Epidemiological trends of isolated and non-isolated central nervous system congenital malformations in live births in a middle-income setting.

OBJECTIVES: This study aimed to analyze, in the São Paulo state of Brazil, time trends in prevalence, neonatal mortality, and neonatal lethality of central nervous system congenital malformations (CNS-CM) between 2004 and 2015. METHODS: Population-based study of all live births with gestational age ≥22 weeks and/or birthweight ≥400 g from mothers living in São Paulo State, during 2004-2015. CNS-CM was defined by the presence of International Classification Disease 10th edition codes Q00-Q07 in the death and/or live birth certificates. CNS-CM was classified as isolated (only Q00-Q07 codes), and non-isolated (with congenital anomalies codes nonrelated to CNS-CM). CNS-CM associated neonatal death was defined as death between 0 and 27 days after birth in infants with CNS-CM. CNS-CM prevalence, neonatal mortality, and lethality rates were calculated, and their annual trends were analyzed by Prais-Winsten Model. The annual percent change (APC) with 95% confidence interval (95%CI) was obtained. RESULTS: 7,237,628 live births were included in the study and CNS-CM were reported in 7526 (0.1%). CNS-CM associated neonatal deaths occurred in 2935 (39.0%). Isolated CNS-CM and non-isolated CNS-CM were found respectively in 5475 and 2051 livebirths, with 1525 (28%) and 1410 (69%) neonatal deaths. CNS-CM prevalence and neonatal lethality were stationary, however neonatal mortality decreased (APC -1.66; 95%CI -3.09 to -0.21) during the study. For isolated CNS-CM, prevalence, neonatal mortality, and lethality decreased over the period. For non-isolated CNS-CM, the prevalence increased, neonatal mortality was stationary, and lethality decreased during the period. The median time of CNS-CM associated neonatal deaths was 18 h after birth. CONCLUSIONS: During a 12-year period in São Paulo State, Brazil, neonatal mortality of infants with CNS-CM in general and with isolated CNS-CM showed a decreasing pattern. Nevertheless CNS-CM mortality remained elevated, mostly in the first day after birth.

A 7-Year Brazilian National Perspective on Plasmid-Mediated Carbapenem Resistance in Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii Complex and the Impact of the Coronavirus Disease 2019 Pandemic on Their Occurrence.

BACKGROUND: Carbapenemase production is a global public health threat. Antimicrobial resistance (AMR) data analysis is critical to public health policy. Here we analyzed carbapenemase detection trends using the AMR Brazilian Surveillance Network. METHODS: Carbapenemase detection data from Brazilian hospitals included in the public laboratory information system dataset were evaluated. The detection rate (DR) was defined as carbapenemase detected by gene tested per isolate per year. The temporal trends were estimated using the Prais-Winsten regression model. The impact of COVID-19 on carbapenemase genes in Brazil was determined for the period 2015-2022. Detection pre- (October 2017 to March 2020) and post-pandemic onset (April 2020 to September 2022) was compared using the χ2 test. Analyses were performed with Stata 17.0 (StataCorp, College Station, TX). RESULTS: 83 282 blaKPC and 86 038 blaNDM were tested for all microorganisms. Enterobacterales DR for blaKPC and blaNDM was 68.6% (41 301/60 205) and 14.4% (8377/58 172), respectively. P. aeruginosa DR for blaNDM was 2.5% (313/12 528). An annual percent increase for blaNDM of 41.1% was observed, and a decrease for blaKPC of -4.0% in Enterobacterales, and an annual increase for blaNDM of 71.6% and for blaKPC of 22.2% in P. aeruginosa. From 2020 to 2022, overall increases of 65.2% for Enterobacterales, 77.7% for ABC, and 61.3% for P. aeruginosa were observed in the total isolates. CONCLUSIONS: This study shows the strengths of the AMR Brazilian Surveillance Network with robust data related to carbapenemases in Brazil and the impact of COVID-19 with a change in carbapenemase profiles with blaNDM rising over the years.

Underreporting of unfavorable outcomes of congenital syphilis on the Notifiable Health Conditions Information System in the state of São Paulo, Brazil, 2007-2018.

