Diagnostic Prediction Model for Tuberculous Meningitis: An Individual Participant Data Meta-Analysis.

No accurate and rapid diagnostic test exists for tuberculous meningitis (TBM), leading to delayed diagnosis. We leveraged data from multiple studies to improve the predictive performance of diagnostic models across different populations, settings, and subgroups to develop a new predictive tool for TBM diagnosis. We conducted a systematic review to analyze eligible datasets with individual-level participant data (IPD). We imputed missing data and explored three approaches: stepwise logistic regression, classification and regression tree (CART), and random forest regression. We evaluated performance using calibration plots and C-statistics via internal-external cross-validation. We included 3,761 individual participants from 14 studies and nine countries. A total of 1,240 (33%) participants had "definite" (30%) or "probable" (3%) TBM by case definition. Important predictive variables included cerebrospinal fluid (CSF) glucose, blood glucose, CSF white cell count, CSF differential, cryptococcal antigen, HIV status, and fever presence. Internal validation showed that performance varied considerably between IPD datasets with C-statistic values between 0.60 and 0.89. In external validation, CART performed the worst (C = 0.82), and logistic regression and random forest had the same accuracy (C = 0.91). We developed a mobile app for TBM clinical prediction that accounted for heterogeneity and improved diagnostic performance (https://tbmcalc.github.io/tbmcalc). Further external validation is needed.

Green solutions for antibiotic pollution: Assessing the phytoremediation potential of aquatic macrophytes in wastewater treatment plants.

We compared the ability of one emergent (Sagittaria montevidensis), two floating (Salvinia minima and Lemna gibba), and one heterophyllous species (Myriophyllum aquaticum) to simultaneously remove sulfamethoxazole, sulfadiazine, ciprofloxacin, enrofloxacin, norfloxacin, levofloxacin, oxytetracycline, tetracycline, doxycycline, azithromycin, amoxicillin, and meropenem from wastewater in a mesocosm-scale constructed wetland over 28 days. Antibiotic concentrations in plants and effluent were analyzed using an LC-MS/MS to assess the removal rates and phytoremediation capacities. M. aquaticum did not effectively mitigate contamination due to poor tolerance and survival in effluent conditions. S. minima and L. gibba demonstrated superior efficiency, reducing the antibiotic concentrations to undetectable levels within 14 days, while S. montevidensis achieved this result by day 28. Floating macrophytes emerge as the preferable choice for remediation of antibiotics compared to emergent and heterophyllous species. Antibiotics were detected in plant tissues at concentrations ranging from 0.32 to 29.32 ng g-1 fresh weight, highlighting macrophytes' ability to uptake and accumulate these contaminants. Conversely, non-planted systems exhibited a maximum removal rate of 65%, underscoring the persistence of these molecules in natural environments, even after the entire experimental period. Additionally, macrophytes improved effluent quality regardless of species by reducing total soluble solids and phosphate concentrations and mitigating ecotoxicological effects. This study underscores the potential of using macrophytes in wastewater treatment plants to enhance overall efficiency and prevent environmental contamination by antibiotics, thereby mitigating the harmful impact on biota and antibiotic resistance. Selecting appropriate plant species is crucial for successful phytoremediation in constructed wetlands, and actual implementation is essential to validate their effectiveness and practical applicability.

Emerging threat: Antimicrobial resistance proliferation during epidemics - A case study of the SARS-CoV-2 pandemic in South Brazil.

The escalating global concern of antimicrobial resistance poses a significant challenge to public health. This study delved into the occurrence of resistant bacteria and antimicrobial resistance genes in the waters and sediments of urban rivers and correlated this emergence and the heightened use of antimicrobials during the COVID-19 pandemic. Isolating 45 antimicrobial-resistant bacteria across 11 different species, the study identifies prevalent resistance patterns, with ceftriaxone resistance observed in 18 isolates and ciprofloxacin resistance observed in 13 isolates. The detection of extended-spectrum ß-lactamases, carbapenemases, and acquired quinolone resistance genes in all samples underscores the gravity of the situation. Comparison with a pre-pandemic study conducted in the same rivers in 2019 reveals the emergence of previously undetected new resistant species, and the noteworthy presence of new resistant species and alterations in resistance profiles among existing species. Notably, antimicrobial concentrations in rivers increased during the pandemic, contributing significantly to the scenario of antimicrobial resistance observed in these rivers. We underscore the substantial impact of heightened antimicrobial usage during epidemics, such as COVID-19, on resistance in urban rivers. It provides valuable insights into the complex dynamics of antimicrobial resistance in environmental settings and calls for comprehensive approaches to combat this pressing global health issue, safeguarding both public and environmental health.

