Nocardiosis: a single-center experience and literature review.

INTRODUCTION: Nocardiosis is a rare bacterial infection caused by Nocardia spp. However, an increasing incidence has been described whereby data about epidemiology and prognosis are essential. METHODS: A retrospective descriptive study was conducted among patients with positive Nocardia spp. culture, from January 2019 to January 2023, at a Terciary Hospital in Portugal. RESULTS: Nocardiosis was considered in 18 cases with a median age of 63.8-years-old. At least one immunosuppressive cause was identified in 70% of patients. Five patients had Disseminated Nocardiosis (DN). The lung was the most common site of clinical disease (77.8%) and Nocardia was most commonly identified in respiratory tract samples. The most frequently isolated species were Nocardia nova/africana (n = 7) followed by Nocardia cyriacigeorgica (n = 3) and Nocardia pseudobrasiliensis (n = 3). The majority of the patients (94.4%) received antibiotic therapy, of whom as many as 55.6% were treated with monotherapy. The most frequently prescribed antibiotic was trimethoprim-sulfamethoxazole. Selected antimicrobial agents were generally effective, with linezolid and cotrimoxazole (100% Susceptibility [S]) and amikacin (94% S) having the most activity against Nocardia species. The median (IQR) duration of treatment was 24.2 (1‒51.4) weeks for DN; The overall one-year case fatality was 33.3% (n = 6) and was higher in the DN (66.7%). No recurrence was observed. CONCLUSION: Nocardiosis is an emerging infectious disease with a poor prognosis, particularly in DN. This review offers essential epidemiological insights and underscores the importance of gaining a better understanding of the microbiology of nocardiosis. Such knowledge can lead to the optimization of antimicrobial therapy and, when necessary, guide appropriate surgical interventions to prevent unfavorable outcomes.

Adverse Events of Latent Tuberculosis Treatment With Isoniazid in People Living With HIV: A Case-Control Study in a Resource-Rich Setting.

Introduction Multiple risk factors, such as human immunodeficiency virus (HIV) infection and immunosuppressive therapies, increase the odds of latent tuberculosis infection (LTBI) reactivation and progression to active tuberculosis. A six-to-nine-month preventive treatment with isoniazid (INH) decreases the risk of LTBI reactivation, but its effectiveness can be limited by its long duration and adverse events (AEs), including liver toxicity. Due to comorbidities and polypharmacy, people living with HIV (PLHIV) may be at increased risk of INH-associated AEs. Our study aimed to assess the prevalence of AEs among patients receiving INH treatment for LTBI, to identify risk factors for their occurrence, and to evaluate whether PLHIV have higher odds of developing INH-associated AEs. Methods We conducted a single-center retrospective case-control study, including 130 outpatients with LTBI treated with INH between July 2019 and March 2022. Participants who developed AE (cases) were compared to controls, and a subgroup of PLHIV was compared to HIV-negative participants. Demographics, socioeconomic variables, comorbidities, and clinical variables were compared between study groups. Patient data were obtained from institutional electronic medical records, and outcomes were measured at regularly scheduled appointments. Results We included 130 participants, of which 54 were PLHIV. The PLHIV subgroup was significantly younger (p = 0.01) and demonstrated significantly higher prevalences of chronic liver disease, previous viral hepatitis, daily alcohol consumption, and intravenous drug use (IDU). One-third of the participants had an AE (45 cases, 34.6%), with liver toxicity being the most common (22.3%). Participants who developed AEs were significantly older (p = 0.030) and had a higher prevalence of economic hardship (p = 0.037), as well as higher scores of the Charlson comorbidity index (p = 0.002) than the controls. INH withdrawal occurred in 17 participants (13.1%) and was mainly associated with liver toxicity (p < 0.01) and gastrointestinal symptoms (p = 0.022). In the adjusted effect model, an age ≥ 65 years, economic hardship, and excessive alcohol consumption were significantly associated with higher odds of AEs, while HIV infection decreased the odds by 68.4% (p = 0.033). Conclusions In our study, INH-associated AEs were common, with liver toxicity being the most frequent. Older age, economic hardship, and excessive alcohol consumption increased the odds of INH-associated AEs, while PLHIV had lower odds of developing INH-associated AEs, even when adjusting for other variables in the multivariate analysis. Further studies should be conducted to assess if these results are replicable in a larger population and in different settings.

