Chlorhexidine susceptibility and Eagle effect in planktonic cells and biofilm of nosocomial isolates.

The aim of this study is to evaluate the chlorhexidine gluconate (CHG) susceptibility in both planktonic cells and biofilm of 32 Gram-negative (Gn) and 6 Gram-positive (Gp) isolates by minimal inhibitory concentration (2-256 µg/mL for Gn and 2-32 µg/mL for Gp), minimal bactericidal concentration (4-256 µg/mL for Gn and 2-32 µg/mL for Gp) in planktonic cells, and minimal biofilm elimination concentration (128 ≥ 16,384 µg/mL in Gn and 32 ≥ 16,384 µg/mL in Gp) in biofilm environment. Our study showed that Gn isolates have higher minimal concentrations than Gp and bacteria in biofilms are more tolerant than planktonic ones. No correlation between MBC or MBEC and biofilm formation was statistically confirmed. The Eagle effect, previously described for antimicrobials and antifungals, was evidenced in this work for CHG, an antiseptic. Besides that, the phenomenon was described in 23/38 isolates (60.5%), raising minimal concentration up to ≥ 16,384 µg/mL. Our study showed that clinical isolates have a high ability to form biofilm allowing them to tolerate CHG concentrations as high as the ones used in clinical practice. Therefore, attention should be given to the occurrence of this phenomenon to avoid false susceptibility results.

Brazilian perspective: antimicrobial stewardship in solid organ transplant.

BACKGROUND: The incidence of multidrug resistant organisms (MDROs) infections among solid organ transplant (SOT) patients is very high in Brazil. METHODS: This review will discuss antimicrobial use and resistance in SOT in Brazil, highlighting the main barriers and facilitators for implementation of an antimicrobial stewardship programme (ASP). RESULTS: The most common group of MDROs is carbapenem-resistant Gram-negative bacteria and vancomycin-resistant Enterococcus. Carbapenem-resistant Enterobacterales (CREs) are the most frequent MDROs and have been reported as donor-derived as well. Although ASPs are mandatory in the country, there is a lack of information regarding ASPs in SOT recipients. The main barriers for the implementation of ASPs in Brazilian hospitals are lack of electronic medical records, absence of national guidelines specific to SOT recipients, lack of recommendations on surveillance culture to evaluate colonization and transmission of donor-derived MDROs, limited availability of rapid diagnostic tests, and insufficient pharmacist and clinician time allocated to ASP activities in some SOT centers. CONCLUSIONS: The incidence of MDRO infections caused mainly by VREs and CREs is very high in the country. There is limited data regarding antimicrobial use among SOT recipients in Brazil. The absence of antimicrobial stewardship national guidelines specific to SOT recipients is one of the main barriers for the implementation of ASPs in Brazilian hospitals.

Correlating drug prescriptions with prognosis in severe COVID-19: first step towards resource management.

BACKGROUND: Optimal COVID-19 management is still undefined. In this complicated scenario, the construction of a computational model capable of extracting information from electronic medical records, correlating signs, symptoms and medical prescriptions, could improve patient management/prognosis. METHODS: The aim of this study is to investigate the correlation between drug prescriptions and outcome in patients with COVID-19. We extracted data from 3674 medical records of hospitalized patients: drug prescriptions, outcome, and demographics. The outcome evaluated was hospital outcome. We applied correlation analysis using a Logistic Regression algorithm for machine learning with Lasso and Matthews correlation coefficient. RESULTS: We found correlations between drugs and patient outcomes (death/discharged alive). Anticoagulants, used very frequently during all phases of the disease, were associated with good prognosis only after the first week of symptoms. Antibiotics very frequently prescribed, especially early, were not correlated with outcome, suggesting that bacterial infections may not be important in determining prognosis. There were no differences between age groups. CONCLUSIONS: In conclusion, we achieved an important result in the area of Artificial Intelligence, as we were able to establish a correlation between concrete variables in a real and extremely complex environment of clinical data from COVID-19. Our results are an initial and promising contribution in decision-making and real-time environments to support resource management and forecasting prognosis of patients with COVID-19.

