range of pathogenic markers, such as biofilm formation, patients did not evolve to infection during the 1-year follow-up. This suggests that the presence of polyclonal C. acnes in multiple deep tissue samples does not necessarily indicate infection.

Clonal dissemination of highly virulent Serratia marcescens strains producing KPC-2 in food-producing animals.

Serratia marcescens is a Gram-negative bacterium presenting intrinsic resistance to polymyxins that has emerged as an important human pathogen. Although previous studies reported the occurrence of multidrug-resistance (MDR) S. marcescens isolates in the nosocomial settings, herein, we described isolates of this extensively drug-resistant (XDR) species recovered from stool samples of food-producing animals in the Brazilian Amazon region. Three carbapenem-resistant S. marcescens strains were recovered from stool samples of poultry and cattle. Genetic similarity analysis showed that these strains belonged to the same clone. Whole-genome sequencing of a representative strain (SMA412) revealed a resistome composed of genes encoding resistance to ß-lactams [blaKPC-2, blaSRT-2], aminoglycosides [aac(6')-Ib3, aac(6')-Ic, aph(3')-VIa], quinolones [aac(6')-Ib-cr], sulfonamides [sul2], and tetracyclines [tet(41)]. In addition, the analysis of the virulome demonstrated the presence of important genes involved in the pathogenicity of this species (lipBCD, pigP, flhC, flhD, phlA, shlA, and shlB). Our data demonstrate that food-animal production can act as reservoirs for MDR and virulent strains of S. marcescens.

Genomic Analysis of Klebsiella pneumoniae ST258 Strain Coproducing KPC-2 and CTX-M-14 Isolated from Poultry in the Brazilian Amazon Region.

This study aimed to characterize a Klebsiella pneumoniae strain (KP411) recovered from the stool samples of poultry (Gallus gallus) in the Brazilian Amazon Region. The whole-genome sequencing of KP411 revealed the presence of an important arsenal of antimicrobial resistance genes to ß-lactams (blaCTX-M-14, blaTEM-1B, blaKPC-2, blaSVH-11), aminoglycosides [aph(3″)- Ib, aph(6)-Id, aph(3')-Ia], sulfonamides (sul1, sul2), quinolones (oqxAB), fosfomycin (fosAKP), and macrolides [mph(A)]. Furthermore, our analyses revealed that the KP411 strain belongs to the ST258 clonal lineage, which is one of the main epidemic clones responsible for the dissemination of KPC-2 worldwide. Our data suggest that food-producing animals may act as reservoirs of multidrug-resistant K. pneumoniae belonging to the ST258 clone, and, consequently, contribute to their dissemination to humans and the environment.

Exploring the Bacteriome and Resistome of Humans and Food-Producing Animals in Brazil.

The epidemiology of antimicrobial resistance (AMR) is complex, with multiple interfaces (human-animal-environment). In this context, One Health surveillance is essential for understanding the distribution of microorganisms and antimicrobial resistance genes (ARGs). This report describes a multicentric study undertaken to evaluate the bacterial communities and resistomes of food-producing animals (cattle, poultry, and swine) and healthy humans sampled simultaneously from five Brazilian regions. Metagenomic analysis showed that a total of 21,029 unique species were identified in 107 rectal swabs collected from distinct hosts, the highest numbers of which belonged to the domain Bacteria, mainly Ruminiclostridium spp. and Bacteroides spp., and the order Enterobacterales. We detected 405 ARGs for 12 distinct antimicrobial classes. Genes encoding antibiotic-modifying enzymes were the most frequent, followed by genes related to target alteration and efflux systems. Interestingly, carbapenemase-encoding genes such as blaAIM-1, blaCAM-1, blaGIM-2, and blaHMB-1 were identified in distinct hosts. Our results revealed that, in general, the bacterial communities from humans were present in isolated clusters, except for the Northeastern region, where an overlap of the bacterial species from humans and food-producing animals was observed. Additionally, a large resistome was observed among all analyzed hosts, with emphasis on the presence of carbapenemase-encoding genes not previously reported in Latin America. IMPORTANCE Humans and food production animals have been reported to be important reservoirs of antimicrobial resistance (AMR) genes (ARGs). The frequency of these multidrug-resistant (MDR) bacteria tends to be higher in low- and middle-income countries (LMICs), due mainly to a lack of public health policies. Although studies on AMR in humans or animals have been carried out in Brazil, this is the first multicenter study that simultaneously collected rectal swabs from humans and food-producing animals for metagenomics. Our results indicate high microbial diversity among all analyzed hosts, and several ARGs for different antimicrobial classes were also found. As far as we know, we have detected for the first time ARGs encoding carbapenemases, such as blaAIM-1, blaCAM-1, blaGIM-2, and blaHMB-1, in Latin America. Thus, our results support the importance of metagenomics as a tool to track the colonization of food-producing animals and humans by antimicrobial-resistant bacteria. In addition, a network surveillance system called GUARANI, created for this study, is ready to be expanded and to collect additional data.