OBJECTIVE: to describe the frequency of underreporting of unfavorable outcomes of congenital syphilis in the state of São Paulo, Brazil, 2007-2018. METHODS: this was a descriptive study of cases of abortion, fetal and non-fetal deaths due to congenital syphilis reported on the Notifiable Health Conditions Information System (Sistema de Informação de Agravos de Notificação - SINAN), and those of congenital syphilis registered in any line in the Death Certificate, on the Mortality Information System (Sistema de Informações sobre Mortalidade - SIM), by means of probabilistic and deterministic linkage. RESULTS: of the 27,713 cases of congenital syphilis reported, 1,320 progressed to death (871 fetal deaths, 449 infant deaths) and were matched to the SIM; 355 deaths (259 fetal deaths, 96 infant deaths) were not included on SINAN; there was an increase in unfavorable outcomes,11.4% for infant deaths due to congenital syphilis, 3.0% for fetal deaths and 1.9% for abortions. CONCLUSION: the use of different relationship techniques proved to be adequate to identify the frequency of underreporting of unfavorable outcomes of congenital syphilis in the state of São Paulo.

The burden of inappropriate birth weight on neonatal survival in term newborns: a population-based study in a middle-income setting.

Introduction: Premature birth, perinatal asphyxia, and infections are the main causes of neonatal death. Growth deviations at birth also affect neonatal survival according to week of gestation at birth, particularly in developing countries. The purpose of this study was to verify the association between inappropriate birth weight and neonatal death in term live births. Methods: This is an observational follow-up study with all term live births from 2004 to 2013 in Sao Paulo State, Brazil. Data were retrieved with the deterministic linkage of death and birth certificates. The definition of very small for gestational age (VSGA) and very large for gestational age (VLGA) used the 10th percentile of 37 weeks and the 90th percentile of 41 weeks + 6 days, respectively, based on the Intergrowth-21st. We measured the outcome in terms of time to death and the status of each subject (death or censorship) in the neonatal period (0-27 days). Survival functions were calculated using the Kaplan-Meier method stratified according to the adequacy of birth weight into three groups (normal, very small, or very large). We used multivariate Cox regression to adjust for proportional hazard ratios (HRs). Results: The neonatal death rate during the study period was 12.03/10,000 live births. We found 1.8% newborns with VSGA and 2.7% with VLGA. The adjusted analysis showed a significant increase in mortality risk for VSGA infants (HR = 4.25; 95% CI: 3.89-4.65), independent of sex, 1-min Apgar score, and five maternal factors. Discussion: The risk of neonatal death in full-term live births was approximately four times greater in those with birth weight restriction. The development of strategies to control the factors that determine fetal growth restriction through planned and structured prenatal care can substantially reduce the risk of neonatal death in full-term live births, especially in developing countries such as Brazil.

Temporal Trend, Causes, and Timing of Neonatal Mortality of Moderate and Late Preterm Infants in São Paulo State, Brazil: A Population-Based Study.

Moderate and late preterm newborns comprise around 85% of live births < 37 weeks gestation. Data on their neonatal mortality in middle-income countries is limited. This study aims to analyze the temporal trend, causes and timing of neonatal mortality of infants with 320/7-366/7 weeks gestation without congenital anomalies from 2004-2015 in the population of São Paulo State, Brazil. A database was built by deterministic linkage of birth and death certificates. Causes of death were classified by ICD-10 codes. Among 7,317,611 live births in the period, there were 545,606 infants with 320/7-366/7 weeks gestation without congenital anomalies, and 5782 of them died between 0 and 27 days. The neonatal mortality rate decreased from 16.4 in 2004 to 7.6 per thousand live births in 2015 (7.47% annual decrease by Prais-Winsten model). Perinatal asphyxia, respiratory disorders and infections were responsible, respectively, for 14%, 27% and 44% of the 5782 deaths. Median time to death was 24, 53 and 168 h, respectively, for perinatal asphyxia, respiratory disorders, and infections. Bottlenecks in perinatal health care are probably associated with the results that indicate the need for policies to reduce preventable neonatal deaths of moderate and late preterm infants in the most developed state of Brazil.

Congenital diaphragmatic hernia in a middle-income country: Persistent high lethality during a 12-year period.

