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Background: Simple radiography in conjunction with pertinent medical history and a comprehensive physical examination is typically adequate for diagnosing chronic osteomyelitis (CO). However, radiographic manifestations of CO lack specificity; therefore, the concordance among specialists in this regard has not been systematically assessed. This study aimed to compare and evaluate the proficiency of orthopedic surgeons and radiologists in identifying radiographic indicators present in simple radiographs for diagnosing CO. Methods: This cross-sectional study was a correlational investigation utilizing plain radiographs obtained from a cohort of 60 patients diagnosed with CO. Comprehensive assessments of the demographic and clinical characteristics, comorbidities, and microbiological parameters were conducted. Additional variables included the anatomical location of the CO, existence of fistulas, disease duration, and presence of pseudoarthrosis. This study meticulously documented the presence or absence of six specific findings: bone destruction, which incorporates erosion and radiolucencies around implants; bone sclerosis; cortical thinning concomitant with erosion; cortical thickening; sequestrum formation; and soft-tissue swelling. Results: Most patients were men (75%), with a mean age of 45.1 years. Hematogenous etiology of CO represented 23%. Bone sclerosis (71.3%) and cortical thickening (67.7%) were the most common radiographic findings, followed by soft-tissue swelling (51.3%), sequestration (47.3%), bone destruction (33.3%), and cortical erosion (30.3%). The mean agreement was 74.2%, showing a marked disagreement rate of 25.8% among all radiographic findings. The presence or absence of soft tissue edema, a prominent radiographic finding that was more important than the other findings, showed the greatest disagreement. Conclusions: Radiographic findings in CO were universally observed in all patients, demonstrating a high degree of concordance among specialists, with the exception of soft tissue swelling. [ABSTRACT FROM AUTHOR]

Human le ishmaniasis is a vector-borne, neglected infectious disease that is widely distributed in America, Africa, Europe, and Asia. Current therapy is based on old and toxic drugs, including antimonials, aminoglycosides, and amphotericin. As a neglected disease, investment in the development of new therapeutic molecules is scarce. Considering these aspects, the optimization of treatment through novel delivery systems for current therapeutic agents is an attractive alternative. The encapsulation into liposomes of drugs used in treating leishmaniasis increases the concentration of these molecules in macrophages, which may not only increase the chance of cure but also expand their therapeutic spectrum to include resistant Leishmania, as well as reducing toxicity since the drug is less exposed to healthy cells. The classical example is the liposomal formulation of amphotericin B, a well-established therapeutic option that uses liposomes to decrease the progression of renal failure in patients. However, loading other leishmanicidal drugs into liposomes, such as pentavalent antimonials, presents an opportunity for innovative and cheaper therapeutic options for the treatment of human leishmaniasis. This review aims to discuss liposomes as a drug delivery system for leishmanicidal drugs. [ABSTRACT FROM AUTHOR]

• Challenges in Measles Diagnosis: Measles diagnosis can be challenging, especially with the reintroduction of the virus in Brazil. This study aimed to compare qPCR results from swab and urine samples with immunological methods for measles diagnosis. • Comparison of diagnostic samples: The study concluded that swab and urine samples produced similar results with real-time qPCR (91.1 % agreement). Swab is the material of choice for qPCR, but urine is a viable alternative. • Accuracy of diagnostic methods: There was a 70 % agreement between the ELISA for IgM and qPCR. Paired IgG analysis demonstrated an accuracy of 67.5 % for IgM and 90.7 % for qPCR. The results suggest the influence of early sample collection for IgM analysis. • Enhancing Sensitivity and Specificity: The study recommends using both qPCR and paired IgG analysis for better sensitivity and specificity in laboratory diagnoses, especially in cases where IgM detection may be limited in early infections. Laboratory diagnosis of measles can be challenging, and the reintroduction of the measles virus in Brazil has brought about new issues. The aim of this study was to analyze the qPCR results of swab and urine samples and compare them with those of immunological methods for the diagnosis of measles. This was a cross-sectional study based on a retrospective analysis of 3,451 suspected cases using laboratory test surveillance databases for qPCR (respiratory swabs and urine) and serologic tests for IgM and paired IgG. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and agreement through kappa and adjusted kappa coefficients (PABAK) were calculated using different diagnostic strategies. The swab and urine samples obtained using real-time qPCR were equivalent. Samples collected simultaneously and the combined samples showed moderate agreement between IgM ELISA and real-time qPCR; however, 48.9 % of the IgM ELISA analyses did not demonstrate detectable qPCR concentrations during simultaneous collections and 43.9 % of combined collections. The paired analysis of IgG showed an accuracy of 67.5 % for IgM and 90.7 % for real-time qPCR. Diagnosis based on IgM presents detection delimitation in samples collected early (1–5 days), suggesting that these individuals satisfy at least two criteria. In addition to qPCR, paired analysis of IgG using ELISA can be used to increase the sensitivity and specificity of laboratory diagnoses. [ABSTRACT FROM AUTHOR]

Background: Liposomal amphotericin B (L-AMB) has been used for mucosal leishmaniasis (ML), but comparative studies on L-AMB and other drugs used for the treatment of ML have not been conducted. The present study aimed to evaluate the outcome of patients with ML who were treated with L-AMB. Methods: This is a 15-year retrospective study of Brazilian patients with a confirmed diagnosis of ML. The therapeutic options for the treatment of ML consisted of L-AMB, amphotericin B lipid complex (ABLC), deoxycholate amphotericin B (d-AMB), itraconazole, antimonial pentavalent, or pentamidine. Healing, cure rate and adverse effects (AEs) associated with the drugs used to treat this condition were analyzed. Results: In 71 patients, a total of 105 treatments were evaluated. The outcome of the treatment with each drug was compared, and results showed that L-AMB was superior to other therapeutic regimens (P = 0.001; odds ratio [OR] = 4.84; 95% confidence interval [CI] = 1.78–13.17). d-AMB had worse AEs than other treatment regimens (P = 0.001, OR = 0.09; 95% CI = 0.09–0.43). Approximately 66% of the patients presented with AEs during ML treatment. Although L-AMB was less nephrotoxic than d-AMB, it was associated with acute kidney injury compared with other drugs (P <0.05). Conclusion: L-AMB was more effective than other therapies for the treatment of ML. However, a high incidence of toxicity was associated with its use. Therapeutic choices should be reassessed, and the development of new drugs is necessary for the treatment of ML. [ABSTRACT FROM AUTHOR]

Background: Understanding the epidemiology of microorganisms associated with surgical site infections related to orthopaedic trauma (SSI-ROT) is important in establishing treatment protocols. The aim of this study was to evaluate the etiology and susceptibility pattern of SSIs related to orthopaedic trauma in a Brazilian reference hospital for trauma.Methods: Patients with SSI-ROT in a Brazilian reference hospital for trauma were retrospectively analyzed. All patients with orthopaedic trauma who underwent a surgical procedure and developed SSI within one year were included. All patients had culture samples from the surgical site obtained from biopsy of bone or soft tissue. Clinical and epidemiological data of the patients were collected.Results: A total of 147 patients with trauma-related infection were included in the analysis. The mean time to infection was 55.5 days, and the mean duration of hospitalization was 20.0 days. The in-hospital mortality rate after infection was 5.4%. Cultures were obtained from all patients, with 104 samples obtained from soft tissues and 43 samples from bone. The positivity rate was 93.2%. Among the isolates, 56.5% (77 patients) were gram-negative bacteria and 43.8% (60 patients) were gram-positive bacteria. Staphylococcus aureus was identified in 34%, Enterobacter spp. in 14.9%, and Pseudomonas aeruginosa in 11.6%. Staphylococcus aureus presented a higher positivity in bone samples (odds ratio, 1.29; 95% CI, 1.01-1.70; p = 0.04). Few microorganisms were multi-resistant.Conclusion: SSI in orthopaedic trauma can be associated with gram-negative bacilli, the susceptibility profile of which suggested that most infections occur after discharge. Staphylococcus aureus infections were commonly caused by methicillin-susceptible isolates, and this susceptibility to oral antibiotic options helps in the dehospitalization of patients. [ABSTRACT FROM AUTHOR]

