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PurposeMethylene blue (MB) has been used to increase blood pressure in patients with septic shock by acting on guanylate cyclase and nitric oxide synthase.ObjectiveTo determine whether the administration of MB to patients in the initial phase of septic shock leads to a reduction in the use of vasopressors compared to the Control group.MethodsThis was a 1:1 randomized clinical trial of two groups (MB and Control). Forty-two patients were included in the present study; 23 patients were allocated to the Control group, and 19 were randomized to the MB group. Both groups had access to standard treatment, consisting of fluid replacement, vasopressors, and antibiotic therapy. Patients received a loading dose of MB (3 mg/kg) and maintenance (0.5 mg/kg/h) for 48 h. Vasopressor doses, laboratory test results, inflammatory and anti-inflammatory cytokine levels, and hemodynamic monitoring were recorded before the infusion of MB (T1) and after 20 min (T2), 2 h (T3), 24 h (T4), 48 h after the infusion started (T5) and 24 h after weaning (T6).ResultsMB therapy was started together with the indication of vasopressin (VAS) as a second vasopressor. The MB group showed an immediate reduction in NOR dosage, an earlier reduction in VAS dosage, and higher IL-10 levels compared to the Control group.ConclusionEarly administration of MB in combination with standard treatment for septic shock might be reduce vasopressors dose. Continuous infusion of MB for 48 h was considered safe and there was no adverse events. These results highlight the potential of MB as a safe adjuvant therapeutic option in the treatment of septic shock.Clinical trial registrationhttps://clinicaltrials.gov/, identifier RBR-96584w4.

Abstract Background Pregnancy-related infections are important contributors to maternal sepsis and mortality. We aimed to describe clinical, microbiological characteristics and use of antibiotics by source of infection and country income, among hospitalized women with suspected or confirmed pregnancy-related infections. Methods We used data from WHO Global Maternal Sepsis Study (GLOSS) on maternal infections in hospitalized women, in 52 low-middle- and high-income countries conducted between November 28th and December 4th, 2017, to describe the frequencies and medians of maternal demographic, obstetric, and clinical characteristics and outcomes, methods of infection diagnosis and causative pathogens, of single source pregnancy-related infection, other than breast, and initial use of therapeutic antibiotics. We included 1456 women. Results We found infections of the genital (n = 745/1456, 51.2%) and the urinary tracts (UTI) (n = 531/1456, 36.5%) to be the most frequent. UTI (n = 339/531, 63.8%) and post-caesarean skin and soft tissue infections (SSTI) (n = 99/180, 55.0%) were the sources with more culture samples taken and microbiological confirmations. Escherichia coli was the major uropathogen (n = 103/118, 87.3%) and Staphylococcus aureus (n = 21/44, 47.7%) was the commonest pathogen in SSTI. For 13.1% (n = 191) of women, antibiotics were not prescribed on the same day of infection suspicion. Cephalosporins (n = 283/531, 53.3%) were the commonest antibiotic class prescribed for UTI, while metronidazole (n = 303/925, 32.8%) was the most prescribed for all other sources. Ceftriaxone with metronidazole was the commonest combination for the genital tract (n = 98/745, 13.2%) and SSTI (n = 22/180, 12.2%). Metronidazole (n = 137/235, 58.3%) was the most prescribed antibiotic in low-income countries while cephalosporins and co-amoxiclav (n = 129/186, 69.4%) were more commonly prescribed in high-income countries. Conclusions Differences in antibiotics used across countries could be due to availability, local guidelines, prescribing culture, cost, and access to microbiology laboratory, despite having found similar sources and pathogens as previous studies. Better dissemination of recommendations in line with antimicrobial stewardship programmes might improve antibiotic prescription.

Abstract Healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) pose threats to global health. Effective hand hygiene is essential for preventing HAIs and the spread of AMR in healthcare. We aimed to highlight the recent progress and future directions in hand hygiene and alcohol-based handrub (ABHR) use in the healthcare setting. In September 2023, 42 experts in infection prevention and control (IPC) convened at the 3rd International Conference on Prevention and Infection Control (ICPIC) ABHR Taskforce in Geneva, Switzerland. The purpose of this meeting was to provide a synthesis of recent evidence and formulate a research agenda on four critical areas for the implementation of effective hand hygiene practices: (1) ABHR formulations and hand rubbing techniques, (2) low-resource settings and local production of ABHR, (3) hand hygiene monitoring and technological innovations, and (4) hand hygiene standards and guidelines.

Heart Rate Variability (HRV) and arterial pressure (AP) variability and their responses to head-up tilt test (HUTT) were investigated in Post-COVID-19 syndrome (PCS) patients reporting tachycardia and/or postural hypotension. Besides tachycardia, PCS patients also showed attenuation of the following HRV parameters: RMSSD [square root of the mean of the sum of the squares of differences between adjacent normal-to-normal (NN) intervals] from statistical measures; the power of RR (beat-to-beat interval) spectra at HF (high frequency) from the linear method spectral analysis; occurrence of 2UV (two unlike variation) pattern of RR from the nonlinear method symbolic analysis; and the new family of statistics named sample entropy, when compared to control subjects. Basal AP and LF (low frequency) power of systolic AP were similar between PCS patients and control subjects, while 0 V (zero variation) patterns of AP from the nonlinear method symbolic analysis were exacerbated in PCS patients. Despite tachycardia and a decrease in RMSSD, no parameter of HRV changed during HUTT in PCS patients compared to control subjects. PCS patients reassessed after 6 months showed higher HF power of RR spectra and a higher percentage of 2UV pattern of RR. Moreover, the reassessed PCS patients showed a lower occurrence of 0 V patterns of AP, while the HUTT elicited HR (heart rate) and AP responses identical to control subjects. The HRV and AP variability suggest an autonomic dysfunction with sympathetic predominance in PCS patients. In contrast, the lack of responses of HRV and AP variability indices during HUTT indicates a marked impairment of autonomic control. Of note, the reassessment of PCS patients showed that the noxious effect of COVID-19 on autonomic control tended to fade over time.

