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ABSTRACT Background: The emergence of antibiotic resistance is increasing and there are few effective antibiotics to treat infections caused by resistant and multidrug resistant bacterial pathogens. This study aimed to evaluate the in vitro activity of ceftolozane-tazobactam against clinical bacterial isolates from Brazil. Methods: A total of 673 Gram-negative bacterial isolates including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and other Enterobacterales collected from 2016 to 2017 were tested, most of them isolated from patients in intensive care units. Minimum inhibitory concentrations (MIC50/90) were determined by broth microdilution for amikacin, aztreonam, cefepime, cefotaxime, cefoxitin, ceftolozane-tazobactam, ceftazidime, ceftriaxone, ciprofloxacin, colistin, ertapenem, imipenem, levofloxacin, meropenem, and piperacillin-tazobactam using dried panels. Antimicrobial susceptibility results were interpreted according to Clinical and Laboratory Standards Institute criteria. Results: Susceptibility rates to ceftolozane-tazobactam ranged from 40.4% to 94.9%. P. aeruginosa susceptibility rate to ceftolozane-tazobactam was 84.9% (MIC50/90, 1/16 µg/mL) and 99.2% to colistin. For E. coli, ceftolozane-tazobactam inhibited 94.9% (MIC50/90, 0.25/1 µg/mL) of the microorganisms. The susceptibility rate of K. pneumoniae to ceftolozane-tazobactam was 40.4% (MIC50/90, 16/>32 µg/mL). Other Enterobacterales have shown susceptibility rates of 81.1% (MIC50/90, 0.5/16 µg/mL) to ceftolozane-tazobactam, 93.9% to meropenem, 90.9% to amikacin (90.9%), and 88.6% to ertapenem. In non-carbapenemase producing isolates, AmpC mutations were found three isolates. Conclusions: Ceftolozane-tazobactam has shown relevant activity against a large variety of the analyzed microorganisms collected from multiple centers in Brazil, showing promising results even in multidrug resistant strains.

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ABSTRACT HIV infection may be considered a chronic condition for people living with HIV with access to antiretrovirals and this has effectively increased survival. Moreover, this has also facilitated the emergence of other comorbidities increasing the risk for drug-drug interactions and polypharmacy. The profile of these interactions as well as their consequences for people living with HIV are still not completely elucidated. The objectives of this study were to describe the profile of these interactions, their prevalence and their classification according to the potential for significant or non-significant drug-drug interactions. From June 2015 to July 2016, people living with HIV on follow-up at an Infectious Diseases Referral Center in Belo Horizonte, Brazil have been investigated for the presence of drug-drug interactions. A total of 304 patients were included and the majority (75%) had less than 50 years of age, male (66.4%), and 37.8% self-defined as brown skinned. Approximately 24% were on five or more medications and half of them presented with drug-drug interactions. Patients older than 50 years had a higher frequency of antiretrovirals drug-drug interactions with other drugs compared to younger patients (p = 0.002). No relationship was found between the number of drug-drug interactions and the effectiveness of antiretrovirals. As expected, the higher the number of non-HIV medications used (OR = 1.129; 95%CI 1.004-1.209; p = 0.04) was associated with an increase in drug-drug interactions. The high prevalence of drug-drug interactions found and the data collected should be useful to establish measures of quaternary prevention and to increase the medication security for people living with HIV.