In vitro susceptibility to fosfomycin in clinical and environmental extended-spectrum beta-lactamase producing and/or ciprofloxacin-non-susceptible Escherichia coli isolates.

Extended-spectrum beta-lactamase producing and ciprofloxacin-non-susceptible Escherichia coli are clinical and environmental issues. We evaluated the susceptibility profile of fosfomycin in non-susceptible E. coli isolated from urine and the environment. We measured the activity of fosfomycin against 319 and 36 E. coli strains from urine and environmental isolates, respectively, collected from rivers. Fosfomycin resistance profiles were investigated using the minimal inhibitory concentration (MIC), according to the Clinical and Laboratory Standards Institute (CLSI) and the European Committee for Antimicrobial Susceptibility Testing (EUCAST) guidelines. Antibiotic susceptibility testing revealed that 5% and 6.6% of urine samples were non-susceptible to fosfomycin according to CLSI and EUCAST guidelines, respectively. The fosfomycin MIC50/90 was 0.5/4 mg/L. Of the 36 E. coli isolates from river water, 11.1% and 13,8% were non-susceptible to fosfomycin according to CLSI and EUCAST, respectively (range ≤0.25 ≥512 mg/L). All the isolates with MIC ≥512 mg/L for fosfomycin showed the fosA3 gene. Fosfomycin resistance was more frequent in the environment than in clinical samples.

Clinical and microbiological profile of health care-associated infections in a tertiary hospital: Comparison between a cohort of hospitalized patients during prepandemic and COVID-19 pandemic periods.

BACKGROUND: During the COVID-19 pandemic, health service practices underwent significant changes, impacting the occurrence of health care-associated infections (HAIs). This study presents the epidemiology of bacterial infections and compares clinical data on nosocomial infections in hospitalized patients before and during the pandemic. METHODS: A unicentric, observational, retrospective cohort study was conducted with descriptive analyses on the microorganism identification and resistance profile. Patient's clinical data who had hospital-acquired infection (HAI), during their hospitalization in a tertiary hospital before and during the COVID-19 pandemic was compared by descriptive and inferential analyses. RESULTS: A total of 1,581 bacteria were isolated from 1,183 hospitalized patients. Among patients coinfected with COVID-19, there was a statistically significant increase in HAI-related deaths (P < .001) and HAI caused by multidrug-resistant organisms (P < .001), mainly by Acinetobacter baumannii and Staphylococcus aureus. A higher odds ratio of HAI-related deaths compared to the prepandemic period was observed (odds ratio 6.98 [95% confidence interval 3.97-12.64]). CONCLUSIONS: The higher incidence of multidrug-resistant bacteria and increased deaths due to HAI, especially in patients with COVID-19 coinfection, might be related to various factors such as increased workload, broad-spectrum antibiotic use, and limited resources. The pandemic has changed the profile of circulating bacteria and antimicrobial resistance. Prevention strategies should be considered to reduce the impact of these infections.

In vitro susceptibility to fosfomycin in clinical and environmental extended-spectrum beta-lactamase producing and/or ciprofloxacin-non-susceptible Escherichia coli isolates

ABSTRACT Extended-spectrum beta-lactamase producing and ciprofloxacin-non-susceptible Escherichia coli are clinical and environmental issues. We evaluated the susceptibility profile of fosfomycin in non-susceptible E. coli isolated from urine and the environment. We measured the activity of fosfomycin against 319 and 36 E. coli strains from urine and environmental isolates, respectively, collected from rivers. Fosfomycin resistance profiles were investigated using the minimal inhibitory concentration (MIC), according to the Clinical and Laboratory Standards Institute (CLSI) and the European Committee for Antimicrobial Susceptibility Testing (EUCAST) guidelines. Antibiotic susceptibility testing revealed that 5% and 6.6% of urine samples were non-susceptible to fosfomycin according to CLSI and EUCAST guidelines, respectively. The fosfomycin MIC50/90 was 0.5/4 mg/L. Of the 36 E. coli isolates from river water, 11.1% and 13,8% were non-susceptible to fosfomycin according to CLSI and EUCAST, respectively (range ≤0.25 ≥512 mg/L). All the isolates with MIC ≥512 mg/L for fosfomycin showed the fosA3 gene. Fosfomycin resistance was more frequent in the environment than in clinical samples.