Evaluation of loop-mediated isothermal amplification assay for detection of Clostridioides difficile infection: A prospective diagnostic performance study.

A novel Loop-mediated isothermal amplification (LAMP) assay, HiberGene's CD was evaluated with 82 unformed stools from patients suspected of C. difficile infection (CDI). Compared to glutamate dehydrogenase (GDH) toxins A/B test (C.diff Quik Chek®), HiberGene's LAMP showed 100% of sensitivity and 95,8% of specificity; and compared to FilmArray™ GI panel ® (BioFire), a sensitivity of 81,2% and a specificity of 100%, with 96.38% of agreement.

Prevalence of Clostridioides difficile associated diarrhea in hospitalized patients in five Brazilian centers: A multicenter, prospective study.

Epidemiological data on CD infection (CDI) in Latin American are scarce. CDI prevalence and strains characterization were prospectively evaluated in 5 Brazilian hospitals from different regions. Prevalence rates of CDI were 15%, ranging from 0 to 37%. ST42 was the most common Sequence Type and hypervirulent strains were not identified.

Synergistic Effect of Ceftazidime-Avibactam with Meropenem against Panresistant, Carbapenemase-Harboring Acinetobacter baumannii and Serratia marcescens Investigated Using Time-Kill and Disk Approximation Assays.

Susceptibility of ceftazidime-avibactam and in vitro synergy with meropenem were investigated using disk approximation and time-kill assays against 11 multiresistant Acinetobacter baumannii isolates harboring oxacillinases and 5 Serratia marcescens isolates carrying blaKPC-2 Ceftazidime-avibactam was very active and synergistic with meropenem against multiresistant S. marcescens isolates. On the other hand, only the A. baumannii isolates coharboring blaOXA-23 and blaOXA-117 displayed synergy. The disk approximation technique presented good sensitivity for synergism in S. marcescens infection.

Fosfomycin in severe infections due to genetically distinct pan-drug-resistant Gram-negative microorganisms: synergy with meropenem.

Background: In vitro and clinical studies using parenteral fosfomycin have suggested the possibility of using this drug against infections caused by MDR microorganisms. The aim of this study was to describe a case series of patients treated with fosfomycin who had severe infections caused by pan-drug-resistant Gram-negative bacteria. Methods: We describe a prospective series of cases of hospitalized patients with infections caused by Gram-negative bacteria resistant to ß-lactams and colistin, treated with 16 g of fosfomycin daily for 10-14 days. Isolates were tested for antimicrobial susceptibility and synergism of fosfomycin with meropenem. We tested for resistance genes and performed typing using PCR and WGS. Results: Thirteen patients received fosfomycin (seven immunosuppressed); they had bloodstream infections (n = 11; 85%), ventilator-associated pneumonia (n = 1; 8%) and surgical site infection (n = 1; 8%), caused by Klebsiella pneumoniae (n = 9), Serratia marcescens (n = 3) and Pseudomonas aeruginosa (n = 1). Overall, eight (62%) patients were cured. Using time-kill assays, synergism between fosfomycin and meropenem occurred in 9 (82%) of 11 isolates. Typing demonstrated that K. pneumoniae were polyclonal. Eight patients (62%) had possible adverse events, but therapy was not discontinued. Conclusions: Fosfomycin may be safe and effective against infections caused by pan-drug-resistant Gram-negative microorganisms with different antimicrobial resistance mechanisms and there seems to be synergism with meropenem.

Simultaneous colonization by Escherichia coli and Klebsiella pneumoniae harboring mcr-1 in Brazil.

