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Objective: The present study aimed to describe ICU antibiotic use based on data reported from 2009 to 2018 to the Nosocomial Surveillance System (NSS) of the State Health Department in the State of Sao Paulo, Brazil., Design: Ecological study., Setting: Data obtained from hospitals located in the state of São Paulo, Brazil from 2009 to 2018., Participants: Intensive care units located at participant hospitals., Methods: Data on healthcare-associated infections, antibiotic usage, and bacterial identification were collected and reported monthly by hospitals. Antibiotic consumption was quantified as defined daily doses (DDD) per 1000 patient-days. The relationship between antibiotic use and bacterial resistance, categorized by hospital type and ICU complexity, was analyzed using statistical methods to assess correlations and significance., Results: Our findings reveal an escalating trend in antibiotic consumption over the study period, with a notable increase from 588.16 DDD per 1000 patient-days in the initial year to 943.12 DDD/1000 patient-days in the final year (p < 0.01). Cephalosporins emerged as the most frequently utilized class, accounting for 33.9% of total antibiotic consumption. Public hospitals exhibited significantly higher antibiotic use compared to private and philanthropic institutions, with a mean of 889.11 DDD/1000 patient-days in public hospitals compared to 849.07 DDD/1000 patient-days in private hospitals and 785.12 DDD/1000 patient-days in philanthropic hospitals (p < 0.05)., Conclusions: The study provides critical insights into antibiotic use and resistance in different hospital settings, emphasizing the importance of tailored antimicrobial stewardship strategies., Competing Interests: All authors report no conflicts of interest relevant to this article., (© The Author(s) 2025.)

Background: Hospital acquired infections (HAI) and liberal use of broad-spectrum antibiotics are common in intensive care unit(ICU)s of low-middle income countries. We investigated the long-term association of a stepwise multifaceted educational program with the incidence of HAIs and antibiotics use in a Brazilian ICU. We also evaluated the program's cost impact., Methods: We retrieved data from a prospective daily collected database of a twelve bedrooms ICU, all admitted patients within a period of eleven years were enrolled., Findings: From 03/15/2007 to 09/11/2019, we admitted 3059 patients where 2406 (79%) survived the ICU stay. Median age was 51 years-old, and median SAPS3 was 53. The initial density of catheter related blood infection (4.3 events / 1000 patients-day), urinary tract infection (9.2 event / 1000 patients-day) and ventilator associated pneumonia (54.9 events / 1000 patients-day) felt during the observed period to (0.35 events / 1000 patients-day), (0 events / 1000 patients-day), and (1.5 events / 1000 patients-day) respectively. The days of antibiotic therapy also decreased from 797.9 days of therapy / 1000 patients day to 292.3 days of therapy / 1000 patients day. The total cost per patient also decreased. The adjusted mortality rate was steady during the studied period from 23.2% to 22.9%., Interpretation: A stepwise multifaceted educational program is an effective way to reduce hospital-associated infections, improve the rational use of antibiotics, and reduce costs. This impact occurred in a long term, and is probably consistent., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Overcrowded emergency departments (EDs) may increase the risk of carbapenem-resistant Enterobacterales (CRE) transmission., Methods: We conducted a quasi-experimental study divided into 2 phases (baseline and intervention) to investigate the impact of an intervention on the acquisition rate and identify risk factors for CRE colonization in an ED of a tertiary academic hospital in Brazil. In both phases, we did universal screening with rapid molecular test (blaKPC, blaNDM, blaOXA48, blaOXA23, and blaIMP) and culture. At baseline, both screening test results were not reported, and patients were put under contact precautions (CP) based on previous colonization or infection by multidrug-resistant organisms. During the intervention, all patients hospitalized in the ED were placed in empiric CP and the result of CRE screening was reported; if negative, patients were released from CP. Patients were rescreened if they stayed >7 days in the ED or were transferred to an intensive care unit., Results: A total of 845 patients were included: 342 in baseline and 503 in intervention. Colonization at admission was 3.4% by culture and molecular test. Acquisition rates during ED stay dropped from 4.6% (11/241) to 1% (5/416) during intervention (P = .06). The aggregated antimicrobial use in the ED decreased from phase 1 to phase 2 (804 defined daily doses [DDD]/1000 patients to 394 DDD/1000 patients, respectively). Length of stay >2 days in the ED was a risk factor for CRE acquisition (adjusted odds ratio, 4.58 [95% confidence interval, 1.44-14.58]; P = .01)., Conclusions: Early empiric CP and rapid identification of CRE-colonized patients reduce cross-transmission in ED. Nevertheless, staying >2 days in ED compromised efforts., Competing Interests: Potential conflicts of interest. M. C. S. received research funding from FAPESP, CDC, and JHPiego; grants from Cepheid as a speaker; and holds stocks with Petrobras and Vale do Rio Doce. I. B. received funding from FAPESP to support this study and additional funding from the CDC and JHPiego. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Regulatory authorities authorize the clinical use of generic drugs (GD) based on bioequivalence studies, which consist of the evaluation of pharmacokinetics after a single dose in vitro or in healthy individuals. There are few data on clinical equivalence between generic and branded antibiotics. Our aim was to synthesize and analyze the available evidence on the clinical efficacy and safety of generic antibiotics compared to their original formulations. A systematic review was performed on Medline ( PubMed ) and Embase and validated through Epistemonikos and Google Scholar . The last search was conducted on 30 June 2022. Meta-analyses of clinical cure and mortality outcomes were performed. One randomized clinical trial (RCT) and 10 non-randomized intervention studies were included. No differences in clinical cure were observed between groups in the meta-analysis (OR = 0.89, 95% CI [0.61-1.28]; I 2 = 70%, p = 0.005). No difference was observed between groups when considering the use of carbapenems for overall mortality (OR = 0.99, 95% CI [0.63-1.55]; I 2 = 78%) or death associated with infections (OR = 0.79, 95% CI [0.48-1.29], I 2 = 67%). Most of the studies were observational, and the duration of follow-up, the characteristics of the participants, and the sites of infections were heterogeneous. Due to the uncertainty of the evidence, it is not possible to contraindicate the use of generics, which is an important strategy to expand access.

