Fourier transform infrared (FT-IR) spectroscopy typing: a real-time analysis of an outbreak by carbapenem-resistant Klebsiella pneumoniae.

The spread of multidrug-resistant (MDR) Klebsiella pneumoniae in the nosocomial setting represents a big challenge to infection control teams. We have recently developed a simple spectroscopic-based method with excellent accuracy, turnaround time and cost-effectiveness (Rodrigues et al. mSystems 2020) for bacterial typing. Here, we applied our method in a real clinical context to support early identification of an outbreak involving KPC-3-producing K. pneumoniae ST147 isolates. Our results further support that attenuated total reflectance Fourier transform infrared (FT-IR) spectroscopy can provide enough information to support early and adequate infection control measures and therapeutic choices in the context of nosocomial outbreaks and hospital surveillance.

Fecal microbiota transplantation in the intestinal decolonization of carbapenamase-producing enterobacteriaceae.

BACKGROUND AND AIMS: fecal microbiota transplantation (FMT) is effective for recurrent Clostridium difficile infection (CDI). Intestinal decolonization of carbapenamase-producing enterobacteriaceae (CPE) can prevent transmission and infection by these agents. The aim of this study was to assess CPE decolonization after FMT. METHODS: this was a case-series study that consecutively included all CPE-carriers that underwent FMT between 2014 and 2019. The indications included refractory/recurrent CDI and CPE-decolonization. RESULTS: out of 21 CPE-carriers, eight were excluded due to incomplete post-FMT testing. CPE decolonization was confirmed in 76.9 % (n = 10). The median decolonization time was 16-weeks (IQR-23) and ranged from two to 53 weeks. CONCLUSION: FMT may be used in the clinical practice for CPE-decolonization as an alternative to combined antibiotic regimens.

Fecal microbiota transplantation in refractory or recurrent Clostridium difficile infection: a real-life experience in a non-academic center.

AIM: this study aimed to describe the efficacy and safety of fecal microbiota transplantation (FMT) for the treatment of refractory and recurrent Clostridium difficile infection (CDI). METHODS: this was an observational study of patients with refractory or recurrent CDI treated with FMT between June 2014 and January 2017. Primary and secondary outcomes were the resolution of diarrhea without CDI recurrence within two months after one or more FMT. A descriptive analysis was performed. RESULTS: thirty-four FMT were performed in 28 patients, 88.2% (n = 30) using an upper route with a gastroscopy and 11.8% (n = 4) with colonoscopy; 50% (n = 17) of FMT were due to recurrent CDI and 50% (n = 17) were due to refractory CDI. The overall cure rate of upper FMT was 87.5% (21/24) and 100% (4/4) when colonoscopy was performed. A cure was achieved after one FMT in 88% (22/25) of cases and after two or more FMT in 8% (2/25) of cases, resulting in an overall cure rate of 96% (24/25). No severe adverse events were reported. CONCLUSION: FMT constitutes an effective and safe approach for the management of refractory and recurrent CDI, with an overall cure rate of 96% and no reported severe adverse events.

Fecal microbiota transplantation: is there a role in the eradication of carbapenem-resistant Klebsiella pneumoniae intestinal carriage?

The authors present the case of a 66-year-old woman with four hospitalizations due to recurrent Clostridium difficile infection (CDI) non responsive to vancomycin and fidaxomicin. Furthermore, intestinal colonization with carbapenem-resistant Klebsiella pneumoniae (CRKP) was identified after a positive stool culture in a screening routinely performed in our center in patients recently hospitalized.

HIV patients have impaired diastolic function that is not aggravated by anti-retroviral treatment.