Comparative Phenotypic and Genomic Features of Staphylococci from Sonication Fluid of Orthopedic Implant-Associated Infections with Poor Outcome.

Staphylococcus spp. remain the leading biofilm-forming agents causing orthopedic implant-associated infections (OIAI). This is a descriptive study of phenotypic and genomic features identified in clinical isolates of S. aureus and coagulase-negative Staphylococcus (CoNS) recovered from OIAIs patients that progressed to treatment failure. Ten isolates were identified by matrix-time-of-flight laser-assisted desorption mass spectrometry (MALDI-TOF-MS) and tested for antibiotic susceptibility and biofilm formation. Genotypic characteristics, including, MLST (Multi Locus Sequence Typing), SCCmec typing, virulence and resistance genes were assessed by whole-genome sequencing (WGS). All S. aureus harbored mecA, blaZ, and multiple resistance genes for aminoglycosides and quinolones. All MRSA were strong biofilm producers harboring the complete icaADBC and icaR operon. Seven CoNS isolates comprising five species (S. epidermidis, S. haemolyticus, S. sciuri, S. capitis and S. lugdunensis) were analyzed, with mecA gene detected in five isolates. S. haemolitycus (isolate 95), and S. lugdunensis were unable to form biofilm and did not harbor the complete icaADBCR operon. High variability of adhesion genes was detected, with atl, ebp, icaADBC operon, and IS256 being the most common. In conclusion, MRSA and CoNS isolates carrying genes for biofilm production, and resistance to ß-lactam and aminoglycosides are associated with treatment failure in OIAIs.

Case Report: Invasive Sinusitis due to Sporothrix Brasiliensis in a Renal Transplant Recipient.

Sporotrichosis is usually a subcutaneous infection caused by thermodimorphic fungi of the genus Sporothrix. The disease occurs worldwide, but endemic areas are located in tropical and subtropical regions. The epidemiology of sporotrichosis in Brazil is peculiar because of the cat's entry in the chain of transmission of this mycosis, associated with Sporothrix brasiliensis, the most virulent species in the genus. Sinusitis caused by Sporothrix species is unusual and may be underdiagnosed or confused with other fungal etiologies, like mucormycosis. We report a case of sinusitis due to a Sporothrix species in a 6-year renal transplant recipient. Direct examination of smears of exudate of the sinus specimen (aspirate, biopsy) revealed budding yeasts and cigar-shaped cells. Sporothrix was subsequently recovered from the patient's exudate culture and identified as S. brasiliensis using species-specific polymerase chain reaction, and she was successfully treated with antifungal therapy. Her parents also developed the disease a week later, both only cutaneous involvement. Sporotrichosis sinusitis is a rare disease, even in immunocompromised patients. Diagnosis is crucial, and benefits from good epidemiological history.

Risk factors for colonization and infection by resistant microorganisms in kidney transplant recipients.

