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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). 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. 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. 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.

Staphylococcus aureus are frequently associated with biofilm formation on intravascular devices. Biofilms limit antimicrobial penetration and promote phenotypic resistance, challenging conventional treatment strategies. Vancomycin (VAN) and gentamicin (GEN) have been used clinically, but their combined antibiofilm activity remains underexplored. This study evaluates the efficacy of VAN and GEN, alone and in combination, against biofilms formed by methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) on polyurethane. MICs were determined for VAN and GEN. Biofilm biomass and metabolic activity were quantified using crystal violet and MTT assays, respectively. Biofilm viability was assessed through fluorescence microscopy and a modified Calgary Biofilm Device. A continuous-flow peristaltic model was developed to test treatment under simulated catheter conditions. While monotherapy with VAN or GEN had modest effects, their combination significantly reduced biomass and metabolic activity. VAN 20 mg/L + GEN 8 mg/L and VAN 40 mg/L + GEN 8 mg/L achieved over 70% reduction in MRSA biofilm viability and complete eradication in MBEC assays. Dynamic model assays confirmed biofilm reduction with combination therapy. The combination of VAN/GEN exhibits synergistic antibiofilm activity against S. aureus, particularly MRSA. These findings support its potential application in catheter salvage strategies, including antibiotic lock therapy.

Pseudomonas aeruginosa is associated with several human infections, mainly related to healthcare services. In the hospital, it is associated with resistance to several antibiotics, which poses a great challenge to therapy. However, one of the biggest challenges in treating P. aeruginosa infections is that related to biofilms. The complex structure of the P. aeruginosa biofilm contributes an additional factor to the pathogenicity of this microorganism, leading to therapeutic failure, in addition to escape from the immune system, and generating chronic infections that are difficult to eradicate. In this review, we address several molecular aspects of the pathogenicity of P. aeruginosa biofilms.

Background: Central venous catheters (CVCs) are essential in intensive care units (ICUs) for monitoring and administering treatments; however, catheter-related bloodstream infections (CRBSIs) are significant complications, leading to severe outcomes and increased healthcare costs. The objective of this study was to evaluate the effectiveness of a simple and inexpensive impregnated dressing (intervention) compared to a non-impregnated dressing in reducing catheter-related infections among critically ill patients using vancomycin and chlorhexidine. Methods: This was a randomized, double-blind, controlled clinical trial in a university hospital in Brazil with 207 beds from June 2022 to October 2023. Patients over 18 years old admitted to the ICU and needing a CVC for a period exceeding 72 h were included. A CVC inserted outside the ICU and the need for two CVCs in the same patient simultaneously were exclusion criteria. One group received an impregnated dressing (intervention) compared to the other group, which received a standard dressing (comparator). The incidence of CRBSIs and the microbiological outcomes were evaluated. The primary endpoint was CRBSI. Results: The clinical trial included 516 patients randomized to receive either the new antimicrobial dressing or a control dressing. The dressing significantly reduced CVC colonization but not CRBSI rates. Conclusions: This new dressing provides enhanced antimicrobial protection but does not decrease CRBSI incidence. Future studies should further explore the cost-effectiveness and long-term benefits of this approach.

The increasing demand for orthopedic and neurosurgical implants has driven advancements in biomaterials, additive manufacturing, and antimicrobial strategies. With an increasingly aging population, and a high incidence of orthopedic trauma in developing countries, the need for effective, biocompatible, and infection-resistant implants is more critical than ever. This review explores the role of polymers in 3D printing for medical applications, focusing on their use in orthopedic and neurosurgical implants. Polylactic acid (PLA), polycaprolactone (PCL), and polyetheretherketone (PEEK) have gained attention due to their biocompatibility, mechanical properties, and potential for antimicrobial modifications. A major challenge in implantology is the risk of periprosthetic joint infections (PJI) and surgical site infections (SSI). Current strategies, such as antibiotic-loaded polymethylmethacrylate (PMMA) spacers and bioactive coatings, aim to reduce infection rates, but limitations remain. Additive manufacturing enables the creation of customized implants with tailored porosity for enhanced osseointegration while allowing for the incorporation of antimicrobial agents. Future perspectives include the integration of artificial intelligence for implant design, nanotechnology for smart coatings, and bioresorbable scaffolds for improved bone regeneration. Advancing these technologies will lead to more efficient, cost-effective, and patient-specific solutions, ultimately reducing infection rates and improving long-term clinical outcomes.

