Streptococcus bovis infection of the central nervous system in adults: Report of 4 cases and literature review.

OBJECTIVES: To describe the clinical features, history and association with intestinal disease in central nervous system (CNS) S. bovis infections. METHODS: Four cases of S. bovis CNS infections from our institution are presented. Additionally a systematic literature review of articles published between 1975 and 2021 in PubMed/MEDLINE was conducted. RESULTS: 52 studies with 65 cases were found; five were excluded because of incomplete data. In total 64 cases were analyzed including our four cases: 55 with meningitis and 9 with intracranial focal infections. Both infections were frequently associated with underlying conditions (70.3%) such as immunosuppression (32.8%) or cancer (10.9%). In 23 cases a biotype was identified, with biotype II being the most frequent (69.6%) and S. pasteurianus the most common within this subgroup. Intestinal diseases were found in 60.9% of cases, most commonly neoplasms (41.0%) and Strongyloides infestation (30.8%). Overall mortality was 17.1%, with a higher rate in focal infection (44.4% vs 12.7%; p=0.001). CONCLUSIONS: CNS infections due to S. bovis are infrequent and the most common clinical form is meningitis. Compared with focal infections, meningitis had a more acute course, was less associated with endocarditis and had a lower mortality. Immunosuppression and intestinal disease were frequent in both infections.

Cloxacillin plus fosfomycin versus cloxacillin alone for methicillin-susceptible Staphylococcus aureus bacteremia: a randomized trial.

Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III-IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), -5.95-16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345 .

Cutibacterium spp. Infections after Instrumented Spine Surgery Have a Good Prognosis Regardless of Rifampin Use: A Cross-Sectional Study.

Infection after spinal instrumentation (IASI) by Cutibacterium spp. is being more frequently reported. The aim of this study was to analyse the incidence, risk factors, clinical characteristics, and outcome of a Cutibacterium spp. IASI (CG) compared with non-Cutibacterium IASI (NCG) infections, with an additional focus on the role of rifampin in the treatment. All patients from a multicentre, retrospective, observational study with a confirmed IASI between January 2010 and December 2016 were divided into two groups: (CG and NCG) IASI. Baseline, medical, surgical, infection treatment, and follow-up data were compared for both groups. In total, 411 patients were included: 27 CG and 384 NCG. The CG patients were significantly younger. They had a longer median time to diagnosis (23 vs. 13 days) (p = 0.025), although 55.6% debuted within the first month after surgery. Cutibacterium patients were more likely to have the implant removed (29.6% vs. 12.8%; p = 0.014) and received shorter antibiotic regimens (p = 0.014). In 33% of Cutibacterium cases, rifampin was added to the baseline therapy. None of the 27 infections resulted in treatment failure during follow-up regardless of rifampin use. Cutibacterium spp. is associated with a younger age and may cause both early and late IASIs. In our experience, the use of rifampin to improve the outcome in the treatment of a Cutibacterium spp. IASI is not relevant since, in our series, none of the cases had therapeutic failure regardless of the use of rifampin.

Assessment of Post-COVID Symptoms Using the C19-YRS Tool in a Cohort of Patients from the First Pandemic Wave in Northwestern Spain.

Introduction: The emergence or persistence of symptoms after acute SARS-CoV-2 infection has made it necessary to develop tools to detect them and assess their impact on patients' quality of life. One of these tools is the COVID-19 Yorkshire Rehabilitation Screening (C19-YRS) scale. We present the results of this tool in a cohort of first pandemic wave patients. Methods: A cross-sectional study of patients with confirmed SARS-CoV-2 infection from March to May 2020 in Lugo (northwestern Spain). C19-YRS was administered via phone 10 months after the acute infection to both former inpatients and outpatients. Electronic medical records were reviewed and relevant data from the acute episode were collected. The main outcome was the presence of impairment in different areas measured by the C19-YRS scale. Results: The answer rate was 63.2%. The mean age was 54 ± 16 years, 38.4% were male and 190 (42.9%) had some comorbidity. Eighty-seven patients (19.6%) required hospitalization and 10 (2.3%) required intensive care unit admission. Ten (3.5%) patients lost their job due to the pandemic. Two hundred seventy-six patients (62.3%) related any symptoms; fatigue (37.2%) and exertional dyspnea (33.4%) were the most common with significant worsening in both cases compared with the situation before the infection. Subgroup analysis showed that more symptom domains were impaired in women than men. Older patients, those with comorbidity and those who needed hospital admission, demanded more health resources after the acute infection. Discussion: C19-YRS is useful for the detection and quantification of symptoms after COVID-19 and provides relevant social, health, and occupational information.

Derivation and external validation of a simple prediction rule for the development of respiratory failure in hospitalized patients with influenza.