Nocardiosis: a single-center experience and literature review

ABSTRACT Introduction: Nocardiosis is a rare bacterial infection caused by Nocardia spp. However, an increasing incidence has been described whereby data about epidemiology and prognosis are essential. Methods: A retrospective descriptive study was conducted among patients with positive Nocardia spp. culture, from January 2019 to January 2023, at a Terciary Hospital in Portugal. Results: Nocardiosis was considered in 18 cases with a median age of 63.8-years-old. At least one immunosuppressive cause was identified in 70% of patients. Five patients had Disseminated Nocardiosis (DN). The lung was the most common site of clinical disease (77.8%) and Nocardia was most commonly identified in respiratory tract samples. The most frequently isolated species were Nocardia nova/africana (n = 7) followed by Nocardia cyriacigeorgica (n = 3) and Nocardia pseudobrasiliensis (n = 3). The majority of the patients (94.4%) received antibiotic therapy, of whom as many as 55.6% were treated with monotherapy. The most frequently prescribed antibiotic was trimethoprim-sulfamethoxazole. Selected antimicrobial agents were generally effective, with linezolid and cotrimoxazole (100% Susceptibility [S]) and amikacin (94% S) having the most activity against Nocardia species. The median (IQR) duration of treatment was 24.2 (1-51.4) weeks for DN; The overall one-year case fatality was 33.3% (n = 6) and was higher in the DN (66.7%). No recurrence was observed. Conclusion: Nocardiosis is an emerging infectious disease with a poor prognosis, particularly in DN. This review offers essential epidemiological insights and underscores the importance of gaining a better understanding of the microbiology of nocardiosis. Such knowledge can lead to the optimization of antimicrobial therapy and, when necessary, guide appropriate surgical interventions to prevent unfavorable outcomes.

Secondary Organising Pneumonia Among COVID-19 Patients: A Retrospective Case-Control Study.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Secondary organising pneumonia (OP) induced by SARS-CoV-2 infection is a recently recognised complication of COVID-19. We aimed to evaluate the prevalence of OP among hospitalised patients with COVID-19 pneumonia and to assess whether disease severity and other clinical factors and comorbidities are correlated with OP development. We conducted a retrospective case-control study including hospitalised patients due to COVID-19 who performed a chest CT scan during hospitalisation and compared patients with clinical and radiological evidence of OP to patients without evidence of OP. Demographics, comorbidities, disease severity, dexamethasone/remdesivir treatment, laboratory results, and outcomes were compared between groups. One hundred fifteen patients were included, of whom 48 (41.7%) fulfilled clinical and imaging criteria for OP. Among OP patients, the most common chest CT-scan findings were consolidations, arciform condensations, and subpleural bands. OP patients had longer hospitalisation (19.5 vs 10 days, p=0.002) and more frequent ICU admission, but no significant differences in readmittance or mortality rates within 180 days compared to controls. In the adjusted effects model, the need for supplementary oxygen on the 21st day after symptom onset, the presence of Ordinal Scale for Clinical Improvement (OSCI) = 4, when compared to OSCI ≤ 3, and higher C-reactive protein on admission, were significantly associated with higher odds for OP. No other differences were identified between OP and controls after adjusting for other factors. The use of remdesivir or dexamethasone did not impact the diagnosis of OP. Only 38% of OP patients required treatment with high-dose corticosteroids. In conclusion, SARS-CoV-2-induced OP may be more frequent than previously thought, especially among hospitalised patients and patients with a more severe disease, particularly those who fail to improve after the second week of disease or who present higher inflammatory markers on admission. It increases the length of stay, but not all patients require specific treatment and OP may improve despite the absence of high-dose corticosteroid treatment.