PURPOSE: Recent studies have shown that HIV infection is independently associated with heart failure. Diastolic dysfunction (DD) is frequent in HIV patients, but it is unclear whether this is an effect of the HIV infection itself or of the anti-retroviral therapy (ART). Our aim was to compare diastolic function in HIV treatment-naïve, HIV-ART patients and controls. METHODS: We prospectively enrolled 206 consecutive patients with HIV-1 infection and 30 controls, selected by frequency matching for age and sex. HIV patients were divided in two subgroups: ART-naïve (n = 88) and ART (n = 118). Diastolic function was assessed and graded by echocardiography, according to modern consensus criteria and using tissue Doppler analysis. RESULTS: Compared to controls, ART-naïve patients had lower E' velocities (E' septal: 10.2 ± 2.4 vs 11.9 ± 2.6 cm/s, p = 0.02), higher E/E' ratio (7.8 ± 1.9 vs 6.9 ± 1.6,p = 0.02) and higher prevalence of DD (19 % vs 3.3 %,p = 0.05). HIV patients under ART also had worse diastolic function compared to controls (E' septal: 10.3 ± 2.5 cm/s;p < 0.01; E/E'ratio: 8.0 ± 2.0,p < 0.01; DD prevalence: 23 %;p = 0.01), but no significant differences were found between ART-naïve and ART HIV subgroups. In multivariable logistic regression analysis, age and body mass index were the only independent predictors of reduced diastolic reserve in HIV patients. Regarding systolic function, there were no significant differences in ejection fraction or S' velocities between controls and HIV subgroups. CONCLUSIONS: HIV treatment-naïve patients have reduced diastolic reserve that is not worsened by ART. These data reinforce the association of diastolic dysfunction with the HIV infection itself and not with the anti-retroviral therapy.

Initial experience with fecal microbiota transplantation in Clostridium difficile infection - transplant protocol and preliminary results.

BACKGROUND AND AIMS: Clostridium difficile infection (CDI) constitutes an important cause of antibiotic-associated diarrhea. Recurrence after first-line treatment with antibiotics is high and fecal microbiota transplantation (FMT) may be effective for refractory and recurrent CDI. This series aims to describe the efficacy of FMT in the treatment of refractory and recurrent CDI. METHODS: A prospectively recorded single-centre case series of patients with persistent or recurrent CDI treated with FMT between June 2014 and March 2015 was analyzed. Primary and secondary outcomes were defined as resolution of diarrhea without recurrence of CDI within 2 months after one or more FMT, respectively. A descriptive analysis was performed. RESULTS: 8 FMT were performed in 6 patients, 3 with refractory CDI and 3 with recurrent CDI. The median age of recipients was 71 years and 66.7% were women. One FMT was delivered through colonoscopy and the remaining 87.5% through esophagogastroduodenoscopy. One upper FMT was excluded due to recurrence of CDI after antibiotic exposure for a respiratory infection. The overall cure rate of FMT was total with lower route and 83.3% with upper route. Primary cure rate was achieved in 83.3% of patients and secondary cure rate was achieved in all patients. Median time to resolution of diarrhea after FMT was 1 day and no complications were reported during follow-up. CONCLUSION: FMT appears to constitute a safe and effective approach in the management of refractory and recurrent CDI. Difference between primary and secondary cure rates may result of insufficient restoration of intestinal microbiota with a single FMT.

Real-World Effectiveness and Safety of Glecaprevir/Pibrentasvir for the Treatment of Chronic Hepatitis C: A Prospective Cohort Study in Portugal.