The article discusses use of mass drug administration (MDA) approaches for the control of several neglected tropical diseases (NTDs) in China for the elimination of lymphatic filariasis. Topics discussed include evaluation of effect of MDA on the prevalence of Strongyloides stercoralis antibodies; importance of hygiene, food washing, shoes, and boiling water for success of soil-transmitted helminths (STHs) infection control; and role of poverty as risk factor for the development of NTDs.

Introduction: The use of contact lenses has progressively increased around the world, thereby increasing the risk of complications. The most serious complication is microbial keratitis (corneal infection) that can progress to a corneal ulcer. Methods: Fourteen multipurpose contact lens solutions were tested on mature biofilms comprising Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens and Candida albicans, using the minimum disinfection times recommended by the manufacturers. The biofilm was induced in the lens case, and 24 h later, the solutions were added. Activity against planktonic and sessile cells was evaluated and quantified as colony forming units per millilitre. The minimum concentration for biofilm eradication was defined as a 99.9% reduction in viable cells. Results: Although most solutions exhibited activity against planktonic cells, only five of the 14 solutions produced a significant reduction in the S. marcescens biofilm. No solution achieved the minimal biofilm eradication of S. aureus, P. aeruginosa and C. albicans. Conclusion: Multipurpose contact lens solutions provide greater bactericidal and/or fungicidal activity on planktonic cells than biofilms. The minimal eradication biofilm concentration was only achieved for S. marcescens. [ABSTRACT FROM AUTHOR]

The article focuses on a study related to likelihood of acute kidney injury (AKI) occurrence in patients of Klebsiella pneumoniae bloodstream infection (BSI) taking amikacin. Topics discussed include antibiotic susceptibility of carbapenem-resistant Enterobacteriacae (CRE) favouring the use of amikacin, high mortality rates of patients using amikacin, new aminoglycosides and beta-lactams being the alternatives for polymyxin and association of nephrotoxic drugs with AKI.

Tuberculous meningitis (TBM) is a severe infection of the central nervous system, particularly in developing countries. Prompt diagnosis and treatment are necessary to decrease the high rates of disability and death associated with TBM. The diagnosis is often time and labour intensive; thus, a simple, accurate and rapid diagnostic test is needed. The adenosine deaminase (ADA) activity test is a rapid test that has been used for the diagnosis of the pleural, peritoneal and pericardial forms of tuberculosis. However, the usefulness of ADA in TBM is uncertain. The aim of this study was to evaluate ADA as a diagnostic test for TBM in a systematic review. A systematic search was performed of the medical literature (MEDLINE, LILACS, Web of Science and EMBASE). The ADA values from TBM cases and controls (diagnosed with other types of meningitis) were necessary to calculate the sensitivity and specificity. Out of a total of 522 studies, 13 were included in the meta-analysis (380 patients with TBM). The sensitivity, specificity and diagnostic odds ratios (DOR) were calculated based on arbitrary ADA cut-off values from 1 to 10 U/l. ADA values from 1 to 4 U/l (sensitivity >93% and specificity <80%) helped to exclude TBM; values between 4 and 8 U/l were insufficient to confirm or exclude the diagnosis of TBM ( p = 0.07), and values >8 U/l (sensitivity <59% and specificity >96%) improved the diagnosis of TBM ( p < 0.001). None of the cut-off values could be used to discriminate between TBM and bacterial meningitis. In conclusion, ADA cannot distinguish between bacterial meningitis and TBM, but using ranges of ADA values could be important to improve TBM diagnosis, particularly after bacterial meningitis has been ruled out. The different methods used to measure ADA and the heterogeneity of data do not allow standardization of this test as a routine. [ABSTRACT FROM AUTHOR]

Summary: Background: Candiduria is a hospital-associated infection and a daily problem in the intensive care unit. The treatment of asymptomatic candiduria is not well established and the use of amphotericin B bladder irrigation (ABBI) is controversial. The aim of this systematic review was to determine the best place for this therapy in practice. Methods: The databases searched in this study included MEDLINE, EMBASE, Web of Science, and LILACS (January 1960–June 2007). We included manuscripts with data on the treatment of candiduria using ABBI. The studies were classified as comparative, dose-finding, or non-comparative. Results: From 213 studies, nine articles (377 patients) met our inclusion criteria. ABBI showed a higher clearance of the candiduria 24hours after the end of therapy than fluconazole (odds ratio (OR) 0.57, 95% confidence interval (CI) 0.32–1.00). Fungal culture 5 days after the end of both therapies showed a similar response (OR 1.51, 95% CI 0.81–2.80). The evaluation of ABBI using an intermittent or continuous system of delivery showed an early candiduria clearance (24hours after therapy) of 80% and 82%, respectively (OR 0.87, 95% CI 0.52–1.36). Candiduria clearance at >5 days after the therapy showed a superior response using continuous bladder irrigation with amphotericin B (OR 0.52, 95% CI 0.29–0.94). The use of continuous ABBI for more than 5 days showed a better result (88% vs. 78%) than ABBI for less than 5 days, but without significance (OR 0.55, 95% CI 0.34–1.04). Conclusion: Although the strength of the results in the underlying literature is not sufficient to allow the drawing of definitive conclusions, ABBI appears to be as effective as fluconazole, but it does not offer systemic antifungal therapy and should only be used for asymptomatic candiduria. [Copyright &y& Elsevier]

Background Recently, there has been an increase in the incidence of cutaneous leishmaniasis (CL), which represents an important health problem. This increase may be related to the epidemiologic expansion of the infective agent and the increase in tourism in tropical areas. The difficulty in clinical diagnosis, mainly in areas in which CL is not the first consideration of local physicians, has intensified efforts to describe diagnostic tests, which should be specific, sensitive, and practical. Amongst the new tests described are those including nucleic acid amplification (polymerase chain reaction, PCR) and immunohistochemistry (IHC). Methods In this study, we evaluated the sensitivity of a PCR based on small subunit (SSU) ribosomal DNA, in comparison with IHC using Leishmania spp. antibodies, in biopsies embedded in paraffin. Result The results indicated a total sensitivity of 96% (90.9% with PCR and 68.8% with IHC), showing the possibility of using paraffin-embedded biopsies to diagnose CL. Conclusion We propose the use of the two tests together as a routine protocol for diagnosis. This would require the provision of local medical services to perform molecular biology techniques and adequate Leishmania antibodies. [ABSTRACT FROM AUTHOR]