Analysis of Clostridioides difficile Infection in Children with Diarrhea in Two Hospitals in Southern Brazil.

Clostridioides difficile infection (CDI) has been increasingly observed in children, but there is a lack of epidemiological and molecular data on CDI in Latin America. This prospective cohort study aimed to investigate the role of CDI in children with diarrhea. It included 105 children with antimicrobial-associated diarrhea (AAD) and analyzed the molecular characteristics of strains isolated from two hospitals in southern Brazil between 2017 and 2020. Fecal samples from the participants were tested for glutamate dehydrogenase (GDH) and A/B toxins using a rapid enzyme immunoassay. GDH-positive samples underwent automated real-time polymerase chain reaction and toxigenic culture. Toxigenic C. difficile isolates were selected for whole genome sequencing. Out of the 105 patients, 14 (13.3%) met the criteria for CDI. Children with a history of previous CDI and the presence of mucus in their stool were more likely to have CDI. Metronidazole was the most used treatment (71.4%), and three patients (23.1%) experienced CDI recurrence (rCDI). Although the number of sequenced isolates was limited, a wide diversity of sequence types (ST) was observed. In addition to toxin genes (tcdA, tcdB, cdtA, and cdtB), the isolates also exhibited virulence factors involved in adhesion (cwp66, groEL, slpA, fbpA/fbp68) and immune evasion (rmlA, rmlB, rmlC, gnd, rfbA-1), along with multiple resistance factors (gyrA mutation, norA, ermB, dfrF, and vanG). These findings highlight the prevalence and recurrence of CDI among hospitalized children. Longitudinal studies are needed to better understand the characteristics of CDI-associated diarrhea and its impact on the healthcare system in this population.

Colonization by multidrug-resistant bacteria in hematological patients undergoing hematopoietic stem cell transplantation and clinical outcomes: A single-center retrospective cohort study.

BACKGROUND: Bloodstream infections are a leading cause of death in patients who undergo hematopoietic stem cell transplantation (HSCT) and are more severe when caused by multidrug-resistant (MDR) bacteria. This study proposed to investigate if colonization by MDR bacteria negatively affects the clinical outcomes in hematological patients after HSCT, as well as to evaluate possible risk factors for death due to bacteremia by the same colonizing agent. METHODS: A single-center retrospective cohort study was conducted with 405 hematological patients submitted to a single HSCT procedure between 2015 and 2021. Patients were classified as colonized (n = 132) or noncolonized (n = 273) based on the surveillance cultures from D-30 to D+30 of transplantation, and their relevant clinical and laboratory data were collected until D+100. RESULTS: Colonization by MDR bacteria increased blood culture positivity by all micro-organisms and also specifically by MDR bacteria, with a more pronounced effect when caused by carbapenemase-producing Klebsiella pneumoniae. Patients colonized with carbapenem-resistant K. pneumoniae had increased overall mortality (HR = 4.07, 95% CI 1.85-8.91, P = .0005) and had prolonged hospital length of stay in the context of autologous transplantation. Risk factors for death due to bacteremia by the same colonizing agent were neutropenia, colonization by carbapenem-resistant K. pneumoniae and use of high-dose total body irradiation in conditioning. CONCLUSION: Hematological patients colonized by MDR bacteria presented a higher incidence of bloodstream infections, and colonization by carbapenemase-producing K. pneumoniae was associated with reduced overall survival.

Laboratory diagnosis of Clostridioides difficile infection in symptomatic patients: what can we do better?

The laboratory diagnosis of Clostridioides difficile infection (CDI) is challenging since this bacteria may be detected in healthy people and toxin production detection is not sensitive enough to be used alone. Thus, there is no single test with adequate sensitivity and specificity to be used in laboratory diagnosis. We evaluated the performance of tests used in the diagnosis of CDI in symptomatic patients with risk factors in hospitals in southern Brazil. Enzyme immunoassays (EIA) for glutamate dehydrogenase antigen (GDH) and toxins A/B, real-time polymerase chain reaction (qPCR), GeneXpert system, and a two-step algorithm comprising GDH/TOXIN EIA performed simultaneously followed by GeneXpert for outliers were evaluated. Toxigenic strain in stool culture was considered CDI positive (gold standard). Among 400 samples tested, 54 (13.5%) were positive for CDI and 346 (86.5%) were negative. The diagnosis of the two-step algorithm and qPCR had an excellent performance with an accuracy of 94.5% and 94.2%, respectively. The Youden index showed that GeneXpert as a single test (83.5%) and the two-step algorithm (82.8%) were the most effective assays. Diagnosing CDI and non-CDI diarrhea could be successfully attained by the combination of clinical data with accuracy of laboratory tests.