ABSTRACT Background: Cases of coronavirus disease 2019 (COVID-19) requiring hospitalization continue to appear in vulnerable populations, highlighting the importance of novel treatments. The hyperinflammatory response underlies the severity of the disease, and targeting this pathway may be useful. Herein, we tested whether immunomodulation focusing on interleukin (IL)-6, IL-17, and IL-2, could improve the clinical outcomes of patients admitted with COVID-19. Methods: This multicenter, open-label, prospective, randomized controlled trial was conducted in Brazil. Sixty hospitalized patients with moderate-to-critical COVID-19 received in addition to standard of care (SOC): IL-17 inhibitor (ixekizumab 80 mg SC/week) 1 dose every 4 weeks; low-dose IL-2 (1.5 million IU per day) for 7 days or until discharge; or indirect IL-6 inhibitor (colchicine) orally (0.5 mg) every 8 hours for 3 days, followed by 4 weeks at 0.5 mg 2x/day; or SOC alone. The primary outcome was accessed in the “per protocol” population as the proportion of patients with clinical improvement, defined as a decrease greater or equal to two points on the World Health Organization’s (WHO) seven-category ordinal scale by day 28. Results: All treatments were safe, and the efficacy outcomes did not differ significantly from those of SOC. Interestingly, in the colchicine group, all participants had an improvement of greater or equal to two points on the WHO seven-category ordinal scale and no deaths or patient deterioration were observed. Conclusions: Ixekizumab, colchicine, and IL-2 were demonstrated to be safe but ineffective for COVID-19 treatment. These results must be interpreted cautiously because of the limited sample size.

Abstract This study aimed to assess the ultrapure cannabidiol (CBD) antibacterial activity and to investigate the antibacterial activity of the combination CBD + polymyxin B (PB) against Gram-negative (GN) bacteria, including PB-resistant Gram-negative bacilli (GNB). We used the standard broth microdilution method, checkerboard assay, and time-kill assay. CBD exhibited antibacterial activity against Gram-positive bacteria, lipooligosaccharide (LOS)-expressing GN diplococcus (GND) (Neisseria gonorrhoeae, Neisseria meningitidis, Moraxella catarrhalis), and Mycobacterium tuberculosis, but not against GNB. For most of the GNB studied, our results showed that low concentrations of PB (≤ 2 µg/mL) allow CBD (≤ 4 µg/mL) to exert antibacterial activity against GNB (e.g., Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii), including PB-resistant GNB. CBD + PB also showed additive and/or synergistic effect against LOS-expressing GND. Time-kill assays results showed that the combination CBD + PB leads to a greater reduction in the number of colony forming units per milliliter compared to CBD and PB alone, at the same concentration used in combination, and the combination CBD + PB was synergistic for all four PB-resistant K. pneumoniae isolates evaluated. Our results show that CBD has translational potential and should be further explored as a repurposed antibacterial agent in clinical trials. The antibacterial efficacy of the combination CBD + PB against multidrug-resistant and extensively drug-resistant GNB, especially PB-resistant K. pneumoniae, is particularly promising.

We conducted a prospective cohort study in a population with diverse ethnic backgrounds from Brazil to assess clinically meaningful symptoms after surviving coronavirus disease. For most of the 175 patients in the study, clinically meaningful symptoms, including fatigue, dyspnea, cough, headache, and muscle weakness, persisted for >120 days after disease onset.

Abstract To describe the medium-term ophthalmological findings in patients recovering from COVID-19. Patients recovered from the acute phase of COVID-19 underwent a complete ophthalmological evaluation, including presenting and best-corrected visual acuity (BCVA), refractometry, biomicroscopy, tonometry, break-up time and Schirmer tests, indirect ophthalmoscopy, color fundus picture, and retinal architecture evaluation using optical coherence tomography. Socio-demographic data and personal medical history were also collected. According to the severity of systemic manifestations, patients were classified into mild-to-moderate, severe, and critical. Sixty-four patients (128 eyes) were evaluated 82 ± 36.4 days after the onset of COVID’s symptoms. The mean ± SD duration of hospitalization was 15.0 ± 10.7 days. Seven patients (10.9%) had mild-to-moderate, 33 (51.5%) severe, and 24 (37.5%) critical disease. Median [interquartile ranges (IQR)] presenting visual acuity was 0.1 (0–0.2) and BCVA 0 (0–0.1). Anterior segment biomicroscopy was unremarkable, except for dry eye disease, verified in 10.9% of them. The mean ± SD intraocular pressure (IOP) in critical group (14.16 ± 1.88 mmHg) was significantly higher than in severe group (12.51 ± 2.40 mmHg), both in the right (p 0.02) and left eyes (p 0.038). Among all, 15.6% had diabetic retinopathy, and two patients presented with discrete white-yellowish dots in the posterior pole, leading to hyporreflective changes at retinal pigment epithelium level, outer segment, and ellipsoid layers. The present study identified higher IOP among critical cases, when compared to severe cases, and discrete outer retina changes 80 days after COVID-19 infection. No sign of uveitis was found.

Contexto: A Peritonite Bacteriana Espontânea (PBE) é uma complicação grave e frequente entre pacientes cirróticos com ascite, diagnosticada por meio da análise citológica do líquido ascítico. A cultura microbiológica do líquido ascítico, por sua vez, é positiva em menos de 40% dos casos de PBE, o que resulta frequentemente na instituição de terapia antimicrobiana inapropriada. A terapia empírica pode ser subótima, aumentando o risco de agravamento do paciente, ou superestimada, impulsionando desnecessariamente a resistência bacteriana. Objetivo: Estudo experimental laboratorial, propôs padronizar e verificar a viabilidade técnica da filtração a vácuo do líquido ascítico, como forma de otimizar o diagnóstico etiológico na PBE, comparativamente ao sistema automatizado de culturas de sangue. Método: O método avaliado e padronizado neste estudo foi a da filtragem a vácuo do líquido ascítico. Esse tem como princípio a concentração da bactéria em uma membrana filtrante. Resultados: Nesse estudo, foram incluídos 36 pacientes cirróticos atendidos em um hospital público universitário, entre 13.11.2017 e 30.06.2019. Entre eles, 47,2% (17/36) apresentaram citologia compatível com PBE. Nesses, a sensibilidade da cultura pelo método semi-automatizado foi de 35,3% (6/17) e da cultura pelo método da filtragem a vácuo foi de 11,8% (2/17). Conclusão: Em conclusão, a filtragem a vácuo não melhora o diagnóstico microbiológico da PBE em relação ao método automatizado.