INTRODUCTION: Information about pan-genotypic treatments for hepatitis in Portugal is scarce. We aimed to evaluate the effectiveness and safety of glecaprevir plus pibrentasvir (GLE/PIB) treatment for hepatitis C virus (HCV) infection in real-world clinical practice. METHODS: An observational prospective study was implemented in six hospitals with 121 adult HCV patients who initiated treatment with GLE/PIB between October 2018 and April 2019, according to clinical practice. Eligible patients had confirmed HCV infection genotype (GT) 1 to 6 and were either treatment-naïve or had experience with interferon-, ribavirin- or sofosbuvir-based regimens, with or without compensated cirrhosis. Baseline sociodemographic and safety data are described for the total population (N = 115). Effectiveness [sustained virologic response 12 weeks after treatment (SVR12)] and patient-reported outcomes are presented for the core population with sufficient follow-up data (n = 97). RESULTS: Most patients were male (83.5%), aged < 65 years (94.8%), with current or former alcohol consumption (77.3%), illicit drug use (72.6%), and HCV acquisition through intravenous drug use (62.0%). HIV co-infection occurred in 22.6% of patients. The prevalence of each GT was: GT1 51.3%, GT2 1.7%, GT3 30.4%, GT4 16.5%, and GT5.6 0%. Most patients were non-cirrhotic (80.9%) and treatment-naïve (93.8%). The SVR12 rates were 97.9% (95% CI: 92.8 - 99.4), and > 95% across cirrhosis status, GT, illicit drug use, alcohol consumption, and HCV treatment experience. The adverse event rate was 2.6%, and no patient discontinued treatment due to adverse events related to GLE/PIB. CONCLUSION: Consistent with other real-world studies and clinical trials, treatment with GLE/PIB showed high effectiveness and tolerability overall and in difficult-to-treat subgroups (ClinicalTrials.gov: NCT03303599).

[Symptomatic acute hepatitis C: the importance of diagnosis]. / Hepatite C aguda sintomática--a importância do diagnóstico.

Chronic infection by the hepatitis C virus (HCV) is one of the leading causes of chronic liver disease with an estimate worldwide prevalence of over 200 million people. Acute hepatitis C infection is usually asymptomatic and rarely identified in clinical practice, leading to chronic infection in about 80% of all cases. However, when symptomatic, only about 50% of acute infections progress to chronicity. Correctly identifying acute HCV infection is of paramount importance once it presents itself as an unique treatment opportunity with sustained virological response of about 90%, which is very distant from the 30% to 80% of sustained virological response achieved with standard chronic HCV treatment. The authors present four cases of acute HCV infection. There was spontaneous viral clearance in two pa- tients at week 12 of follow-up. In one case viral RNA was positive at week 12 but sustained virological response was eventually achieved after peginterferon alpha2a monotherapy.

Same Pathogen, Different Manifestations: A Case of Extrapulmonary Tuberculosis.

Tuberculosis (TB) remains the most prevalent contagious disease worldwide and a significant cause of morbidity, ranking as the second most deadly disease globally. The transmission of the disease occurs through aerosols via the respiratory route, predominantly affecting pulmonary tissue. However, the pathogen can disseminate and infect any organ within the body. Up to 15% of patients exhibit extrapulmonary involvement. The case involves a 59-year-old male who presented to the emergency department complaining of abdominal pain and subfebrile episodes, without any other significant symptoms or findings on physical examination. Laboratory investigations revealed elevated inflammatory markers and abnormal liver biochemistry parameters. A computed tomography (CT) scan showed a neoformative lesion in the liver - a collection with a vascularized, thick, irregular wall. This raised the possibility of a potentially hypervascular hepatic neoformation or an encysted inflammatory lesion. The patient was started on empirical broad-spectrum antibiotics and was admitted to the Internal Medicine ward for further investigation. Later, the patient began to exhibit a decline in overall condition, a slowed and less complex speech pattern, loss of balance, and distal tremors in the upper limbs, as well as a symmetric and distal reduction in strength in all four limbs. A cerebral CT scan revealed no significant abnormalities, and a lumbar puncture yielded no immediate notable findings. Simultaneously, a repeated abdominal CT scan showed the previously known hepatic lesion, albeit with features more indicative of a multiloculated collection. An aspirative biopsy of the hepatic abscess was conducted. From the extensive analysis conducted, a positive PCR result for mycobacterium tuberculosis was identified in both the pus from the hepatic abscess and the cerebrospinal fluid. This led to the conclusion that the case presented was an instance of extrapulmonary TB involving the liver and the central nervous system. Following the identification of the causative agent, the patient commenced antibacterial therapy comprising rifampicin, ethambutol, and isoniazid with adjunctive dexamethasone. Despite targeted treatment and instituted supportive therapy, the patient exhibited an unfavorable progression and eventually succumbed 57 days after diagnosis. This case highlights an unusual manifestation of a patient with disseminated extrapulmonary TB, emphasizing the importance of early diagnostic suspicion for clinicians. The unfavorable disease progression despite appropriate targeted treatment prompts reflection on whether the delay in diagnosis and provision of anti-TB drugs may have played a major role in the prognosis of the patient.

