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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.

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., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Vitelhe F de Almeida, Raquel CC Dantas, Melina L Ferreira, Jane E Urzedo, Elias R de Almeida Junior, Sabrina Royer, Paulo P Gontijo-Filho, Rosineide M Ribas.)

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.

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 bla KPC-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, IS Kpn13 , in a strain recovered from the blood that have bla KPC-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 .

Background: Studies show that healthcare-associated infections (HAIs) represent a crucial issue in healthcare and can lead to substantial economic impacts in intensive care units (ICUs)., Aim: To estimate direct costs associated with the most significant HAIs in 50 teaching hospitals in Brazil, affiliated to the unified health system (Sistema Único de Saúde: SUS)., Methods: A Monte Carlo simulation model was designed to estimate the direct costs of HAIs; first, epidemiologic and economic parameters were established for each HAI based on a cohort of 949 critical patients (800 without HAI and 149 with); second, simulation based on three Brazilian prevalence scenarios of HAIs in ICU patients (29.1%, 51.2%, and 61.6%) was used; and third, the annual direct costs of HAIs in 50 university hospitals were simulated., Findings: Patients with HAIs had 16 additional days in the ICU, along with an extra direct cost of US$13.892, compared to those without HAIs. In one hypothetical scenario without HAI, the direct annual cost of hospital care for 26,649 inpatients in adult ICUs of 50 hospitals was US$112,924,421. There was an increase of approximately US$56 million in a scenario with 29.1%, and an increase of US$147 million in a scenario with 61.6%. The impact on the direct cost became significant starting at a 10% prevalence of HAIs, where US$2,824,817 is added for each 1% increase in prevalence., Conclusion: This analysis provides robust and updated estimates showing that HAI places a significant financial burden on the Brazilian healthcare system and contributes to a longer stay for inpatients., (Copyright © 2021 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

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 bla NDM-1 gene, in which some genes of the Tn 125 transposon were lost. Besides, on the chromosome, the strain reported here presented bla OXA-106 gene, a variant of bla OXA-51 gene, and bla ADC-25 with IS Aba1 upstream. The isolation of new STs of A. baumannii carrying bla NDM-1 genes elicits our concerns about the possible spread of these genes among clinically relevant bacteria.

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.

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-β-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.

Background: Little is known about the economic burden of healthcare-associated infections (HAIs) in Brazil., Aim: To analyse the costs of hospitalization by reimbursement from the Brazilian government, via the Brazilian Unified Health System (SUS) affiliation, and direct costs in the adult Intensive Care Unit (ICU)., Methods: The matched-pairs case-control study (83 patients with HAIs and 83 without HAIs) was performed at a referral tertiary-care teaching hospital in Brazil in January 2018. In order to calculate the HAI costs from the perspective of the payer, the total cost for each hospitalization was obtained through the Hospital's Billing Sector. Direct costs were calculated annually for 949 critical patients during 2018., Findings: The reimbursement cost per hospitalization of patients with HAIs was 75% (US$2721) higher than patients without HAIs (US$1553). When a patient has an HAI, in addition to a longer length of stay (15 days), there was an extra increase (US$996) in the reimbursement cost per hospitalization. An HAI in the ICU was associated with a total direct cost eight times higher compared with patients who did not develop infections in this unit, US$11,776 × US$1329, respectively. The direct cost of hospitalization in the ICU without HAI was 56.5% less than the reimbursement (US$1329 × US$3052, respectively), whereas for the patient with an HAI, the direct cost was 111.5% above the reimbursement (US$11,776 × US$5569, respectively)., Conclusion: HAIs contribute to a longer stay and an eight-fold increase in direct costs. It is necessary to reinforce programmes that prevent HAIs in Brazilian hospitals., (Copyright © 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

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.

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 bla KPC-2 gene on a non-Tn4401 genetic element (NTE KPC -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 bla KPC-2 gene on NTE KPC -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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

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.

Carbapenemase-producing organisms are pandemic and a significant threat to public health. We investigated the clonal relatedness of colistin-resistant Klebsiella pneumoniae strains producing KPC-type carbapenemase (KPC-KP) causing subsequent infections or colonization. Moreover, we aimed to gain insight into the ability of biofilm production in K. pneumoniae strains producing carbapenemase. Twenty-two consecutive KPC-KP and one KPC-negative strain was identified from an adult intensive care unit in Brazil. Seventy-five percent of isolates that harbored the bla KPC gene exhibited genetic relatedness by pulsed-field gel electrophoresis, and none presented the plasmid-mediated mcr-1 and bla NDM genes. This study showed that the majority of repeated KPC infections in adults were caused by a clone that caused the previous infections/colonizations even after a long period of time and illustrates the capacity of multiple clones producing biofilms to coexist in the same patient at the same time, becoming a reservoir of KPC-KP in the hospital environment.