Abstract Background/objective After wearing powdered gloves, healthcare workers (HCW) are supposed to wash their hands instead of using alcohol-based hand-rub (ABHR). Washing hands takes longer than using ABHR, and the use of powdered gloves may be an obstacle to hand-hygiene compliance. This study aimed to evaluate the impact of replacing powdered gloves with powder-free gloves on hand-hygiene compliance among HCW of an intensive care unit (ICU). Methods A quasi-experimental study was conducted in a general ICU of a tertiary care university hospital in Brazil. From June 1st to July 15th, 2017, all HCW were provided with powdered latex gloves only for all clinical procedures. From July 15th to August 31st, 2017, HCW were provided with nitrile powder-free gloves only. Hand-hygiene compliance was assessed through direct observation, and evaluated according to the World Health Organization Hand Hygiene guidelines. We calculated that a sample size of 544 hand hygiene opportunities needed to be observed per period. Data analysis were performed using the STATA SE® version 14, and we compared the individual’s percentage of compliance using the t test for paired data before and after the intervention. Results Overall, 40 HCW were assessed before and after the introduction of nitrile powder-free gloves, with 1114 and 1139 observations of hand hygiene opportunities, respectively. The proportion of compliance with hand hygiene was 55% (95% confidence interval [CI] 51–59%) using powdered latex gloves and 60% (95% CI 57–63%) using powder-free gloves. The difference in proportions between the two types of gloves was 5.1% (95% CI 2.5–7.6%, p

Summary: Background: Worldwide, healthcare facilities face high and often inappropriate consumption of antimicrobials. However, there are limited antimicrobial stewardship (ASP) studies from low- and middle-income countries that include restrictive measures and their impacts on antimicrobial consumption. Aim: This study aims to assess the impact of a restrictive bundle (preauthorization requirements and offering consultation with an infectious diseases physician 24 hours a day) on antimicrobial consumption, in a tertiary hospital in Brazil. Methods: We conducted an interrupted time series analysis (ITS) with pharmacy-based data from January 2010 to December 2018 to evaluate changes of level and slope in antimicrobial consumption (expressed in DDD/1,000 patient-days) after the implementation of the restrictive bundle in September 2014. Fourteen restricted antimicrobials (amphotericin B deoxycholate, liposomal amphotericin B, micafungin, voriconazole, ganciclovir, amikacin, ampicillin/sulbactam, daptomycin, ertapenem, levofloxacin, linezolid, piperacillin/tazobactam, polymyxin B, and tigecycline) and eight unrestricted were analysed. Findings: Among the 14 restricted antimicrobials, four presented a significant negative level change: micafungin (-2,14, p=.027), voriconazole (-14.72, p

Abstract Background Harmonization in hand hygiene training for infection prevention and control (IPC) professionals is lacking. We describe a standardized approach to training, using a “Train-the-Trainers” (TTT) concept for IPC professionals and assess its impact on hand hygiene knowledge in six countries. Methods We developed a three-day simulation-based TTT course based on the World Health Organization (WHO) Multimodal Hand Hygiene Improvement Strategy. To evaluate its impact, we have performed a pre-and post-course knowledge questionnaire. The Wilcoxon signed-rank test was used to compare the results before and after training. Results Between June 2016 and January 2018 we conducted seven TTT courses in six countries: Iran, Malaysia, Mexico, South Africa, Spain and Thailand. A total of 305 IPC professionals completed the programme. Participants included nurses (n = 196; 64.2%), physicians (n = 53; 17.3%) and other health professionals (n = 56; 18.3%). In total, participants from more than 20 countries were trained. A significant (p

Abstract INTRODUCTION: This epidemiological household survey aimed to estimate the prevalence of the current and past SARS-CoV-2 infections in Ribeirão Preto, a municipality of southeast Brazil. METHODS: The survey was conducted in two phases using a clustered sampling scheme. The first phase spanned May 1-3 and involved 709 participants. The second phase spanned June 11-14, 2020, and involved 646 participants. RESULTS: During the first phase, RT-PCR performed on nasopharyngeal swabs was positive at 0.14%. The serological tests were positive in 1.27% of the patients during the first phase and 2.79% during the second phase. People living in households with more than five members had a prevalence of 10.83% (95%CI: 1.58-74.27) higher than those living alone or with someone other. Considering the proportion of the positive serological test results with sex and age adjustments, approximately 2.37% (95%CI: 1.32-3.42) of the population had been cumulatively infected by mid-June 2020, which is equivalent to 16,670 people (95%CI: 9,267-24,074). Considering that 68 deaths from the disease in the residents of the city had been confirmed as at the date of the second phase of the survey, the infection fatality rate was estimated to be 0.41% (95%CI: 0.28-0.73). Our results suggest that approximately 88% of the cases of SARS-CoV-2 infection at the time of the survey were not reported to the local epidemiological surveillance service. CONCLUSIONS: The findings of this study provide in-depth knowledge of the COVID-19 pandemic in Brazil and are helpful for the preventive and decision-making policies of public managers.

A panel of experts was convened by the International Society for Infectious Diseases (ISID) to overview evidence based strategies to reduce the transmission of pathogens via the hands of healthcare workers and the subsequent incidence of hospital acquired infections with a focus on implementing these strategies in low- and middle-income countries. Existing data suggests that hospital patients in low- and middle-income countries are exposed to rates of healthcare associated infections at least 2-fold higher than in high income countries. In addition to the universal challenges to the implementation of effective hand hygiene strategies, hospitals in low- and middle-income countries face a range of unique barriers, including overcrowding and securing a reliable and sustainable supply of alcohol-based handrub. The WHO Multimodal Hand Hygiene Improvement Strategy and its associated resources represent an evidence-based framework for developing a locally-adapted implementation plan for hand hygiene promotion. Keywords: Hand hygiene, Infection prevention and control, Low- and middle-income countries

