Daptomycin and Ceftaroline Combination Therapy in Complicated Endovascular Infections Caused by Methicillin-Resistant Staphylococcus epidermidis.

Background In complicated endovascular infections by methicillin-resistant Staphylococcus aureus (MRSA) or Staphylococcus epidermidis (MRSE), when first-line therapy with vancomycin (VAN) or daptomycin (DAP) fails, combination therapy with ceftaroline (CFT) and DAP has been shown to be a useful approach as salvage therapy for persistent MRSA bacteremia. Objectives This study aimed to describe experience with daptomycin and ceftaroline combination therapy in MRSE-complicated endovascular infections. Methods A single-center retrospective review of consecutive patients with MRSE-complicated endovascular infections treated with ≥72 hours of DAP+CFT at any time during the course of treatment, from January 1, 2016 to December 31, 2020, at Centro Hospitalar Universitário São João (CHUSJ), Porto, Portugal, was conducted. The exclusion criteria were known resistance to daptomycin or ceftaroline, total time of combination therapy <72 hours and loss to follow-up. Results We identified seven cases that matched our criteria: five endocarditis and two central venous catheter infections. Six patients switched to combination therapy due to treatment failure with first-line agents - three due to persistent bacteremia and three due to progression of infection despite negative blood cultures. Effective surgical source control took one to four weeks to occur. Three patients died during the treatment, one from progression of the disease and two due to another infection. Conclusions We consider the DAP+CFT combination therapy to be a valid and safe therapeutic choice in complicated patients, such as those with severe infection, poor functional status, and impossibility or delay of surgical source control. However, conclusions on the role of combination therapy should be careful due to the low number of patients and the several confounding factors.

EPI-Net One Health reporting guideline for antimicrobial consumption and resistance surveillance data: a Delphi approach.

Strategic and standardised approaches to analysis and reporting of surveillance data are essential to inform antimicrobial resistance (AMR) mitigation measures, including antibiotic policies. Targeted guidance on linking full-scale AMR and antimicrobial consumption (AMC)/antimicrobial residues (AR) surveillance data from the human, animal, and environmental sectors is currently needed. This paper describes the initiative whereby a multidisciplinary panel of experts (56 from 20 countries-52 high income, 4 upper middle or lower income), representing all three sectors, elaborated proposals for structuring and reporting full-scale AMR and AMC/AR surveillance data across the three sectors. An evidence-supported, modified Delphi approach was adopted to reach consensus among the experts for dissemination frequency, language, and overall structure of reporting; core elements and metrics for AMC/AR data; core elements and metrics for AMR data. The recommendations can support multisectoral national and regional plans on antimicrobials policy to reduce resistance rates applying a One Health approach.

Appropriateness of Empirical Prescriptions of Ceftriaxone and Identification of Opportunities for Stewardship Interventions: A Single-Centre Cross-Sectional Study.

Third-generation cephalosporins are widely used due to the convenient spectrum of activity, safety, and posology. However, they are associated with the emergence of multidrug-resistant organisms, which makes them important targets for antimicrobial stewardship interventions. We aimed to assess the appropriateness of empirical prescriptions of ceftriaxone in a tertiary hospital. This cross-sectional study analysed empirical ceftriaxone prescriptions in January and June 2021. Patients under other antimicrobials 48 h before admission were excluded. The quality of ceftriaxone prescription was assessed regarding the initial appropriateness, duration of inappropriate ceftriaxone therapy, and missed opportunities for de-escalation. Of 465 prescriptions, 46.5% were inappropriate. The ceftriaxone prescription was inappropriate in 95.7% of lower respiratory tract infections (LRTI) globally and in nearly 40% of urinary tract infections (UTI) in medical and intensive care departments. Intensive care, internal medicine, and palliative care departments showed the highest number of inappropriate ceftriaxone prescriptions and longer length of inappropriate ceftriaxone prescriptions compared to the hospital's average. Improvement of empirical ceftriaxone prescription in LRTI and urinary infections, adherence to local guidelines and de-escalation practices, and targeted interventions focusing on critical departments may significantly reduce the inappropriate empirical use of ceftriaxone.