BACKGROUND: Influenza viruses cause seasonal epidemics worldwide with a significant morbimortality burden. Clinical spectrum of Influenza is wide, being respiratory failure (RF) one of its most severe complications. This study aims to elaborate a clinical prediction rule of RF in hospitalized Influenza patients. METHODS: A prospective cohort study was conducted during two consecutive Influenza seasons (December 2016-March 2017 and December 2017-April 2018) including hospitalized adults with confirmed A or B Influenza infection. A prediction rule was derived using logistic regression and recursive partitioning, followed by internal cross-validation. External validation was performed on a retrospective cohort in a different hospital between December 2018 and May 2019. RESULTS: Overall, 707 patients were included in the derivation cohort and 285 in the validation cohort. RF rate was 6.8% and 11.6%, respectively. Chronic obstructive pulmonary disease, immunosuppression, radiological abnormalities, respiratory rate, lymphopenia, lactate dehydrogenase and C-reactive protein at admission were associated with RF. A four category-grouped seven point-score was derived including radiological abnormalities, lymphopenia, respiratory rate and lactate dehydrogenase. Final model area under the curve was 0.796 (0.714-0.877) in the derivation cohort and 0.773 (0.687-0.859) in the validation cohort (p < 0.001 in both cases). The predicted model showed an adequate fit with the observed results (Fisher's test p > 0.43). CONCLUSION: we present a simple, discriminating, well-calibrated rule for an early prediction of the development of RF in hospitalized Influenza patients, with proper performance in an external validation cohort. This tool can be helpful in patient's stratification during seasonal Influenza epidemics.

Relationship among Streptococcus gallolyticus Subsp. gallolyticus, Enterococcus faecalis and Colorectal Neoplasms in Recurrent Endocarditis: A Historical Case Series.

OBJECTIVES: The role of colorectal neoplasms (CRN) as a common potential source of recurrent Streptococcus gallolyticus subsp. gallolyticus (SGG) and Enterococcus faecalis (EF) endocarditis remains unstudied. We aimed to investigate what proportion of episodes of recurrent endocarditis are caused by a succession of SGG and EF, or vice versa, and to assess the role of a colonic source in such recurrent episodes. METHODS: we conducted a retrospective analysis of two prospective endocarditis cohorts (1979-2019) from two Spanish hospitals, providing descriptive analyses of the major features of the endocarditis episodes, colonoscopy findings, and histologic results. RESULTS: among 1552 IE episodes, 204 (13.1%) were caused by EF and 197 (12.7%) by SGG, respectively. There were 155 episodes (10%) of recurrent IE, 20 of which (12.9%) were due to a succession of SGG/EF IE in 10 patients (the first episode caused by SGG in eight cases, and by EF in two cases). The median follow-up was 86 (interquartile range 34-156) months. In 8/10 initial episodes, the causative microorganism was SGG, and all patients were diagnosed with CRN either during the initial episode or during follow-up. During the second episode of IE or follow-up, colonoscopies revealed CRN in six patients. CONCLUSIONS: There seems to be an association between SGG and EF in recurrent endocarditis that warrants further investigation. Our findings reinforce the need for systematically performing colonoscopy in the event of endocarditis caused by both microorganisms.

Streptococcus suis spondylodiscitis: 2 new cases and a literature review.

INTRODUCTION: Streptococcus suis (S. suis) infection is poorly described zoonosis in our country, which is related with exposure to pigs or their meat. The most common clinical presentation is meningitis, while spine's involvement is rare. METHODS: We report 2 cases of S. suis infection and perform a systematic review of the articles published on S. suis spondylodiscitis between January 1994 and May 2020 with the aim of defining the clinical characteristics, predisposing factors and evolution. RESULTS: 17 cases are described, 76.5% males with a mean age of 57.6 years, generally without associated underlying disease. Enolism was a factor present in 17.6%. 70.6% had exposure to pigs or their meat and 20% hand injuries. The mean duration of symptoms was 10.2 days and the most affected segment was the lumbar level. 70.6% had meningitis. All were treated with beta-lactams with an average duration of 53.2 days. There was a recurrence and none died. CONCLUSION: There are few cases of S. suis spondylodiscitis in the literature. When occurs, it is associated with another type of infection in most cases. They present a good response to medical treatment and a good prognosis.

Prognosis of unexpected positive intraoperative cultures in arthroplasty revision: A large multicenter cohort.