CASE PRESENTATION: We present a case report of a woman, concurrently colonized by polymyxin-resistant E. coli and K. pneumoniae. A Brazilian female patient, in her mid-fifties, was hospitalized with schistosomiasis. During hospitalization, polymyxin-resistant E. coli and K. pneumoniae were isolated from surveillance cultures. METHODS: Identification, antimicrobial susceptibility testings, PCR for mcr-1, plasmid transfer by conjugation and whole genome sequencing were performed. RESULTS: E. coli ST744 and K. pneumoniae ST101 carrying mcr-1 gene were described. Transconjugant E. coli was positive for mcr-1 and IncX4 by PCR. The plasmid is a 33,304-base pair plasmid, and the mcr-1 gene was the only antimicrobial resistance gene present in the plasmid. CONCLUSIONS: This study presents a case report of a hospitalized woman, concurrently colonized by mcr-1-harboring E. coli ST744, a different ST from previously described in Brazil, and a K. pneumoniae ST101.

Human Rabies during the COVID-19 Pandemic: Insights into Rabies Worldwide and Brazil.

Human Rabies (HR) is a fatal zoonotic disease caused by lyssaviruses, with the rabies virus (RABV) identified as the causative agent. While the incidence of HR transmitted by dogs has decreased in Latin America, there has been a corresponding rise in transmission via wild animals. Given the lack of effective treatments and specific therapies, the management of HR relies on the availability of post-exposure prophylaxis and animal control measures. This review examines the dynamics and spread of HR during the global pandemic.

Two cases of testicular tuberculosis in HIV patients with distinct clinical presentations.

Genito-urinary tuberculosis (TB) corresponds to the second most common cause of extrapulmonary tuberculosis EPTB worldwide. It is however rare and is often clinically indistinguishable from testicular malignancy and infarction. HIV hugely increases the risk of TB in unusual sites; we present two such cases of testicular tuberculosis. The diagnosis was based respectively on histopathological findings, acid-bacilli smear of biopsy, semen, and culture.

COVID-19 IN INFLAMMATORY BOWEL DISEASE: SHOULD WE BE MORE CAREFUL WITH THE USE OF SALICYLATES?

BACKGROUNDS: Fortunately, much has been studied about COVID-19 in patients with inflammatory bowel diseases (IBD). Evidence suggests that these patients do not appear to be at increased risk of severe COVID-19. However, there are still some uncertainties regarding the clinical manifestations of COVID-19 in patients with immune-mediated diseases. OBJECTIVE: This study aimed to describe the main symptoms of COVID-19 and their frequency in IBD patients and evaluate the impact of the IBD therapeutic drugs on clinical presentation of COVID-19 and to determine factors associated with COVID-19 in this population. METHODS: Adult patients with IBD from three tertiary-care public, teaching hospitals in Ceará, Northeastern Brazil, were evaluated during one scheduled appointment from March to December 2020. Patients with possible or confirmed COVID-19 were compared with patients without COVID-19. Furthermore, incidences of each symptom were evaluated based on the use of IBD therapeutic drugs. RESULTS: A total of 515 patients with IBD were included in the study: 234 with CD, and 281 with UC. Of these, 174 patients (34%) had possible/confirmed COVID-19 of whom 156 (90%) were symptomatic. Main symptoms were fever (65%) and headache (65%); gastrointestinal symptoms occurred in one third of patients and were higher than COVID-19 in general population. The factors associated with having COVID-19 were female gender (OR 1.71, 95%CI: 1.17-2.50); contact at home (OR 5.07, 95%CI: 3.31-7.78) and outside the home (OR 3.14, 95%CI: 2.10-4.71) with a case of COVID-19; work outside of the home (OR 1.87, 95%CI: 1.26-2.78); family history of COVID-19 (OR 2.29, 95%CI 1.58-3.33) use of salicylate (OR 1.71, 95%CI: 1.17-4.28); and asthma (OR 7.10, 95%CI: 1.46-34.57). CONCLUSION: IBD patients at high risk of COVID-19 infection may need to avoid salicylate therapy but further studies are necessary to confirm this association.

Development of H51Y and E157Q mutations for integrase inhibitor resistance in a patient undergoing treatment for pulmonary tuberculosis: A case report.