This brief review discusses the history of leishmaniasis, considering its origin from the Paleoartic, Neoartic or Neotropic. We reassess some of the theories of the likely origin of this protozoan since the beginning of life on Earth, passing through the Mesozoic and continuing to the appearance of humans. The relationship between this parasite or its ancestors, possible vectors and hosts with regard to ecological modifications is discussed. Recent molecular techniques have helped to elucidate some of the evolutionary questions regarding Leishmania, but have also brought doubts about the origin and evolution of this human parasite. PCR has been used for studies in the new discipline of paleoparasitology, helping to elucidate some of the remaining evolutionary questions. Understanding of this global condition is fundamental in determining the best approach to use against the parasite, specifically for the development of an efficient vaccine. [ABSTRACT FROM AUTHOR]

Abstract: Recurrence of mucosal leishmaniasis (ML) is frequent, but the causative mechanisms are unknown. Our aim was to compare cellular and cytokine patterns of lesions from ML that evolved to recurrence or cure in order to determine the risk factor associated with recurrence. Lesions were evaluated by immunohistochemistry before and after therapy, and patients were followed-up for five years. Higher levels of CD4+ T and IFN-γ-producing cells were detected in active lesions and decreased after therapy. Macrophages and IL-10 were markedly increased in cured patients. Conversely, CD8+ T and NK cells were higher in relapsed than in cured cases. Notably, a decrease in these cells in addition to decreased IL-10 and IFN-γ was also observed after therapy. These data suggest that exacerbated CD8+ activity, in addition to a poor regulatory response, could underlie an unfavorable fate with regard to ML. These markers may be useful for predicting the prognosis of ML in lesion studies. [Copyright &y& Elsevier]

Background New World leishmaniasis is an important endemic disease and public health problem in developing countries. The increase in ecologic tourism has extended this problem to developed countries. Few drugs have emerged over the past 50 years, and drug resistance has increased, such that the cure rate is no better than 80% in large studies. Despite these data, there has been no systematic review with a meta-analysis of the therapy used in this important tropical disease. The aim of this study was to determine the best drug management in the treatment of cutaneous leishmaniasis (CL) in Latin America based on the best studies published in the medical literature. Methods MEDLINE, LILACS, EMBASE, Web of Science, and Cochrane Library databases were searched to identify articles related to CL and therapy. Articles with adequate data on cure and treatment failure, internal and external validity information, and more than four patients in each treatment arm were included. Results Fifty-four articles met our inclusion criteria and 12 were included in the meta-analysis. Pentavalent antimonials were the most studied drugs, with a total of 1150 patients, achieving a cure rate of 76.5%. The cure rate of pentamidine was similar to that of pentavalent antimonials. Other drugs showed variable results, and all demonstrated an inferior response. Conclusion Although pentavalent antimonials are the drugs of choice in the treatment of CL, pentamidine showed similar results. Nevertheless, several aspects, such as cost, adverse effects, local experience, and availability of drugs to treat CL, must be considered when determining the best management of this disease, especially in developing countries where resources are scarce. [ABSTRACT FROM AUTHOR]

Abstract: Leishmaniasis causes significant morbidity and mortality and thus constitutes a serious public health problem. Even though it has long been endemic in developing countries, in recent years the economic globalization and the increased volume of international travel have extended its prevalence in developed countries. In addition, native populations may be exposed to the infection through blood transfusion and the use of blood products produced from infected asymptomatic individuals. Mucosal leishmaniasis (ML) is a chronic form of this infection, which attacks the mucosa. In most cases this form of leishmaniasis results from the metastatic spread of Leishmania (Viannia) braziliensis from cutaneous lesions. It is a healthcare issue because of its wide demographic distribution, its association with significant morbidity levels, and because of the pressing concern that tourists who travel to endemic areas might present the disease even years later. The treatment currently available for ML is based on drugs such as pentavalent antimony-containing compounds, amphotericin B deoxycholate and pentamidine and often guarantees a satisfactory clinical response. Nevertheless, it also frequently provokes serious side effects. This review offers a critical analysis of the drugs now available for the treatment of ML as also of the future prospects for the treatment of the disease. [Copyright &y& Elsevier]

Abstract: Although, pleural (PT) and disseminated tuberculosis (DT) have been considered as extreme endpoints of the Th1–Th2 immunological spectrum of the Mycobacterium tuberculosis infection, these conditions can occur together. The presence of PT and DT could be explained by (1) PT as primary condition, with progression of HIV infection possibly leading to dissemination of bacilli located in the pleura; (2) preexisting PT, with reinfection at lower LTCD4+ count explaining the DT form; (3) simultaneous acute PT and DT, considering immune compartmentalization phenomena in pleura. There are several important aspects of the immune response and its compartmentalization in co-infected patients with tuberculosis and HIV. PT and DT should not be always considered as extremes of the immunological response against M. tuberculosis, both diseases together may be explained after the understanding of compartmentalization of immune response. Associations between these entities are not so rare, while they remain incompletely explained. This brief review discusses several points of this contradictory association. [Copyright &y& Elsevier]

Restoration of the immune system after highly active antiretroviral therapy (HAART) resulting from a quantitative and qualitative process of cell immune activity recovery may evolve with adverse clinical phenomena, known as the immune reconstitution inflammatory syndrome (IRIS). It can occur in association with several opportunist infections, although most reported cases have been related to mycobacterial infection caused by Mycobacterium tuberculosis and Mycobacterium avium. We describe three clinical cases of mycobacterial infection with different presentation patterns of IRIS after HAART. In each of these patients, immune reconstitution led to clinical manifestation of a latent infection, or clinical worsening of preexisting lesions, or manifestation of new lesions in the central nervous system. Clinical aspects of IRIS are presented in the paper and clinical management options for this event are carefully discussed. [ABSTRACT FROM AUTHOR]

Abstract: Backgrounds: Adenosine deaminase (ADA) activity in pericardial fluid is a valuable aid in the diagnosis of tuberculous pericarditis (TP), but there is no systematic review performed to evaluate the benefits of ADA activity as an adjunctive test for TP diagnosis. The objective of this systematic review was to evaluate the utility of ADA activity as a diagnostic marker of TP on patients presenting with pericardial effusion. Methods: MEDLINE, LILACS and Cochrane Library databases (1980–2005) searches to identify articles related to adenosine deaminase activity on TP diagnosis. Articles with patients with at least one TP diagnostic criteria were included. The controls were patients with other pericardial diseases with moderate or large pericardial effusion. To calculate the sensitivity, specificity, as well as positive and negative likelihood ratios we extracted the total number of confirmed TP cases over all patients with pericardial effusion as well as the number of cases with ADA activity values of 40U/L and over. Results: Thirty one studies met our initial inclusion criteria and five articles were selected. The heterogeneity limited the specificity analysis (p =0.004). The method yielded a sensitivity and specificity of 88% and 83%, respectively. The SROC curve presented an area with a tendency towards 1 (value of 0.9539) and corroborates the diagnostic value of ADA activity. Conclusions: The present study confirms the clinical value of ADA activity as adjunctive diagnostic marker of TP among other causes of pericardial effusion. [Copyright &y& Elsevier]

