Towards an update on the antimicrobial use in Adult Care Units in Brazil: insights from multi-hospital prevalence study.

Introduction. Efforts to understand the burden of antibiotic use in low- and middle-income countries such as Brazil are essential for developing strategies that are effective and appropriate in the context of endemic multidrug-resistant organisms.Aim. This study aims to determine antimicrobial-prescribing practices among patients hospitalized in intensive care units (ICUs) for adults in Brazil.Methodology. A 1-day point prevalence multicentre survey was conducted in 58 adult ICUs across the five regions of Brazil. The institutions were categorized according to their type and size. Detailed antimicrobial prescription data were prospectively provided to all patients hospitalized on the day of data collection.Results. A total of 620 patients were included in the study, of whom 63.9% were receiving at least one antimicrobial. Of these, 34.6% were treated for an infection, but only 39.9% of the cases were based on microbiological criteria. Empirical treatment was applied to 72.3% of the patients. Significant differences in antibiotic usage were observed across the different hospitals included in the study. Overall, treatment was most commonly directed towards pneumonia (51.8%) and bloodstream infections (29.6%). Glycopeptides (19.4%) and carbapenems (18.5%) were the most prescribed in teaching hospitals, while in non-teaching hospitals, carbapenems (17.8%) and broad-spectrum cephalosporins (16.8%) were most frequently used.Conclusion. Our study reveals alarming data on antibiotic use in adult ICUs in Brazil, with high frequencies of severe healthcare-associated infections acquired in these units, where patients are frequently subjected to empirical treatment.

Relationship between antimicrobial use and the highest number of multidrug-resistant-Pseudomonas aeruginosa: a 10-year study.

INTRODUCTION: Multi-drug-resistant (MDR) Pseudomonas aeruginosa is a dangerous pathogen causing nosocomial infection, particularly in low- and middle-income countries like Brazil. This retrospective study at a Brazilian university hospital examined the relationship between antimicrobial use and MDR-P. aeruginosa. METHODOLOGY: Data was collected from 358 patients with non-repetitive P. aeruginosa infections from 2009 to 2019. Antibiotic use was measured in grams and expressed as defined daily dose (DDD) per 1000 patient-days for meropenem, imipenem, polymyxin, and tigecycline. RESULTS: Extensively drug-resistant (XDR) P. aeruginosa occurred in 36.1%, and MDR in 32.6% of cases. Risk factors for XDR infection were hospitalization prior to infection (OR = 0.9901), intensive care unit (ICU) admission (OR = 0.4766), previous antibiotic use (OR = 1.4417), and use of cefepime (OR = 0.3883). Over the ten-year period, utilization of the monitored antibiotics increased, and there was a positive correlation between the rise in MDR-P. aeruginosa and the consumption of ceftriaxone, imipenem, meropenem, and polymyxin B. The 30-day mortality rate was 40.0% for all patients and 41.0% for those infected with XDR-P. aeruginosa. CONCLUSIONS: This study highlights the negative impact of the indiscriminate use of antimicrobials, which has led to a significant increase in multidrug-resistant P. aeruginosa strains in hospitals.

Appraising epidemiology data and antimicrobial resistance of urinary tract infections in critically ill adult patients: a 7-year retrospective study in a referral Brazilian hospital.