BACKGROUND: In high- and middle-income countries, mortality associated to congenital diaphragmatic hernia (CDH) is high and variable. In Brazil, data is scarce regarding the prevalence, mortality, and lethality of CDH. This study aimed to analyze, in São Paulo state of Brazil, the temporal trends of prevalence, neonatal mortality and lethality of CDH and identify the time to CDH-associated neonatal death. METHODS: Population-based study of all live births with gestational age ≥ 22 weeks, birthweight ≥400g, from mothers residing in São Paulo State, Brazil, during 2004-2015. CDH definition and its subgroups classification were based on ICD-10 codes reported in the death and/or live birth certificates. CDH-associated neonatal death was defined as death up to 27 days after birth of infants with CDH. CDH prevalence, neonatal mortality and lethality were calculated and their annual percent change (APC) with 95% confidence intervals (95%CI) was analyzed by Prais-Winsten. Kaplan-Meier estimator identified the time after birth that CDH-associated neonatal death occurred. RESULTS: CDH prevalence was 1.67 per 10,000 live births, with a significant increase throughout the period (APC 2.55; 95%CI 1.30 to 3.83). CDH neonatal mortality also increased over the time (APC 2.09; 95%CI 0.27 to 3.94), while the lethality was 78.78% and remained stationary. For isolated CDH, CDH associated to non-chromosomal anomalies and CDH associated to chromosomal anomalies the lethality was, respectively, 72.25%, 91.06% and 97.96%, during the study period. For CDH as a whole and for all subgroups, 50% of deaths occurred within the first day after birth. CONCLUSIONS: During a 12-year period in São Paulo State, Brazil, CDH prevalence and neonatal mortality showed a significant increase, while lethality remained stable, yet very high, compared to rates reported in high income countries.

NDM-producing Enterobacterales prevalence associated to COVID-19 in a tertiary hospital.

Colonizations/Infections caused by carbapenem-resistant Enterobacterales are of great clinical and epidemiological importance due to their rapid dissemination and high mortality rates. In this scenario, the use of antibiotics intensified by the COVID-19 pandemic has brought about a great warning on the real impact that this pandemic could have on antimicrobial management programs and long-term antimicrobial resistance rates. The objective of this study was to evaluate the increase of New Delhi Metallo ß-Lactamase (NDM)-producing Enterobacterales cases in COVID-19 units of a complex Brazilian tertiary hospital. This retrospective observational study included all patients admitted to the hospital identified as colonized or infected by NDM-producing Gram negative bacilli (GNB), from January 2017 to April 2021. Forty-two NDM-producing Enterobacterales were identified in 39 patients. The rate of NDM cases per total surveillance cultures increased progressively between 2017 and 2021 (chi-2 for trend, p < 0.0001) and was associated with a higher occurrence specifically in COVID units (Fisher exact, p < 0.0001). The molecular investigation of the NDM-producing Klebsiella pneumoniae strains revealed the emergence of diverse clones during the COVID-19 period, also with possible evidence of horizontal transmission among patients within COVID units. NDM-producing Enterobacterales with multiple and different clonalities in the COVID-19 units also raised questions about the importance of other factors besides horizontal clonal transfer, including the increase of antimicrobial consumption by these patients.

Subnotificação de desfechos desfavoráveis da sífilis congênita no Sistema de Informação de Agravos de Notificação no estado de São Paulo, 2007-2018 / Underreporting of unfavorable outcomes of congenital syphilis on the Notifiable Health Conditions Information System in the state of São Paulo, Brazil, 2007-2018 / Subnotificación de resultados desfavorables de sífilis congénita en el Sistema de Información de Enfermedades de Declaración Obligatoria en el estado de São Paulo, Brasil, 2007-2018

Objetivo: descrever a frequência de subnotificação de desfechos desfavoráveis da sífilis congênita no estado de São Paulo, Brasil, 2007-2018. Métodos: estudo descritivo dos casos de aborto, óbitos fetais e não fetais por sífilis congênita notificados no Sistema de Informação de Agravos de Notificação (Sinan), e daqueles registrados com sífilis congênita, em qualquer linha da Declaração de Óbito, no Sistema de Informações sobre Mortalidade (SIM), mediante relacionamentos probabilístico e determinístico. Resultados: dos 27.713 casos de sífilis congênita notificados, 1.320 evoluíram para óbito (871 fetais, 449 infantis) e foram pareados com o SIM; 355 óbitos (259 fetais, 96 infantis) não constavam no Sinan; ocorreu incremento de desfechos desfavoráveis, de 11,4% para óbitos infantis por sífilis congênita, 3,0% para óbitos fetais e 1,9% para abortos. Conclusão: o emprego de diferentes técnicas de relacionamento mostrou-se adequado para identificar a frequência da subnotificação dos desfechos desfavoráveis da sífilis congênita no estado de São Paulo.