Antimicrobial resistance is a public health burden with worldwide impacts and was recently identified as one of the major causes of death in 2019. Fosfomycin is an antibiotic commonly used to treat urinary tract infections, and resistance to it in Enterobacteriaceae is mainly due to the metalloenzyme FosA3 encoded by the fosA3 gene. In this work, we adapted a CRISPR-Cas9 system named pRE-FOSA3 to restore the sensitivity of a fosA3+  Escherichia coli strain. The fosA3+  E. coli strain was generated by transforming synthetic fosA3 into a nonpathogenic E. coli TOP10. To mediate the fosA3 disruption, two guide RNAs (gRNAs) were selected that used conserved regions within the fosA3 sequence of more than 700 fosA3+  E. coli isolates, and the resensitization plasmid pRE-FOSA3 was assembled by cloning the gRNA into pCas9. gRNA_195 exhibited 100% efficiency in resensitizing the bacteria to fosfomycin. Additionally, the edited strain lost the ampicillin resistance encoded in the same plasmid containing the synthetic fosA3 gene, despite not being the CRISPR-Cas9 target, indicating plasmid clearance. The in vitro analysis presented here points to a path that can be explored to assist the development of effective alternative methods of treatment against fosA3+ bacteria. [ABSTRACT FROM AUTHOR]

Clinical diagnosis of human brucellosis (HB) is often difficult due to non-specific symptoms. Immunological tests have been the most common method used in HB diagnosis, but molecular methods based on quantitative polymerase chain reaction (qPCR) have largely replaced these diagnostic methods. The aim of this study was to validate a HB diagnostic qPCR method; assessing different target Brucella genes, and the influence of biological matrices (serum vs. whole blood) on analytical parameters. Two target genes, IS711 and bcsp31, for HB molecular diagnosis were evaluated, together with biological matrix type (whole blood and serum) using samples spiked with Brucella abortus. In addition, diagnostic parameters of this qPCR method were evaluated in paired whole blood and serum samples from patients with suspected HB. Both genes could be potential diagnostic targets, but IS711 showed a lower limit of detection. In spiked matrix experiments, whole blood showed a lower limit of detection than serum after probit regression (224 vs. 3681 CFU/mL) and ANOVA analysis showed a significant (p < 0.001) difference between the Cq of whole blood at all dilutions and that of serum. In 12 paired clinical samples, no serum samples and only one whole blood sample tested positive for Brucella using this qPCR detection method. This standardized qPCR-based Brucella detection method could improve diagnosis of HB, serving as a rapid, highly sensitive, and specific test. Whole blood is better suited to qPCR-based HB diagnosis due to the presence of higher target DNA loads in this matrix, compared to serum. • The diagnosis of human brucellosis is a challenge, and the improvement of molecular methods can modify this panorama. • IS711 and bcsp31 are the most common genes used for amplification in the molecular diagnosis of human brucellosis. • The lower limit of detection of IS711 gene supports this gene in preference to bcsp31 for molecular tests. • Whole blood is better suited to qPCR-based human brucellosis diagnosis. [ABSTRACT FROM AUTHOR]

American tegumentary leishmaniasis (ATL), an endemic anthropozoonosis in various countries in the world, is caused by parasites of the genus Leishmania. Despite reports on ATL reactivation as a result of immunosuppression, to the best of our knowledge, this paper describes the first case of ATL reactivation in its localized form (cutaneous leishmaniasis) associated with the administration of systemic corticosteroids. The possible action of corticosteroids on the host immune response to the parasite in patients with localized cutaneous leishmaniasis is discussed. This report demonstrates the possibility of ATL reactivation in patients using corticosteroids, an observation that should be considered in individuals treated with this medication. [ABSTRACT FROM AUTHOR]

Background: Human brucellosis is a neglected, re-emerging, and endemic zoonosis in many countries. The debilitating and disabling potential of the disease is a warning about its morbidity, generating socioeconomic impact. This review aims to update the current evidence on the efficacy and safety of therapeutic options for human brucellosis using the network meta-analysis (NMA). Methodology: A systematic search was conducted in four different databases by independent reviewers to assess overall therapy failure, adverse events, and time to defervescence associated with different therapies. Randomized clinical trials (RCTs) evaluating any therapeutic drug intervention were selected, excluding non-original studies or studies related to localized forms of the disease or with less than 10 participants. Data were analyzed by frequentist statistics through NMA by random effects model. The risk of bias and certainty of evidence was assessed, this review was registered at PROSPERO. Results: Thirty-one (31) RCTs involving 4167 patients were included. Three networks of evidence were identified to evaluate the outcomes of interest. Triple therapy with doxycycline + streptomycin + hydroxychloroquine for 42 days (RR: 0.08; CI 95% 0.01–0.76) had a lower failure risk than the doxycycline + streptomycin regimen. Doxycycline + rifampicin had a higher risk of failure than doxycycline + streptomycin (RR: 1.96; CI 95% 1.27–3.01). No significant difference was observed between the regimens when analyzing the incidence of adverse events and time to defervescence. In general, most studies had a high risk of bias, and the results had a very low certainty of evidence. Conclusions: This review confirmed the superiority of drugs already indicated for treating human brucellosis, such as the combination of doxycycline and aminoglycosides. The association of hydroxychloroquine to the dual regimen was identified as a potential strategy to prevent overall therapy failure, which is subject to confirmation in future studies. Author summary: Human brucellosis it is a disease with transmission associated with the handling of animals and ingestion of contaminated products. The disease usually presents with a subacute to chronic febrile condition characterized by nonspecific symptoms such weight loss, and sudoresis. Therapeutic regimens combining two or more drugs have been shown to be superior to monotherapy. The debilitating and disabling potential of the disease is a warning about its morbidity, whose symptoms can persist for weeks or months, generating socioeconomic impact. So far, the accumulated evidence is based on clinical trials that compared the interventions of interest against different comparators. The authors this reviewed all published studies and performed an analysis was capable of comparing the effect of therapeutic regimens to identify the best combinations to treat human brucellosis. The combination of three medicines (doxycycline + streptomycin + hydroxychloroquine) showed the best results compared to the option previously identified as more effective (doxycycline + streptomycin), so this research points to new perspectives for the treatment of brucellosis. This result point that more studies dedicated to studying this combination must be developed to confirm this trend and enable the adoption of new practices in the treatment of this disease. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the oral switch (OS) stewardship intervention in the intensive care unit (ICU).Methods: This was a retrospective study with a convenience sample in two Brazilian ICUs from different hospitals in patients with sepsis receiving antibiotic therapy. The stewardship intervention included OS in patients diagnosed with sepsis when clinical stability was achieved. The primary outcome was overall mortality. Other variables evaluated were as follows: cost of antimicrobial treatment, daily costs of intensive care, acute kidney injury, and length of stay.Results: There was no difference in mortality between the OS and non-OS groups (p = 0.06). Length of stay in the ICU (p = 0.029) was shorter and acute kidney injury incidence (p = 0.032) and costs of antimicrobial therapy (p < 0.001) were lower in the OS group.Conclusion: OS stewardship programs in the ICU may be considered a safe strategy. Switch therapy reduced the cost and shortened the length of stay in ICUs. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate different concentrations of vancomycin and/or gentamicin loaded polymethylmethacrylate (PMMA) against biofilm formation of Staphylococcus aureus. Biofilm production of S. aureus in PMMA loaded with different concentrations of vancomycin and gentamicin were evaluated by quantitative analysis of biofilm cells, scanning electronic microscopy, viability assay, Fourier transform infrared spectroscopy, and checkerboard. Statistical analysis was performed by Mann Whitney test. The difference in colony forming units per mL was significant when p < 0.05. All loaded PMMA presented a reduction in the number of colony forming units per mL (p < 0.05). The gentamicin-loaded PMMA could inhibits the grown of sessile cells (p < 0.05), where the group vancomycin 4 g + gentamicin 500 mg presented a better result. The Fourier transform infrared spectra showed no significant differences, and checkerboard of vancomycin and gentamicin showed synergism. Effects against adherence and bacterial development in PMMA loaded with antibiotics were mainly seen in the group vancomycin 4 g + gentamicin 500 mg, and synergic effect can be applied in antibiotic-loaded cement. [ABSTRACT FROM AUTHOR]