BACKGROUND: The positive-intraoperative-cultures-type prosthetic joint infection (PIOC-PJI) is considered when surgical cultures yield microorganisms in presumed aseptic arthroplasty revisions. Herein we assess the risk factors for failure in the largest cohort of PIOC-PJI patients reported to date. METHODS: A retrospective, observational, multicenter study was performed during 2007-2017. Surgeries leading to diagnose PIOC-PJI included only one-stage procedures with either complete or partial prosthesis revision. Failure was defined as recurrence caused by the same microorganism. RESULTS: 203 cases were included (age 72 years, 52% females). Coagulase-negative staphylococci (n = 125, 62%) was the main etiology, but some episodes were caused by virulent bacteria (n = 51, 25%). Prosthesis complete and partial revision was performed in 93 (46%) and 110 (54%) cases, respectively. After a median of 3.4 years, failure occurred in 17 episodes (8.4%, 95%CI 5.3-13.1). Partial revision was an independent predictor of failure (HR 3.63; 95%CI 1.03-12.8), adjusted for gram-negative bacilli (GNB) infection (HR 2.68; 95%CI 0.91-7.89) and chronic renal impairment (HR 2.40; 95%CI 0.90-6.44). Treatment with biofilm-active antibiotics (rifampin/fluoroquinolones) had a favorable impact on infections caused by staphylococci and GNB. CONCLUSION: Overall prognosis of PIOC-PJI is good, but close follow-up is required in cases of partial revision and in infections caused by GNB.

Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial.

INTRODUCTION: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. METHODS: We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician.Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation).We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. TRIAL REGISTRATION NUMBER: The protocol has been approved by AEMPS with the Trial Registration Number EudraCT 2018-001207-37. ClinicalTrials.gov Identifier: NCT03959345; Pre-results.

Infections after spine instrumentation: effectiveness of short antibiotic treatment in a large multicentre cohort.

BACKGROUND AND OBJECTIVES: Available information about infection after spine instrumentation (IASI) and its management are scarce. We aimed to analyse DAIR (debridement, antibiotics and implant retention) prognosis and evaluate effectiveness of short antibiotic courses on early forms. METHODS: Multicentre retrospective study of patients with IASI managed surgically (January 2010-December 2016). Risk factors for failure were analysed by multivariate Cox regression and differences between short and long antibiotic treatment were evaluated with a propensity score-matched analysis. RESULTS: Of the 411 IASI cases, 300 (73%) presented in the first month after surgery, 48 in the second month, 22 in the third and 41 thereafter. Infections within the first 2 months (early cases) occurred mainly to older patients, with local inflammatory signs and predominance of Enterobacteriaceae, unlike those in the later periods. When managed with DAIR, prognosis of early cases was better than later ones (failure rate 10.4% versus 26.1%, respectively; P = 0.02). Risk factors for DAIR failure in early cases were female sex, Charlson Score, large fusions (>6 levels) and polymicrobial infections (adjusted HRs of 2.4, 1.3, 2.6 and 2.26, respectively). Propensity score matching proved shorter courses of antibiotics (4-6 weeks) as effective as longer courses (failure rates 11.4% and 10.5%, respectively; P = 0.870). CONCLUSIONS: IASIs within the first 2 months could be managed effectively with DAIR and shorter antibiotic courses. Clinicians should be cautious when faced with patients with comorbidities, large fusions and/or polymicrobial infections.

Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial.

BACKGROUND: We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis. METHODS: A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy. RESULTS: Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93-1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018). CONCLUSIONS: Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events. CLINICAL TRIALS REGISTRATION: NCT01898338.

Streptococcus suis spondylodiscitis: 2 new cases and a literature review. / Espondilodiscitis por Streptococcus suis: 2 nuevos casos y revisión bibliográfica.

INTRODUCTION: Streptococcus suis (S. suis) infection is poorly described zoonosis in our country, which is related with exposure to pigs or their meat. The most common clinical presentation is meningitis, while spinés involvement is rare. METHODS: We report 2 cases of S. suis infection and perform a systematic review of the articles published on S. suis spondylodiscitis between January 1994 and May 2020 with the aim of defining the clinical characteristics, predisposing factors and evolution. RESULTS: 17 cases are described, 76.5% males with a mean age of 57.6 years, generally without associated underlying disease. Enolism was a factor present in 17.6%. 70.6% had exposure to pigs or their meat and 20% hand injuries. The mean duration of symptoms was 10.2 days and the most affected segment was the lumbar level. 70.6% had meningitis. All were treated with beta-lactams with an average duration of 53.2 days. There was a recurrence and none died. CONCLUSION: There are few cases of S. suis spondylodiscitis in the literature. When occurs, it is associated with another type of infection in most cases. They present a good response to medical treatment and a good prognosis.

Community acquired pneumonia by Legionella pneumophila: Study of 136 cases. / Neumonía comunitaria por Legionella pneumophila: estudio de 136 casos.