Abstract Background The World Health Organization (WHO) ethanol-based handrub (EBHR) formulation contains 1.45% glycerol as an emollient to protect healthcare workers’ (HCWs) skin against dryness and dermatitis. However, glycerol seems to negatively affect the antimicrobial efficacy of alcohols. In addition, the minimal concentration of glycerol required to protect hands remain unknown. We aim to evaluate the tolerance of HCWs to the WHO EBHR formulation using different concentrations of glycerol in a tropical climate healthcare setting. Methods We conducted a cluster-randomized, double-blind, crossover study among 40 HCWs from an intensive care unit of a tertiary-care hospital in Brazil, from June 1st to September 30, 2017. We tested the WHO EBHR original formulation containing 1.45% glycerol against three other concentrations (0, 0.5, and 0.75%). HCWs used one formulation at a time for seven working days during their routine practice and then had their hands evaluated by an external observer using the WHO scale for visual inspection. Participants also used a WHO self-evaluation tool to rate their own skin condition. We used a generalized estimating equations of the logit type to compare differences between the tolerability to different formulations. Results According to the independent observation, participants had 2.4 times (95%CI: 1.12–5.15) more chance of having a skin condition considered good when they used the 0.5% compared to the 1.45% glycerol formulation. For the self-evaluation scale, participants were likely to have a worst evaluation (OR: 0.23, 95%CI: 0.11–0.49) when they used the preparation without glycerol compared to the WHO standard formulation (1.45%), and there were no differences between the other formulations used. Conclusion In a tropical climate setting, the WHO-modified EBHR formulation containing 0.5% glycerol led to better ratings of skin tolerance than the original formulation, and, therefore, may offer the best balance between skin tolerance and antimicrobial efficacy.

Abstract INTRODUCTION: We evaluated the performance of Bayesian vector autoregressive (BVAR) and Holt’s models to forecast the weekly COVID-19 reported cases in six units of a large hospital. METHODS: Cases reported from epidemiologic weeks (EW) 12-37 were selected as the training period, and from EW 38-41 as the test period. RESULTS: The models performed well in forecasting cases within one or two weeks following the end of the time-series, but forecasts for a more distant period were inaccurate. CONCLUSIONS: Both models offered reasonable performance in very short-term forecasts for confirmed cases of COVID-19.

ABSTRACT Objective: To assess the surgical antibiotic prophylaxis. Methods: This was a descriptive study performed at a public tertiary care university hospital gathering prescription, sociodemographic and hospitalization data of inpatients admitted in 2014 who used antimicrobial drugs. This data were obtained from the hospital electronic database. The antimicrobial data were classified according to the anatomical, therapeutic chemical/defined daily dose per 1,000 inpatients. An exploratory analysis was performed using principal component analysis. Results: A total of 5,182 inpatients were prescribed surgical antibiotic prophylaxis. Of the total antimicrobial use, 11.7% were for surgical antibiotic prophylaxis. The orthopedic, thoracic and cardiovascular postoperative units, and postoperative intensive care unit comprised more than half of the total surgical antibiotic prophylaxis use (56.3%). The duration of antimicrobial use of these units were 2.2, 2.0, and 1.4 days, respectively. Third-generation cephalosporins and fluoroquinolones had the longest use among antimicrobial classes. Conclusion: Surgical antibiotic prophylaxis was inadequate in the orthopedic, postoperative intensive care, thoracic and cardiovascular postoperative, gynecology and obstetrics, and otolaryngology units. Therefore, the development and implementation of additional strategies to promote surgical antibiotic stewardship at hospitals are essential.

Abstract With the large number of individuals infected and recovered from Covid-19, there is intense discussion about the quality and duration of the immunity elicited by SARS-CoV-2 infection, including the possibility of disease recurrence. Here we report a case with strong clinical, epidemiological and laboratorial evidence of, not only reinfection by SARS-CoV-2, but also clinical recurrence of Covid-19.

Objective To evaluate changes in awareness of maternal sepsis among healthcare providers resulting from the WHO Global Maternal Sepsis Study (GLOSS) awareness campaign.Design Independent sample precampaign/postcampaign through online and paper-based surveys available for over 30 days before campaign roll-out (pre) and after study data collection (post). Descriptive statistics were used for campaign recognition and exposure, and odds ratio (OR) and percentage change were calculated for differences in awareness, adjusting for confounders using multivariate logistic regression.Setting and participants Healthcare providers from 398 participating facilities in 46 low, middle and high-income countries.Intervention An awareness campaign to accompany GLOSS launched 3 weeks prior to data collection and lasting the entire study period (28 November 2017 to 15 January 2018) and beyond.Main outcome measures Campaign recognition and exposure, and changes in awareness.Results A total of 2188 surveys were analysed: 1155 at baseline and 1033 at postcampaign. Most survey respondents found the campaign materials helpful (94%), that they helped increase awareness (90%) and that they helped motivate to act differently (88%). There were significant changes with regard to: not having heard of maternal sepsis (−63.4% change, pre-OR/post-OR 0.35, 95% CI 0.18 to 0.68) and perception of confidence in making the right decisions with regard to maternal sepsis identification and management (7.3% change, pre-OR/post-OR 1.44, 95% CI 1.01 to 2.06).Conclusions Awareness raising campaigns can contribute to an increase in having heard of maternal sepsis and an increase in provider perception of confidence in making correct decisions. Offering the information to make accurate and timely decisions while promoting environments that enable self-confidence and support could improve maternal sepsis identification and management.

Summary: Background: Maternal infections are an important cause of maternal mortality and severe maternal morbidity. We report the main findings of the WHO Global Maternal Sepsis Study, which aimed to assess the frequency of maternal infections in health facilities, according to maternal characteristics and outcomes, and coverage of core practices for early identification and management. Methods: We did a facility-based, prospective, 1-week inception cohort study in 713 health facilities providing obstetric, midwifery, or abortion care, or where women could be admitted because of complications of pregnancy, childbirth, post-partum, or post-abortion, in 52 low-income and middle-income countries (LMICs) and high-income countries (HICs). We obtained data from hospital records for all pregnant or recently pregnant women hospitalised with suspected or confirmed infection. We calculated ratios of infection and infection-related severe maternal outcomes (ie, death or near-miss) per 1000 livebirths and the proportion of intrahospital fatalities across country income groups, as well as the distribution of demographic, obstetric, clinical characteristics and outcomes, and coverage of a set of core practices for identification and management across infection severity groups. Findings: Between Nov 28, 2017, and Dec 4, 2017, of 2965 women assessed for eligibility, 2850 pregnant or recently pregnant women with suspected or confirmed infection were included. 70·4 (95% CI 67·7–73·1) hospitalised women per 1000 livebirths had a maternal infection, and 10·9 (9·8–12·0) women per 1000 livebirths presented with infection-related (underlying or contributing cause) severe maternal outcomes. Highest ratios were observed in LMICs and the lowest in HICs. The proportion of intrahospital fatalities was 6·8% among women with severe maternal outcomes, with the highest proportion in low-income countries. Infection-related maternal deaths represented more than half of the intrahospital deaths. Around two-thirds (63·9%, n=1821) of the women had a complete set of vital signs recorded, or received antimicrobials the day of suspicion or diagnosis of the infection (70·2%, n=1875), without marked differences across severity groups. Interpretation: The frequency of maternal infections requiring management in health facilities is high. Our results suggest that contribution of direct (obstetric) and indirect (non-obstetric) infections to overall maternal deaths is greater than previously thought. Improvement of early identification is urgently needed, as well as prompt management of women with infections in health facilities by implementing effective evidence-based practices. Funding: UNDP–UNFPA–UNICEF–WHO–World Bank Special Programme of Research, Development and Research Training in Human Reproduction, WHO, Merck for Mothers, and United States Agency for International Development.