BACKGROUND: Urinary tract infections (UTI) are highly preventable and have significant clinical and financial impact on the patient and the health care system. OBJECTIVE: To investigate UTIs in critically ill adult patients and the relationship of antimicrobial consumption and multidrug-resistant isolate. DESIGN AND SETTING: A cohort study performed in a Brazilian tertiary-care university hospital in the city of Uberlandia (MG), located at the Federal University of Uberlandia, southeast region of the country. METHODS: We analyzed a cohort of 363 patients with first episode of UTIs from the adult intensive care unit (ICU), from January 2012 to December 2018. The daily doses of antimicrobial administered were calculated. RESULTS: The incidence rate of UTI was 7.2/1000 patient days, with 3.5/1000 patient-days of bacteriuria, and 2.1/1000 patient-days of candiduria. Of 373 microorganisms identified, 69 (18.4%) were Gram-positive cocci, 190 (50.9%) Gram-negative bacilli, and 114 yeasts (30.7%). Escherichia coli and Candida spp. were the most common. Patients with candiduria had higher comorbidity score (Charlson Comorbidity Index ≥ 3), longer length of stay (P = 0.0066), higher mortality (P = < 0.0001) severe sepsis, septic shock, and were immunocompromised when compared with patients with bacteriuria. We observed correlation between antibiotics consumption and multidrug-resistant (MDR) microorganisms. CONCLUSION: The UTIs incidence was high and was mainly caused by Gram-negative bacteria that were resistant to common antibiotics. We observed increase in the consumption of broad-spectrum antibiotics in ICU correlating with MDR microorganisms. In general, ICU-acquired candiduria may be associated with critical illness and poor prognosis.

Appraising epidemiology data and antimicrobial resistance of urinary tract infections in critically ill adult patients: a 7-year retrospective study in a referral Brazilian hospital

ABSTRACT BACKGROUND: Urinary tract infections (UTI) are highly preventable and have significant clinical and financial impact on the patient and the health care system. OBJECTIVE: To investigate UTIs in critically ill adult patients and the relationship of antimicrobial consumption and multidrug-resistant isolate. DESIGN AND SETTING: A cohort study performed in a Brazilian tertiary-care university hospital in the city of Uberlandia (MG), located at the Federal University of Uberlandia, southeast region of the country. METHODS: We analyzed a cohort of 363 patients with first episode of UTIs from the adult intensive care unit (ICU), from January 2012 to December 2018. The daily doses of antimicrobial administered were calculated. RESULTS: The incidence rate of UTI was 7.2/1000 patient days, with 3.5/1000 patient-days of bacteriuria, and 2.1/1000 patient-days of candiduria. Of 373 microorganisms identified, 69 (18.4%) were Gram-positive cocci, 190 (50.9%) Gram-negative bacilli, and 114 yeasts (30.7%). Escherichia coli and Candida spp. were the most common. Patients with candiduria had higher comorbidity score (Charlson Comorbidity Index ≥ 3), longer length of stay (P = 0.0066), higher mortality (P = < 0.0001) severe sepsis, septic shock, and were immunocompromised when compared with patients with bacteriuria. We observed correlation between antibiotics consumption and multidrug-resistant (MDR) microorganisms. CONCLUSION: The UTIs incidence was high and was mainly caused by Gram-negative bacteria that were resistant to common antibiotics. We observed increase in the consumption of broad-spectrum antibiotics in ICU correlating with MDR microorganisms. In general, ICU-acquired candiduria may be associated with critical illness and poor prognosis.

Inappropriate empirical antimicrobial treatment in bloodstream infections patients in the era of multidrug resistance / Terapia Empírica Inapropriada no Tratamento de Infecções de Corrente Sanguínea na Era da Multirresistência Antimicrobiana / Tratamiento antimicrobiano empírico inadecuado en pacientes con infecciones del torrente sanguíneo

Background and objectives: Bloodstream infection (BSI) by multidrug-resistant Pseudomonas aeruginosa is a severe infection. This study aimed to evaluate and identify the predictors of mortality in patients who had bloodstream infection by carbapenem-resistant P. aeruginosa. Methods: This is a retrospective cohort study, approved by Committee of Ethics in Research with Human Participants, which included 87 consecutive patients hospitalized in a referral hospital in Brazil. Clinical and demographic information about each patient were obtained from hospital records. The Student's T-test was used to compare continuous variables and x2 or Fisher's exact tests to compare categorical variables. To determine independent risk factors for 30-day mortality, a multiple logistic regression model was used. A survival curve was constructed using the Kaplan­Meier method. Results: Among the patients, 87.3% use antibiotics previously, 60.9% received inadequate empirical treatment, and the 30-day mortality rate was 57.5%. Inappropriate antibiotic empirical therapy was independently associated with a 30-days death and mortality rate. Conclusion: These findings can show some insights about the relationship between higher mortality and inappropriate empirical therapy for patients with BSI by P. aeruginosa. There is a need for better diagnostic tests and infection control programs should focus on de-escalation the antibiotic inappropriate therapy, mainly in BSI caused by carbapenem-resistant P. aeruginosa.(AU)