OBJECTIVE: Most of the data on Legionella pneumonia in our country come from the Mediterranean area, and there are few studies from the Northwest area. This study tries to assess the situation of this infection in this area. METHOD: Retrospective study of all patients with positive Legionella antigenuria treated at the University Hospital Lucus Augusti in Lugo (Spain) from 2001, the year in which this test was introduced in our centre, until 2015. We analysed epidemiological data, risk factors, clinical, radiological and biochemical findings, and clinical outcome. RESULTS: The sampled included 136 patients. When comparing the first five years of the study with the last five, the incidence increased from 10.9 to 64.5 cases/1,000,000; the number of antigenuria requests increased 3.4 times, and compared to other pneumonia aetiologies Legionella increased from 0.9% to 15%. The mean age was 64.1years and 84.6% were males; 74.3% had comorbidities. Males were significantly younger (62.7±16.6 vs 71.9±17.3) and consumed more alcohol (26.1% vs 0%) and tobacco (67.8% vs 14.3%). Diagnosis was established within the first 72hours in 88.9% of cases and most received levofloxacin (95.6%). Hospitalisation was needed in 85% of cases, 11.7% in ICU and 4.4% died. CONCLUSIONS: After the introduction of antigenuria there was an increase in the incidence of Legionella pneumonia recorded in our health area. Its rate in recent years has been one of the highest in our country. Despite the fact that the patients had advanced age and comorbidities, mortality was low.

Colorectal neoplasm in cases of Clostridium septicum and Streptococcus gallolyticus subsp. gallolyticus bacteraemia.

BACKGROUND: Bacteremia with Clostridium septicum (CS) and Streptococcus gallolyticus subsp. gallolyticus (SGG) have both been associated with colorectal neoplasms (CRN) and colonoscopic examination is advised, however the differences and similarities in colorectal findings are not well known. METHODS: This is a multicenter, comparative study of patients with CS bacteremia [44 of 664 cases (6.6%) of Clostridium spp.] and SGG bacteremia [257 of 596 cases (44.2%) of S. bovis group], carried out in three hospitals from Spain. Clinical findings related to bacteremia and associated CRN were collected. RESULTS: The main sources of infection were abdominal (77.7%) for CS bacteremia and endovascular (75%) for SGG bacteremia. CS bacteremia was more often associated with malignancies, (72.6% vs. 19.4%) and neutropenia (29.5% vs. 3.1%), and was more acute, with shock at presentation (63.6% vs. 3.9%) and higher 30-day mortality (47.7% vs. 9.7%) compared to SGG (P<0.05 for all). Both, patients with CS and SGG bacteremia often had concomitant CRN (43.1% vs. 49.8%) and most of them presented as occult CRN (73.7% vs. 91.4%; P=0.02). CS cases more often had invasive carcinomas (94.7% vs. 19.5%), location of CRN in the right colon (73.7% vs. 23.4%), larger tumor size (median 7 vs. 1.5cm), and a higher overall CRN related mortality rate (68.4% vs. 7.8%) compared to SGG cases (P<0.05 for all). CONCLUSIONS: Both, CS and SGG bacteremia are associated with occult CRN. CS cases more often had advanced carcinomas than SGG cases, suggesting a distinct temporal association with CRN.

Streptococcus bovis septic arthritis and osteomyelitis: A report of 21 cases and a literature review.

BACKGROUND: The Streptococcus bovis group (SBG) is a well-known cause of endocarditis, but its role in osteoarticular infections (OAIs) has not been well described. METHODS: We analyzed all patients with OAIs by SBG diagnosed in our hospital (1988-2014). We selected those cases with septic arthritis and osteomyelitis, as defined according to clinical, microbiological, and imaging studies. Identification of the strains was performed by using the API 20 Strep and the GP card of the Vitek 2 system, and confirmed the identification by molecular methods. In addition, we reviewed the literature to select all cases of OAI by SBG during the period 1980-2015. RESULTS: From the 83 cases of OAI included in the analysis (21 from our center and 62 from the literature review), 59 were osteomyelitis (57 of them spondylodiscitis) and 24 were arthritis (2 with associated spondylodiscitis). The mean age was 66.9 years, and 79.2% of the patients were men. Endocarditis (IE) was associated with 59% of the cases and this association was greater for osteomyelitis than for arthritis (78.9% vs. 13.6%; P = 0.001). OAI was a presenting symptom in 63% of the cases of IE. Colonoscopy was performed in 64 cases, which detected colorectal neoplasm (CRN) in 46 patients (71.8%), almost all asymptomatic. Some 69.5% of these neoplasm were carcinomas or advanced adenomas. The blood cultures were positive in 78.3% cases. In 45 cases, the S. bovis species was identified; in 82.2% of the cases the cause was Streptococcus gallolyticus subsp. gallolyticus. The mortality was 7.2%, which in no case was attributable to the OAI. CONCLUSIONS: OAIs are frequently the initial manifestation of IE caused by SBG. S. gallolyticus causes most of these infections. Echocardiogram and colonoscopy are therefore mandatory, given the species' close association with IE and CRN.