OBJECTIVES: to assess the prevalence of colonization and infection by multidrug-resistant bacteria in patients undergoing kidney transplantation and identify the rate of infection, morbidity and mortality and associated risk factors. METHODS: a prospective cohort of 200 randomly included kidney transplant recipients. Epidemiological surveillance of the studied microorganisms was carried out in the first 24 hours and 7 days after transplantation. RESULTS: ninety (45%) patients were considered colonized. Female sex, hypertension and diabetes (p<0.005), dialysis time (p<0.004), length of stay after transplantation, delayed renal function, and length of stay were identified as risk factors. The microorganisms were isolated from surgical site, bloodstream and urinary tract infections. CONCLUSIONS: colonization by resistant microorganisms in kidney transplant patients was frequent and risk factors associated with infection were identified. The results should guide the care team in order to minimize morbidity and mortality related to infectious causes in this population.

Seasonality and weather dependance of Acinetobacter baumannii complex bloodstream infections in different climates in Brazil.

Recent studies report seasonality in healthcare-associated infections, especially those caused by Acinetobacter baumannii complex. We conducted an ecologic study aimed at analyzing the impact of seasons, weather parameters and climate control on the incidence and carbapenem-resistance in A. baumannii complex bloodstream infections (ABBSI) in hospitals from regions with different climates in Brazil. We studied monthly incidence rates (years 2006-2015) of ABBSI from hospitals in cities from different macro-regions in Brazil: Fortaleza (Ceará State, Northeast region), Goiânia (Goiás State, Middle-west) and Botucatu (São Paulo State, Southeast). Box-Jenkins models were fitted to assess seasonality, and the impact of weather parameters was analyzed in Poisson Regression models. Separate analyses were performed for carbapenem-resistant versus carbapenem-susceptible isolates, as well as for infections occurring in climate-controlled intensive care units (ICUs) versus non-climate-controlled wards. Seasonality was identified for ABSSI ICUs in the Hospitals from Botucatu and Goiânia. In the Botucatu hospital, where there was overall seasonality for both resistance groups, as well as for wards without climate control. In that hospital, the overall incidence was associated with higher temperature (incidence rate ratio for each Celsius degree, 1.05; 95% Confidence Interval, 1.01-1.09; P = 0.006). Weather parameters were not associated with ABBSI in the hospitals from Goiânia and Fortaleza. In conclusion, seasonality was found in the hospitals with higher ABBSI incidence and located in regions with greater thermal amplitude. Strict temperature control may be a tool for prevention of A. baumanii infections in healthcare settings.

Capsular genotype distribution of Group B Streptococcus colonization among at-risk pregnant women in Sao Paulo, Brazil.

BACKGROUND: Vaccines in development against Group B Streptococcus (GBS) should contain the most prevalent capsular genotypes screened in the target population. In low- and middle-income countries epidemiological data on GBS carriage among pregnant women, a prerequisite condition for GBS neonatal sepsis, is needed to inform vaccine strategies. OBJECTIVE: To investigate the prevalence of different GBS capsular genotypes that colonizes at-risk pregnant women in a private maternity hospital in São Paulo, Brazil. METHODS: GBS strains isolated in routine maternity procedures from at-risk pregnant women from 2014 to 2018 were confirmed by mass spectrometry (MALDI-TOF) with subsequent DNA extraction for identification of capsular genotype through polymerase chain reaction (PCR). Demographic and gestational data were analyzed. RESULTS: A total of 820 Todd-Hewitt broths positive for GBS were selected for streptococcal growth. Recovery and confirmation of GBS by MALDI-TOF were possible in 352. Strains were processed for determination of capsular genotype by PCR. From the total of 352 GBS isolates, 125 strains (35.5%) were genotyped as Ia; 23 (6.5%) as Ib; 41 (11.6%) as II; 36 (10.2%) as III; 4 (1.1%) as IV; 120 (34.1%) as V and 1 strain (0.3%) as VIII. Two isolates (0.7%) were not genotyped by used methodology. No statistically significant correlation between gestational risk factors, demographic data and distribution of capsular genotypes were found. CONCLUSIONS: GBS capsular genotypes Ia, Ib, II, III, and V were the most prevalent isolates colonizing at risk pregnant women in the present study. The inclusion of capsular genotypes Ia and V in the composition of future vaccines would cover 69.6% of capsular genotypes in the studied population. No statistically significant differences were observed between capsular genotype and gestational and demographic data and risk factors.