Leishmaniasis, a neglected tropical disease caused by protozoa of the genus , presents a wide clinical spectrum from self-healing cutaneous lesions to life-threatening visceral disease. Its epidemiology and severity vary by geography and species (Old vs. New World), vector biology, and host factors. Pathogenesis reflects a tripartite interplay among parasite, host, and sand fly saliva. Parasite virulence determinants-including lipophosphoglycan, GP63, proteophosphoglycans, and GPI-anchored antigens-facilitate complement evasion, macrophage entry, and suppression of microbicidal pathways. Innate defenses (complement, neutrophils, dendritic cells, NK cells) and PRR signaling (TLRs/NLRs) shape early outcomes, while the balance between Th1-mediated macrophage activation and Th2/regulatory responses dictates clearance versus persistence. Clinically, most infections remain cutaneous; a minority disseminate to mucosa, driven by immunopathology and species traits. Management must be individualized by species, lesion burden/site, immune status, geographic region and drug availability. Local therapies (intralesional antimonials, cryo-/thermotherapy) are suitable for limited disease, whereas systemic agents (antimonials, amphotericin B, miltefosine, pentamidine, azoles) are reserved for complex, mucosal, disseminated, or immunosuppressed cases. Drug resistance-via altered uptake/efflux, metabolic rewiring, and genomic plasticity-increased toxicity and treatment failure. Targeting parasite virulence and unique metabolic pathways, improving species-specific diagnostics, and integrating host-directed strategies are priorities to shorten therapy and improve clinical outcomes.

Staphylococcus aureus is a microorganism frequently associated with implant-related infections, owing to its ability to produce biofilms. These infections are difficult to treat because antimicrobials must cross the biofilm to effectively inhibit bacterial growth. Although some antibiotics can penetrate the biofilm and reduce the bacterial load, it is important to understand that the results of routine sensitivity tests are not always valid for interpreting the activity of different drugs. In this review, a broad discussion on the genes involved in biofilm formation, quorum sensing, and antimicrobial activity in monotherapy and combination therapy is presented that should benefit researchers engaged in optimizing the treatment of infections associated with S. aureus biofilms.