Justificativa e objetivos: Infecção da corrente sanguínea (ICS) por Pseudomonas aeruginosa multirresistente é grave. Este estudo teve como objetivo avaliar e identificar os preditores de mortalidade em pacientes admitidos em uma Unidade de Terapia Intensiva que apresentaram infecção da corrente sanguínea por P. aeruginosa resistente aos carbapenêmicos. Métodos: Trata-se de um estudo de coorte retrospectivo, aprovado pelo Comitê de Ética em Pesquisa com Seres Humanos, que incluiu 87 pacientes consecutivos internados em um hospital de referência no Brasil. As informações clínicas e demográficas de cada paciente foram obtidas através de análise dos prontuários dos pacientes. O teste T de Student foi usado para comparar variáveis contínuas e o teste x2 ou exato de Fisher para comparar variáveis categóricas. Para determinar fatores de risco independentes para mortalidade em 30 dias, foi utilizado um modelo de regressão logística múltipla. Uma curva de sobrevida foi construída pelo método de Kaplan-Meier. Resultados: Do total de pacientes, 87,3% faziam uso prévio de antibióticos, 60,9% receberam tratamento empírico inadequado e a mortalidade em 30 dias foi de 57,5%. A terapia empírica inadequada foi fator de risco independente para mortalidade. Conclusão: Esses achados revelam alguns insights sobre a relação entre maior mortalidade e terapia empírica inadequada para pacientes com ICS por P. aeruginosa. Além disso, destacam a necessidade de melhores testes diagnósticos e os programas de controle de infecção devem se concentrar na redução da terapia inadequada com antibióticos, principalmente na ICS causada por P. aeruginosa resistente a carbapenêmicos.(AU)

Justificación y objetivos: La infección del torrente sanguíneo por Pseudomonas aeruginosa multirresistente es grave. Este estudio tuvo como objetivo evaluar e identificar predictores de mortalidad en pacientes ingresados en una Unidad de Cuidados Intensivos que presentaban infección del torrente sanguíneo por P. aeruginosa resistente a carbapenémicos. Métodos: Se trata de un estudio de cohorte retrospectivo, aprobado por el Comité de Ética en Investigación con Participantes Humanos, que incluyó 87 pacientes consecutivos ingresados en un hospital de referencia en Brasil. La información clínica y demográfica de cada paciente se obtuvo mediante el análisis de las historias clínicas de los pacientes. Se utilizó la prueba t de Student para comparar variables continuas y x2 o prueba exacta de Fisher para comparar variables categóricas. Para determinar los factores de riesgo independientes para la mortalidad a los 30 días, se utilizó un modelo de regresión logística múltiple. Se construyó una curva de supervivencia utilizando el método de Kaplan-Meier. Resultados: Del total de pacientes, el 87,3% utilizaba antibióticos previamente, el 60,9% recibió tratamiento empírico inadecuado y la tasa de mortalidad a los 30 días fue del 57,5%. La terapia empírica inadecuada fue un factor de riesgo independiente de mortalidad. Conclusión: Estos hallazgos revelan algunos conocimientos sobre la relación entre el aumento de la mortalidad y la terapia empírica inadecuada para los pacientes con infección del torrente sanguíneo por P. aeruginosa. Además, destacan la necesidad de mejores pruebas de diagnóstico y los programas de control de infecciones deben centrarse en reducir la terapia con antibióticos inapropiados, particularmente en infección del torrente sanguíneo causados por P. aeruginosa resistente a carbapenémicos.(AU)

Genetic Alterations Associated with Polymyxin B Resistance in Nosocomial KPC-2-Producing Klebsiella pneumoniae from Brazil.