Corynebacterium striatum cardiac device-related endocarditis: A case report.

Corynebacterium striatum is an emerging Gram-positive bacillus associated with invasive infection in both immunocompetent and immunocompromised patients, especially associated with medical devices. Its ability to form biofilms has been demonstrated and it has been occasionally associated with cardiac device-related infective endocarditis with few cases described in literature. We report a case of C. striatum cardiac device-related infective endocarditis of complex management.

Late Hepatitis B reactivation after treatment with rituximab.

There is a large reservoir of individuals with past hepatitis B virus (HBV) infection that are in risk for HBV reactivation when immunosuppressed. On the setting of hematologic malignancy, the malignancy itself and currently used treatments, especially anti-CD20 agents, have risk of HBV reactivation. Antiviral prophylaxis is recommended by some international societies. We present a case of HBV reactivation more than 12 months after stopping rituximab containing treatment and 6 months of antiviral prophylaxis with entecavir, in a patient with HBV functional cure. The patient was restarted on antivirals and again obtain functional cure. The antiviral was stopped 1 year after seroconversion and the patient followed for another year without evidence of new reactivation. Most literature supports the use of antiviral prophylaxis in patients treated with rituximab. However, there are still conflicting indications and no consensus regarding the duration of prophylaxis. This clinical case and review of the literature supports a longer prophylaxis duration (more than 18 months after finishing rituximab treatments) instead of standard 12 months prophylaxis.

Outbreak of KPC-producing Klebsiella pneumoniae at a Portuguese university hospital: Epidemiological characterization and containment measures.

Background: KPC-producing K pneumoniae (KPC-Kp) is a public health problem with important clinical and epidemiological implications. We describe an outbreak of KPC-Kp at vascular surgery and neurosurgery wards in a central hospital in Porto, Portugal. Methods: A case of KPC-Kp was considered to be a patient positive for KPC-Kp with strong epidemiological plausibility of having acquired this microorganism in the affected wards and/or with genetic relationship ≥92% between KPC-Kp isolates. Active surveillance cultures (ASCs) and real-time polymerase chain reaction were used for the detection of carbapenemase genes through rectal swab in a selected population. Molecular analysis was performed using pulsed-field gel electrophoresis at the National Reference Laboratory. Patient risk factors were collected from the electronic medical record system. Information regarding outbreak containment strategy was collected from the Infection Control Unit records. Results: Of the 16 cases, 11 (69%) were identified through active screening, representing 1.4% of the total 766 ASCs collected. The most frequent risk factors identified were previous admission (63%), antibiotic exposure in the past 6 months (50%), and immunodepression (44%). The length of stay until KPC-Kp detection was high (0-121 days, mean 35.6), as was the total length of stay (5-173 days, mean 56.6). Three patients (19%) were infected by KPC-Kp, 2 of whom died. One previously colonized patient died later because of KPC-Kp infection. Conclusions: Multifactorial strategy based on contact precautions (with patient and healthcare professional cohorts) and ASC, as well as Antibiotic Stewardship Program reinforcement, allowed to contain this KPC-Kp outbreak.

Granulomatous Hepatitis Following Intra-Vesical Instillation of Bacillus Calmette-Guérin for Treatment of Bladder Cancer.

Intra-vesical instillation of bacillus Calmette-Guérin (BCG) is an important treatment modality of superficial bladder cancer. It is usually well tolerated, although some adverse reactions can occur. One possible yet rare complication is granulomatous hepatitis, that is thought to be caused either by BCG infection or a hypersensitivity reaction to the bacillus. We present a case of a 79-year-old apparently immunocompetent patient who developed granulomatous hepatitis a few months after BCG administration for bladder cancer immunotherapy. It is important to notice that acid-fast smears and cultures are often negative, and these should not exclude diagnosis nor delay treatment. Our case highlights the importance of clinical suspicion and prompt initiation of appropriate treatment.

Post Vaccine Rubella During a Measles Outbreak: Clinical Case.