Objectives: Bacterial and aseptic meningitis after neurosurgery can present similar clinical signs and symptoms. The aims of this study were to develop and test a molecular method to diagnose bacterial meningitis (BM) after neurosurgery., Methods: A 16S ribosomal RNA gene PCR-based strategy was developed using artificially inoculated cerebrospinal fluid (CSF) followed by sequencing. The method was tested using CSF samples from 43 patients who had undergone neurosurgery and were suspected to suffer from meningitis, and from 8 patients without neurosurgery or meningitis. Patients were classified into five groups, confirmed BM, probable BM, possible BM, unlikely BM, and no meningitis., Results: Among the samples from the 51 patients, 21 samples (41%) were culture-negative and PCR-positive. Of these, 3 (14%) were probable BM, 4 (19%) were possible BM, 13 (62%) were unlikely BM, and 1 (5%) was meningitis negative. Enterobacterales, non-fermenters (Pseudomonas aeruginosa and Acinetobacter baumannii), Staphylococcus haemolyticus, Granulicatella, Variovorax, and Enterococcus cecorum could be identified. In the group of patients with meningitis, a good agreement (3 of 4) was observed with the results of cultures, including the identification of species., Conclusion: Molecular methods may complement the diagnosis, guide treatment, and identify non-cultivable microorganisms. We suggest the association of methods for suspected cases of BM after neurosurgery, especially for instances in which the culture is negative.

Objectives: Enterobacterales and other non-fermenting Gram-negative bacteria have become a threat worldwide owing to the frequency of multidrug resistance in these pathogens. On the other hand, efficacious therapeutic options are quickly diminishing. The aims of this study were to describe the susceptibility of 50 multiresistant Gram-negative bacteria, mostly pan-resistant, against old and less-used antimicrobial drugs and to investigate the presence of antimicrobial resistance genes., Methods: A total of 50 genetically distinct isolates were included in this study, including 14 Acinetobacter baumannii (belonging to ST79, ST317, ST835 and ST836), 1 Pseudomonas aeruginosa (ST245), 8 Serratia marcescens and 27 Klebsiella pneumoniae (belonging to ST11, ST340, ST258, ST16, ST23, ST25, ST101, ST234, ST437 and ST442). The isolates were submitted to antimicrobial susceptibility testing and whole-genome sequencing to evaluate lineages and resistance genes., Results: Our results showed that some strains harboured carbapenemase genes, e.g. bla KPC-2 (28/50; 56%) and bla OXA-23 (11/50; 22%), and other resistance genes encoding aminoglycoside-modifying enzymes (49/50; 98%). Susceptibility rates to tigecycline (96%) in all species (except P. aeruginosa), to minocycline (100%) and doxycycline (93%) in A. baumannii, to ceftazidime/avibactam in S. marcescens (100%) and K. pneumoniae (96%), and to fosfomycin in S. marcescens (88%) were high. Chloramphenicol and quinolones (6% susceptibility each) did not perform well, making their use in an empirical scenario unlikely., Conclusions: This study involving genetically distinct bacteria showed promising results for tigecycline for all Gram-negative bacteria (except P. aeruginosa), and there was good activity of minocycline against A. baumannii, ceftazidime/avibactam against Enterobacterales, and fosfomycin against S. marcescens., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Use of antibiotic and bacterial resistance is the result of a complex interaction not completely understood., Objectives: To evaluate the impact of entire antimicrobial use (community plus hospitals) on the incidence of bloodstream infections in intensive care units adjusted by socioeconomic factors, quality of healthcare, and access to the healthcare system., Design: Ecologic study using a hierarchical spatial model., Setting: Data obtained from 309 hospitals located in the state of São Paulo, Brazil from 2008 to 2011., Participants: Intensive care units located at participant hospitals., Outcome: Hospital acquired bloodstream infection caused by MDRO in ICU patients was our primary outcome and data were retrieved from São Paulo Health State Department. Socioeconomic and healthcare indexes data were obtained from IBGE (Brazilian Foundation in charge of national decennial census) and SEADE (São Paulo Planning and Development Department). Information on antimicrobial sales were obtained from IMS Brazil. We divided antibiotics into four different groups (1-4)., Results: We observed a direct association between the use of group 1 of antibiotics and the incidences of bloodstream infections caused by MRSA (1.12; 1.04-1.20), and CR-Acinetobacter sp. (1.19; 1.10-1.29). Groups 2 and 4 were directly associated to VRE (1.72; 1.13-2.39 and 2.22; 1.62-2.98, respectively). Group 2 was inversely associated to MRSA (0.87; 0.78-0.96) and CR-Acinetobacter sp. (0.79; 0.62-0.97). Group 3 was inversely associated to Pseudomonas aeruginosa (0.69; 0.45-0.98), MRSA (0.85; 0.72-0.97) and VRE (0.48; 0.21-0.84). No association was observed for third generation cephalosporin-resistant Klebsiella pneumoniae and Escherichia coli., Conclusions: The association between entire antibiotic use and resistance in ICU was poor and not consistent for all combinations of antimicrobial groups and pathogens even after adjusted by socioeconomic indexes. Selective pressure exerted at the community level seemed not to affect the incidences of MDRO infection observed in intensive care setting., (Copyright © 2020 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The global spread of carbapenemase-producing organisms (CPO) has been considered by international health authorities as a critical public health concern. Brazil has a high CPO prevalence according to distinct publications but many routine microbiology laboratories have only phenotypic resources to evaluate this epidemiological situation, which is time-consuming and detects only carbapenem-resistant isolates missing CPO susceptible expressing a slightly decreased susceptibility. New molecular platforms can detect CPO faster but a local evaluation is essential., Aim: To evaluate the performance of CPO detection direct from rectal swabs with the Xpert Carba-R™ assay (Cepheid, Sunnyvale, CA) in the largest Brazilian University Hospital., Methods: A prospective diagnostic accuracy study of CPO was performed with the collection of rectal swabs from patients admitted into the Intensive Care Unit (ICU) and into the Emergency Department (ED) between April and July 2016. The Xpert Carba-R™ assay results were compared with carbapenem-resistant Enterobacterales (CRE) surveillance cultures plus in-house PCR carbapenemase detection (reference method). In case of discordant results between methods, additional tests were performed. The limit of detection (LoD) for the CRE culture and the Xpert Carba-R™ assay were performed with contrived isolates of known carbapenemases genes., Results: A total of 921 clinical rectal swabs were analyzed being 21% (196/921) from the ICU and 79% (725/921) from the ED. Overall, the Xpert Carba-R™ assay detected 9.9% (91/921) of CPOs being 9.5% (87/921) positive only for bla KPC and 0.4% (4/921) positive only for bla NDM. The reference method detected 9.1% (84/921) CPO being 77 (8.4%) bla KPC, 5 bla VIM (0.5%) and 2 bla NDM (0.2%). No IMP or OXA-48 like gene was detected. Overall, twelve samples, 1.3% (10 bla KPC , 2 bla NDM ) were Xpert Carba-R™ positive but negative by the reference method. Five isolates (0.5%) were positive for bla VIM only by in-house PCR and confirmed to be bla VIM-2 by DNA sequencing. The Kappa value, sensitivity, specificity, positive/negative predictive values and accuracy of the Xpert Carba-R™ assay were; 0.893 (95% confidence interval [CI], 0.842-0.944), 94% (86.7-98.0), 98.6% (97.5-99.3), 86.8% (78.1-93.0), 99.4% (98.6-99.8) and 98.2% (97.3-99.1), respectively. The LoD for bla KPC of the Xpert Carba-R™ assay and the CRE cultures were 10 1  CFU/swab., Conclusion: The Xpert Carba-R™ assay is an accurate test to detect CPO directly from the rectal swabs with significant lower turnaround time (TAT) when compared to the reference method (CRE culture plus in-house PCR). Xpert Carba-R™ may, therefore, be regarded as a good and fast epidemiological tool., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Case Presentation: We present a case report of a woman, concurrently colonized by polymyxin-resistant E. coli and K. pneumoniae. A Brazilian female patient, in her mid-fifties, was hospitalized with schistosomiasis. During hospitalization, polymyxin-resistant E. coli and K. pneumoniae were isolated from surveillance cultures., Methods: Identification, antimicrobial susceptibility testings, PCR for mcr-1, plasmid transfer by conjugation and whole genome sequencing were performed., Results: E. coli ST744 and K. pneumoniae ST101 carrying mcr-1 gene were described. Transconjugant E. coli was positive for mcr-1 and IncX4 by PCR. The plasmid is a 33,304-base pair plasmid, and the mcr-1 gene was the only antimicrobial resistance gene present in the plasmid., Conclusions: This study presents a case report of a hospitalized woman, concurrently colonized by mcr-1-harboring E. coli ST744, a different ST from previously described in Brazil, and a K. pneumoniae ST101.