The rapid increased multidrug resistance in Klebsiella pneumoniae has led to a renewed interest in polymyxin antibiotics, such as colistin, as antibiotics of last resort, not least in low/middle income countries. We conducted a genomic survey of clinical polymyxin-resistant K. pneumoniae to investigate the genetic alterations in isolates harboring blaKPC-2. Whole-genome sequencing was performed using an Illumina NextSeq 500 paired-end reads. Mutations and insertion sequence detection were analyzed to seven isolates recovered from clinical specimens of patients hospitalized in Brazil, focusing on key genes associated with polymyxin resistance. Furthermore, the levels of mRNA expression of genes associated with resistance to polymyxin B and other antimicrobials were evaluated by quantitative real-time PCR. Eighty-five percent of the isolates were assigned to clonal complex 258, with a minimum inhibitory concentration range of 4 to >256 mg/L for polymyxin B. It was possible to observe the presence of one important insertion element, ISKpn13, in a strain recovered from the blood that have blaKPC-2. Deleterious mutations reported in PmrB (R256G), YciM (N212T), and AcrB (T598A) were common, and mobile colistin resistance (mcr) genes were absent in all the isolates. RT-qPCR analysis revealed an overexpression of the pmrC (1.160-fold), pmrD (2.258-fold), and kpnE (1.530-fold) genes in the polymyxin B-resistant isolates compared with the expression of the polymyxin B-susceptible K. pneumoniae isolate. Overall, these results demonstrate the diversity of genetic variations in polymyxin-resistant populations derived from the different clonal strains, but the same sequence types, and suggest that there are still unknown mechanisms of polymyxin resistance in K. pneumoniae.

Gram-negative bacilli bacteremia: a 7 year retrospective study in a referral Brazilian tertiary-care teaching hospital.

Introduction. Bloodstream infection is one of the most frequent and challenging hospital-acquired infections and it is associated with high morbidity, mortality and additional use of healthcare resources.Hypothesis/Gap Statement: Bloodstream infections have consequences for the patient, such as the evolution to mortality and inappropriate empirical antibiotic prescription, especially when caused by multidrug-resistant Gram-negative bacilli.Objective. To assess the impact of bloodstream infection and the status of multidrug resistance (MDR) in the evolution of patients who received inappropriate initial antibiotic therapy.Methods. A retrospective surveillance was conducted on nosocomial bloodstream infections caused by Gram-negative bacilli (GNB) from January 2012 to December 2018 in an adult intensive care unit of a Brazilian tertiary teaching hospital.Results. We identified 270 patients with GNB nosocomial bacteremia. Non-survivors were older (with an average age of 58.8 years vs 46.9 years, P=<0.0001), presented more severe illnesses, were immunosuppressed (73.7 vs 37.6%, P=<0.0001), were more likely to have septic shock (55.8 vs 22.4%, P=<0.0001) and had an increased usage of mechanical ventilators (98.6 vs 89.6%, P=0.0013) than survivors. In a logistic regression model, inappropriate empirical antibiotic therapy was not an independent predictor of mortality, different from mechanical ventilator (P=<0.0001; OR=28.0; 95% CI=6.3-123.6), septic shock (P=0.0051; OR=2.5; 95% CI=1.3-4.9) and immunosuppression (P=0.0066; OR=2.6; 95% CI=1.3-5.2). In contrast, in a separate model, MDR was strongly associated with the prescription of inappropriate initial antibiotic therapy (P=0.0030; OR=5.3; 95% CI=1.7-16.1). The main isolated pathogens were Acinetobacter baumannii (23.6 %) and Klebsiella pneumoniae (18.7 %). The frequency of MDR organisms was high (63.7 %), especially among non-fermenting bacilli (60.9 %), highlighting A. baumannii (81.6 %) and Pseudomonas aeruginosa (41.8 %).Conclusion. Illness severity (septic shock and immunosuppression) and mechanical ventilation were identified as predictors of mortality. Additionally, MDR was a major determinant of inappropriate antibiotic empirical therapy, but not associated with mortality, and both characteristics were not statistically associated with death.