Background: Human brucellosis (HB) is a bacterial zoonosis that is more frequent in low income and middle-income countries; it is sometimes associated with outbreaks. The aim of this study was to describe the largest outbreak of HB in Brazil. Methods: A retrospective cohort study of patients suspected of having contracted HB in the state of Paraná, Southern Brazil from January 2009 to January 2017. Following an outbreak of 51 cases of HB in a slaughterhouse at Paiçandu in 2014, HB was defined as an obligatory reportable disease in the State. Diagnostic tests for HB included serum agglutination, ELISA (IgG or IgM) and polymerase chain reaction (PCR). Clinical, laboratorial and epidemiological data were analyzed. A P value of 0.05 was considered statistically significant. Results: Out of a total of 3,941 patients, 754 presented with a positive test result for HB. After 2014, there was a significant increase in the number of cases, exceeding 100 cases per trimester. In the beginning of 2015, the workgroup of HB started several actions for prevention and treatment, and the number of cases progressively diminished to fewer than 20 cases per trimester. Of 191 reported cases, an occupational risk was found in 84.7%; most cases occurred in farmers (60.0%), veterinarians (17.6%) and slaughterhouse workers (14.7%). Manipulation of animals and unpasteurized milk consumption were associated with positive Brucella IgM ELISA with an odds ratio (OR) of 1.42 (1.09–1.84) and 1.48 (1.01–2.15), respectively. Conclusions: HB outbreaks can occur in low to middle-income countries and are associated with slaughterhouse work, handling of unpasteurized milk and animal manipulation. Intensive programs for control of HB are important to reduce the number of cases. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Treatment of New World Cutaneous Leishmaniasis: A Systematic Review With a Meta-Analysis," by F.F. Tuon, V.S. Amato and M.E. Graf.

A letter to the editor is presented that discusses the mucosal leishmaniasis.

A letter to the editor about the treatment of mucosal leishmaniasis with a lipid formulation of Amphotericin is presented.

Introduction: Pseudomonas aeruginosa respiratory infections are challenging, and the risk of recurrence is a frequent problem. The aim of this study was to investigate the risk factors associated with the presence of P. aeruginosa, and the risk factors related to the recurrence and death of lower airway infections in inpatients in a Brazilian hospital. Methods: Retrospective cohort with inpatients that had a sample of airways culture (tracheal aspirate or bronchoalveolar lavage) with the detection of P. aeruginosa. The patients with clinical criteria of infection were classified as ventilator‐associated, hospital‐acquired, or community‐acquired pneumonia. P. aeruginosa in respiratory samples without symptoms was considered colonization. The antimicrobial treatment adequacy and the clinical data were evaluated. Outcome variables included mortality and recurrence. Results: One hundred and fifty‐four patients were included in the study, most of them were men, and the majority (102) were considered infected. The average length of stay was superior to 30 days. Previous pulmonary disease was associated with the occurrence of colonization. Aminoglycosides were the most active drug according to susceptibility tests and were successfully used as monotherapy. Septic shock was a risk factor for death in the infected patients. The use of adequate antimicrobial therapy was associated with major survival, independent of the infection classification. Conclusion: It is possible to evaluate clinical data associated with recurrence and mortality in patients with different lung infections by P. aeruginosa. Aminoglycoside monotherapy is safe and effective in P. aeruginosa respiratory infections. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is an old and silent pandemic. Resistant organisms emerge in parallel with new antibiotics, leading to a major global public health crisis over time. Antibiotic resistance may be due to different mechanisms and against different classes of drugs. These mechanisms are usually found in the same organism, giving rise to multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria. One resistance mechanism that is closely associated with the emergence of MDR and XDR bacteria is the efflux of drugs since the same pump can transport different classes of drugs. In Gram-negative bacteria, efflux pumps are present in two configurations: a transmembrane protein anchored in the inner membrane and a complex formed by three proteins. The tripartite complex has a transmembrane protein present in the inner membrane, a periplasmic protein, and a porin associated with the outer membrane. In Pseudomonas aeruginosa, one of the main pathogens associated with respiratory tract infections, four main sets of efflux pumps have been associated with antibiotic resistance: MexAB-OprM, MexXY, MexCD-OprJ, and MexEF-OprN. In this review, the function, structure, and regulation of these efflux pumps in P. aeruginosa and their actions as resistance mechanisms are discussed. Finally, a brief discussion on the potential of efflux pumps in P. aeruginosa as a target for new drugs is presented. [ABSTRACT FROM AUTHOR]

Mannose-binding lectin (MBL) is a pattern recognition receptor of the lectin pathway of complement system. MBL binds to carbohydrates on microorganism’s surfaces leading to complement activation, opsonization and phagocytosis. Polymorphisms in the MBL gene ( MBL2 ) are associated with variations on MBL serum levels and with the susceptibility to various infectious and autoimmune diseases. The involvement of the lectin pathway in rheumatoid arthritis (RA) has been demonstrated by several studies and although MBL has been considered to have a dual role in the pathogenesis of the disease, the association between MBL and RA remains inconclusive. In an attempt to clarify this relationship, we developed this short review summarizing accumulated evidences in regard to MBL and RA and a meta-analysis to evaluate the influence of MBL2 polymorphisms on the susceptibility to RA. Among a total of 217 articles that were identified following a predefined search strategy on PubMed, Scopus, Scielo, EMBASE and Cochrane databases, only 13 met all inclusion criteria and were included in the meta-analysis. Data assessment was conducted by three independent investigators and presented in odds ratio (OR) and 95% confidence intervals (CIs) using forest plot charts. Both heterogeneity and publication bias were analyzed. The results of the meta-analysis evidenced that MBL2 low producing OO and XX genotypes do not confer higher risk to RA, even when data were analyzed according to cohort's ethnicity. Further studies are needed in order to clarify the importance of other genes of the lectin pathway in the pathogenesis of RA. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe a case of a patient with ocular toxoplasmosis, which has resulted in Kyrieleis plaques formation (segmental periarteritis associated with severe inflammation) and later follow-up and alternative treatment due to documented allergy to sulfonamide. A 33-year-old Brazilian woman diagnosed with acute toxoplasmosis, initially treated with sulfonamide, developed a critical cutaneous rash. Cotrimoxazole was changed to clindamycin and pyrimethamine, and prednisone was started. The medication was maintained for 45 days. Four months later, she developed retinal lesions suggestive of toxoplasmosis with Kyrieleis plaques in the upper temporal vessels. Pyrimethamine, clindamycin, and prednisone were initiated until healing. She presented reactivation months later, and a suppressive treatment with pyrimethamine was instituted for one year. This is the first report to use the combination of clindamycin with pyrimethamine in the treatment and recurrence prophylaxis for OT in a documented allergy to sulfonamide. [ABSTRACT FROM AUTHOR]