Deprescription in Palliative Care.

Individuals with limited life expectancy represent a significant proportion of healthcare consumers and are usually patients with multiple diseases and high levels of frailty. Polypharmacy and the prescription of long lists of drugs are frequent in patients with reduced life expectancy and often, as the patient's health status deteriorates, the list of drugs increases substantially as new medications are introduced to address new symptoms or complications. A key priority for healthcare professionals managing the care of these patients should be balancing the pharmacological approach to chronic diseases with the palliation of acute symptoms and complications. An important element of this process is to ensure that the benefit of any prescription decision outweighs potential risks. We reviewed the pros and cons of deprescribing drugs in individuals with limited life expectancy, how to identify the expected disease trajectory, which drugs are to be discontinued, identified some models trying to achieve rigorous deprescribing criteria, and the psychosocial effects of deprescribing in late phases of life. Deprescribing is not a one-time event but rather a continuous process that requires ongoing evaluation and monitoring. It is vital to continuously monitor and evaluate the pharmacological and non-pharmacological prescriptions for patients with chronic illnesses to align them with their goals of care and life expectancy.

Gonococcal Infection: Case Report of Bacteremia and Brief Review of a Series of Cases.

Neisseria (N) gonorrhoeae is the microorganism responsible for the second-most reported sexually transmitted disease in the world, commonly infecting mucosal surfaces such as the endocervix, urethra, and pharynx. Gonococcal disease is generally non-symptomatic or pauci-symptomatic, but if untreated, it can progress to a more serious disease with joint, cardiac, or nervous system involvement. Disseminated gonococcal infection occurs in 0.5 to 3% of patients with gonorrhea and can present with purulent arthritis or a combination of dermatitis, tenosynovitis, and migratory polyarthralgia. This article presents the case of a 45-year-old woman examined in the emergency room for fever and acute pain in her right shoulder and knee. A few days later, the patient developed petechiae and vesiculopustular lesions on her right hand. Blood analysis showed elevated inflammation markers, and cultures yielded gram-negative diplococcus identified as N. gonorrhoeae. The patient was successfully treated with ceftriaxone, with complete remission of signs and symptoms of infection. The article then examines a series of 42 cases of gonococcal disease diagnosed in a tertiary hospital, their microbiologic susceptibilities, and the antibiotics chosen to treat them.

A Rare and Difficult Diagnosis: A Case of Hepatoid Carcinoma of the Gallbladder.

Extrahepatic metastasis of hepatocellular carcinoma is usually associated with extensive intrahepatic lesions. Hepatoid adenocarcinoma is a rare variant of extrahepatic malignant adenocarcinoma that exhibits remarkable histological and immunohistochemical similarity to hepatocellular carcinoma, which can result in an underestimated diagnosis. This case report describes a patient with a newly found gallbladder polyp. Following cholecystectomy, the initial histological and immunohistochemical evaluation suggested a metastasis of hepatocellular carcinoma. However, after multiple scans, no primary intrahepatic lesion was found. A subsequent review of the gallbladder specimens showed negative staining for CK7 and CK19, leading to a diagnosis of hepatoid carcinoma of the gallbladder.

Kaposi Sarcoma as Presentation of HIV - A Clinical Case.

Kaposi sarcoma (KS) is the most common neoplasm of people with human immunodeficiency virus (HIV) infection. Although, in the antiretroviral therapy (ART) era, KS is a rare form of presentation of HIV/acquired immunodeficiency syndrome. The authors present a case of disseminated KS in a 23-year-old male. Just after the diagnosis the patient started ART and then chemotherapy with placlitaxel with clinical improvement. This case is highly representative of the complexity of HIV. The authors aim to bring awareness of an unusual form of presentation of HIV, and recall the severity and the necessity of an early diagnosis and treatment.