Objective: to describe the frequency of underreporting of unfavorable outcomes of congenital syphilis in the state of São Paulo, Brazil, 2007-2018. Methods: this was a descriptive study of cases of abortion, fetal and non-fetal deaths due to congenital syphilis reported on the Notifiable Health Conditions Information System (Sistema de Informação de Agravos de Notificação - SINAN), and those of congenital syphilis registered in any line in the Death Certificate, on the Mortality Information System (Sistema de Informações sobre Mortalidade - SIM), by means of probabilistic and deterministic linkage. Results: of the 27,713 cases of congenital syphilis reported, 1,320 progressed to death (871 fetal deaths, 449 infant deaths) and were matched to the SIM; 355 deaths (259 fetal deaths, 96 infant deaths) were not included on SINAN; there was an increase in unfavorable outcomes,11.4% for infant deaths due to congenital syphilis, 3.0% for fetal deaths and 1.9% for abortions. Conclusion: the use of different relationship techniques proved to be adequate to identify the frequency of underreporting of unfavorable outcomes of congenital syphilis in the state of São Paulo.

Objetivo: describir la frecuencia de la subnotificación de resultados desfavorables por sífilis congénita en el estado de São Paulo, de 2007 a 2018. Métodos: estudio descriptivo de los casos de aborto espontáneo, muertes fetales y no fetales por sífilis congénita notificados en la Información Sistema de Enfermedades de Declaración Obligatoria (Sinan), y las registradas con sífilis congénita en el Sistema de Información de Mortalidad (SIM) mediante relaciones probabilísticas y determinísticas. Resultados: de los 27.713 casos de sífilis congénita, fallecieron 1.320 (871 fetales, 449 infantiles) y se emparejaron con SIM; 355 muertes (259 fetales, 96 infantiles) no se incluyeron en Sinan. Hubo un aumento en los resultados desfavorables: 11,4% muertes infantiles por sífilis congénita; 3,0% muertes fetales y 1,9% abortos. Conclusión: el uso de diferentes técnicas de vinculación demostró ser adecuado para identificar la frecuencia de subregistro de resultados desfavorables de sífilis congénita en el estado de São Paulo.

NDM-producing Enterobacterales prevalence associated to COVID-19 in a tertiary hospital

Abstract Colonizations/Infections caused by carbapenem-resistant Enterobacterales are of great clinical and epidemiological importance due to their rapid dissemination and high mortality rates. In this scenario, the use of antibiotics intensified by the COVID-19 pandemic has brought about a great warning on the real impact that this pandemic could have on antimicrobial management programs and long-term antimicrobial resistance rates. The objective of this study was to evaluate the increase of New Delhi Metallo β-Lactamase (NDM)-producing Enterobacterales cases in COVID-19 units of a complex Brazilian tertiary hospital. This retrospective observational study included all patients admitted to the hospital identified as colonized or infected by NDM-producing Gram negative bacilli (GNB), from January 2017 to April 2021. Forty-two NDM-producing Enterobacterales were identified in 39 patients. The rate of NDM cases per total surveillance cultures increased progressively between 2017 and 2021 (chi-2 for trend, p < 0.0001) and was associated with a higher occurrence specifically in COVID units (Fisher exact, p < 0.0001). The molecular investigation of the NDM-producing Klebsiella pneumoniae strains revealed the emergence of diverse clones during the COVID-19 period, also with possible evidence of horizontal transmission among patients within COVID units. NDM-producing Enterobacterales with multiple and different clonalities in the COVID-19 units also raised questions about the importance of other factors besides horizontal clonal transfer, including the increase of antimicrobial consumption by these patients.

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.

Temporal Trend and Risk Factors for Respiratory Distress Syndrome-Associated Neonatal Mortality in Preterm Infants: A Population-Based Study in a Middle-Income Country.