Rubella is a vaccine preventable infection, and congenital rubella the most feared complication of this disease. Although young adult women are at greatest risk of post-vaccine rubella, this is also the group who potentially benefits the most from vaccine protection. Since post-vaccine disease has a mild and self-limited course, the benefit clearly exceeds the risk. During a measles outbreak in the north of Portugal, a 38-year-old woman presented with cervical posterior lymphadenopathies, fever and a maculo-papular rash one week after the administration of the measles, mumps and rubella vaccine. Measles was discarded and rubella viremia was demonstrated. Symptoms of rubella are non-specific and laboratory confirmation is essential. This is particularly relevant during a measles outbreak.

A rubéola é uma infeção prevenível por vacina, sendo a rubéola congénita a apresentação mais grave da doença. Apesar de serem o grupo que mais beneficia dela, as mulheres em idade fértil são também o grupo com maior risco de doença associada à vacina. Uma vez que as manifestações clínicas são ligeiras e transitórias, o benefício compensa largamente o risco. Durante o surto de sarampo que ocorreu no Porto em 2018, uma mulher de 38 anos recebeu a primeira dose da vacina contra o sarampo, rubéola e papeira. Uma semana depois, recorreu ao Serviço de Urgência por febre, exantema maculo-papular e adenopatias cervicais posteriores. Foi excluído sarampo e demonstrada viremia pelo vírus da rubéola. Os sintomas da rubéola são inespecíficos pelo que a confirmação laboratorial é essencial. Isto é ainda mais relevante em contexto de surto de sarampo.

Ralstonia mannitollylitica endocarditis: A case report.

Ralstonia mannitolilytica (R. mannitolilytica.) is an emerging aerobic Gram-negative bacteria causing infection among immunocompromised patients. R. mannitolilytica, has been described in hospital outbreaks, mainly as bloodstream infection, but also as meningitis, hemoperitoneum infection and post renal transplant infection. We describe the first reported case of R. mannitolilytica infective endocarditis.

Panton-Valentine Leukocidin-Producing Staphylococcus aureus Infection: A Case Series.

Panton-Valentine leukocidin-producing Staphylococcus aureus (PVL-SA) is associated with relapsing multifocal skin and soft tissue infections (SSTI), necrotizing pneumonia (NP) and severe musculoskeletal infections. Epidemiology is underknown and underdiagnosis is likely. Recent travel abroad, case clustering and relapsing disease are often reported. We reviewed all cases of PVL-SA infection diagnosed at our center, and found 21 cases over a 43-month period. Most patients were adult males, had relevant travel history, reported recurrent disease and presented with SSTI. Etiologic diagnosis took up to five years; meanwhile, 42% of patients had antibiotic treatments. Draining procedures were required in 43% of patients and intensive care support in 19%. All patients recovered. Methicillin-resistance prevalence was 24%. Only 2/13 decolonized patients had posterior relapsing SSTI, both with likely infected contacts. PVL-SA infection's severity and impact are clear, even in small case series as ours. Physician awareness and active PVL-gene search are crucial for an adequate management.

Validation of a semi-automated surveillance system for surgical site infections: Improving exhaustiveness, representativeness, and efficiency.

OBJECTIVES: To assess whether electronic records data could improve the efficiency, exhaustiveness, and representativeness of SSI surveillance by selecting a group of high-risk patients for manual review. METHODS: Colorectal surgeries (2016-2018) and cholecystectomies (2017-2018) were selected. Post-surgical antibiotic use, positive culture, C-reactive protein (CRP) values, body temperature, leukocyte count, surgical re-intervention, admission to the emergency room, and hospital readmission were retrieved. For representativeness, procedures registered in HAI-Net were compared with non-included procedures, and the validity of each variable (or combination) was tested considering the presence of SSI as the gold standard. The proportion of procedures flagged for manual review by each criterion was estimated. RESULTS: Little more than 50% of procedures were included in HAI-Net (SSI risk: 10.6% for colorectal and 2.9% for cholecystectomies). Non-included procedures showed higher proportions of infection markers. Antibiotic use and CRP >100 mg/dl presented the highest sensitivity for both surgical groups, while antibiotic use achieved the highest positive predictive value in both groups (22% and 21%, respectively) and flagged fewer colorectal procedures (47.7%). CONCLUSIONS: Current SSI surveillance has major limitations. Thus, the reported incidence seems unreliable and underestimated. Antibiotic use appears to be the best criterion to select a sub-sample of procedures for manual review, improving the exhaustiveness and efficiency of the system.