Background: Titanium and polyether-ether-ketone (PEEK) interbody cages are commonly used for spine fusion. Few data are known about bacterial and yeast biofilms formation in these implants. The aim of this study was to compare Staphylococcus aureus and Candida albicans biofilm formation in the surface of two different interbody devices used routinely in spine surgery. Methods: Six bodies of proof specimens of PEEK and titanium alloy were used for microbiological tests, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. Experimental biofilm was produced with Staphylococcus aureus and Candida albicans, followed by quantitative analysis of planktonic cells and sessile cells. The comparison between the medians of biofilm quantification between the two models was performed using the Mann–Whitney test and considered the statistical difference for a p < 0.05. Results: In the S. aureus model, in both planktonic and sessile cell counts, titanium-alloy samples showed lower values for colony forming units per milliliter (UFC/mL) (p < 0.05). The evaluation through the optic density of planktonic and sessile cells showed lower values in the titanium-alloy samples, however, only statistically significant in planktonic cell count (p < 0.05). The count of planktonic yeast cells in PEEK was similar to titanium-alloy samples, while the count of sessile yeast cells in titanium alloy was lower when compared to PEEK (p < 0.05). Conclusion: Titanium-alloy models were associated with less staphylococcal and Candida biofilm formation when compared with PEEK. [ABSTRACT FROM AUTHOR]

Background: During the COVID-19 pandemic, the burden of nosocomial infections caused by MDR pathogens has caused a shortage of polymyxins. Thus, we evaluated the in vitro synergism and antibiofilm activity of antimicrobial combinations and propose a test kit for synergism against carbapenem-resistant Acinetobacter baumannii (CRAB).Methods: Fifty-six CRAB isolates were tested for synergy between meropenem, gentamicin and ampicillin/sulbactam. MICs were determined by broth microdilution. Synergism was tested using chequerboard analysis, followed by a time-kill curve. Additionally, minimum biofilm eradication concentration was determined and the antibiofilm activity of the combinations was evaluated by MTT assay and biomass reduction. A test kit was developed for routine laboratory testing to detect synergism.Results: All CRAB isolates were resistant to gentamicin and ampicillin/sulbactam. Chequerboard synergism occurred against 75% of the isolates. Meropenem + ampicillin/sulbactam was the most frequent combination with synergism (69%), followed by ampicillin/sulbactam + gentamicin (64%) and meropenem + gentamicin (51%). All combinations presented only bacteriostatic activity and no bactericidal or antibiofilm effects. The routine laboratory test showed 100% accuracy compared with other in vitro assays.Conclusions: Our study demonstrates the potential role of antibiotic combinations against planktonic bacteria. In vitro synergism is possible and can be an alternative treatment for patients with CRAB infection during a polymyxin shortage. [ABSTRACT FROM AUTHOR]

Background: Telemedicine has grown significantly in recent years, mainly during the COVID-19 pandemic, and there has been a growing body of literature on the subject. Another topic that merits increased attention is differences in patient and family experience between telehealth and in-person visits. To our team’s knowledge, this is the first study evaluating pediatric and obstetrics outpatients experience with telemedicine and in-person visit types in an academic maternal and children’s hospital, and its correlation with geographic distance from the medical center throughout 2020, during the COVID-19 crisis. Methods: We aim to evaluate and compare patients’ telemedicine and in-person experience for ambulatory encounters based on survey data throughout 2020, during the COVID-19 pandemic, with particular focus on the influence of distance of the patient’s home address from the medical facility. A total of 9,322 patient experience surveys from ambulatory encounters (6,362 in-person and 2,960 telemedicine), in a maternal and children’s hospital during 2020 were included in this study. The percentage of patients who scored the question “Likelihood to recommend practice” with a maximum 5/5 (top box) score was used to evaluate patient experience. The k-means model was used to create distance clusters, and statistical t-tests were conducted to compare mean distances and Top Box values between telemedicine and in-person models. Logistic regression analysis was used to evaluate the correlation between Top Box scores and patients’ distance to the hospital. Results: Top Box likelihood to recommend percentages for in-person and telemedicine were comparable (in-person = 81.21%, telemedicine = 81.70%, p-value = 0.5624). Mean distance from the hospital was greater for telemedicine compared to in-person patients (in-person = 48.89 miles, telemedicine = 61.23 miles, p-value < 0.01). Patients who live farther displayed higher satisfaction scores regardless of the visit type (p-value < 0.01). Conclusions: There is a direct relationship between the family experience and the distance from the considered medical center, during year 2020, i.e., patients who live farther from the hospital record higher Top Box proportion for “Likelihood to Recommend” than patients who live closer to the medical center, regardless of the approach, in-person or telemedicine. [ABSTRACT FROM AUTHOR]

Background: Health care is a complex economic and social system, which combines market elements and public and social interest. This combination in Brazil, like systems in China and United States of America, is operationalized through the public and private system. The sector represents approximately 9% of the country's GDP, of which 56% is privately sourced and 44% is of public origin. In the private sector includes a structure with 711 private health institutions, 47 million beneficiaries and revenues of US$30 billion a year.Methods: Therefore, this research describes and analyzes the complementarity of Private Health before the Brazilian Unified Health System, highlighting its main characteristics, scenarios, and trends in the face of the health system and the Brazilian market. This descriptive and exploratory research uses secondary data from various sources, submitted to quantitative data analysis methods. The object of the research is the history of private health in Brazil and its main actors.Results: The data are organized into three groups, each with its approach of collection and analysis. Thus, it is perceived as the notorious growth of large operators, to the detriment of operators with a lower concentration of beneficiaries; the increasing concentration of the market through mergers and acquisitions promoted by large publicly traded corporations, especially in regions with a lower rate of private health coverage; and the growth of the sector through business plans, whose central characteristic is the dependence on the country's employability rate.Conclusions: It is possible to perceive an intense trend of concentration of Brazilian private health in large institutions that have capitalized and have a great appetite for growth through mergers and acquisitions, whether from smaller operators or health institutions that integrate their health networks, following complementary health models already consolidated in countries such as China, and the United States of America, among others. This concentration projects a market with fewer options and competitiveness, reduction in transaction costs and increase the operational effectiveness of health care. [ABSTRACT FROM AUTHOR]

Summary: Background: The definitive diagnosis of visceral leishmaniasis (VL) requires invasive procedures with demonstration of amastigotes in tissue or promastigotes in culture. Unfortunately, these approaches require laboratory materials not available in poor countries where the disease is endemic. The correct diagnosis of VL is important, and made more difficult by the fact that several common tropical diseases such as malaria, disseminated tuberculosis, and enteric fever share the same clinical presentation. Serological tests have been developed to replace parasitological diagnosis in the field. A commercially available K39-based strip test for VL has been developed for this purpose. The endemic area of leishmaniasis in Brazil overlaps the endemic area of Chagas disease, a disease that can cause false-positive serological test results. The aim of this study was to evaluate the incidence of false-positive exams using a rapid test for VL in patients with Chagas disease. Methods: A rapid test based on the recombinant K39 antigen of Leishmania was used in: (1) 30 patients with confirmed Chagas disease, (2) 30 patients with a serological diagnosis of Chagas disease by ELISA, indirect immunofluorescence, indirect hemagglutination, and chemiluminescence, (3) 30 healthy patients from a non-endemic area as the control group, (4) 30 patients with confirmed VL, and (5) 20 patients with proved cutaneous leishmaniasis. Results: The sensitivity and specificity of the rapid strip test were 100% when compared with healthy volunteers and those with confirmed Chagas disease. One false-positive result occurred in the group with Chagas disease diagnosed by serological tests (specificity of 96%). Conclusion: The rapid test based on recombinant K39 is a useful diagnostic assay, and a false-positive result rarely occurs in patients with a serological diagnosis of Chagas disease. [Copyright &y& Elsevier]