Background: Failure of first-line regimens with dolutegravir, a high genetic barrier antiretroviral of the integrase inhibitor class, although uncommon, tends to increase in prevalence due to broader use. Objective: To describe the clinical case of an HIV/Tuberculosis coinfected patient who developed Human Immunodeficieny Virus (HIV) treatment failure during dolutegravir therapy. Case report: Male, 29 years old, presented with a right cervical mass, dry cough, and hyporexia, which lasted 2 weeks. Diagnostic tests were positive for tuberculosis and HIV. The viral load was 437,927 cp/mL (Log = 5.64). Antiretroviral therapy was initiated with Tenofovir/Lamivudine and Dolutegravir (TDF/3TC and DTG), the latter at a dose of 50 mg/day, as was a regimen for tuberculosis. After 8 months, therapeutic failure was verified. Genotyping was requested, with detection of the H51Y and E157Q mutations in the integrase. Conclusion: Attention when determining the antiretroviral therapy treatment regimen of HIV/TB coinfected patients is paramount. Poor adherence to antiretroviral therapy and follow-up may have contributed to treatment failure and resistance.

Streptococcus constellatus causing concomitant extra and intracranial abscesses complicated with sagittal sinus thrombosis.

Streptococcus constellatus is a gram-positive coccus member of the Streptococcus anginosus group (SAG). It can be found in the oral flora, and may cause abscess more commonly in the gastrointestinal tract, lungs, and heart. Brain abscesses are severe neurological infections with high mortality rates. Streptococcus species other than S. pneumoniae are rare causes of brain abscesses. This case report highlights a severe case of extra and intracranial abscesses due to S. constellatus in an immunocompetent host.

Severe mpox in patients with advanced AIDS: long-term disease and fatal outcome.

Herein, we report two cases of severe mpox in patients with advanced acquired immunodeficiency syndrome from Brazil who developed atypical lesions and prolonged illness, one of whom had a fatal outcome. Both patients experienced serious complications involving the perianal and genital regions and prolonged disease with persistent viremia.

Case Report: Successful Treatment of Recurrent Urinary Tract Infection Due to Extensively Drug-Resistant Klebsiella Pneumoniae in a Kidney Transplant Recipient Using Chloramphenicol.

Effective therapies for multidrug-resistant (MDR) microorganisms, especially Gram-negative bacteria, are becoming rare. Also, solid-organ transplant recipients are at high risk of MDR Gram-negative bacilli infection. Urinary tract infections are the most frequent bacterial infections in kidney transplant recipients and are an important cause of mortality after renal transplantation. We describe a case of complicated urinary tract infection in a kidney transplant patient due to extensively drug-resistant (XDR) K. pneumoniae treated successfully with a regimen comprising a combination of chloramphenicol and ertapenem. We do not recommend chloramphenicol as a first-line choice for treating complicated urinary tract infections. Still, we believe it is an alternative for infections caused by MDR and/or XDR pathogens in renal transplant patients, as other options are nephrotoxic.

Meningitis caused by Capnocytophaga canimorsus in a COVID-19 patient: a rare complication of dog bites.

Capnocytophaga canimorsus is a gram-negative rod that is part of the commensal microbiota of dogs' and cats' mouths. In this case, we report an 85-year-old man with COVID-19 who had his right arm bitten by a dog. His symptoms were impaired consciousness, agitation and aggressive behavior. Physical examination revealed neck stiffness and Brudzinski's sign. The cerebrospinal fluid culture was compatible with Capnocytophaga canimorsus. He required intensive care and received a 14-day prescription of meropenem. After 40 days of hospitalization, the patient was fully recovered and was discharged. This case highlights the importance of physician and microbiologist be awareness of this disease, mainly in patients with neurological symptoms after a dog or cat bite.

Phenotypic and genotypic characteristics of a carbapenem-resistant Serratia marcescens cohort and outbreak: describing an opportunistic pathogen.