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ABSTRACT Urinary tract infection (UTI) is a common condition in women. There is an increased concern on reduction of bacterial susceptibility resulting from wrongly prescribing antimicrobials. This paper summarizes the recommendations of four Brazilian medical societies (SBI - Brazilian Society of Infectious Diseases, FEBRASGO - Brazilian Federation of Gynecology and Obstetrics Associations, SBU - Brazilian Society of Urology, and SBPC/ML - Brazilian Society of Clinical Pathology/Laboratory Medicine) on the management of urinary tract infection in women.Asymptomatic bacteriuria should be screened at least twice during pregnancy (early and in the 3rd trimester). All cases of significant bacteriuria (≥105 CFU/mL in middle stream sample) should be treated with antimicrobials considering safety and susceptibility profile. In women with typical symptoms of cystitis, dipsticks are not necessary for diagnosis. Urine cultures should be collected in pregnant women, recurrent UTI, atypical cases, and if there is suspicion of pyelonephritis. First line antimicrobials for cystitis are fosfomycin trometamol in a single dose and nitrofurantoin, 100 mg every 6 hours for five days. Second line drugs are cefuroxime or amoxicillin-clavulanate for seven days. During pregnancy, amoxicillin and other cephalosporins may be used, but with a higher chance of therapeutic failure.In recurrent UTI, all episodes should be confirmed by urine culture. Treatment should be initiated only after urine sampling and with the same regimens indicated for isolated episodes. Prophylaxis options of recurrent UTI are behavioral measures, non-antimicrobial and antimicrobial prophylaxis. Vaginal estrogens may be recommended for postmenopausal women. Other non-antimicrobial prophylaxis, including cranberry and immunoprophylaxis, have weak evidence supporting their use. Antimicrobial prophylaxis may be offered as a continuous or postcoital scheme. In pregnant women, options are cephalexin, 250-500 mg and nitrofurantoin, 100 mg (contraindicated after 37 weeks of pregnancy). Nonpregnant women may use fosfomycin trometamol, 3 g every 10 days, or nitrofurantoin, 100 mg (continuous or postcoital).

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ABSTRACT In recent years, the number of cases with severe Plasmodium vivax malaria has shown an increasing trend. It is, therefore, important to identify routine laboratory markers that best characterize the acute disease phase and can serve as a tool for clinical follow-up of patients. In a cohort study, we followed 87 patients with acute P. vivax monoinfection acquired in an endemic region of the Brazilian Amazon. Forty-two different biochemical and hematological parameters frequently tested in clinical routine were evaluated at the acute phase and the convalescent phase. A total of 42 laboratory tests were performed: biochemical parameters measured were serum lipids levels, aminotransferases, bilirubin, amylase, glucose, urea, creatinine, albumin, globulin, uric acid, C-reactive protein, and alpha-1-acid glycoprotein. Hematological parameters included total and differential white blood cell and platelet counts, hemoglobin concentration, mean platelet volume, platelet width distribution, and plateletcrit. Our results show that several biochemical and hematological parameters were associated with acute phase P. vivax malaria and these parameters reverted to normal values in the convalescent phase. The use of these parameters during diagnosis and follow-up of the infection is a useful clinical tool to evaluate the clinical course and therapeutic response of patients with uncomplicated vivax malaria.

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ABSTRACT Diabetes mellitus (DM) has important implications for tuberculosis (TB), as it increases the risk for disease activation and is associated with unfavorable TB treatment outcomes. This study analyzed the association between TB and DM (TBDM) in Brazil from 2007 to 2014. This was a retrospective cohort study carried out in 709,429 new cases of TB reported to the national disease notification system of the Brazilian Ministry of Health. Sociodemographic and clinical data, test results, and treatment outcomes were analyzed. TBDM was found in 6.0% of TB cases, mostly in men aged 18-59 years. The lethality rate was 5.1% higher in all age groups with diabetes, except in those older than 60 years of age. The frequency of multi-drug-resistant tuberculosis (MDR-TB) in patients with DM was higher in those without DM, with a 1.6- to 3.8-fold increase in the odds of MDR-TB. The elderly showed an increase in the prevalence of TBDM from 14.3% to 18.2%. Women were more likely to have DM, and elderly women had 41.0% greater chance of having DM. Relapse was significant among patients younger than 17 years of age. TBDM was high in Brazil, affected all age groups, and was associated with unfavorable TB treatment outcomes. We emphasize the need for strategies for the clinical management of diabetic tuberculosis patients in Brazil aiming at minimizing relapses, deaths, and MDR-TB.