Background: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is spreading worldwide, but little is known about the epidemiology of this pathogen in Brazil. Objective: To evaluate clinical and microbiological features of children with S. aureus infections admitted to a university hospital. Methods: This was a cross-sectional study evaluating the potential risk factors for CA-MRSA, and a retrospective cohort evaluating in-hospital clinical outcomes. To include patients with both community and hospital-associated infections, we screened the results of the microbiological laboratory tests from January 1, 2012, to December 31, 2016. According to the phenotype, we classified the isolates in Methicillin-Susceptible S. aureus (MSSA), Hospital-Associated Methicillin-Resistant S. aureus (HA-MRSA), and CA-MRSA. Clinical data were collected from the patients’ medical records. Results: We identified 279 cases of S. aureus infections (MSSA = 163, CA-MRSA = 69, HA-MRSA = 41). Overall, the incidence density of CA-MRSA and MSSA infections increased while the HA-MRSA incidence density decreased over the study period. CA-MRSA infected patients were more likely to present with skin and soft tissue infections (OR: 2.83, 95%CI: 1.54–5.33, p

Abstract Background Although alcohol-based surgical hand preparation offers potential advantages over the traditional surgical scrubbing technique, implementing it may be challenging due to resistance of surgeons in changing their practice. We aimed to implement alcohol-based surgical hand preparation in the hospital setting evaluating the impact of that on the quality and duration of the procedure, as well as on the prevention of surgical site infections. Methods A quasi-experimental study conducted at a tertiary-care university hospital from April 01 to November 01, 2017. Participants were cardiac and orthopedic surgical teams (n = 56) and patients operated by them (n = 231). Intervention consisted of making alcohol-based handrub available in the operating room, convincing and training surgical teams for using it, promoting direct observation of surgical hand preparation, and providing aggregated feedback on the quality of the preparation. The primary study outcome was the quality of the surgical hand preparation, inferred by the compliance with each one of the steps predicted in the World Health Organization (WHO) technique, evaluated through direct observation. Secondary study outcome was the patient’s individual probability of developing surgical site infection in both study periods. We used the Wilcoxon for paired samples and McNemar’s test to assess the primary study outcome and we build a logistic regression model to assess the secondary outcome. Results We observed 534 surgical hand preparation events. Among 33 participants with full data available for both study periods, we observed full compliance with all the steps predicted in the WHO technique in 0.03% (1/33) of them in the pre-intervention period and in 36.36% (12/33) of them in the intervention period (OR:12.0, 95% CI: 2. 4-59.2, p = 0.002). Compared to the pre-intervention period, the intervention reduced the duration of the preparation (4.8 min vs 2.7 min, respectively; p

Abstract Background The Leuconostoc mesenteroides are members of the Streptococcae family and currently has been recognized as potential pathogens. This case describes a bacteremia caused by L. mesenteroides in an immunocompetent patient affected by Chagas disease. Case presentation A 67-year-old female patient with chagasic megaesophagus and megacolon was submitted to a Heller myotomy for achalasia in 2000 and endoscopic dilatation in 2015. Patient was admitted to the Nutrology Ward in May 2016 with protein-calorie malnutrition associated with achalasia and receiving enteral nutrition. In July 2016, the patient underwent a Serra-Doria surgery. In the third postoperative day she presented an important abdominal distension. She was submitted to a new surgical intervention, and then a terminal ileum perforation was detected, leading the surgeon to perform an enterectomy with side-to-side anastomosis. The next day after the surgery (4th postoperative day) the patient presented a decreased level of consciousness (Glasgow coma scale = 8), hypotension and hypoxemia. In two samples of blood cultures there was growth of Leuconostoc mesenteroides. Susceptibility pattern was evaluated by the diffusion disk method. The microorganism was susceptible to penicillin, ampicillin, chloramphenicol, erythromycin, and fluoroquinolones, but resistant to rifampin, tetracycline, vancomycin and teicoplanin. Conclusion We concluded that infections caused by L. mesenteroides is serious and should be considered not only in settings of immunosuppression and prolonged antimicrobial use, but also in immunocompetent patients undergoing surgeries involving the gastrointestinal tract.

Abstract Background Hand hygiene has evolved over the last decades and many terminologies emerged. We aimed to analyse the evolution in the frequency of utilization of key hand hygiene terms in the literature along the years. Methods We identified keywords and Medical Subject Headings (MeSH) used in MEDLINE® indexation related to hand hygiene by searching international guidelines and the MeSH database. We performed a MEDLINE® search combining the selected keywords and MeSH and analysed the number of publications retrieved yearly. Results The literature search yielded 9019 publications when all hand hygiene related search terms were combined, between 1921 and November 2016. The total number of publications per year increased from a median of 4 (IQR 3, 6) in the 1950’s to 554 (IQR 478, 583) between 2011 and 2015. The most frequently used keywords are hand disinfection, hand hygiene, hand washing, handrub, hand sanitizer and alcohol-based hand rub (ABHR). Until the 1990s, hand disinfection and hand washing were the most frequently used terms. Whilst the last decade has seen a remarkable increase in publications mentioning hand disinfection and hand hygiene and for the first time handrub, hand sanitizers and ABHR were introduced in the literature. Hand disinfection, hand hygiene and hand sanitizers are the main MeSH used by MEDLINE®. Since 2013 hand hygiene is the most frequently used MeSH and keyword. Conclusions The change seen in literature in the last two decades, from hand washing and hand disinfection to hand hygiene, most probably reflect the paradigm shift favouring use of ABHR over soap and water promoted by international guidelines in the early 2000s.