Risk factors for colonization and infection by resistant microorganisms in kidney transplant recipients / Factores de riesgo de colonización e infección por microorganismos resistentes en receptores de trasplante renal / Fatores de risco para colonização e infecção por microrganismos resistentes em transplantados renais

ABSTRACT Objectives: to assess the prevalence of colonization and infection by multidrug-resistant bacteria in patients undergoing kidney transplantation and identify the rate of infection, morbidity and mortality and associated risk factors. Methods: a prospective cohort of 200 randomly included kidney transplant recipients. Epidemiological surveillance of the studied microorganisms was carried out in the first 24 hours and 7 days after transplantation. Results: ninety (45%) patients were considered colonized. Female sex, hypertension and diabetes (p<0.005), dialysis time (p<0.004), length of stay after transplantation, delayed renal function, and length of stay were identified as risk factors. The microorganisms were isolated from surgical site, bloodstream and urinary tract infections. Conclusions: colonization by resistant microorganisms in kidney transplant patients was frequent and risk factors associated with infection were identified. The results should guide the care team in order to minimize morbidity and mortality related to infectious causes in this population.

RESUMEN Objetivos: evaluar la prevalencia de colonización e infección por bacterias multirresistentes en pacientes sometidos a trasplante renal, identificar la tasa de infección, morbimortalidad y factores de riesgo asociados. Métodos: cohorte prospectiva de 200 receptores de trasplante renal incluidos aleatoriamente. La vigilancia epidemiológica de los microorganismos estudiados se realizó en las primeras 24 horas y 7 días posteriores al trasplante. Resultados: noventa (45%) pacientes fueron considerados colonizados. Se identificaron como factores de riesgo: sexo femenino, hipertensión y diabetes (p<0,005), tiempo en diálisis (p<0,004), tiempo de estancia después del trasplante, función renal retrasada, tiempo de estancia. Los microorganismos se aislaron de infecciones del sitio quirúrgico, del torrente sanguíneo y del tracto urinario. Conclusiones: la colonización por microorganismos resistentes en pacientes con trasplante renal fue frecuente y se identificaron factores de riesgo asociados a infección. Los resultados deben orientar al equipo asistencial para minimizar la morbimortalidad relacionada con causas infecciosas en esta población.

RESUMO Objetivos: avaliar a prevalência de colonização e infecção por bactéria multirresistente em pacientes em transplante renal, identificar a taxa de infecção, morbimortalidade e os fatores de risco associados. Métodos: coorte prospectivo de 200 transplantados renais incluídos aleatoriamente. Realizou-se vigilância epidemiológica dos microrganismos em estudo nas primeiras 24 horas e 7 dias pós-transplante. Resultados: noventa (45%) pacientes foram considerados colonizados. Identificaram-se como fatores de risco: sexo feminino, hipertensão arterial e diabetes (p<0,005), tempo de diálise (p<0,004), tempo de internação pós-transplante, função renal retardada, tempo de internação. Os microrganismos foram isolados das infecções em sítio cirúrgico, corrente sanguínea e trato urinário. Conclusões: a colonização por microrganismos resistentes nos pacientes transplantados renais foi frequente e os fatores de riscos associados à infecção foram identificados. Os resultados devem direcionar a equipe assistencial, a fim de minimizar a morbimortalidade relacionada às causas infecciosas nesta população.

Capsular genotype distribution of Group B Streptococcus colonization among at-risk pregnant women in Sao Paulo, Brazil