Cerebrospinal fluid lactate as a predictive biomarker for tuberculous meningitis diagnosis.

OBJECTIVES: The definitive diagnosis of tuberculous meningitis (TBM) is achieved by identifying Mycobacterium tuberculosis (MTb) in cerebrospinal fluid (CSF); however, diagnostic confirmation is difficult due to the inability of current tests for an effective diagnosis. Our objective was to retrospectively assess the characteristics of CSF lactate (CSF-LA) as an adjunct biomarker in the diagnosis of TBM. METHODS: 608 CSF laboratory reports were assessed. Of these, 560 had clinically suspected TBM. These were classified as definite (n=36), probable (23), possible (278), or non-TBM (223) according to the international consensus TBM case definitions. An additional 48 CSF samples were negative controls with normal CSF. RESULTS: Against a reference standard of definite TBM, the cut-off value for CSF-LA was 4.0 mmol/L, the area under the ROC curve was 0.88 (95% CI, 0.82-0.94; p=0.0001), sensitivity was 69%, specificity 90%, negative predictive value 98%. These diagnostic parameters decreased when calculated against those of the other categories of TBM. CSF-LA exhibited high specificity, efficiency, negative predictive value, and clinical utility index in all the groups studied. CONCLUSIONS: CSF-LA is a useful diagnostic marker to rule out TBM when associated with conventional microbiology tests, nucleic acid amplification assays, and clinical algorithms, particularly in endemic areas.

Prevalence and Seasonality of Clostridiodes difficile over 12 Years at a Tertiary Hospital in Brazil.

Clostridioides difficile is the main pathogen responsible for antibiotic-associated diarrhea in adults. Besides its challenging diagnosis, C. difficile infection (CDI) causes substantial morbidity and mortality. Commercially, there are assays with different targets and performances in sensitivity and specificity. The objectives of this study were to: (1) evaluate the prevalence and seasonal variability of CDI rates at a tertiary hospital in southern Brazil over 12 years and (2) determine the impact of using a two-step algorithm test in the laboratory diagnosis. Between January 2007 and May 2019, fecal samples from 2275 patients were analyzed in a cross-sectional study. Four commercial tests were adopted for the diagnosis of CDI, the immunochromatographic test for toxin A from 2007 to 2010; the enzyme-linked immunosorbent assay method for toxins A and B from 2011 to March 2017; and the rapid enzyme immunoassay (EIA) for GDH and toxins A and B, associated with a Polymerase Chain Reaction (PCR) for the toxin B gene from June 2017 to 2019. The annual prevalence was 8.7% from 2007 to March 2017, increasing between June 2017 and 2019 to 14.7% when the C. diff Quik Chek Complete + GeneXpert C. difficile (two-step algorithm) test was adopted. The number of samples (691) and percentage of CDI cases (10.5%) were higher in winter, but the difference has no statistical significance (P > 0.05). An accurate diagnosis and adequate knowledge of the local seasonality of CDI allow the effective implementation of prevention and control strategies for nosocomial CDI, in addition to effective treatment for patients.

Do anti-HIV drugs pose a threat to photosynthetic microorganisms?

We investigated the occurrence and risk assessment of three anti-HIV drugs [(tenofovir (TNF), lamivudine (LMV) and efavirenz (EFV)] in urban rivers from Curitiba (Brazil), as well as the individual and combined effects of their environmental representative concentrations on the freshwater periphytic species Synechococcus elongatus (Cyanobacteria) and Chlorococcum infusionum (Chlorophyta). The three studied drugs, except TNF, were found in 100% of the samples, and concentrations in samples ranged from 165 to 412 ng TNF L-1, 173-874 ng LMV L-1 and 13-1250 ng EFV L-1. Bioassays using artificial contaminated water showed that at environmental concentrations, TNF and LMV did not represent environmental risks to the studied photosynthetic organisms. However, EFV was shown to be toxic, affecting photosynthesis, respiration, and oxidative metabolism. The studied drugs demonstrated interactive effects. Indeed, when submitted to the combination of TNF and LMV, decreased photosynthesis was observed in C. infusionum cells. Moreover, the toxic effects of EFV were amplified in both species when TNF and/or LMV were added to the media. The simultaneous presence of TNF, LMV and EFV in environmental matrices associated with their interactive effects, lead to increased toxicological effects of water contaminated by anti-HIV drugs and thus to an ecological threat to photosynthetic microorganisms.