OBJECTIVE: This article aimed to report a temporal series of respiratory distress syndrome (RDS)-associated neonatal mortality rates in preterm live births in São Paulo state, Brazil, and to identify social, maternal, and neonatal characteristics associated with these deaths. STUDY DESIGN: This is a population-based study of all live births with gestational age (GA) between 22 and 36 weeks, birth weight ≥400 g, without congenital anomalies from mothers living in São Paulo state during 2004 to 2015. RDS-associated neonatal mortality was defined as death up to 27 days after birth with ICD-10 codes P22.0 or P28.0. RDS-associated neonatal mortality rate (annual percent change [APC] with 95% confidence intervals [95% CIs]) was analyzed by Prais-Winsten. Kaplan-Meier estimator identified the time after birth that the RDS-associated neonatal death occurred. Poisson's regression model compared social maternal and neonatal characteristics between preterm live births that survived the neonatal period and those with RDS-associated neonatal deaths, with results expressed in incidence rate ratio and 95% CI. RESULTS: A total of 645,276 preterm live births were included in the study, of which 612,110 survived and 11,078 had RDS-associated neonatal deaths. RDS-associated neonatal mortality rate was 17.17 per thousand preterm live births, with a decreasing annual trend (APC: -6.50%; 95% CI: -9.11 to -3.82%). The median time of these deaths was 48 hours after birth. The following risk factors for RDS-associated neonatal death were identified: maternal schooling ≤7 years (1.18; 1.09-1.29), zero to three prenatal care visits (1.25; 1.18-1.32), multiple pregnancy (1.24; 1.16-1.33), vaginal delivery (1.29; 1.22-1.36), GA 22 to 27 weeks (106.35; 98.36-114.98), GA 28 to 31 weeks (20.12; 18.62-21.73), male sex (1.16; 1.10-1.22), and 5-minute Apgar scores of 0 to 3 (6.74; 6.08-7.47) and 4 to 6 (3.97; 3.72-4.23). CONCLUSION: During the study period, RDS-associated neonatal mortality rates showed significant reduction. The relationship between RDS-associated neonatal deaths and social, maternal, and neonatal factors suggests the need for perinatal strategies to reduce prematurity and to improve the initial management of preterm infants. KEY POINTS: · RDS is associated with preterm live births.. · Impact of RDS-associated neonatal mortality in middle-income countries is scarce.. · Qualified perinatal care can reduce RDS-associated neonatal mortality..

Clusters of preterm live births and respiratory distress syndrome-associated neonatal deaths: spatial distribution and cooccurrence patterns.

BACKGROUND: Prematurity and respiratory distress syndrome (RDS) are strongly associated. RDS continues to be an important contributor to neonatal mortality in low- and middle-income countries. This study aimed to identify clusters of preterm live births and RDS-associated neonatal deaths, and their cooccurrence pattern in São Paulo State, Brazil, between 2004 and 2015.  METHODS: Population-based study of all live births with gestational age ≥ 22 weeks, birthweight ≥ 400 g, without congenital anomalies from mothers living in São Paulo State, Brazil, during 2004-2015. RDS-associated neonatal mortality was defined as deaths < 28 days with ICD-10 codes P22.0 or P28.0. RDS-associated neonatal mortality and preterm live births rates per municipality were submitted to first- and second-order spatial analysis before and after smoothing using local Bayes estimates. Spearman test was applied to identify the correlation pattern between both rates. RESULTS: Six hundred forty-five thousand two hundred seventy-six preterm live births and 11,078 RDS-associated neonatal deaths in São Paulo State, Brazil, during the study period were analyzed. After smoothing, a non-random spatial distribution of preterm live births rate (I = 0.78; p = 0.001) and RDS-associated neonatal mortality rate (I = 0.73; p = 0.001) was identified. LISA maps confirmed clusters for both, with a negative correlation (r = -0.24; p = 0.0000). Clusters of high RDS-associated neonatal mortality rates overlapping with clusters of low preterm live births rates were detected. CONCLUSIONS: Asymmetric cluster distribution of preterm live births and RDS-associated neonatal deaths may be helpful to indicate areas for perinatal healthcare improvement.

Large Scale Genome-Centric Metagenomic Data from the Gut Microbiome of Food-Producing Animals and Humans.