The Impact of SARS-CoV-2 Viral Load on the Mortality of Hospitalized Patients: A Retrospective Analysis.

Introduction Coronavirus disease 2019 (COVID-19) has emerged worldwide since December 2019. The standard method for diagnosis is via nucleic acid amplification testing, usually with a reverse-transcription polymerase chain reaction (RT-PCR). Hospitalized infected individuals may require ventilation and may have higher mortality rates. We aim to evaluate the clinical impact of nasopharyngeal viral load on these outcomes. Materials and methods We conducted a retrospective cohort study of patients hospitalized with COVID-19 from 17 March 2020 to 1 June 2020 at a tertiary care hospital. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load was assessed using cycle threshold (Ct) values from an RT-PCR assay applied to nasopharyngeal swab samples. We compared the clinical characteristics of survivors vs. non-survivors and assessed whether the viral load was independently associated with in-hospital 30-day mortality. Results We evaluated 197 patients. Thirty-day mortality was verified in 71 (36%) subjects. In the adjusted effects model, only the E-gene Ct value [odd ratio (OR) .873; confidence interval (CI) 95% .769-.992; p .037], age, the number of days of symptoms before admission, lactate dehydrogenase (LDH), and the oxygen saturation (SatO2)-to-fraction of inspired oxygen (FiO2) ratio remained significantly associated with 30-day mortality. There was no identified association between the viral loads and disease severity, the need for ventilation, or length of stay. Discussion Our results are, in part, concordant with previous papers. One possible limitation to our study is the fact that possibly included disproportionately more patients with poorer outcomes since hospitalization was required. Therefore, further research is required. Conclusion SARS-CoV-2 viral load on admission may be an independent predictor of 30-day mortality among hospitalized patients with COVID-19. Providing this information to clinicians could potentially be used to guide risk stratification.

Clinical Features and Prognostic Factors of 245 Portuguese Patients Hospitalized With COVID-19.

Introduction Since the declaration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in March 2020, Portugal was considered a role model with regards to the first COVID-19 wave. However, a third wave started in 2021 started, turning the country into the worst in the world regarding new infections and death rate per capita in the last weeks of January 2021. No significant data regarding the country's first wave of hospitalized patients have been published. Those data may help understand the differences over time regarding patients and the clinical approach to them. Herein, we present data of COVID-19 patients hospitalized at the main tertiary hospital of the second-most affected county at the time and identify risk factors associated with disease progression and outcomes. Materials and methods We performed a prospective observational study of patients admitted with COVID-19 to a central hospital between March 20 and June 1, 2020. The primary endpoint of this study was 30-day mortality or the need for ventilatory support and the secondary outcomes were both outcomes individually. Results 245 patients were included, with a median age of 79 years, 52% males. Hypertension (n = 172) and dyslipidemia (n = 114) were the most frequent comorbidities. Half of the patients (n = 121) were treated with hydroxychloroquine. The primary outcome occurred in 114 patients; mortality at 30 days was 35%. Age (OR 1.05; 1.02-1.07) and active cancer (OR 3.89; 1.43-10.57) were associated with the primary outcome, with dyslipidemia being protective (OR 0.46; 0.25-0.80). Treatment with hydroxychloroquine or lopinavir/ritonavir was not associated with the main outcome. Patients who had been symptomatic for more than 7 days had lower mortality (OR 0.23; 0.09-0.63). Discussion In the present study, age and cancer were associated with higher mortality, as noted in prior articles. The population had a higher median age than reported in previous studies, which may explain the increased mortality. The protective association of dyslipidemia was not previously described. This association was not related to statin intake. Conclusion The reported high mortality of COVID-19 is rarely seen in other infectious diseases. Our elderly population probably reflects more reliably the incidence of COVID-19 in European countries with constricted age pyramids.

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.

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.