Background: Acute kidney injury (AKI) is a common complication in critical care patients. The presence of AKI is a marker for poor outcomes such as longer hospitalization durations, more hospital readmissions, and especially, higher mortality rates. Sepsis is one of the major causes of AKI within the intensive care unit (ICU) population. Sepsis-related AKI occurs in approximately 20% of patients, reaching more than 50% in patients with septic shock. The diagnosis of AKI depends on urine output and/or serum creatinine measurements. Unfortunately, serum creatinine is a late and unreliable (insensitive and nonspecific) indicator of AKI. However, biomarkers of renal damage have great potential in facilitating early diagnosis of AKI. Several biomarkers, including urinary neutrophil gelatinase-associated lipocalin (uNGAL), have been used in the early detection of AKI. Objectives: The aim of this study was to evaluate uNGAL for the diagnosis and prognosis of AKI in critical ill patients with infections. Design: Original study (Cohort Prospective Observational). Setting: Study in 2 ICUs of different Brazilian hospitals, in the city of Curitiba: Hospital de Clínicas da Universidade Federal do Paraná and Hospital da Polícia Militar do Paraná, from November 12, 2016 to May 15, 2018. Participants: Critically ill patients with infections, sepsis, or septic shock were selected. The inclusion criteria were patients older than 18 years with infection. They were followed up for 30 days in the analysis of outcomes. We requested that consent forms be signed by all eligible patients or their caregivers. Measurements: The urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels of the patients were measured on 4 consecutive days and was assayed using a chemiluminescent microparticle immunoassay system. The screening time occurred within 72 hours of admission to the ICU. The first urine sample was collected within the first 24 hours of the screening hours. Mortality and AKI were assessed during first 30 days. Methods: clinical and laboratory data, including daily uNGAL levels, were assessed. The AKI stage using the KDIGO criteria was evaluated. Sensitivity, specificity, and the area under the curve-receiver operating characteristic (AUC-ROC) values were calculated to determine the optimal uNGAL level for predicting AKI. Results: We had 38 patients who completed the study during the screening period. The incidence of AKI was 76.3%. The hospitalization period was longer in the group that developed AKI, with 21 days of median (interquartile range [IQR]: 13.5-25); non-AKI group had a median of 13 days (IQR 7-18; P = .019). We found a direct relationship between uNGAL levels and the progression to AKI. Increased values of the biomarker were associated with the worsening of AKI (P < .05). The cutoff levels of uNGAL that identified patients who would progress to AKI were the following: (d1) >116 ng/mL, (d2) >100 ng/mL, and (d3) 284 ng/mL. The value of the fourth and last measurement was not predictive of patients who would progress to AKI. The median urinary uNGAL was also associated with mortality on Days 1, 3, and 4: d1, P = .039; d3, P = .005; d4, P = .005. The performance of uNGAL in detecting AKI patients (AUC-ROC = 0.881). There were no risk factors other than AKI that could be correlated with increased uNGAL levels on Day 1. Limitations: The study was carried out in 2 centers, having used only 1 biomarker, and our small number of patients were limitations. Conclusion: the uNGAL had an association in its values with the diagnosis and prognosis of patients with severe infections and AKI. We suggest that studies with a greater number of patients could better establish the cutoff values of uNGAL and/or serum NGAL in the identification of infected patients who are at a high risk of developing AKI.

Antibiotics misuse and overuse are concerning issues worldwide, especially in low middle-income countries. These practices contribute to the increasing rates of antimicrobial resistance. One efficient strategy to avoid them is antimicrobial stewardship programs. In this review, we focus on the possible approaches to spare the prescription of polymyxins and carbapenems for the treatment of Acinetobacter baumannii, carbapenem-resistant Enterobacterales, and Pseudomonas aeruginosas infections. Additionally, we highlight how to implement cumulative antibiograms and biomarkers to a sooner de-escalation of antibiotics.

PurposeCeftazidime–avibactam is an antimicrobial association active against several Enterobacteriaceae species, including those resistant to carbapenem. Considering the importance of this drug in the current panorama of multidrug-resistant bacteria, we performed a systematic review about ceftazidime–avibactam with emphasis on clinical and pharmacological published data.MethodsA systematic search of the medical literature was performed. The databases searched included MEDLINE, EMBASE and Web of Science (until September 2017). The search terms used were ‘avibactam’, ‘NXL104’ and ‘AVE1330A’. Bibliographies from those studies were also reviewed. Ceftazidime was not included as a search term, once relevant studies about avibactam in association with other drugs could be excluded. Only articles in English were selected. No statistical analysis or quality validation was included in this review.ResultsA total of 151 manuscripts were included. Ceftazidime–avibactam has limited action against anaerobic bacteria. Avibactam is a potent inhibitor of class A, class C, and some class D enzymes, which includes KPC-2. The best pharmacodynamic profile of ceftazidime–avibactam is ƒT > MIC, validated in an animal model of soft tissue infection. Three clinical trials showed the efficacy of ceftazidime–avibactam in patients with intra-abdominal and urinary infections. Ceftazidime–avibactam has been evaluated versus meropenem/doripenem in hospitalized adults with nosocomial pneumonia, neutropenic patients and pediatric patients.ConclusionCeftazidime–avibactam has a favorable pharmacokinetic profile for severe infections and highly active against carbapenemases of KPC-2 type.