Background: Healthcare-associated infection (HAI) represents a major problem for patient safety worldwide., Aim: To provide an up-to-date picture of the extent, aetiology, risk factors and patterns of infections in intensive care units (ICUs) in 28 Brazilian hospitals of different sizes., Methods: A one-day point prevalence survey in 2016 enrolled the ICUs of hospitals from the 12 meso-regions in Minas Gerais state, south-east Brazil. Hospitals were classified as university or non-university hospitals. All patients with >48 h of admission to the study ICUs at the time of the survey were included., Findings: In total, 303 patients were studied; of these, 155 (51.2%) were infected and 123 (79.4%) had at least one ICU-acquired infection. The most common ICU-acquired infections were pneumonia (53.0%) and bloodstream infection (27.6%). One hundred and nineteen bacterial isolates were cultured; the most common were Acinetobacter baumannii (27.1%), Pseudomonas aeruginosa (27.1%) and Staphylococcus aureus (39.0%). According to type of infection, the most common pathogens were P. aeruginosa (30.4%) in pneumonia, coagulase-negative staphylococci (23.4%) and Enterobacteriaceae (23.4%) in bloodstream infections, and Enterobacteriaceae (47.6%) in urinary tract infections., Conclusion: This study found that the overall prevalence of ICU-acquired infections in surveyed Brazilian hospitals was higher than that reported in most European countries and the USA. A greater proportion of infections were caused by non-fermenting Gram-negative bacteria. These observations, along with a high rate of antimicrobial use, illustrate the urgent need for HAIs to be a priority in the public health agenda of Brazil., (Copyright © 2018 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

The emergence of infections associated to new antimicrobial resistance in Acinetobacter baumannii (Ab) genotypes represents a major challenge. In this context, this study aimed to determine the diversity of resistance mechanisms and investigate clonal dissemination and predominant sequence types (STs) in multidrug-resistant Ab strains of clinical (tracheal aspirate, n = 17) and environmental (surface, n = 6) origins. Additionally, the major clones found in clinical (A) and environmental (H) strains had their complete genomes sequenced. All strains were submitted to polymerase chain reactions (PCR) for the detection of the ISAba1/blaOXA-51-like and ISAba1/blaOXA-23-like genes, while the expression of genes encoding the carO porin, AdeABC (adeB), AdeFGH (adeG), and AdeIJK (adeJ) efflux pumps was determined by real time PCR (qPCR). Most of the strains were characterized as extensively drug-resistant (XDR) with high minimal inhibitory concentrations (MICs) detected for tigecycline and carbapenems. Associations between ISAba1/OXA-51 and ISAba1/OXA-23 were observed in 91.3% and 52.2% of the strains, respectively. Only the adeB gene was considered hyper-expressed. Furthermore, most of the strains analyzed by the MuLtilocus Sequence-Typing (MLST) were found to belong to the clonal complex 113 (CC113). In addition, a new ST, ST1399, belonging to CC229, was also discovered herein. Strains analyzed by whole genome sequencing presented resistance genes linked to multidrug-resistance phenotypes and confirmed the presence of Tn2008, which provides high levels carbapenem-resistance., Competing Interests: The authors have declared that no competing interests exist.

In this study, we describe the frequency of virulence genes in Klebsiella pneumoniae carbapenemase-2-producing Klebsiella pneumoniae (KPC-KP), including hypervirulent (hv) and hypermucoviscous (hm) strains by whole-genome sequencing. We also evaluate the capacity for biofilm formation by using phenotypic techniques. The occurrence of several virulence genes (fimABCDEFGHIK, mrkABCDFHJ, ecpA, wabG, entB, ugE, irp1, irp2, traT, iutA and ureADE) and a high frequency of hvhmKPC-KP isolates was found. Most hospital-associated lineages of KPC-KP belong to the international clonal group 258 (CG258). Biofilm formation was a constant feature among 90.9 % of KPC-KP strains. This report suggests a close relationship between ST437 and weak biofilm production, given that all weakly biofilm-producing strains belonged to this sequence type. This also supports the dissemination of KPC-KP containing numerous virulence determinants belonging to the biofilm-producing CG258 type in Brazil, including hv and hm strains. These factors allow this pathogen to cause infections, leading to its rapid expansion and persistence in hospital settings.