An unusual cause of chest discomfort: case report of oesophageal hirudiniasis.

Hirudiniasis is caused by sanguivorous leeches feeding on mucous membranes with possible severe obstructive or haemorrhagic manifestations. Few cases have been reported in humans, and most occur in tropical countries. A seventy-year-old female patient presented to our Emergency Department (ED) with retrosternal discomfort. She was taking warfarin for a mechanical prosthetic heart valve. While in the ED, a leech was spontaneously extruded from her mouth, with symptomatic resolution. Endoscopy revealed an area of previous leech attachment in the distal oesophageal, without severe bleeding. Albeit uneventful, this case could have had a devastating outcome.

Aseptic Meningitis Caused by Coxiella Burnetii.

Acute Q fever can have multiple presentations but neurologic involvement is rare. We describe the case of a 16-year-old female with severe headache and aseptic meningitis with acute Coxiella burnetii infection.

Nocardia-induced granulocyte macrophage colony-stimulating factor is neutralized by autoantibodies in disseminated/extrapulmonary nocardiosis.

BACKGROUND: Nocardia species cause infections in both immunocompromised and otherwise immunocompetent patients, although the mechanisms defining susceptibility in the latter group are elusive. Anticytokine autoantibodies are an emerging cause of pathogen-specific susceptibility in previously healthy human immunodeficiency virus-uninfected adults, including anti-granulocyte macrophage colony-stimulating factor (GM-CSF) autoantibodies with cryptococcal meningitis. METHODS: Plasma from patients with disseminated/extrapulmonary nocardiosis and healthy controls was screened for anticytokine autoantibodies using a particle-based approach. Autoantibody function was assessed by intranuclear staining for GM-CSF-induced STAT5 phosphorylation in normal cells incubated with either patient or normal plasma. GM-CSF-mediated cellular activation by Nocardia was assessed by staining for intracellular cytokine production and intranuclear STAT5 phosphorylation. RESULTS: We identified neutralizing anti-GM-CSF autoantibodies in 5 of 7 patients studied with central nervous system nocardiosis and in no healthy controls (n = 14). GM-CSF production was induced by Nocardia in vitro, suggesting a causative role for anti-GM-CSF autoantibodies in Nocardia susceptibility and dissemination. CONCLUSIONS: In previously healthy adults with otherwise unexplained disseminated/extrapulmonary Nocardia infections, anti-GM-CSF autoantibodies should be considered. Their presence may suggest that these patients may be at risk for later development of pulmonary alveolar proteinosis or other opportunistic infections, and that patients may benefit from therapeutic GM-CSF administration.

Prevention of mother-to-child transmission: experience of a Portuguese centre.

INTRODUCTION: HIV infection during pregnancy still raises controversial issues. Combined antiretroviral therapy (cART) has been successful in reducing mother-to-child transmission (MTCT). Routine screening in pregnancy and in pre-conception consultation proved to be one of the best methods able to get this treatment on time. We review our experience with pregnant patients with HIV infection. MATERIALS AND METHODS: Retrospective and descriptive study. Data obtained from HIV-infected pregnant women from 1999 to 2012 with delivery and subsequent infectious diseases follow-up at our hospital. RESULTS: We evaluated 136 patients (169 pregnancies), with a total of 147 living newborns (2 twin pregnancies) and 1 stillbirth. Median age at pregnancy was 30 (SD 5.7) years. Four patients were HIV-2 infected and one HIV-1+2 infected. 26 (19.1%) women were HCV co-infected and 6 (4.4%) HBV co-infected; 1 patient has HCV and HBV co-infection. Sexual risk for HIV acquisition was determined in 102 (75%) patients and 31 (22.8%) were intravenous drug users. 33/136 (24.2%) women were diagnosed on routine screening in pregnancy, 4 during delivery and 2 immediately after delivery. 36 (26.4%) patients had an AIDS-defining entity before pregnancy and no new opportunistic infections were diagnosed. ART was used in 157 (92.9%) pregnancies and 15 (9.5%) of them were treated only with NRTIs. At the time of delivery 86/144 (59.7%) patients had undetectable viral load (VL) (25 patients without VL determined), 91.7% of those on ART. 119 (70.4%) had a TCD4 cell count above 200 cells/mm(3). MTCT occurred in 3/147 cases (2%): in one mother HIV-1 infection was diagnosed three weeks before delivery, other immediately after delivery and the third woman started cART (2NRTI+1PI/r) in the second trimester of pregnancy, always adherent and without secondary effects, VL at delivery was 50 copies/mL and elective C-section was performed. CONCLUSIONS: The fact that 24% of patients were diagnosed during pregnancy shows the importance of routine screening to all pregnant women. MTCT occurred in three children, but only one was administered cART for prevention.