Serratia marcescens is an emerging opportunistic pathogen with high genetic diversity. This article describes the microbiological characteristics of isolates and the risk factors for infections caused by carbapenem-resistant S. marcescens. A retrospective study of patients colonized (n=43) and infected (n=20) with carbapenem-resistant S. marcescens over a 3-year period was conducted. Polymerase chain reaction for carbapenemase genes and molecular typing of all available strains was performed. Forty-two isolates were analysed, including three environmental samples identified during an outbreak. Thirty-five carbapenem-resistant S. marcescens carried blaKPC-2, one isolate was blaNDM-positive and four isolates carried blaOXA-101. The genomes were grouped into three clusters with 100% bootstrap; three patterns of mutations on ompC and ompF were found. The strains carried virulence genes related to invasion and haemolysis, and the environmental strains presented fewer mutations on the virulence genes than the clinical strains. Multi-variate analysis showed that previous use of polymyxin (P=0.008) was an independent risk factor for carbapenem-resistant S. marcescens infection. This study highlighted that blaKPC-2 in association with ompC or ompF mutation was the most common mechanism of resistance in the study hospital, and that previous use of polymyxin was an independent risk factor for carbapenem-resistant S. marcescens. There was a predominant clone, including the environmental isolates, suggesting that cross-transmission was involved in the dissemination of this pathogen.

Clostridioides difficile from Brazilian hospitals: characterization of virulence genes by whole genome sequencing.

Clostridioides difficile (CD) is the most frequent cause of healthcare related diarrhea and its severity has increased in the last decade by the spread of hypervirulent strains. Most important CD virulence factor is toxin production; however, not only toxins are responsible for Clostridioides virulence. We sequenced 38 strains and analyzed the presence and integrity of 24 virulence (including toxin) genes. We identified 28 toxigenic strains, six also presented the cdt genes. Only six strains didn't present all others genes searched. All absent genes were adhesion related. Understand others CD virulence factors can lead to a best understanding on this matter.

Understanding Sabiá virus infections (Brazilian mammarenavirus).

BACKGROUND: Only two naturally occurring human Sabiá virus (SABV) infections have been reported, and those occurred over 20 years ago. METHODS: We diagnosed two new cases of SABV infection using metagenomics in patients thought to have severe yellow fever and described new features of histopathological findings. RESULTS: We characterized clinical manifestations, histopathology and analyzed possible nosocomial transmission. Patients presented with hepatitis, bleeding, neurological alterations and died. We traced twenty-nine hospital contacts and evaluated them clinically and by RT-PCR and neutralizing antibodies. Autopsies uncovered unique features on electron microscopy, such as hepatocyte "pinewood knot" lesions. Although previous reports with similar New-World arenavirus had nosocomial transmission, our data did not find any case in contact tracing. CONCLUSIONS: Although an apparent by rare, Brazilian mammarenavirus infection is an etiology for acute hemorrhagic fever syndrome. The two fatal cases had peculiar histopathological findings not previously described. The virological diagnosis was possible only by contemporary techniques such as metagenomic assays. We found no subsequent infections when we used serological and molecular tests to evaluate close contacts.

Cotrimoxazole enhances the in vitro susceptibility of Coccidioides posadasii to antifungals.

The aim of the present study was to evaluate the effect of cotrimoxazole on the in vitro susceptibility of Coccidioides posadasii strains to antifungals. A total of 18 strains of C. posadasii isolated in Brazil were evaluated in this study. The assays were performed in accordance with the Clinical and Laboratory Standards Institute guidelines and the combinations were tested using the checkerboard method. The minimum inhibitory concentrations were reduced by 11, 2.4, 4.3 and 3.5 times for amphotericin B, itraconazole, fluconazole and voriconazole, respectively. Moreover, it was seen that cotrimoxazole itself inhibited C. posadasii strains in vitro. The impairment of folic acid synthesis may be a potential antifungal target for C. posadasii.