Novel ST1465/CC216 Nosocomial Lineage of Carbapenem-Resistant Acinetobacter baumannii Harboring an Unusual Plasmid Carrying blaNDM-1 Gene.

This study used whole-genome sequencing to analyze the first case of NDM-1-producing Acinetobacter baumannii belonging to the novel sequence type 1465/CC216 recovered in Brazil. The study identified an unusual plasmid carrying blaNDM-1 gene, in which some genes of the Tn125 transposon were lost. Besides, on the chromosome, the strain reported here presented blaOXA-106 gene, a variant of blaOXA-51 gene, and blaADC-25 with ISAba1 upstream. The isolation of new STs of A. baumannii carrying blaNDM-1 genes elicits our concerns about the possible spread of these genes among clinically relevant bacteria.

High mortality by nosocomial infections caused by carbapenem-resistant P. aeruginosa in a referral hospital in Brazil: facing the perfect storm.

Introduction. Carbapenem-resistant Pseudomonas aeruginosa is responsible for increased patient mortality.Gap Statement. Five and 30 day in-hospital all-cause mortality in patients with P. aeruginosa infections were assessed, followed by evaluations concerning potential correlations between the type III secretion system (TTSS) genotype and the production of metallo-ß-lactamase (MBL).Methodology. This assessment comprised a retrospective cohort study including consecutive patients with carbapenem-resistant infections hospitalized in Brazil from January 2009 to June 2019. PCR analyses were performed to determine the presence of TTSS-encoding genes and MBL genes.Results. The 30-day and 5-day mortality rates for 262 patients were 36.6 and 17.9 %, respectively. The unadjusted survival probabilities for up to 5 days were 70.55 % for patients presenting exoU-positive isolates and 86 % for those presenting exo-negative isolates. The use of urinary catheters, as well as the presence of comorbidity conditions, secondary bacteremia related to the respiratory tract, were independently associated with death at 5 and 30 days. The exoS gene was detected in 64.8 % of the isolates, the presence of the exoT and exoY genes varied and exoU genes occurred in 19.3 % of the isolates. The exoU genotype was significantly more frequent among multiresistant strains. MBL genes were not detected in 92 % of the isolates.Conclusions. Inappropriate therapy is a crucial factor regarding the worse prognosis among patients with infections caused by multiresistant P. aeruginosa, especially those who died within 5 days of diagnosis, regardless of the genotype associated with TTSS virulence.

Infections and antimicrobial resistance in an adult intensive care unit in a Brazilian hospital and the influence of drug resistance on the thirty-day mortality among patients with bloodstream infections.

INTRODUCTION: The present study aimed to determine the incidence of health care-associated infections (HCAIs) and identify the main resistant microorganisms in intensive care unit (ICU) patients in a Brazilian university hospital. METHODS: A retrospective cohort study was conducted in a Brazilian teaching hospital between 2012 and 2014. RESULTS: Overall, 81.2% of the infections were acquired in the ICU. The most common resistant pathogenic phenotypes in all-site and bloodstream infections were oxacillin-resistant coagulase-negative staphylococci and carbapenem-resistant Acinetobacter spp. (89.9% and 87.4%; 80.6% and 70.0%), respectively. CONCLUSIONS: There is an urgent need to focus on HCAIs in ICUs in Brazil.

Novel small IncX3 plasmid carrying the blaKPC-2 gene in high-risk Klebsiella pneumoniae ST11/CG258.