Hansen's disease - a forgotten disease?

Hansen's disease, also known as leprosy, is an infection caused by the bacteria Mycobacterium leprae. The authors present the case of a 52-year-old man, born in Tondela and living in Espinho, with no pathological antecedents. The clinical picture began in April 2017, when macular lesions appeared in the lower limbs and rapidly progressed to the trunk and upper limbs, associated with complaints of pruritus but without alterations in the analytical study. After several topical and systemic treatments with glucocorticoids, antifungals, antibacterials and unsuccessful antihistamines, he was referred to an external consultation of Dermatology. He performed a biopsy of one of the lesions that revealed the definitive diagnosis: "Lepromatous Leprosy". After the biopsy result, he started triple treatment with rifampicin, clofazimine and dapsone with improvement of the condition.

Multiplicity of Carbapenemase-Producers Three Years after a KPC-3-Producing K. pneumoniae ST147-K64 Hospital Outbreak.

Carbapenem resistance rates increased exponentially between 2014 and 2017 in Portugal (~80%), especially in Klebsiella pneumoniae. We characterized the population of carbapanemase-producing Enterobacterales (CPE) infecting or colonizing hospitalized patients (2017-2018) in a central hospital from northern Portugal, where KPC-3-producing K. pneumoniae capsular type K64 has caused an initial outbreak. We gathered phenotypic (susceptibility data), molecular (population structure, carbapenemase, capsular type) and biochemical (FT-IR) data, together with patients' clinical and epidemiological information. A high diversity of Enterobacterales species, clones (including E. coli ST131) and carbapenemases (mainly KPC-3 but also OXA-48 and VIM) was identified three years after the onset of carbapenemases spread in the hospital studied. ST147-K64 K. pneumoniae, the initial outbreak clone, is still predominant though other high-risk clones have emerged (e.g., ST307, ST392, ST22), some of them with pandrug resistance profiles. Rectal carriage, previous hospitalization or antibiotherapy were presumptively identified as risk factors for subsequent infection. In addition, our previously described Fourier Transform infrared (FT-IR) spectroscopy method typed 94% of K. pneumoniae isolates with high accuracy (98%), and allowed to identify previously circulating clones. This work highlights an increasing diversity of CPE infecting or colonizing patients in Portugal, despite the infection control measures applied, and the need to improve the accuracy and speed of bacterial strain typing, a goal that can be met by simple and cost-effective FT-IR based typing.

Behçet's disease--a contemporary review.

Behçet's disease (BD) is a systemic vasculitis disorder of unknown etiology, characterized by relapsing episodes of oral aphthous ulcers, genital ulcers, skin lesions and ocular lesions. It can affect other systems including vascular, gastrointestinal and neurological systems. It occurs most frequently in an area that coincides with the Old Silk Route (between latitudes 30 degrees and 45 degrees north in Asia and Europe). BD is slightly more frequent and has a worse clinical course in men. It is believed to be due to an auto-immune process triggered by an infectious or environmental agent in a genetically predisposed individual. HLA-B51 is the most strongly associated risk factor. The International Study Group (ISG) for Behçet's Disease created a set of criteria for the diagnosis of BD. Available treatments include corticosteroids, azathioprine, cychlophosphamide, cyclosporine A, interferon-alpha, anti-tumour necrosis factor alpha agents, among others. BD has a variable course characterized by relapses and remissions. Prognosis depends on the clinical involvement. Loss of visual acuity and neurological disease are major causes of morbidity and disability.

Antibiotic Clinic: Two Years' Experience in Outpatient Parenteral Antimicrobial Therapy in a Portuguese Hospital.