The One Health concept is a global strategy to study the relationship between human and animal health and the transfer of pathogenic and non-pathogenic species between these systems. However, to the best of our knowledge, no data based on One Health genome-centric metagenomics are available in public repositories. Here, we present a dataset based on a pilot-study of 2,915 metagenome-assembled genomes (MAGs) of 107 samples from the human (N = 34), cattle (N = 28), swine (N = 15) and poultry (N = 30) gut microbiomes. Samples were collected from the five Brazilian geographical regions. Of the draft genomes, 1,273 were high-quality drafts (≥90% of completeness and ≤5% of contamination), and 1,642 were medium-quality drafts (≥50% of completeness and ≤10% of contamination). Taxonomic predictions were based on the alignment and concatenation of single-marker genes, and the most representative phyla were Bacteroidota, Firmicutes, and Proteobacteria. Many of these species represent potential pathogens that have already been described or potential new families, genera, and species with potential biotechnological applications. Analyses of this dataset will highlight discoveries about the ecology and functional role of pathogens and uncultivated Archaea and Bacteria from food-producing animals and humans. Furthermore, it also represents an opportunity to describe new species from underrepresented taxonomic groups.

Multicenter, Prospective Validation of a Phenotypic Algorithm to Guide Carbapenemase Testing in Carbapenem-Resistant Pseudomonas aeruginosa Using the ERACE-PA Global Surveillance Program.

BACKGROUND: Carbapenemase-producing, carbapenem-resistant Pseudomonas aeruginosa (CP-CRPA) is a global challenge. However, detection efforts can be laborious because numerous mechanisms produce carbapenem resistance. A minimum inhibitory concentration-based algorithm (imipenem- or meropenem-resistant plus ceftazidime-nonsusceptible plus cefepime-nonsusceptible) was proposed to identify the isolates most likely to harbor a carbapenemase; however, prospective validation in geographies displaying genotypic diversity and varied carbapenemase prevalence is warranted. METHODS: CRPA isolates were collected during the Enhancing Rational Antimicrobials for P. aeruginosa (ERACE-PA) global surveillance program from 17 sites in 12 countries. Isolates underwent susceptibility testing following local standards to ceftazidime, cefepime, and ceftolozane/tazobactam. Isolates underwent initial phenotypic carbapenemase screening followed by molecular testing if positive. The primary algorithm criteria were applied, and results were compared with phenotypic carbapenemase results to assess the performance of the algorithm. A secondary criterion, the algorithm criterion or imipenem- or meropenem-resistant plus ceftolozane/tazobactam-nonsusceptible, was assessed. RESULTS: A total of 807 CRPA were assessed, and 464 isolates met the algorithm criteria described above. Overall, testing was reduced by 43% compared with testing all CRPA. Carbapenemase-positive isolates missed by the algorithm were largely driven by Guiana extended spectrum (GES). Addition of the criterion of imipenem- or meropenem-resistant plus ceftolozane/tazobactam-nonsusceptible decreased the number of CP-CRPA missed by the algorithm (21 vs 40 isolates, respectively), reducing number of isolates tested by 39%. CONCLUSIONS: Application of the initial algorithm (imipenem- or meropenem-resistant plus ceftazidime-nonsusceptible plus cefepime-nonsusceptible) performed well in a global cohort, with 33% phenotypically carbapenemase-positive isolates. The addition of imipenem- or meropenem-resistant plus ceftolozane/tazobactam-nonsusceptible reduced the number of phenotypically carbapenemase-positive isolates missed and may be useful in areas with a prominence of GES.

Broad-spectrum antimicrobial consumption trends and correlation with bacterial infections and antimicrobial resistance over 5 years.