This study used whole-genome sequencing (WGS) and PFGE to analysis KPC-2-producing Klebsiella pneumoniae strains from clinical specimens collected in Brazilian hospitals. The study identifies the emergence of a novel small IncX3 plasmid (pKPB11), 12,757-bp in length, in a high-risk K. pneumoniae ST11/CG258 lineage, a successful clonal group in Brazil, carrying the blaKPC-2 gene on a non-Tn4401 genetic element (NTEKPC-Ic). Comparative analysis of the pKPB11 showed that this plasmid reduced its size, losing part of its conjugation apparatus. The pKPB11 was also compared to another strain sequenced in this study (KPC89) that had the hybrid IncX3-IncU plasmid (pKP89), of approximately 45 kb in length, similarly carrying the blaKPC-2 gene on NTEKPC-Ic. To the best of our knowledge, pKPB11 is the first example of small IncX3 plasmid found in a high-risk KPC-2-producing K. pneumoniae ST11/CG258.

Infections and antimicrobial resistance in an adult intensive care unit in a Brazilian hospital and the influence of drug resistance on the thirty-day mortality among patients with bloodstream infections

Abstract INTRODUCTION: The present study aimed to determine the incidence of health care-associated infections (HCAIs) and identify the main resistant microorganisms in intensive care unit (ICU) patients in a Brazilian university hospital. METHODS: A retrospective cohort study was conducted in a Brazilian teaching hospital between 2012 and 2014. RESULTS: Overall, 81.2% of the infections were acquired in the ICU. The most common resistant pathogenic phenotypes in all-site and bloodstream infections were oxacillin-resistant coagulase-negative staphylococci and carbapenem-resistant Acinetobacter spp. (89.9% and 87.4%; 80.6% and 70.0%), respectively. CONCLUSIONS: There is an urgent need to focus on HCAIs in ICUs in Brazil.

Incidence of infections caused by carbapenem-resistant Acinetobacter baumannii.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CR-Ab) has become a worrying health care problem, mainly in developing countries, such as Brazil. The objective was to investigate the prevalence and prognostic factors for CR-Ab infections at a Brazilian university hospital and examine the impact of inappropriate antimicrobial therapy on patient outcome. METHODS: A retrospective study on hospitalized patients with CR-Ab infections was carried out from January 2013 to December 2017. An epidemiologic analysis was carried out to determine the frequency of infections, the epidemiologic indicators by year, the risk factors for 30-day mortality, and the impact of inappropriate therapy. RESULTS: A total of 489 patients were included in the study. A rate of 0.7 per 1,000 patient-day CR-Ab infections was observed, mostly in the lungs (54.7%), and predominantly in the adult intensive care unit. The occurrence of infections by CR-Ab per 1,000 patient-days in November 2014 exceeded the established control limit, confirming an outbreak. CONCLUSIONS: The prevalence of CR-Ab increased in the investigated hospital, passing to an endemic pathogen with a direct impact on mortality and the control of these strains.

Molecular Detection of Class 1 Integron-Associated Gene Cassettes in KPC-2-Producing Klebsiella pneumoniae Clones by Whole-Genome Sequencing.

The dissemination of antimicrobial resistance genes and the bacterium that harbor them have increasingly become a public concern, especially in low- and middle-income countries. The present study used whole-genome sequencing to analyze 10 KPC-2-producing Klebsiella pneumoniae isolates obtained from clinical specimens originated from Brazilian hospitals. The study documents a relevant "snapshot" of the presence of class 1 integrons in 90% of the strains presenting different gene cassettes (dfrA30, dfrA15, dfrA12, dfrA14, aadA1, aadA2, and aac(6')Iq), associated or not with transposons. Two strains presented nonclassical integron (lacking the normal 3'conserved segment). In general, most strains showed a complex resistome, characterizing them as highly resistant. Integrons, a genetically stable and efficient system, confer to bacteria as highly adaptive and low cost evolution potential to bacteria, even more serious when associated with high-risk clones, indicating an urgent need for control and prevention strategies to avoid the spread of resistance determinants in Brazil. Despite this, although the class 1 integron identified in the KPC-2-producing K. pneumoniae clones is important, our findings suggest that other elements probably have a greater impact on the spread of antimicrobial resistance, since many of these important genes were not related to this cassette.