Abstract: INTRODUCTION Klebsiella pneumoniae has become an increasingly important etiologic agent of nosocomial infections in recent years. This is mainly due to the expression of virulence factors and development of resistance to several antimicrobial drugs. METHODS This retrospective study examines data obtained from the microbiology laboratory of a Brazilian tertiary-care hospital. To assess temporal trends in prevalence and antimicrobial susceptibility, K. pneumoniae isolates were analyzed from 2000 to 2013. The relative frequencies of K. pneumoniae isolation were calculated among all Gram-negative bacilli isolated in each period analyzed. Susceptibility tests were performed using automated systems. RESULTS: From 2000-2006, K. pneumonia isolates comprised 10.7% of isolated Gram-negative bacilli (455/4260). From 2007-2013, this percentage was 18.1% (965/5331). Strictly considering isolates from bloodstream infections, the relative annual prevalence of K. pneumoniae increased from 14-17% to 27-32% during the same periods. A progressive decrease in K. pneumoniae susceptibility to all antimicrobial agents assessed was detected. Partial resistance was also observed to antimicrobial drugs that have been used more recently, such as colistin and tigecycline. CONCLUSIONS Our study indicates that K. pneumoniae has become a major pathogen among hospitalized patients and confirms its recent trend of increasing antimicrobial resistance.

Abstract OBJECTIVE Analyze the factors associated with full hepatitis B vaccination (three doses) in patients with diabetes mellitus. METHOD Cross-sectional study, conducted in a health unit in a city in the state of São Paulo, with 255 patients on outpatient follow-up, in 2014. Data were obtained from the computerized system of the Municipal Health Department and via a structured questionnaire. A logistic regression model was used for analysis. RESULTS Full hepatitis B vaccination was noted in 13.7% of the patients and shown to be directly associated with their educational level (OR=1.30; CI: 1.07-1.57) and current or previous work as a health professional (OR=3.21; CI: 1.16-8.89). CONCLUSION Hepatitis B vaccination coverage was found to be low in patients with diabetes mellitus, indicating their vulnerability to this serious and potentially fatal disease. Higher educational level and working in the field of health were associated with better vaccination coverage.

The original article [1] contained a misspelling in author, Fernando Bellissimo-Rodrigues’s name which has since been corrected.

RESUMO Objetivo Analisar a cobertura vacinal de pacientes com diabetes mellitus para as vacinas recomendadas pelo Programa Nacional de Imunizações e as variáveis associadas. Método Estudo transversal, com 255 pacientes de unidade básica de saúde, da região sudeste do Brasil, realizado em 2015. Utilizou-se o Sistema Informatizado de Gestão em Saúde para identificação da vacinação contra influenza, pneumococo, hepatite B, febre amarela, sarampo/caxumba/rubéola e difteria/tétano. Realizou-se análise estatística multivariada. Resultados 78,8% foram vacinados contra febre amarela, 65,5% contra difteria/tétano, 27,8% contra pneumococo, 27,5% contra hepatite B, 14,9% contra sarampo/caxumba/rubéola e 14,5% contra influenza. Encontrou-se associação entre sexo feminino e vacinação contra hepatite B, febre amarela e difteria/tétano; maior nível de escolaridade e vacinação contra hepatite B, e menor mediana de idade e vacinação contra sarampo/caxumba/rubéola. Conclusão A cobertura vacinal, em geral, foi baixa. Fatores como sexo, idade e escolaridade devem ser considerados nas recomendações de vacinas e na proposição de estratégias de imunização.

INTRODUCTION: Urinary tract infections (UTI) among transplant recipients are usually caused by gram-negative microorganisms and can provoke a high incidence of morbidity and mortality. The aim of this study was to evaluate the risk factors associated with the acquisition of UTIs during the first year after renal transplantation. METHODS: Here, we report a single-center retrospective cohort study of 99 renal transplant patients followed for the first year after surgery. The definition of a UTI episode was a urine culture showing bacterial growth and leucocyturia when patients presented with urinary symptoms. The absence of infection (asymptomatic bacteriuria) was defined as an absence of symptoms with negative urine culture or bacterial growth with any number of colonies. RESULTS: Ninety-nine patients were included in the study. During the study, 1,847 urine cultures were collected, and 320 (17.3%) tested positive for bacterial growth. Twenty-six (26.2%) patients developed a UTI. The most frequent microorganisms isolated from patients with UTIs were Klebsiella pneumoniae (36%), with 33% of the strains resistant to carbapenems, followed by Escherichia coli (20%). There were no deaths or graft losses associated with UTI episodes. CONCLUSIONS: Among the UTI risk factors studied, the only one that was associated with a higher incidence of infection was female sex. Moreover, the identification of drug-resistant strains is worrisome, as these infections have become widespread globally and represent a challenge in the control and management of infections, especially in solid organ transplantation.

INTRODUCTION: Rotavirus is the main etiologic agent of acute infectious diarrhea in children worldwide. Considering that a rotavirus vaccine (G1P8, strain RIX4414) was added to the Brazilian vaccination schedule in 2006, we aimed to study its effectiveness and safety regarding intestinal intussusception. METHODS: A quasi-experimental trial was performed in which the primary outcome was the number of hospitalizations that were presumably due to acute infectious diarrhea per 100,000 children at risk (0-4 years old). The secondary outcomes included mortality due to acute infectious diarrhea and the intestinal intussusception rates in children in the same age range. We analyzed three scenarios: Health Division XIII of the State of São Paulo (DRS XIII) from 2002 to 2008, the State of São Paulo, and Brazil from 2002 to 2012. RESULTS: The averages of the hospitalization rates for 100,000 children in the pre- and post-vaccination periods were 1,413 and 959, respectively, for DRS XIII (RR=0.67), 312 and 249, respectively, for the State of São Paulo (RR=0.79), and 718 and 576, respectively, for Brazil (RR=0.8). The mortality rate per 100,000 children in the pre- and post-vaccination periods was 2.0 and 1.3, respectively, for DRS XIII (RR=0.66), 5.5 and 2.5, respectively, for the State of São Paulo (RR=0.47), and 15.0 and 8.0, respectively, for Brazil (RR=0.53). The average annual rates of intussusception for 100,000 children in DRS XIII were 28.0 and 22.0 (RR=0.77) in the pre- and post-vaccination periods, respectively. CONCLUSIONS: A monovalent rotavirus vaccine was demonstrated to be effective in preventing the hospitalizations and deaths of children that were presumably due to acute infectious diarrhea, without increasing the risk of intestinal intussusception.