IncX-type plasmids have achieved clinical significance for their contribution in the dissemination of genes confering resistance to carbapenems (most bla KPC - and bla NDM -type genes) and polymyxins (mcr-type genes), both antibiotics considered last resort for multidrug-resistant Gram-negative infections. In this study, we report the identification and complete sequence analysis of an IncX3 plasmid (designated pKP1194a) carrying a non-Tn4401 genetic element (NTE KPC ) of tnpR-tnpA (partial)-bla KPC-2 -ΔISKpn6/traN, originating from a hospital-associated lineage of K. pneumoniae belonging to the ST340/CG258, with epidemiological link to Brazil., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Plasmid-mediated quinolone resistance (PMQR) determinants combined with mutations in quinolone resistance-determining regions (QRDRs) and clonal dissemination were investigated in 40 fluoroquinolone-resistant Klebsiella pneumoniae and Escherichia coli isolates from nosocomial and community-acquired infections. We observed nucleotide substitutions in gyrA (Ser83Ile, Val37Leu, Lys154Arg, Ser171Ala, Ser19Asn, Ile198Val, Ser83Tyr, Ser83Leu, Asp87Asn and Asp87Gly) and parC genes (Ser80Ile, Glu84Lys, Ala129Ser, Val141Ala and Glu84Gly). Two novel substitutions were detected in the gyrA gene (Val37Leu and Ile198Val). The presence of PMQR genes predominated in community isolates (55.5 %). In addition to the frequent presence of the class 1 integron in isolates from community-acquired infections, the genetic similarity results obtained by PFGE showed high genomic diversity. This study suggests that management of multidrug-resistant Enterobacteriaceae isolates from the community are a possible source of genetic mobile elements that carry genes that confer resistance to fluoroquinolones. More attention should be paid to the surveillance of community-acquired infections.

Background: Healthcare-associated infections (HCAIs) challenge public health in developing countries such as Brazil, which harbour social inequalities and variations in the complexity of healthcare and regional development., Aim: To describe the prevalence of HCAIs in hospitals in a sample of hospitals in Brazil., Methods: A prevalence survey conducted in 2011-13 enrolled 152 hospitals from the five macro-regions in Brazil. Hospitals were classified as large (≥200 beds), medium (50-199 beds) or small sized (<50 beds). Settings were randomly selected from a governmental database, except for 11 reference university hospitals. All patients with >48 h of admission to the study hospitals at the time of the survey were included. Trained epidemiologist nurses visited each hospital and collected data on HCAIs, subjects' demographics, and invasive procedures. Univariate and multivariate techniques were used for data analysis., Findings: The overall HCAI prevalence was 10.8%. Most frequent infection sites were pneumonia (3.6%) and bloodstream infections (2.8%). Surgical site infections were found in 1.5% of the whole sample, but in 9.8% of subjects who underwent surgical procedures. The overall prevalence was greater for reference (12.6%) and large hospitals (13.5%), whereas medium- and small-sized hospitals presented rates of 7.7% and 5.5%, respectively. Only minor differences were noticed among hospitals from different macro-regions. Patients in intensive care units, using invasive devices or at extremes of age were at greater risk for HCAIs., Conclusion: Prevalence rates were high in all geographic regions and hospital sizes. HCAIs must be a priority in the public health agenda of developing countries., (Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

The bacterial factors associated with bacteremia by multidrug-resistant and extensively drug-resistant P. aeruginosa, including overexpression of efflux pumps, AmpC overproduction, and loss/alteration of the OprD porin in isolates that are non-Metallo-β-Lactamase producing were analyzed in a retrospective study. Molecular analyses included strain typing by Pulsed Field Gel Electrophoresis and identification of key genes via qualitative and quantitative PCR-based assays. Previous use of carbapenems and tracheostomy was independently associated with the development of bacteremia by extensively drug-resistant and multidrug-resistant strains of P. aeruginosa. A high consumption of antimicrobials was observed, and 75.0% of the isolates contained amplicons with the blaSPM-1 and blaVIM genes. Of the 47 non-Metallo-β-Lactamase isolates, none had another type of carbapenemase. However, the isolates exhibited high rates of hyperproduction of AmpC, loss of the OprD porin (71.4%) and the presence of MexABOprM (57.1%) and MexXY (64.3%). This study suggests that in non-Metallo-β-Lactamase isolates, the association of intrinsic resistance mechanisms could contributes to the expression of multidrug-resistant/extensively drug-resistant phenotypes.