Standardisation and validation of an in-house quantitative real-time polymerase chain reaction (qPCR) assay for the diagnosis of Clostridioides difficile infection.

OBJECTIVES: Clostridioides difficile is an emerging enteric pathogen that causes nosocomial diarrhoea in adults. The excessive cost of commercial molecular tests restricts the access of developing countries to its diagnosis. This study aimed to develop and validate in-house quantitative polymerase chain reaction (qPCR) targeting the C. difficile toxin B gene (tcdB) using two detection methodologies-SYBR Green and hydrolysis probes-for the diagnosis of C. difficile infection (CDI). METHODS: Glutamate dehydrogenase (GDH) plus toxigenic culture was the standard reference diagnostic method. The SYBR Green method and hydrolysis probes were used to study 392 samples simultaneously to assess the diagnostic value of these real-time PCR assays in detecting CDI from clinical samples. RESULTS: The SYBR Green and hydrolysis probe assays showed 97.9% and 87.5% sensitivity; 99.1% and 100.0% specificity; 94.0% and 100.0% positive predictive value; 99.7% and 98.3% negative predictive value; and 99.0% and 98.5% accuracy, respectively. CONCLUSIONS: The two qPCR methodologies evaluated could offer an adequate tool as part of an algorithm in the laboratory diagnosis of CDI.

Cost-Effectiveness of Molecular Method Diagnostic for Rapid Detection of Antibiotic-Resistant Bacteria.

OBJECTIVES: This study aimed to perform a cost-effectiveness analysis (CEA) of the molecular diagnostic method (MM) associated with conventional diagnostic method (CM) compared with the CM alone, for the detection of resistant profile in bacteremia, from the perspective of the Brazilian Public Health System, in intensive care units setting. METHODS: The clinical parameters regarding methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Gram-negative bacteria (CRGNB), and vancomycin-resistant Enterococcus spp. (VRE) infections were collected from searches on PubMed, Scopus, and SciELO, using specific keywords. Data on direct medical costs to treat these infections were collected according to Brazilian Public Health System perspective from Brazilian databases, in tables of 2018 to 2019. CEA was performed after building a dynamic model, which was calibrated and validated according to international recommendations. The incremental cost-effectiveness ratio of the MM + CM compared with the CM was calculated using the outcomes "avoided death" and "avoided resistant infections." One-way sensitivity analyses were performed. RESULTS: This CEA demonstrated that the MM + CM was dominant in all scenarios. Estimates showed that for MRSA, CRGNB, and VRE infections, every avoided death would lead to savings of Brazilian real (R$) 4.9 million ($937 301), R$2.2 million ($419 899), and R$1.3 million ($248 919), respectively. The same infections assessed by avoided resistant infections savings were projected to be R$24 964 ($4686), R$40 260 ($7558), and R$23 867 ($4480). CONCLUSIONS: MM leads to cost reduction and increased benefits, optimizing the use of financial resources on the health system in the intensive care unit setting, in bacteremia caused by MRSA, CRGNB, and VRE.

Métodos diagnósticos para tuberculose: uma revisão integrativa / Diagnostic methods for tuberculosis: an integrative review