ABSTRACT Background: Vaccines in development against Group B Streptococcus (GBS) should contain the most prevalent capsular genotypes screened in the target population. In low- and middle-income countries epidemiological data on GBS carriage among pregnant women, a prerequisite condition for GBS neonatal sepsis, is needed to inform vaccine strategies. Objective: To investigate the prevalence of different GBS capsular genotypes that colonizes at-risk pregnant women in a private maternity hospital in São Paulo, Brazil. Methods: GBS strains isolated in routine maternity procedures from at-risk pregnant women from 2014 to 2018 were confirmed by mass spectrometry (MALDI-TOF) with subsequent DNA extraction for identification of capsular genotype through polymerase chain reaction (PCR). Demographic and gestational data were analyzed. Results: A total of 820 Todd-Hewitt broths positive for GBS were selected for streptococcal growth. Recovery and confirmation of GBS by MALDI-TOF were possible in 352. Strains were processed for determination of capsular genotype by PCR. From the total of 352 GBS isolates, 125 strains (35.5%) were genotyped as Ia; 23 (6.5%) as Ib; 41 (11.6%) as II; 36 (10.2%) as III; 4 (1.1%) as IV; 120 (34.1%) as V and 1 strain (0.3%) as VIII. Two isolates (0.7%) were not genotyped by used methodology. No statistically significant correlation between gestational risk factors, demographic data and distribution of capsular genotypes were found. Conclusions: GBS capsular genotypes Ia, Ib, II, III, and V were the most prevalent isolates colonizing at risk pregnant women in the present study. The inclusion of capsular genotypes Ia and V in the composition of future vaccines would cover 69.6% of capsular genotypes in the studied population. No statistically significant differences were observed between capsular genotype and gestational and demographic data and risk factors.

Genomic Analysis of Carbapenem-Resistant Acinetobacter baumannii Isolates Belonging to Major Endemic Clones in South America.

Carbapenem-resistant Acinetobacter baumannii (CRAB) are emerging worldwide. In South America, clinical isolates presenting such a phenotype usually do not belong to the globally distributed international clone 2 (IC2). The majority of these isolates are also resistant to multiple other antimicrobials and are often designated extremely drug-resistant (XDR). The aim of this study was to characterize the resistance mechanisms presented by 18 carbapenem-resistant A. baumannii isolates from five different Brazilian hospitals. Species identification was determined by rpoB sequencing, and antimicrobial susceptibility was determined by broth microdilution. Isolates were submitted to whole genome sequencing using Illumina platform and genetic similarity was determined by PFGE, MLST, and cgMLST. Genome analysis was used to identify intrinsic and acquired resistance determinants, including mutations in the AdeRSABC efflux system and in outer membrane proteins (OMPs). All isolates were identified as A. baumannii and grouped into 4 pulsotypes by PFGE, which belonged to clonal complexes (CC) 15 Pas /103 Ox (n = 4) and 79 Pas /113 Ox (n = 14), corresponding to IC4 and IC5, respectively. High MIC values to carbapenems, broad-spectrum cephalosporins, amikacin, and ciprofloxacin were observed in all isolates, while MICs of ampicillin/sulbactam, gentamicin, and tigecycline varied among the isolates. Minocycline was the most active antimicrobial agent tested. Moreover, 12 isolates (66.7%) were considered resistant to polymyxins. Besides intrinsic OXA-51 and ADC variants, all isolates harbored an acquired carbapenem-hydrolyzing class D ß-lactamase (CHDL) encoding gene, either bla OXA- 23 or bla OXA- 72. A diversity of aminoglycoside modifying enzymes and resistance determinants to other antimicrobial classes were found, as well as mutations in gyrA and parC. Non-synonymous mutations have also been identified in the AdeRSABC efflux system and in most OMPs, but they were considered natural polymorphisms. Moreover, resistance to polymyxins among isolates belonging to IC5 were associated to non-synonymous mutations in pmrB, but no known polymyxin resistance mechanism was identified in isolates belonging to IC4. In conclusion, A. baumannii clinical isolates belonging to South America's major clones present a myriad of antimicrobial resistance determinants. Special attention should be paid to natural polymorphisms observed in each clonal lineage, especially regarding non-synonymous mutations in constitutive genes associated with distinct resistance phenotypes.