OBJECTIVES: to evaluate the Nosocomial Infection Control Programs in hospital institutions regarding structure and process indicators.METHOD: this is a descriptive, exploratory and quantitative study conducted in 2013. The study population comprised 13 Nosocomial Infection Control Programs of health services in a Brazilian city of the state of São Paulo. Public domain instruments available in the Manual of Evaluation Indicators of Nosocomial Infection Control Practices were used.RESULTS: The indicators with the highest average compliance were "Evaluation of the Structure of the Nosocomial Infection Control Programs" (75%) and "Evaluation of the Epidemiological Surveillance System of Nosocomial Infection" (82%) and those with the lowest mean compliance scores were "Evaluation of Operational Guidelines" (58.97%) and "Evaluation of Activities of Control and Prevention of Nosocomial Infection" (60.29%).CONCLUSION: The use of indicators identified that, despite having produced knowledge about prevention and control of nosocomial infections, there is still a large gap between the practice and the recommendations.

Worldwide aging of the human population has promoted an increase in the incidence of neoplasia, including hematological cancers, which render patients particularly vulnerable to invasive fungal infections. For this reason, air filtration in hemato-oncology units has been recommended. However, scarce literature has assessed the impact of microbiological air quality on the occurrence of fungal infections in this population. We performed an integrative review of studies in the MEDLINE database that were published between January 1980 and October 2012, using the following combinations of keywords: air × quality × HEPA, air × quality × hematology, and airborne fungal infections. The search yielded only 13 articles, suggesting that high-efficiency filtering of the ambient air in hemato-oncology units can prevent the incidence of invasive fungal infections. However, no randomized clinical trial was found to confirm this suggestion. Currently, there is no consensus about the maximum allowable count of fungi in the air, which complicates filtration monitoring, including filter maintenance and replacement, and needs to be addressed in future studies.

Paracoccidioidomycosis should be differentiated from other opportunistic diseases in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients who live in Latin America. Laboratory investigation can begin with serological tests, which are rapid and efficient. In the present study, double immunodiffusion (DID), counterimmunoelectrophoresis (CIEP) and an enzyme linked immunosorbent assay (ELISA) tests were assessed for the detection of anti-Paracoccidioides brasiliensis antibodies in 40 patients coinfected with HIV. The results were compared to those obtained for 75 non-HIV-infected patients with endemic paracoccidioidomycosis. Anti-P. brasiliensis antibodies were detected in 65% (DID), 79% (CIEP) and 95% (ELISA) of the patients with HIV/AIDS, significantly lower rates than those detected in cases of endemic paracoccidioidomycosis, which were 89%, 99% and 100%, respectively. The reactive sera of HIV-infected patients also showed lower anti-P. brasiliensis antibody titres than those of non-HIV-infected patients. Despite the lower intensity of the specific humoral response, serological tests are useful for the diagnosis of opportunistic paracoccidioidomycosis in the HIV/AIDS population. We suggest optimization of the laboratory diagnosis by combining the ELISA test with CIEP or DID.

INTRODUCTION: Polymyxins are antimicrobial agents capable of controlling carbapenemase-producing Klebsiella pneumoniae infection. METHODS: We report a cluster of four patients colonized or infected by polymyxin-resistant and Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae. RESULTS: Three patients were hospitalized in adjacent wards, and two were admitted to the intensive care unit. The index case maintained prolonged intestinal colonization by KPC-producing K. pneumoniae. Three patients received polymyxin B before the isolation of polymyxin-resistant K. pneumoniae. CONCLUSIONS: Colonization by KPC-producing K. pneumoniae and previous use of polymyxin B may be causally related to the development of polymyxin-resistant microorganisms.

Cryptococcus gattii causes a form of endemic mycosis that most commonly affects the lungs and central nervous system of immunocompetent patients living in tropical and subtropical areas of the world. Case report. A 66-year-old man who had chronic obstructive pulmonary disease without HIV infection and had been on systemic corticotherapy for several years developed extensive ulceration of the left forearm that was associated with ipsilateral supraclavicular adenomegaly, consequent to infection with Cryptococcus gattii. The patient was treated with fluconazole 400mg/day for eight months, which led to complete healing of the lesion. This case emphasizes that, although rare, C. gattii may cause opportunistic cutaneous-lymphatic infection in patients living in the southeastern region of Brazil who are immunocompromised through chronic corticotherapy.Cryptococcus gattii é agente causador de uma micose endêmica que afeta principalmente os pulmões e o sistema nervoso central de pacientes imunocompetentes em regiões tropicais e subtropicais do globo. Relato de caso. Um paciente de 66 anos, portador de doença pulmonar obstrutiva crônica, não infectado pelo vírus HIV, em corticoterapia sistêmica prolongada, desenvolveu extensa ulceração do antebraço esquerdo, associada a adenomegalia supraclavicular ipsilateral, em conseqüência à infecção por Cryptococcus gattii. O paciente foi tratado com fluconazol 400mg/dia durante 8 meses, obtendo resolução completa da lesão. Este caso enfatiza que, ainda que raramente, C. gattii pode causar infecção cutâneo-linfática oportunista, em paciente imunocomprometido pelo uso sistêmico de corticosteróides vivendo na região sudeste do Brasil.