INTRODUCTION: Outpatient antimicrobial therapy programs have been in place for more than four decades. They provide safe and effective treatment for a selected group of patients while reducing costs. In Europe in general, and in Portugal in particular, these programs are still a relatively new phenomenon. The aim of this study is to describe our center's two years' experience with such a program (Antibiotic Clinic). MATERIAL AND METHODS: The cohort of treatments administered by the Antibiotic Clinic in its first two years of existence (September 12th 2016 to September 11th 2018) was analyzed and data pertaining to patients, infections, infectious agents, antimicrobials and outcomes (infection resolution, adverse events and death) were characterized. RESULTS: The Antibiotic Clinic treated 231 patients in 250 episodes, providing a total of 2357 days of antibiotic treatment. The urinary tract was the most common site (39.2%) and Enterobacteriaceae the most common agents (63.7% of isolates). Infections were resolved in 90.8% of treatments (95.6% of patients), adverse events were few (1.2%) and direct mortality was not found. The dropout rate was 1.6%. DISCUSSION: Infection resolution and adverse event rates were comparable to other centers. High treatment and low dropout rates point to high physician and patient acceptance. CONCLUSION: Our experience with this program suggests it is a safe and effective alternative to inpatient admission. This is in line with current literature which suggests efforts should be made to expand this treatment modality.

Introdução: Os programas de administração de antimicrobianos parentéricos em ambulatório (outpatient parenteral antimicrobial therapy) iniciaram-se há mais de quatro décadas. Para além de proporcionarem tratamento seguro e eficaz num grupo selecionado de doentes, permitem também a redução de custos. Na Europa, e em particular em Portugal, a implementação destes programas é um fenómeno recente. O objetivo deste estudo é descrever dois anos de experiência de Clínica do Antibiótico. Material e Métodos: Foram incluídos todos os doentes tratados na Clínica do Antibiótico nos dois primeiros anos de existência (12 de setembro de 2016 a 11 de setembro de 2018), sendo descritas variáveis relativas à população, infeções, agentes infeciosos, tratamentos e outcomes (resolução de infeção, eventos adversos e morte). Resultados: A Clínica do Antibiótico tratou 231 doentes em 250 episódios, garantindo 2357 dias de antibioterapia. O local de infeção mais comum foi o trato urinário (39,2%) e os agentes mais comuns foram as Enterobacteriaceae (63,7% dos isolamentos). Obteve-se resolução da infeção em 90,8% dos tratamentos (95,6% dos doentes), ocorreram poucos eventos adversos (1,2%) e a mortalidade direta foi nula. Houve uma taxa de abandono de 1,6%. Discussão: As taxas de resolução e de complicações foram comparáveis às de outros centros. Elevado número de tratamentos e baixa taxa de abandono apontam para boa aceitação por médicos e doentes. Conclusão: A nossa experiência sugere ser uma alternativa eficaz e segura ao tratamento em internamento. Estes resultados estão de acordo com a literatura, sugerindo que esforços deverão ser feitos para expandir a utilização destes programas.

Acute hepatitis C from heterosexual transmission.

The diagnosis of acute hepatitis C (HCV) infection is rare since the majority of cases are asymptomatic, which makes the infection usually detected in a chronic phase, most of the time using serological tests. The main route of HCV transmission is percutaneous, with sexual transmission occurring more often in men who have sex with men. The analytical alterations of acute hepatitis C are varied but usually present with ALT elevation higher than AST, very rarely with hepatic insufficiency. We report a case of a patient with a clinical and analytical picture compatible with toxic acute hepatitis, accompanied by hepatic insufficiency, with negative serology for hepatotropic viruses and with no history compatible with the use of substances with hepatic toxicity other than alcohol. During the diagnostic investigation it was concluded that the patient had acute HCV hepatitis and that the transmission route was heterosexual.

A Rare and Potentially Catastrophic Infection: Primary Intestinal Aspergillosis-Case Report in an HIV Patient.

Aspergillus species are ubiquitous in nature; however, infection is uncommon, except in immunocompromised or immunosuppressed hosts. We present the case of a 71-year-old woman with a history of human immunodeficiency virus infection who presented with fever, weight loss, and diarrhea, posteriorly diagnosed with intestinal aspergillosis after examination of a segmental enterectomy piece. The diagnosis was made postmortem once the patient died after fast and progressive deterioration in the postoperative period.