Invasive pneumococcal disease in children with cancer: Incidence density, risk factors and isolated serotypes

ABSTRACT Background: Pediatric oncology patients (POP) have a high risk of infections due to impaired immunity. Invasive pneumococcal disease (IPD) is an important cause of severe infection in these patients and it is associated with high mortality. This study aimed to evaluate the incidence and risk factors associated with IPD at a Pediatric Oncology Center in Brazil. Methods: This was a retrospective case-control study. All IPD cases in children with cancer from 2005 through 2016 were reviewed. Each case of IPD was matched with two controls from a cohort of patients matched for year of IPD, age and disease in order to assess risk factors. The incidence density was calculated as the number of IPD per 100,000 patients-year. Results: A total of 51 episodes of IPD in 49 patients was identified. All pneumococci were isolated from blood cultures. The median age was five years and 67% were male; mortality rate was 7.8%. The IPD incidence density rate in POP was 311.21 per 100,000 patients-year, significantly higher than the rate in the general pediatric population. Severe neutropenia was the only risk factor associated with IPD, after multivariate conditional logistic regression analysis. Conclusion: Although pneumococcal disease decreased after the introduction of 10-valent pneumococcal vaccine in the Brazilian national immunization schedule in 2010, there was no decrease in the IPD incidence rate in our cohort. A higher coverage rate of pneumococcal vaccination in children in the general population might be necessary to reduce the incidence rate in this high-risk population.

Invasive pneumococcal disease in children with cancer: Incidence density, risk factors and isolated serotypes.

BACKGROUND: Pediatric oncology patients (POP) have a high risk of infections due to impaired immunity. Invasive pneumococcal disease (IPD) is an important cause of severe infection in these patients and it is associated with high mortality. This study aimed to evaluate the incidence and risk factors associated with IPD at a Pediatric Oncology Center in Brazil. METHODS: This was a retrospective case-control study. All IPD cases in children with cancer from 2005 through 2016 were reviewed. Each case of IPD was matched with two controls from a cohort of patients matched for year of IPD, age and disease in order to assess risk factors. The incidence density was calculated as the number of IPD per 100,000 patients-year. RESULTS: A total of 51 episodes of IPD in 49 patients was identified. All pneumococci were isolated from blood cultures. The median age was five years and 67% were male; mortality rate was 7.8%. The IPD incidence density rate in POP was 311.21 per 100,000 patients-year, significantly higher than the rate in the general pediatric population. Severe neutropenia was the only risk factor associated with IPD, after multivariate conditional logistic regression analysis. CONCLUSION: Although pneumococcal disease decreased after the introduction of 10-valent pneumococcal vaccine in the Brazilian national immunization schedule in 2010, there was no decrease in the IPD incidence rate in our cohort. A higher coverage rate of pneumococcal vaccination in children in the general population might be necessary to reduce the incidence rate in this high-risk population.

Patients with Sore Throat: A Survey of Self-Management and Healthcare-Seeking Behavior in 13 Countries Worldwide.

BACKGROUND: Acute sore throat is one of the most common problems for which patients consult their general practitioner and is a key area for inappropriate antibiotic prescribing. The objective of this study was to investigate patients' attitudes related to healthcare-seeking behavior and self-management of sore throat. METHODS: We conducted an observational, questionnaire-based study across 13 countries (Australia, Brazil, China, France, Germany, Italy, the Philippines, Russia, Saudi Arabia, South Africa, Thailand, the UK and the USA) on respondents who reported having had a sore throat in the previous 12 months. Data were collected on their experiences, contact with healthcare professionals, treatment practices and opinions about antibiotics. RESULTS: A total of 5196 respondents (approximately 400 per country) completed the survey. Over 80% of respondents sought advice for a sore throat, with 30% consulting a general practitioner. The desire to limit the worsening of symptoms was the main reason for seeking treatment. Other reasons concerned resolving persistent symptoms and reducing the impact on daily life/sleep. Self-management for sore throat was mainly medicated sore throat remedies. "Wanting an antibiotic" was rated much lower (55%) than most other reasons for visiting a doctor, but this differed greatly between countries. The percentage of respondents using antibiotics varied widely, for example, 10% in the UK and 45% in Saudi Arabia. There was considerable variation in the proportion of respondents who thought that antibiotics would be effective against sore throat (from 24% in France to 94% in Saudi Arabia). CONCLUSIONS: Our findings suggest that knowledge of effective treatments for sore throat varied widely. The results of this study should enable healthcare professionals to better anticipate patients' needs. This will support healthcare professionals in their role as antibiotic stewards, helping to reduce the misuse of antibiotics, and further guiding patients towards symptomatic self-management of sore throat.