A tuberculose é doença muito prevalente, com 5,8 milhões de casos ao ano, podendo apresentar padrão multissistêmico de acometimento, sendo mais comum a forma pulmonar. Objetivo: Revisão de literatura acerca dos métodos existentes de diagnóstico da tuberculose, focada em suas eficácias. Método: Foi realizada revisão integrativa por meio de publicações de 2016 a 2022 obtidas na base de dados PubMed e Scielo. Foram usados os descritores: Mycobacterium tuberculosis AND diagnosis. Foram obtidos 14 artigos que satisfizeram os critérios de inclusão. Resultado: Das formas de diagnóstico existem exames de imagem (Raio-X e tomografia computadorizada), baciloscopia, cultura e moleculares. Conclusão: Os métodos por imagem têm relevância quando seus achados são correlacionados com a clínica e podem auxiliar no diagnóstico. Nos métodos bacteriológicos, o sistema do GeneXpert Ultra apresenta maior custo-benefício, com valores de sensibilidade e especificidade altos - acima de 90% - superior à baciloscopia, e com menor tempo para realização em comparação com a cultura

nd may present a multisystem pattern of involvement, with the pulmonary form being the most common. Objective: Literature review on existing methods used to diagnose tuberculosis. Method: An integrative review was carried out through publications from 2016 to 2022 in the PubMed and Scielo publication database. The descriptors were used: Mycobacterium tuberculosis AND diagnosis. Fourteen articles that met the inclusion criteria were obtained. Result: Among the ways of diagnosing tuberculosis, there are imaging tests (X-ray and computed tomography), bacilloscopy, culture and molecular tests. Conclusion: Imaging methods have their findings correlated and can aid in the diagnosis. In bacteriological methods, the GeneXpert Ultra system is cost-effective, with high sensitivity and specificity values - above 90% -, superior to bacilloscopy, with a shorter time to perform compared to culture

Evaluation of MicroScan WalkAway for Determination of Ceftazidime-Avibactam and Ceftolozane-Tazobactam Susceptibility in Carbapenem-Resistant Gram-Negative Bacilli.

We evaluated the performance of ceftazidime-avibactam and ceftolozane-tazobactam MicroScan Neg multidrug-resistant MIC 1 (NMR1) panel for clinical carbapenem-nonsusceptible Gram-negative bacilli isolates. We evaluated 212 clinically significant carbapenem-nonsusceptible Gram-negative bacilli (139 Pseudomonas aeruginosa and 73 KPC-producing Enterobacterales) from 71 Brazilian hospitals (2013 to 2020). Ceftazidime-avibactam and ceftolozane-tazobactam MICs from the panel were compared with a broth microdilution (BMD) test as the reference method. Essential agreement (EA) and categorical agreement (CA) were assessed. For P. aeruginosa, antimicrobial susceptibility testing error rates were calculated using the error-rate bound method. Discrepancies were initially observed with 11 isolates; 4 resolved after retesting, 2 in favor of the NMR1 and 2 in favor of the BMD method. The ceftazidime-avibactam EA (overall and evaluable) was 100% for P. aeruginosa and Enterobacterales. The CA was 100% for Enterobacterales and 98.6% for P. aeruginosa. The ceftolozane-tazobactam EA was 98.6% and 100% (overall and evaluable, respectively), and the CA was 96.4% for P. aeruginosa. For ceftazidime/avibactam, no very major error (VME) was found, and the major error (ME) rate was 4.2% (2/48). For ceftolozane-tazobactam and P. aeruginosa, using the CLSI breakpoints, the minor error (mE) was 11.4%, and no VME or ME was found. While using EUCAST breakpoints, the VME was 11.4% with no ME. The mE becomes ME or VME in the absence of the intermediate category. All categorical errors were also within 1 log of MIC variation, and the adjusted error rate for CLSI/EUCAST was 0% (0/212). The NMR1 panel is an option to test ceftazidime-avibactam for KPC-producing Enterobacterales and carbapenem-nonsusceptible P. aeruginosa. When a MIC of 4 mg/liter for ceftolozane-tazobactam is obtained using this method, an alert could be created, and the results could be confirmed by an alternative method.

Ceftriaxone and methicillin-susceptible staphylococcus aureus: a perspective from pharmacokinetics/pharmacodynamics studies.