Pseudomonas aeruginosa is an opportunistic pathogen that causes frequently nosocomial infections, currently becoming more difficult to treat due to the various resistance mechanisms and different virulence factors. The purpose of this study was to determine the risk factors independently associated with the development of bacteremia by carbapenem-resistant P. aeruginosa, the frequency of virulence genes in metallo-β-lactamases producers and to evaluate their ability to produce biofilm. We conducted a case-control study in the Uberlândia Federal University - Hospital Clinic, Brazil. Polymerase Chain Reaction was performed for metallo-β-lactamases and virulence genes. Adhesion and biofilm assays were done by quantitative tests. Among the 157 strains analyzed, 73.9% were multidrug-resistant, 43.9% were resistant to carbapenems, 16.1% were phenotypically positive for metallo-β-lactamases, and of these, 10.7% were positive for bla SPM gene and 5.3% positive for bla VIM . The multivariable analysis showed that mechanical ventilation, enteral/nasogastric tubes, primary bacteremia with unknown focus, and inappropriate therapy were independent risk factors associated with bacteremia. All tested strains were characterized as strongly biofilm producers. A higher mortality was found among patients with bacteremia by carbapenem-resistant P. aeruginosa strains, associated independently with extrinsic risk factors, however it was not evident the association with the presence of virulence and metallo-β-lactamases genes., (Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Background: Carbapenem-resistant Enterobacteriaceae (CRE), especially those that produce Klebsiella pneumoniae carbapenemase (KPC) and are associated with colistin resistance, pose a severe health threat due to the limited treatment options., Aim: To describe two outbreaks of KPC-producing K. pneumoniae in an adult intensive care unit (AICU) in Brazil. In May 2015, 14 patients had colistin-susceptible KPC-producing strains (ColS-KPC), and in July 2015, nine patients had colistin-resistant KPC-producing strains (ColR-KPC)., Methods: Between September 2014 and August 2015, we performed surveillance at a university hospital and all CRE were tested for bla KPC genes. Clonality was investigated by pulsed-field gel electrophoresis. Resistance to colistin was confirmed by broth microdilution method. Consumption of carbapenems and colistin was expressed as defined daily doses., Findings: In all, 111 patients with CRE were identified during the surveillance period; K. pneumoniae was the major isolate (77.13%). The two outbreaks were identified when infection rates (KPC per 1000 patient-days) exceeded the background level. Rates of carbapenem and colistin consumption were high. Control measures (bedside alcohol gel, contact precautions, regular rectal swabs) did not curtail the outbreaks. Mortality rates were 42.9% and 44.4% for ColS-KPC- and ColR-KPC-infected patients, respectively. After the death of four infected patients with ColR-KPC, the unit was closed to new admissions., Conclusion: Our experience demonstrates the serious risks presented by KPC, and especially ColR-KPC, in Brazilian AICUs. Selective pressure from excessive antibiotic use and transmission on healthcare workers' hands were likely the major factors in transmission., (Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

We described a comprehensive analysis of the molecular epidemiology of multidrug-resistant (MDR) P. aeruginosa. Molecular analysis included typing by Pulsed Field Gel Electrophoresis, identification of genes of interest through PCR-based assays and sequencing of target genes. Case-control study was conducted to better understand the prognostic of patients and the impact of inappropriate therapy in patients with bacteremia, as well as the risk factors of MDR infections. We observed a high rate of MDR isolates (40.7%), and 51.0% of them was independently associated with inappropriate antibiotic therapy. Bacteremia was detected in 66.9% of patients, and prolonged hospital stay was expressive in those resistant to fluoroquinolone. Plasmid-mediated quinolone resistance genes (PMQR), qnrS1 and aac(6')Ib-cr, were detected in two different nosocomial isolates (5.3%), and the aac(6')-Ib7 variant was detected at a high frequency (87.5%) in those negative to PMQR. The presence of mutations in gyrA and parC genes was observed in 100% and 85% of selected isolates, respectively. Isolates harboring PMQR genes or mutations in gyrA and parC were not closely related, except in those containing SPM (São Paulo metallo-β-lactamase) clone. In addition, there is no study published in Brazil to date reporting the presence of Pseudomonas aeruginosa isolates harboring both qnrS1 and aac(6')Ib-cr genes, with alarming frequency of patients with inappropriate therapy.