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ABSTRACT Introduction: Malnutrition is associated with an increased risk of complications in hospitalized patients, and parenteral nutrition (PN) is used when oral or enteral feeding is not possible. This study aimed at analyzing associations between PN characteristics and infectious complications in hospitalized patients. Material and methods: This was a retrospective cohort study conducted in a tertiarycare university hospital. Data from consecutive adult patients submitted to PN (January 2016 to December 2017; ICU and ward) were reviewed by means of an electronic database. Patient’s clinical characteristics, PN prescription and catheter insertion procedure data were extracted and analyzed. The main outcome was the development of central line-associated bloodstream infection (CLABSI). The secondary outcomes were other infectious complications and mortality, as well as factors associated with CLABSI. Results: We analyzed 165 patients and 247 catheters used for parenteral nutrition infusion. The CLABSI rate was 6.47 per 1000 catheter-days. In the univariable analysis, CLABSI was associated with longer hospitalization time, longer PN time, longer catheter time, catheter insertion performed by a surgeon or a surgical resident, and procedures performed outside the ICU. In an extended time-dependent Cox regression, no variable was associated with a higher risk of CLABSI, and additional PN days did not increase the rate of CLABSI. The overall mortality rate was 24.8%. Only the patients’ comorbidity index was associated with death in the multivariable analysis. Discussion: In our study, patients who needed PN had an overall CLABSI rate of 6.47 per 1000 catheter-days. These outcomes were not associated with PN and catheter characteristics studied after adjustment for catheter time. The overall mortality rate was 24.8% and it was not associated with PN in multivariable analyses, only with Charlson comorbidity index.

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ABSTRACT In recent years, extreme attention has been focused on the role of human herpesvirus-6 (HHV-6) in multiple sclerosis (MS) pathogenesis. However, the pathogenesis of MS associated with HHV-6 infection remains unknown. In this study, we measured the serum levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and vitamin D levels in MS patients with HHV-6 infection and MS patients without HHV-6 infection. Five hundred sixty (including 300 females and 260 males) MS patients along with 560 healthy subjects were analyzed for HHV-6 seropositivity using enzyme-linked immunosorbent assay (ELISA). Subsequently, we measured the serum levels of MMP-2, MMP-9, and vitamin D levels in MS patients with HHV-6 infection and MS patients without HHV-6 infection by ELISA. About 90.7% of MS patients (508/560) were seropositive for HHV-6, while 82.3% (461/560) of healthy subjects were seropositive for this virus (p = 0.001). Moreover, there was a significant increase in the levels of MMP-2, MMP-9, and lower vitamin D in the serum samples of MS patients when compared with healthy subjects. Additionally, we demonstrated that the MMP-9 levels in seropositive MS patients were significantly higher than seronegative MS patients (p = 0.001). Finally, our results demonstrated that the mean of expanded disability status scale (EDSS) in seropositive MS patients was significantly higher in comparison to seronegative MS patients (p < 0.05). In conclusion, we suggest that the HHV-6 infection may play a role in MS pathogenesis.

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ABSTRACT Background: Latent HIV-1 is a major hurdle in obtaining HIV-1 sustained virological remission (SVR). Here we explored histone deacetylation inhibition property of nicotinamide (NAM; n = 17) for the first time in comparison to a combination of methyltransferase inhibitors (MTIs; Chaetocin and BIX01294; n = 25) to reactivate latent HIV ex vivo in CD8-depleted PBMCs from antiretroviral treated aviremic individuals. Results: NAM reactivated HIV-1 from 13/17 (76.4%) samples compared to 20/25 (80.0%) using MTIs with mean viral load (VLs) of 4.32 and 3.22 log10 RNA copies/mL, respectively (p = 0.004). Mean purging time after NAM and MTIs stimulation was 5.1 and 6.75 days, respectively (p = 0.73). Viral purging in autologous cultures exhibited blunted HIV recovery with fluctuating VLs followed by a complete viral extinction when expanded in allogenic system. Electron microscopy from five supernatants revealed anomalous viral particles, with lack of complete viral genomes when characterized by ultradeep sequencing through metagenomics approach (n = 4). Conclusion: NAM alone was more potent HIV-1 activator than combination of MTIs, with potential of clinical use.