ABSTRACT Background: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is spreading worldwide, but little is known about the epidemiology of this pathogen in Brazil. Objective: To evaluate clinical and microbiological features of children with S. aureus infections admitted to a university hospital. Methods: This was a cross-sectional study evaluating the potential risk factors for CA-MRSA, and a retrospective cohort evaluating in-hospital clinical outcomes. To include patients with both community and hospital-associated infections, we screened the results of the microbiological laboratory tests from January 1, 2012, to December 31, 2016. According to the phenotype, we classified the isolates in Methicillin-Susceptible S. aureus (MSSA), Hospital-Associated Methicillin-Resistant S. aureus (HA-MRSA), and CA-MRSA. Clinical data were collected from the patients’ medical records. Results: We identified 279 cases of S. aureus infections (MSSA = 163, CA-MRSA = 69, HA-MRSA = 41). Overall, the incidence density of CA-MRSA and MSSA infections increased while the HA-MRSA incidence density decreased over the study period. CA-MRSA infected patients were more likely to present with skin and soft tissue infections (OR: 2.83, 95%CI: 1.54–5.33, p < 0.001) and osteomyelitis (OR: 4.76; 95%CI: 1.16–22.71, p = 0.014) when compared to MSSA and HA-MRSA infections. Unadjusted case fatality rates were similar between MSSA-infected patients (3.14%, 5/159) and CA-MRSA infected patients (3.80%, 3/79, p = 0.792), while HA-MRSA infected patients were more likely to die in the hospital (12.20%, 5/41, p = 0.013). Conclusions: CA-MRSA is an emergent pediatric pathogen in Brazil. Our results highlight the relevance of choosing an appropriate initial antimicrobial drug for treating children with severe S. aureus infections.

Abstract INTRODUCTION: The prevalence of Toxoplasma gondii infection varies markedly among different populations, especially depending on factors related to socioeconomic development and eating habits. Cássia dos Coqueiros is a small city in Brazil with rural characteristics and increased risk factors traditionally associated with T. gondii infection. METHODS: We carried out a cross-sectional study involving 970 inhabitants aged 18 years or more, selected from patients of the local health unit and home visits in urban and rural areas. Each participant completed a survey with questions regarding demographic, socioeconomic, and risk factors for toxoplasmosis. Blood samples from participants were tested for presence of IgG and IgM antibodies against T. gondii using a chemiluminescent microparticle immunoassay. RESULTS: The prevalence of IgG and IgM antibodies was 62.3% and 2.5%, respectively. Variables that proved to be independent predictors of infection were age, low levels of education, and previous diagnosis of toxoplasmosis. CONCLUSIONS: The high prevalence of toxoplasmosis serological markers in this adult population highlights the need to promote preventive practices, especially those directed toward women of childbearing age, in this part of Brazil.

Abstract INTRODUCTION: Bloodstream infections are the second most common cause of death among patients on hemodialysis. This study aimed to evaluate the incidence of and risk factors associated with central venous catheter-related infections in patients undergoing hemodialysis, and to identify and characterize the type and antimicrobial susceptibility profiles of the primary microorganisms isolated during one year of follow-up. METHODS: A prospective cohort study was conducted in 2014 in a hemodialysis referral center. We included 200 outpatients with acute kidney injury who had no permanent venous access. A nurse assessed the patients for signs of infection three times per week during dressing changes. The clinicopathologic characteristics of patients with and without local or systemic infection were compared. RESULTS: Fifty-five episodes of catheter-related infections occurred in 43 (22%) patients; 38 (69%) were bloodstream infections and 17 (31%) were local infections. Thirty-two (75%) patients with infection had femoral vein catheter placement. In total, 6,240 hemodialysis sessions were performed; the rates of primary bloodstream and local infection were 6.1 and 2.7 episodes per 1,000 patients on daily dialysis, respectively. In the univariate analysis, diabetes was significantly associated with the development of infection, while level of education, ethnicity, age, and sex were not. Gram-negative bacteria were primarily isolated from blood culture specimens (55% of samples). Of the Gram-negative isolates, 56% were resistant to the carbapenems. CONCLUSIONS: We identified a high incidence of catheter-related infections caused by resistant microorganisms in patients undergoing hemodialysis via central venous catheters.

Abstract INTRODUCTION: We aimed to evaluate the effectiveness of a symbiotic product to decolonize the intestinal tract of patients harboring multidrug-resistant (MDR) Gram-negative bacilli and to prevent nosocomial infections. METHODS: This was a randomized, double blind, placebo-controlled clinical trial, conducted in a tertiary-care university hospital. All adult hospitalized patients with a positive clinical culture and a positive rectal swab for any MDR Gram-negative bacilli were potentially eligible. Exclusion criteria were pregnancy, immunosuppression, and bowel obstruction/perforation. The intervention consisted of administering a symbiotic product (Lactobacillus bulgaricus, Lactobacillus rhamnosus, and fructo-oligosaccharides) twice a day for seven days via the oral/enteral route. RESULTS: Between August 1, 2012 and December 22, 2013, 116 of 275 eligible patients were allocated to treatment (n=57) and placebo (n=59). Overall, 101 patients received at least four doses of the study products and were included in the modified intention-to-treat analysis. The primary study outcome, a negative rectal swab for MDR Gram-negative bacilli after treatment, was identified in 16.7% (8/48) and 20.7% (11/53) of patients in the experimental and placebo group, respectively (p=0.60). The secondary outcome, the combined incidence of nosocomial respiratory and urinary tract infections, was 37.5% (18/48) in the experimental group versus 22.6% (12/53) in the control group (adjusted odds ratio: 1.95, 95% confidence interval: 0.69-5.50, p=0.21). Length of stay after the beginning of the intervention, incidence of adverse events, and in-hospital mortality rates were similar in both study groups. CONCLUSIONS: Under the present study conditions, symbiotic administration was not effective for decolonizing hospitalized patients harboring MDR Gram-negative bacilli.

A consolidação da Atenção Primária à Saúde (APS) requer políticas públicas embasadas por evidências científicas. Este artigo apresenta o estudo ELECT, cujo objetivo foi identificar temas prioritários de pesquisa para a fortalecimento da APS no estado de São Paulo, Brasil. Com a participação de especialistas e de um grupo focal com usuários, foi obtida uma lista com os vinte principais obstáculos, bem como dez temas de pesquisa prioritários, na APS. Os resultados apontam para problemas e temas de pesquisas relacionados à: organização da gestão, capacitação de profissionais e gestores, valorização profissional, criação de mecanismos de colaboração entre equipes de saúde e informatização dos recursos. Espera-se, assim, estimular o debate no contexto da APS sobre o papel da priorização de pesquisas, seus obstáculos e proposições de pesquisa. Almeja-se, também, estimular a adoção de modelos mais participativos de seleção de temas de pesquisa.