Abstract: Objective: To determine the frequency of cardiac alterations in necropsies of AIDS patients in pre-HAART era and better understand the pathogenesis of HIV-related cardiomyopathy. Design: Retrospective study of 94 complete necropsies. Method: Macroscopic, histopathologic (histochemical, immunohistochemical and in situ hybridization techniques) and ultra structural myocardial evaluation (23 cases). Results: Cardiac alterations were observed in 94.4%; 74% showed variable degrees of cardiac dilation not related to known cardiovascular diseases. Eighty-two percent (81.8%) of patients with biventricular dilation showed diffuse-regressive alterations (thinning and waving cardiomyocytes with increase of lipofuscin pigment granules). Myocarditis was diagnosed in 27 cases (28.7%), 16 (59.3%) of known etiology. The ultra structural study has revealed cardiomyocytes alterations (mitochondriosis, loss of myofibrils, increase in the amount of perinuclear-lipofuscin pigment granules) associated to activation signals of capillary-endothelial cells (enhancement of pseudopodia and transcellular channels). Cardiomyocytes'' apoptosis was demonstrated at structural level in 10 (43.5%) patients; tumor necrosis factor α (TNF α) was detected in 17/18 cases. Conclusions: This pioneer study described the association of histopathological and ultra structural findings (thinning and waving cardiomyocytes with increase of lipofuscin pigment granules, mitochondriosis and loss of myofibrils) with different degrees of cardiac-chamber dilation probably representing a spectrum of alterations that would lead to myocardial dysfunction and development of HIV-related cardiomyopathy. Cardiomyocytes'' apoptosis observed at ultra structural level and demonstration of TNF α associated to described alterations suggest that this cytokine plays an important role in both negative-inotropic effect and capacity to induce apoptosis through death receptor-controlled pathway. [Copyright &y& Elsevier]

Background: The gold standard for microbial detection in prosthetic joint infections is the multiple culture of the peri-prosthetic tissue. The fluid cultures after sonication can improve the recovery of the microorganisms. Objective: The aim of this study was to evaluate the sonication technique with a plastic bag and the effect of refrigeration on microorganism detection with conventional culturing, MALDI-TOF MS and qPCR assay on an orthopedic screw model. Methods: We produced biofilms of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans on orthopedic screws, which were stored under different conditions and temperatures before sonication. After sonication, the mass spectrometry by MALDI-TOF, qPCR and culture protocols was performed using the sonicated fluid, for detecting the microorganisms involved in the biofilm. Results: The bacterial bioburden decreased by approximately one log after the refrigeration period, in the screws containing P. aeruginosa and S. aureus biofilms. All the microorganisms involved in the screw biofilms were detected with MALDI-TOF and qPCR. Significant reductions in CFU counts occurred only in groups stored in the plastic bag, indicating that changes in temperature and humidity may favor cell death. However, this variation is not important for this model as it did not affect the detection owing to the high counts obtained. Conclusion: Microbial identification by MALDI-TOF in sonicated fluid is feasible. With qPCR, there were no differences between the detection in the screws processed immediately or after refrigeration. It is necessary to consider whether or not the refrigeration period would affect microbial recovery in an explanted prosthesis. [ABSTRACT FROM AUTHOR]

The ceftazidime/avibactam presented the higher susceptibility profile following colistin/polymyxin (96%), with 73% of susceptibility. In resume, ceftazidime/avibactam is an option for the treatment of carbapenem-resistant I P. aeruginosa i in Brazil. To the Editor, In this journal attempts to circumvent carbapenem resistance of I Pseudomonas aeruginosa i were recently reported [[1]]. [Extracted from the article]

Bone cement containing vancomycin or gentamicin is a therapeutic strategy for combating orthopedic infections: however, the activity of these antibiotics is narrow. Silver nanoparticles (AgNPs) are nanocomponents with a wide spectrum, including multidrug-resistant bacteria. In the present study, we aimed to evaluate the effect of AgNP-loaded polymethylmethacrylate (PMMA) on biofilm formation by Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus epidermidis. The effect of AgNP-loaded PMMA with and without vancomycin or gentamicin on biofilm production was quantitatively analyzed. S. aureus, E. coli, P. aeruginosa, and S. epidermidis were included as biofilm-producing microorganisms in the in vitro model. AgNP-loaded PMMA with antibiotics reduced the number of colony-forming units (CFUs; p <0.001). However, AgNP-loaded PMMA alone did not significantly reduce biofilm formation. Our study demonstrated the potential of AgNP-loaded PMMA. Notably, we observed that AgNP-loaded PMMA containing vancomycin or gentamycin exhibited significantly superior efficacy, with satisfactory activity against most biofilm-forming microbial agents examined. [ABSTRACT FROM AUTHOR]

There have historically been concerns of acute kidney injury (AKI) with the use of aminoglycosides. The present study aimed to compare the AKI incidence and mortality rate between critically ill patients treated with aminoglycoside or meropenem in the intensive care unit setting using a propensity score matching approach. This cross-sectional study was conducted at two university hospitals from January 2011 to October 2017. Clinical and laboratorial data were evaluated to exclude potential confounders and to calculate the Charlson index. AKI was classified according to the Acute Kidney Injury Network criteria. All tests were two-tailed, and a p value ≤ 0.05 was considered significant in the univariate and multivariate analyses. We included 494 patients, 95 and 399 of whom used meropenem and aminoglycoside, respectively. Patients in the subgroup that used meropenem were matched with controls (aminoglycoside). Among the 494 patients, 120 developed any grade of AKI (24.2%). After propensity score matching, there were no significant differences in AKI incidence and mortality rate between the aminoglycoside and meropenem groups (p = 0.324 and 0.464, respectively). Patients on the aminoglycoside regimen neither presented a higher AKI incidence nor mortality rate when compared with those on the meropenem regimen. Aminoglycosides may be a safe option for the treatment of critically ill patients on carbapenem sparing antimicrobial stewardship programs. [ABSTRACT FROM AUTHOR]

Purpose: To compare clinical-epidemiological profile and treatment outcome between culture negative and culture positive keratitis patients. Methods: Patients with suspected infectious keratitis seen at two ophthalmic hospitals in Curitiba, Brazil, between June 2014 and April 2016, were prospectively studied. Ophthalmological exam with corneal scraping and microbiological tests were performed. Data regarding follow up, surgical interventions and treatment outcome were collected after 12 weeks of the first visit trough medical chart review. From the results of the culture, two groups were formed: culture negative keratitis (CNK) and culture positive keratitis (CPK). Results: According to inclusion criteria 21 patients were classified as culture negative keratitis and 20 patients as culture positive keratitis. The number of patients on antibiotic drops at the first visit was greater in CNK group (90.5% versus 60%; p=0.032). Surgical procedures were necessary in 3 patients (15%) in CNK group and in 7 patients (36,8%) in CPK group (p=0.155). Treatment success was achieved by 85% (17/20) of the patients in CNK group and by 61% (11/18) of the patients in CPK group (p=0.144). There was no significant difference between groups regarding age, gender, place of residence, presence of comorbidities, risk factors for infectious keratitis, duration of symptoms and characteristics of corneal ulcer. Conclusions: Previous treatment with antibiotics correlates with negative culture results. There was no significant difference in treatment outcome between culture negative and culture positive keratitis patients. [ABSTRACT FROM AUTHOR]