OBJECTIVES: Consumption trends of four broad-spectrum antimicrobials and their correlation with antimicrobial resistance in Gram-negative bacilli (GNB) from 2013-2017 within intensive care units (ICUs) were explored. METHODS: Consumption of meropenem (MEM), polymyxin B (PMB), piperacillin/tazobactam (TZP) and cefepime (FEP) in defined daily doses per 1000 patient-days (DDD/1000PD) was measured. Infection-related GNB isolates were grouped according to specific resistance profiles. Time series of antimicrobial consumption and their parametric correlation with each grouped resistant GNB were explored. RESULTS: A total of 1423 GNB were evaluated. A significant linear decline in consumption was observed for MEM [slope -3.88, 95% confidence interval (CI) -4.96 to -2.81; P < 0.0001] and PMB (slope -3.51, 95% CI -5.528 to -1.495; P = 0.0009). A significant decline in MEM-non-susceptible Acinetobacter spp. (R2 = 0.476; P = 0.006) and an increase in FEP-non-susceptible Escherichia coli (R2 = 0.124; P = 0.006) was observed. A significant correlation between MEM consumption and MEM-non-susceptible Acinetobacter spp. (r = 0.43; P = 0.001) was observed. MEM consumption and MEM-non-susceptible Acinetobacter spp. showed a positive correlation. CONCLUSION: Reduction in the consumption of broad-spectrum antimicrobials may alter the frequency of infection-related isolates and their antimicrobial resistance profiles.

Evaluation of high-concentration EDTA-modified carbapenemase inactivation method (eCIM) for SPM-producing Pseudomonas aeruginosa.

The modified carbapenemase inactivation method (mCIM) and EDTA-modified carbapenemase inactivation method (eCIM) are simple and cost-effective detection methods used for serine- and metallo-carbapenemase determination; however, poor test performance has been reported for IMP- and SPM-producing P. aeruginosa. Recently, we reported that 40 µM EDTA concentrations improved test sensitivity for IMP-producing P. aeruginosa. Herein, we assessed standard and high-concentration EDTA eCIM against SPM-producing P. aeruginosa. Twenty-four SPM-producing P. aeruginosa were evaluated, and 3 well-characterized P. aeruginosa (wild type, n = 1; KPC, n = 1; and VIM, n = 1) were used for quality control. mCIM was conducted as described by the Clinical and Laboratory Standards Institute. Concurrently, eCIM methods were performed at standard (5 µM) and high (40 µM) EDTA concentrations. All mCIM phenotypes responded concordant with its genotype. eCIM phenotype matched its genotype for 3 and 24 SPM-producing isolates using standard and high EDTA concentrations, respectively. The eCIM sensitivity increased from 12% using standard concentrations to 100% using high EDTA concentrations. No EDTA-related adverse effects were observed on bacteria growth. The combination mCIM with 40 µM EDTA eCIM properly captured SPM-producing P. aeruginosa. This methodology should be validated in a multi-center study with various enzymatic-producing P. aeruginosa.

Clusters of cause specific neonatal mortality and its association with per capita gross domestic product: A structured spatial analytical approach.

BACKGROUND: Infant mortality rate is a measure of population health and neonatal mortality account for great proportion of these deaths. Underdevelopment might be associated to higher neonatal mortality risk due to assistant related factors. Spatial and temporal distribution of mortality help identifying and developing strategies for interventions. OBJECTIVE: To investigate the cluster areas of asphyxia-associated neonatal mortality and to explore its association with per capita gross domestic product (GDP) in São Paulo State (SP), Brazil. METHODS: Ecological study including live births residents in SP from 2004-2013. Neonatal deaths (0-27 days) with perinatal asphyxia were defined as intrauterine hypoxia, birth asphyxia or meconium aspiration syndrome written in any line of the Death Certificate. Geoprocessing analytical approach included detection of first order effects through quintiles and spatial moving average maps, followed by second order effects by global and local spatial autocorrelation (Moran and LISA, respectively) before and after smoothing with local Bayesian estimates. Finally, Spearman correlation was applied between asphyxia-associated neonatal mortality and mean per capita GDP rates for the municipalities with significant LISA. RESULTS: There were 6,713 asphyxia-associated neonatal deaths among 5,949,267 live births (rate: 1.13/1000) in SP. Spatial moving average maps showed a non-random distribution among municipalities, with presence of clusters (I = 0.048; p = 0.023). LISA map identified clusters of asphyxia-associated neonatal mortality in the south, southeast and northwest. After applying local Bayes estimates, clusters were more pronounced (I = 0.589; p = 0.001). There was a partial overlap of the areas of higher asphyxia-associated neonatal mortality and lower mean per capita GDP. CONCLUSIONS: Spatial analysis identified cluster areas of high asphyxia-associated neonatal mortality and low per capita GDP rates, with a significant negative correlation. This optimized, structured, and hierarchical approach to identify high-risk areas of cause-specific neonatal mortality may be helpful for guiding public health efforts to decrease neonatal mortality.