Primary drug resistance at diagnosis of HIV-1 infection: a Portuguese cohort.

INTRODUCTION: Presence of viral mutations conferring resistance to antiretroviral drugs has potential impact on success of antiretroviral therapy (ART). The aim of this study was to describe the prevalence of resistance-associated mutations in HIV-infected patients without prior ART in a Portuguese cohort. MATERIALS AND METHODS: Retrospective single-centre study of patients newly diagnosed with HIV-1 infection between 2006 and 2012. Resistance genotyping was obtained with HIV TRUGENE(®) and Viroseq(®) tests and the analysis of drug resistance was based on the Stanford University HIV Drug Resistance Database. Epidemiological data was also gathered. Continuous variables were summarized by mean and standard deviation, whereas categorical variables were presented as proportions. Comparison of proportions was performed with Chi square and Fisher exact test while means were compared with Student test. Statistical significance was assumed when p<0.05. Statistical analysis was performed with SPSS 21.0(®). RESULTS: Resistance testing was performed in 624 patients. General characteristics of the patients are summarized in Table 1. Mutations were found in 291 (46.6%) patients but resistance-associated mutations were present in 79 (12.7%) patients. Resistances to different drug classes were the following: NNRTIs-resistance in 42 (6.7%) patients; NRTIs-resistance in 19 (3.0%) patients; PIs-resistance in 30 (4.8%) patients. Only 10 (1.6%) patients presented simultaneous resistance-associated mutations to more than one class of drugs. There were no statistical significant differences between the years at which HIV-1 was diagnosed. Also no significant difference in the distribution of the parameters age, sex, CD4-cell count, and viral load, between groups with and without resistance was identified. Resistance-associated mutations were significantly more common in patients with non-B HIV-1 subtypes (15.4% vs 9.8%; p=0.048) and in those presenting with AIDS (18.2% vs 11.1%; p=0.03). CONCLUSIONS: Prevalence of resistance-associated mutations identified in this study was similar to those reported in similar studies from Western Europe. Knowledge about the epidemiology of primary resistance in our country is important in order to improve HIV care.

Transverse myelitis and acute HIV infection: a case report.

BACKGROUND: Most HIV infected patients will develop some sort of neurologic involvement of the disease throughout their lives, usually in advanced stages. Neurologic symptoms may occur in acute HIV infection but myelopathy in this setting is rare. Up until this date, only two cases of transverse myelitis as a manifestation of acute HIV infection have been reported in the literature. Therapeutic approach in these patients is not well defined. CASE PRESENTATION: A 35 year-old male Caucasian recently returned from the tropics presented to our hospital with urinary retention and acute paraparesis. After extensive diagnostic workup he was diagnosed with acute HIV infection presenting as transverse myelitis. Full neurologic recovery was observed without the use of anti-retroviral therapy. CONCLUSION: Acute spinal cord disorders are challenging, as they present a wide array of differential diagnosis and may lead to devastating sequelae. Timely and rigorous diagnostic workup is of the utmost importance when managing these cases. Clinicians should be aware of the protean manifestations of acute HIV infection, including central nervous system involvement, and have a low threshold for HIV screening.