Carbapenemase-producing Klebsiella pneumoniae intra-abdominal infection successfully treated with ceftazidime/avibactam plus tigecycline.

Ceftazidime/avibactam combines ceftazidime with a new beta-lactam that successfully that inhibits Amber Class A and D carbapenemases. We report a clinical case of a 61 year-old man with a carbapenemase-producing Klebsiella pneumoniae intra-abdominal infection after an elective abdominal hernia repair. The infection was successfully managed with multiple abdominal surgeries, drainage and combined antibiotic therapy with ceftazidime/avibactam plus tigecycline.

Pleural aspergillosis in a patient with recurrent spontaneous pneumothorax: The challenge of an optimal therapeutic approach.

Pleural aspergillosis (PA) is a rare but potentially fatal disease. Most cases are secondary to bronchopleural fistulae or pleural intervention and can occur in the absence of immunosuppression. We report a case of PA in a young patient after pleurodesis for recurrent pneumothorax. Clinical resolution was achieved with systemic and local antifungal therapy combined with surgical debridement. Hepatotoxicity led to a switch from voriconazole to isavuconazole, with a successful outcome.

Portraying infective endocarditis: results of multinational ID-IRI study.

Infective endocarditis is a growing problem with many shifts due to ever-increasing comorbid illnesses, invasive procedures, and increase in the elderly. We performed this multinational study to depict definite infective endocarditis. Adult patients with definite endocarditis hospitalized between January 1, 2015, and October 1, 2018, were included from 41 hospitals in 13 countries. We included microbiological features, types and severity of the disease, complications, but excluded therapeutic parameters. A total of 867 patients were included. A total of 631 (72.8%) patients had native valve endocarditis (NVE), 214 (24.7%) patients had prosthetic valve endocarditis (PVE), 21 (2.4%) patients had pacemaker lead endocarditis, and 1 patient had catheter port endocarditis. Eighteen percent of NVE patients were hospital-acquired. PVE patients were classified as early-onset in 24.9%. A total of 385 (44.4%) patients had major embolic events, most frequently to the brain (n = 227, 26.3%). Blood cultures yielded pathogens in 766 (88.4%). In 101 (11.6%) patients, blood cultures were negative. Molecular testing of vegetations disclosed pathogens in 65 cases. Overall, 795 (91.7%) endocarditis patients had any identified pathogen. Leading pathogens (Staphylococcus aureus (n = 267, 33.6%), Streptococcus viridans (n = 149, 18.7%), enterococci (n = 128, 16.1%), coagulase-negative staphylococci (n = 92, 11.6%)) displayed substantial resistance profiles. A total of 132 (15.2%) patients had cardiac abscesses; 693 (79.9%) patients had left-sided endocarditis. Aortic (n = 394, 45.4%) and mitral valves (n = 369, 42.5%) were most frequently involved. Mortality was more common in PVE than NVE (NVE (n = 101, 16%), PVE (n = 49, 22.9%), p = 0.042).

Mononeuritis multiplex: an uncommon neurological manifestation of cytomegalovirus reactivation in an HIV-infected patient.