The emergence of Acinetobacter baumannii and Klebsiella pneumoniae strains in the hospital environment has been associated with the presence of multiple genetic elements, virulence factors and the ability to form biofilms. This study evaluated the biofilm formation ability of clinical and environmental A. baumannii and K. pneumoniae strains, isolated from various sources and presenting different molecular characteristics, resistance profiles and pulsed-field gel electrophoresis patterns. Fifty-three isolates were recovered from 2009 to 2014 in a Brazilian university hospital. Investigation of biofilm formation was performed for 10 strains of each species assessed by an initial adhesion assay, biofilm cell concentration and biofilm biomass, evaluated by quantitative assays in replicates, in three independent experiments. All strains of A. baumannii were able to attach to polystyrene plates, although two strains adhered to a lesser degree than the control. K. pneumoniae strains showed opposite behaviour, where only three strains adhered significantly when compared to the control. Quantitative evaluation revealed that in five A. baumannii and four K. pneumoniae isolates the biomass production could be characterised as moderate. None of the isolates were strong biofilm producers. Our results demonstrate: (1) biofilm formation is a heterogeneous property amongst A. baumannii and K. pneumoniae clinical strains and it was not associated with certain clonal types; (2) no relationship between multidrug resistance and biofilm production was observed; (3) more virulent K. pneumoniae strains tended to present higher production of biofilm.

Background: In Brazil, ventilator-associated pneumonia (VAP) caused by carbapenem resistant Acinetobacter baumannii and Pseudomonas aeruginosa isolates are associated with significant mortality, morbidity and costs. Studies on the clonal relatedness of these isolates could lay the foundation for effective infection prevention and control programs., Objectives: We sought to study the epidemiological and molecular characteristics of A. baumannii vs. P. aeruginosa VAP in an adult intensive care unit (ICU)., Methods: It was conducted a cohort study of patients with VAP caused by carbapenem resistant A. baumannii and P. aeruginosa during 14 months in an adult ICU. Genomic studies were used to investigate the clonal relatedness of carbapenem resistant OXA-23-producing A. baumannii and P. aeruginosa clinical isolates. The risk factors for acquisition of VAP were also evaluated. Clinical isolates were collected for analysis as were samples from the environment and were typed using pulsed field gel electrophoresis., Results: Multivariate logistic regression analysis identified trauma diagnosed at admission and inappropriate antimicrobial therapy as independent variables associated with the development of A. baumannii VAP and hemodialysis as independent variable associated with P. aeruginosa VAP. All carbapenem resistant clinical and environmental isolates of A. baumannii were OXA-23 producers. No MBL-producer P. aeruginosa was detected. Molecular typing revealed a polyclonal pattern; however, clone A (clinical) and H (surface) were the most frequent among isolates of A. baumannii tested, with a greater pattern of resistance than other isolates. In P. aeruginosa the most frequent clone I was multi-sensitive., Conclusion: These findings suggest the requirement of constant monitoring of these microorganisms in order to control the spread of these clones in the hospital environment., (Copyright © 2015 Elsevier Editora Ltda. All rights reserved.)

This study evaluated the predictors of mortality and the impact of inappropriate therapy on the outcomes of patients with bacteraemia and ventilator-associated pneumonia (VAP). Additionally, we evaluated the correlation of the type III secretion system (TTSS) effector genotype with resistance to carbapenems and fluoroquinolones, mutations in the quinolone resistance-determining regions (QRDRs), metallo-β-lactamase and virulence factors. A retrospective cohort was conducted at a tertiary hospital in patients with multidrug-resistant (MDR) P. aeruginosa bacteraemia (157 patients) and VAP (60 patients). The genes for blaIMP, blaVIM, blaSIM, blaGIM and blaSPM and virulence genes (exoT, exoS, exoY, exoU, lasB, algD and toxA) were detected; sequencing was conducted for QRDR genes on fluoroquinolone-resistant strains. The multivariate analyses showed that the predictors independently associated with death in patients with bacteraemia were cancer and inappropriate therapy. Carbapenem resistance was more frequent among strains causing VAP (53.3 %), and in blood we observed the blaSPM genotype (66.6 %) and blaVIM genotype (33.3 %). The exoS gene was found in all isolates, whilst the frequency was low for exoU (9.4 %). Substitution of threonine to isoleucine at position 83 in gyrA was the most frequent mutation among fluoroquinolone-resistant strains. Our study showed a mutation at position 91 in the parC gene (Glu91Lys) associated with a mutation in gyrA (Thre83Ile) in a strain of extensively drug-resistant P. aeruginosa, with the exoT(+)exoS(+)exoU(+) genotype, that has not yet been described in Brazil to the best of our knowledge. This comprehensive analysis of resistance mechanisms to carbapenem and fluoroquinolones and their association with TTSS virulence genes, covering MDR P. aeruginosa in Brazil, is the largest reported to date., (© 2015 The Authors.)