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ABSTRACT The increasing rates of nosocomial infection associated with coagulase-negative staphylococci (CoNS) were the rationale for this study, aiming to categorize oxacillin-resistant CoNS species recovered from blood culture specimens of inpatients at the UNESP Hospital das Clínicas in Botucatu, Brazil, over a 20-year period, and determine their sensitivity to other antimicrobial agents. The mecA gene was detected in 222 (74%) CoNS samples, and the four types of staphylococcal chromosomal cassette mec (SCCmec) were characterized in 19.4%, 3.6%, 54.5%, and 14.4% of specimens, respectively, for types I, II, III, and IV. Minimal inhibitory concentration (MIC) values to inhibit 50% (MIC50) and 90% (MIC90) of specimens were, respectively, 2 and >256 µL/mL for oxacillin, 1.5 and 2 µL/mL for vancomycin, 0.25 and 0.5 µL/mL for linezolid, 0.094 and 0.19 µL/mL for daptomycin, 0.19 and 0.5 µL/mL for quinupristin/dalfopristin, and 0.125 and 0.38 µL/mL for tigecycline. Resistance to oxacillin and tigecycline and intermediate resistance to quinupristin/dalfopristin were observed. Eight (2.7%) of all 300 CoNS specimens studied showed reduced susceptibility to vancomycin. Results from this study show high resistance rates of CoNS to antimicrobial agents, reflecting the necessity of using these drugs judiciously and controlling nosocomial dissemination of these pathogens.

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ABSTRACT Epidermal parasitic skin diseases encompass scabies, pediculosis, cutaneous larva migrans, myiasis, and tungiasis. Tungiasis is probably the most neglected of all Neglected Tropical Diseases (NTD). It occurs in South America, the Caribbean and Sub-Saharan Africa and affects marginalized populations where people live in extreme poverty. In endemic communities the prevalence can be up to 30% in general population and 85% in children. Over time, chronic pathology develops characterized by hyperkeratosis, edema around the nail rim, fissures, ulcers, deformation and loss of nails. This leads to a pattern of disabilities, eventually resulting in impairment of mobility.Dimeticones are a family of silicon oils with a potential to kill parasites located on top or inside the epidermis by a physical mode of action. They are considered the treatment of choice for pediculosis capitis and pediculosis pubis. With regard to tungiasis, the so called rear abdominal cone of the parasites has been identified as a target for treatment with dimeticones. NYDA®, a mixture of two dimeticones with different viscosity, is the only dimeticone product for which data on the mode of action, efficacy and safety with regard to tungiasis exists. The product has been shown highly effective against embedded sand fleas, even in very intense infection with more than 500 parasites situated on top of each other. A randomized controlled trial showed that seven days after a targeted application of NYDA® 97% (95% CI 94-99%) of the embedded sand fleas had lost all signs of viability.Comprehensive toxicological investigations on the dimeticones contained in NYDA® showed that there is practically no risk of embryotoxicity, fetotoxicity, teratogenicity, and other toxicity. The safety of dimeticones was also demonstrated in clinical trials with a total of 106 participants with tungiasis, in which not a single adverse event was observed.

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ABSTRACT The accuracy of commercially available tests for COVID-19 in Brazil remains unclear. We aimed to perform a meta-analysis to describe the accuracy of available tests to detect COVID-19 in Brazil. We searched at the Brazilian Health Regulatory Agency (ANVISA) online platform to describe the pooled sensitivity (Se), specificity (Sp), diagnostic odds ratio (DOR) and summary receiver operating characteristic curves (SROC) for detection of IgM/IgG antibodies and for tests using naso/oropharyngeal swabs in the random-effects models. We identified 16 tests registered, mostly rapid-tests. Pooled diagnostic accuracy measures [95%CI] were: (i) for IgM antibodies Se = 82% [76-87]; Sp = 97% [96-98]; DOR = 168 [92-305] and SROC = 0.98 [0.96-0.99]; (ii) for IgG antibodies Se = 97% [90-99]; Sp = 98% [97-99]; DOR = 1994 [385-10334] and SROC = 0.99 [0.98-1.00]; and (iii) for detection of SARS-CoV-2 by antigen or molecular assays in naso/oropharyngeal swabs Se = 97% [85-99]; Sp = 99% [77-100]; DOR = 2649 [30-233056] and SROC = 0.99 [0.98-1.00]. These tests can be helpful for emergency testing during the COVID-19 pandemic in Brazil. However, it is important to highlight the high rate of false negative results from tests which detect SARS-CoV-2 IgM antibodies in the initial course of the disease and the scarce evidence-based validation results published in Brazil. Future studies addressing the diagnostic performance of tests for COVID-19 in the Brazilian population are urgently needed.