BACKGROUND: Cytomegalovirus (CMV) reactivation with neurological involvement in patients with acquired immunodeficiency syndrome (AIDS) is increasingly rare since the introduction of antiretroviral therapy (ART). Manifestations include encephalitis, myelitis, polyradiculopathy and, less commonly, mononeuritis multiplex (MNM). We report a case of disseminated CMV disease with gastrointestinal and peripheral and central nervous system involvement in a patient with AIDS, manifesting primarily as MNM. CASE PRESENTATION: A 31-year old woman with AIDS presented with a clinical picture of MNM. Electromyography confirmed the clinical findings. CMV DNA was detected in cerebrospinal fluid (CSF) and blood. Gastrointestinal involvement was histologically documented. HIV RNA was also detected in CSF and brain MRI was consistent with HIV encephalopathy. A diagnosis of disseminated CMV disease (with esophagitis, colitis, encephalitis and MNM) and HIV encephalopathy was made. Treatment consisted of ganciclovir and foscarnet, followed by maintenance therapy with valganciclovir. Evolution was favorable and valganciclovir was stopped after sustained immune recovery following ART initiation. CONCLUSION: We discuss the diagnostic approach to CMV neurological disease, with a focus on MNM and CMV encephalitis. Combination therapy with ganciclovir and foscarnet should be considered for all forms of neurological involvement, although available data are scarce. Since there is significant overlap between CMV encephalitis and HIV encephalopathy, ART drugs with higher CSF penetration may have to be considered. ART and immune recovery are essential to improve outcomes.

Routine CD4 monitoring in HIV patients with viral suppression: Is it really necessary? A Portuguese cohort.

PURPOSE: CD4 cell-count has been regarded as the key surrogate marker for prognostic staging and therapeutic monitoring of HIV-infected individuals. Our purpose was to assess the probability of maintaining a CD4 count >200 cells/µL in patients with continuous viral suppression and CD4 cell counts >200 cells/µL. METHODS: Retrospective cohort study of HIV-infected patients, treatment naïve, who started antiretroviral therapy between 2007 and 2011. We estimated the probability of maintaining CD4 counts >200 cells/µL during continuous viral suppression using the Kaplan-Meier method. The hazard ratios of a CD4 count <200 cells/µL were estimated and compared using Cox proportional hazards regression. RESULTS: 401 patients were included: 70.1% men; median age 37 years; 98.8% HIV-1 infected. The median duration of continuous viral suppression with CD4 counts >200 cells/µL was 40.5 months. Ninety-three percent of patients maintained CD4 counts ≥200 cells/µL during the period of continuous viral suppression. Compared with those with an initial CD4 count ≥350 cells/µL, patients with initial CD4 count <300 cells/µL had a significantly higher risk of a CD4 count <200 cells/µL. Patients with viral suppression and CD4 counts ≥350 cells/µL had a 97.1% probability of maintaining CD4 cell counts ≥200 cells/µL for 48 months. CONCLUSIONS: The probability of a CD4 count <200 cells/µL in an HIV-infected patient with viral suppression and CD4 ≥350 cells/µL was very low. These data suggests less frequent monitoring of CD4 counts in these patients.

Severe Tuberculosis Requiring Intensive Care: A Descriptive Analysis.

Background. This study aims to describe the characteristics of tuberculosis (TB) patients requiring intensive care and to determine the in-hospital mortality and the associated predictive factors. Methods. Retrospective cohort study of all TB patients admitted to the ICU of the Infectious Diseases Department of Centro Hospitalar de São João (Porto, Portugal) between January 2007 and July 2014. Comorbid diagnoses, clinical features, radiological and laboratory investigations, and outcomes were reviewed. Univariate analysis was performed to identify risk factors for death. Results. We included 39 patients: median age was 52.0 years and 74.4% were male. Twenty-one patients (53.8%) died during hospital stay (15 in the ICU). The diagnosis of isolated pulmonary TB, a positive smear for acid-fast-bacilli and a positive PCR for Mycobacterium tuberculosis in patients of pulmonary disease, severe sepsis/septic shock, acute renal failure and Multiple Organ Dysfunction Syndrome on admission, the need for mechanical ventilation or vasopressor support, hospital acquired infection, use of adjunctive corticotherapy, smoking, and alcohol abuse were significantly associated with mortality (p < 0.05). Conclusion. This cohort of TB patients requiring intensive care presented a high mortality rate. Most risk factors for mortality were related to organ failure, but others could be attributed to delay in the diagnostic and therapeutic approach, important targets for intervention.

Presentation and diagnosis of acute Q fever in Portugal - A case series.