Aim: We assessed late onset sepsis (LOS) rates of neonates in a neonatal intensive care unit (NICU) before and after implementing an evidence-based bundle to prevent these infections in a country with poor resources., Methods: We evaluate trends of LOS between October 2010 and August 2012 in a large tertiary hospital in Brazil. We designed a protocol based of CDC guidelines for insertion of maintenance of central venous catheter targeted to reduction of bloodstream infections. During this period two major events occurred: a great increase of LOS rates in January months and relocation of the unit to a provisory place. Additionally we evaluated the risk factors and etiology of these infections., Results: A total of 112 (20.3%) cases defined as LOS were found. The overall incidence rate of LOS in the study was 16.1/1000 patient/days and 23.0/1000 CVC-days. Our monthly rates data of LOS/1000 patient-day reveal fluctuations over the studied period, with incidence rates of these infections in staff vacation period (January 2011 and 2012) significantly higher (59.6/1000 patients-days) than compared with the other months rates (16.6/1000 patients-days) (IRR=3.59; p<0.001). As opposite, the incidence rates of LOS during relocation period was lower (10.3/1000 patients-days) when compared with baseline period 26.7/1000 patients-days (IRR=2.59; p=0.007). After the intervention period, these rates decreased in the post intervention period, when compared with preintervention 14.7/1000 patients-days and 23.4/1000 patients-days, respectively (IRR=1.59; p=0.04)., Conclusion: Through simple infection control measures, LOS can be successfully controlled especially in NICUs of limited resources countries such as ours., (Copyright © 2014 Elsevier Editora Ltda. All rights reserved.)

The rates of multidrug-resistant, extensively drug-resistant and pandrug-resistant isolates amongst non-fermenting Gram-negative bacilli, particularly Pseudomonas aeruginosa, have risen worldwide. The clinical consequence of resistance and the impact of adverse treatment on the outcome of patients with P. aeruginosa bacteraemia remain unclear. To better understand the predictors of mortality, the clinical consequence of resistance and the impact of inappropriate therapy on patient outcomes, we analysed the first episode of P. aeruginosa bacteraemia in patients from a Brazilian tertiary-care hospital during the period from May 2009 to August 2011. Antimicrobial susceptibility testing was conducted; phenotypic detection of metallo-β-lactamase (MBL) and PCR of MBL genes were performed on carbapenem-resistant strains. Amongst the 120 P. aeruginosa isolates, 45.8 % were resistant to carbapenem and 36 strains were tested for MBL detection. A total of 30 % were phenotypically positive and, of these, 77.8 % expressed an MBL gene, bla(SPM-1) (57 %) and bla(VIM-type) (43 %). The resistance rates to ceftazidime, cefepime, piperacillin/tazobactam, carbapenem, fluoroquinolone and aminoglycoside were 55, 42.5, 35, 45.8, 44 and 44 %, respectively. Previous antibiotic use, length of a hospital stay ≥30 days prior to P. aeruginosa, haemodialysis, tracheostomy, pulmonary source of bacteraemia and Intensive Care Unit admission were common independent risk factors for antimicrobial resistance. Cefepime resistance, multidrug resistance and extensive drug resistance were independently associated with inappropriate therapy, which was an important predictor of mortality, being synergistic with the severity of the underlying disease., (© 2014 The Authors.)

This study evaluated the relationship between previous colonization of the oropharynx and development of ventilator-associated pneumonia through the classification of genomic fingerprint pattern by pulsed-field gel electrophoresis of both oxacillin-resistant and oxacillin-susceptible Staphylococcus aureus isolates obtained from hospitalized patients in an intensive care unit.