Introduction: Usage of ceftriaxone-based therapy to treat Methicillin-Susceptible Staphylococcus aureus (MSSA) infections is a controversial issue, from in vitro to clinical studies.Area covered: We conducted a literature review using PubMed of articles with ceftriaxone pharmacokinetics parameters and built a probability of target attainment (PTA) based on PK values from stable conditions (non-critically-ill patients) with goals of fT>55%, fT>75%, and fT>100%. Ceftriaxone's minimal inhibitory concentration from 31 MSSA strains (0.25-64 mg/L) was used to build the cumulative fraction response (CFR). The isolates were clinically relevant from blood, bronchoalveolar lavage, and soft tissue biopsy.Expert opinion: The results from controversies about using ceftriaxone for MSSA infections have been commonly addressed in the literature. However, variables such as (i) pharmacokinetic profile, (ii) pharmacodynamic target, (iii) site of infection, and (iv) MIC distributions may influence divergences. From this pharmacokinetics-pharmacodynamics perspective, ceftriaxone may be a reasonable option for MSSA infections when the MIC50 and MIC90 were 4 mg/L and 8 mg/L. CFR analysis demonstrated that ceftriaxone 1 g q24 h could be used if bacteriostasis is the aim (fT>55%), while 1 g q12h should be used for bactericidal effects (fT>75% or fT>100%). These dosing regimens should be considered in other clinical trials.

Predictive factors, outcomes, and molecular epidemiology of Clostridioides difficile diarrhea in Brazilian hospitals.

Little is known about the role of lineage of strains of Clostridioides difficile (CD) on the clinical presentation of CD infection (CDI) in Latin America, especially regarding the treatment response. We conducted a multicenter, prospective study to investigate the predictive factors and treatment outcomes of CDI in hospitalized patients and to performed phenotypical and molecular characterization of CD strains. A total of 361 diarrheic patients at 5 hospitals from different regions of the country were enrolled. All stool samples were tested for glutamate dehydrogenase (GDH), toxins A and B, and toxin genes using a nucleic acid amplification test (NAAT). Specimens were cultured and susceptibility profile and whole-genome sequencing (WGS) were performed. CDI positivity was 15% (56/377). Predictive factors for CDI were prior use of meropenem (OR 4.09, 95% CI 2.097-7.095; p<0.001), mucus in stools (OR 3.29; 95% CI 1.406-7.722; p=0.006) and neutrophil left-shift with >20% of bands (OR 3.77; 95% IC 1.280-11.120; p=0.016). Overall mortality was 19%, with no deaths attributed to CDI. Oral metronidazole was used in 74% of cases, with 85% of cure and 14% of recurrence. A total of 35 CD isolates were recovered, all of them susceptible to metronidazole and vancomycin. The WGS revealed 17 different STs, six of which were novel. ST42 was the most common ST and hypervirulent strains were not found. Severe CDI were caused by ST42, ST5, ST8, ST48, ST33 and a novel ST667. The ermB gene was more frequently found in isolates of ST42 (p=0.004).

The Xpert® MTB/RIF diagnostic test for pulmonary and extrapulmonary tuberculosis in immunocompetent and immunocompromised patients: Benefits and experiences over 2 years in different clinical contexts.

Xpert® MTB/RIF has been widely used for tuberculosis (TB) diagnosis in Brazil, since 2014. This prospective observational study aimed to evaluate the performance of Xpert in different contexts during a two-year period: (i) laboratory and clinical/epidemiological diagnosis; (ii) HIV-positive and -negative populations; (iii) type of specimens: pulmonary and extrapulmonary. Overall, 924 specimens from 743 patients were evaluated. The performance of the assays was evaluated considering culture (Lowenstein Jensen or LJ medium) results and composite reference standard (CRS) classification as gold standard. According to CRS evaluation, 219 cases (29.5%) were classified as positive cases, 157 (21.1%) as 'possible TB', and 367 (49.3%) as 'not TB'. Based on culture, Xpert and AFB smear achieved a sensitivity of 96% and 62%, respectively, while based on CRS, the sensitivities of Xpert, AFB smear, and culture were 40.7%, 20%, and 25%, respectively. The pooled sensitivity and specificity of Xpert were 96% and 94%, respectively. Metric evaluations were similar between pulmonary and extrapulmonary samples against culture, whereas compared to CRS, the sensitivities were 44.6% and 29.3% for the pulmonary and extrapulmonary cases, respectively. The Xpert detected 42/69 (60.9%) patients with confirmed TB and negative culture on LJ medium, and 52/69 (75.4%) patients with negative AFB smear results. There was no significant difference in the diagnostic accuracy based on the types of specimens and population (positive- and negative-HIV). Molecular testing detected 13 cases of TB in culture-negative patients with severe immunosuppression. Resistance to rifampicin was detected in seven samples. Herein, Xpert showed improved detection of pulmonary and extrapulmonary TB cases, both among HIV-positive and -negative patients, even in cases with advanced immunosuppression, thereby performing better than multiple other diagnostic parameters.