The dissemination of NDM-1 carbapenemases (New Delhi Metallo-β-lactamase) is a global public health problem, mainly in developing countries. The aim of this study was to characterize the spread of NDM-producing bacteria in the Southern Brazilian states analyzing epidemiological, molecular, and antimicrobial susceptibility aspects. A total of 10,684 carbapenem-resistant isolates of Enterobacterales, Pseudomonas spp. and Acinetobacter spp. obtained from several hospitals in eight cities in Southern Brazil were screened, and 486 NDM-producing bacteria were selected. The incidence varied from 0.5 to 77 cases/100.000 habitants. ST11, ST15, ST340 and ST674 were the most common in K. pneumoniae. A total of 5 plasmids were identified in one K. pneumoniae strain: Col440I, Col440II, IncFIA(HI1), IncFIB(K), IncFIB(pQil)/ IncFII(K), and IncR. The number of patients with NDM-producing bacteria has increased in Southern Brazil, whose gene is present in different plasmids, explaining the expansion of this enzyme. [ABSTRACT FROM AUTHOR]

Plazomicin is a next-generation aminoglycoside with activity against Enterobacteriaceae , including carbapenemase-producing Enterobacteriaceae (CPE). The aim of this study was to evaluate the activity of plazomicin against CPE ( Klebsiella spp., Escherichia coli , Serratia spp., Enterobacter spp., Citrobacter spp., Morganella spp ., Proteus spp., Providencia spp.) from different Brazilian hospitals. A total of 4000 carbapenem-resistant Enterobacteriaceae isolates were collected from clinical samples in 50 Brazilian hospitals during 2013–2015. Of these, 499 carbapenem-resistant isolates (CLSI criteria) were selected for further evaluation via broth microdilution to assess for the activity of plazomicin, colistin, tigecycline, meropenem, amikacin, and gentamicin. Additionally, the isolates were assessed for the presence of carbapenemase genes ( bla KPC , bla NDM , bla OXA-48-like , bla IMP , bla BKC , bla GES , and bla VIM ) by polymerase chain reaction (PCR). When PCR was positive to bla OXA-48-like , bla IMP , bla GES , and bla VIM, the carbapenemase genes were sequenced. bla KPC was the most prevalent carbapenemase gene found ( n = 397), followed by bla NDM ( n = 81), bla OXA-48 ( n = 12), and bla IMP-1 ( n = 3). Other genes were identified in only 1 isolate each: bla BKC-1 , bla GES-16 , bla GES-1 , bla OXA-370 , and bla VIM-1 . One isolate had 2 carbapenemase genes ( bla KPC and bla NDM ). Thirty-three percent of the isolates were nonsusceptible to colistin, 24% to tigecycline, 97% to meropenem, 51% to amikacin, and 81% to gentamicin (via EUCAST criteria). The plazomicin MIC 50/90 was 0.5/64 mg/L, with 85% of MICs ≤2 mg/L and 87% of MICs ≤4 mg/L. Elevated MICs to plazomicin were not associated with a specific carbapenemase or bacterial species. The MICs of plazomicin against CPE were lower than those of other aminoglycosides. Plazomicin is a promising drug for the treatment of CPE infections. [ABSTRACT FROM AUTHOR]

Background: The best available treatment against carbapenemase-producing Enterobacteriaceae (CPE) is unknown. The objective of this study was to investigate the effect of appropriate therapy and of appropriate combination therapy on mortality of patients with bloodstream infections (BSIs) due to CPE.Methods: In this retrospective cohort study, we included patients with clinically significant monomicrobial BSIs due to CPE from the INCREMENT cohort, recruited from 26 tertiary hospitals in ten countries. Exclusion criteria were missing key data, death sooner than 24 h after the index date, therapy with an active antibiotic for at least 2 days when blood cultures were taken, and subsequent episodes in the same patient. We compared 30 day all-cause mortality between patients receiving appropriate (including an active drug against the blood isolate and started in the first 5 days after infection) or inappropriate therapy, and for patients receiving appropriate therapy, between those receiving active monotherapy (only one active drug) or combination therapy (more than one). We used a propensity score for receiving combination therapy and a validated mortality score (INCREMENT-CPE mortality score) to control for confounders in Cox regression analyses. We stratified analyses of combination therapy according to INCREMENT-CPE mortality score (0-7 [low mortality score] vs 8-15 [high mortality score]). INCREMENT is registered with ClinicalTrials.gov, number NCT01764490.Findings: Between Jan 1, 2004, and Dec 31, 2013, 480 patients with BSIs due to CPE were enrolled in the INCREMENT cohort, of whom we included 437 (91%) in this study. 343 (78%) patients received appropriate therapy compared with 94 (22%) who received inappropriate therapy. The most frequent organism was Klebsiella pneumoniae (375 [86%] of 437; 291 [85%] of 343 patients receiving appropriate therapy vs 84 [89%] of 94 receiving inappropriate therapy) and the most frequent carbapenemase was K pneumoniae carbapenemase (329 [75%]; 253 [74%] vs 76 [81%]). Appropriate therapy was associated with lower mortality than was inappropriate therapy (132 [38·5%] of 343 patients died vs 57 [60·6%] of 94; absolute difference 22·1% [95% CI 11·0-33·3]; adjusted hazard ratio [HR] 0·45 [95% CI 0·33-0·62]; p<0·0001). Among those receiving appropriate therapy, 135 (39%) received combination therapy and 208 (61%) received monotherapy. Overall mortality was not different between those receiving combination therapy or monotherapy (47 [35%] of 135 vs 85 [41%] of 208; adjusted HR 1·63 [95% CI 0·67-3·91]; p=0·28). However, combination therapy was associated with lower mortality than was monotherapy in the high-mortality-score stratum (30 [48%] of 63 vs 64 [62%] of 103; adjusted HR 0·56 [0·34-0·91]; p=0·02), but not in the low-mortality-score stratum (17 [24%] of 72 vs 21 [20%] of 105; adjusted odds ratio 1·21 [0·56-2·56]; p=0·62).Interpretation: Appropriate therapy was associated with a protective effect on mortality among patients with BSIs due to CPE. Combination therapy was associated with improved survival only in patients with a high mortality score. Patients with BSIs due to CPE should receive active therapy as soon as they are diagnosed, and monotherapy should be considered for those in the low-mortality-score stratum.Funding: Spanish Network for Research in Infectious Diseases, European Development Regional Fund, Instituto de Salud Carlos III, and Innovative Medicines Initiative. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a major public health problem worldwide. Although next generation sequencing technology has been widely used in the diagnosis of infectious diseases, it has been scarcely applied in identification of Leishmania species. The aim of this study was to compare the efficiency of MinION™ nanopore sequencing and polymerase chain reaction restriction fragment length polymorphism in identifying Leishmania species. Our results showed that the MinION™ sequencer was able to discriminate reference strains and clinical samples with high sensitivity in a cost and time effective manner without the prior need for culture. • The identification of Leishmania species is essential to assist in the proper treatment. • We use the latest generation sequencing for identification of Leishmania species. • In this study we used the third generation MinION sequencer for the first time. • MinION sequencer was able to discriminate reference strains and clinical samples with high sensitivity. [ABSTRACT FROM AUTHOR]