Q fever is a worldwide zoonotic infection caused by the obligate intracellular bacterium Coxiella burnetii that can course with acute or chronic disease. This series describes 7 cases of acute Q fever admitted in a Portuguese University Hospital between 2014 and 2015. All cases presented with hepatitis and had epidemiological history. Diagnosis was done by PCR on majority (5) and by serology and PCR in only 2. Serological tests can be negative in the initial period of the disease. Molecular biology methods by polymerase chain-reaction are extremely important in acute disease, allowing timely diagnosis and treatment.

Artemether-lumefantrine and liver enzyme abnormalities in non-severe Plasmodium falciparum malaria in returned travellers: a retrospective comparative study with quinine-doxycycline in a Portuguese centre.

BACKGROUND: Artemisinin-based therapy is the current standard treatment for non-severe malaria due to Plasmodium falciparum. The potential for asymptomatic liver toxicity of this therapy and its implication in clinical practice is currently unknown. The aim of this study is to assess the hepatic function in patients treated with a standard three-day artemisinin-based regimen and to compare it with the quinine-doxycycline regimen. METHODS: Retrospective and comparative study of returned adult travellers admitted with non-severe P. falciparum malaria. Fifty-seven patients were included: 19 treated with artemisinin-based therapy and 38 with quinine-doxycycline therapy. RESULTS: During treatment, when compared with quinine-doxycycline group, the artemisinin-lumefantrine group presented a higher proportion of significant liver enzyme abnormalities (42 vs. 5%, p < 0.01) and a higher peak value of aspartate aminotransferase (131 vs. 64 U/L, p < 0.01) and alanine aminotransferase (99 vs. 75 U/L, p = 0.05). None of the patients was symptomatic, there were no treatment interruptions and all patients achieved clinical cure. CONCLUSIONS: Treatment of uncomplicated falciparum malaria with artemisinin-based therapy might cause asymptomatic liver enzyme abnormalities in the first days of treatment. Nevertheless, these liver enzyme abnormalities seem to be harmless, asymptomatic and self-limited.

Characterization of HIV-1 subtypes in a Portuguese cohort.

INTRODUCTION: Distribution of HIV-1 subtypes is variable around the world, with the most common subtype in western Europe being subtype B. The aim our study was to describe the prevalence of different HIV-1 subtypes in newly diagnosed patients and identify demographic and epidemiological characteristics related with different subtypes. MATERIALS AND METHODS: Retrospective single-centre study of patients newly diagnosed with HIV-1 infection between 2006 and 2012. Epidemiological data was gathered and genotyping was performed in each patient identified. Demographic and epidemiological characteristics were compared between patients with subtype B and other subtypes. Continuous variables were summarized by mean and standard deviation whereas categorical variables were presented as proportions. Comparison of groups was performed using the Chi square, Fisher exact test and Student T test. Statistical significance was assumed when p<0.05. RESULTS: In the period of the study, 624 patients newly diagnosed with HIV-1 infection were submitted to genotypic testing but information about subtype was available only for 592 patients. General characteristics of the patients are summarized in Table 1. The distribution of the identified subtypes was the following: 286 (48.3%) patients had subtype B, 157 (26.5%) had subtype G, 54 (9.1%) had subtype C, 36 (6.1%) had subtype A, 32 (5.4%) had subtype F and 25 (4.2%) had CRF's. Patients with subtype B were more commonly male (p=0.001) and younger (p<0.0001) than those with subtypes other than B. Subtype B was more common in MSM patients, while non-B subtypes were more common in heterosexual patients and in injecting drug users (p=0.001). CD4-cell count, viral load and AIDS at presentation were not significantly different between subtypes. Resistance associated mutations were significantly more common in patients with non-B subtypes (15.4% vs 9.8%; p=0.048). CONCLUSIONS: The most commonly identified subtype was B in accordance with previous reports from other western European countries. However, in our cohort the proportion of non-B subtypes is higher than that reported for other European countries, probably reflecting the influence of strong bonds with Portuguese speaking African countries. Knowledge about HIV subtypes distribution may help understanding transmission dynamics and can be an important tool in the design of preventive measures.