qSOFA combined with suPAR for early risk detection and guidance of antibiotic treatment in the emergency department: a randomized controlled trial.

BACKGROUND: Sepsis guidelines suggest immediate start of resuscitation for patients with quick Sequential Organ Failure Assessment (qSOFA) 2 or 3. However, the interpretation of qSOFA 1 remains controversial. We investigated whether measurements of soluble urokinase plasminogen activator receptor (suPAR) may improve risk detection when qSOFA is 1. METHODS: The study had two parts. At the first part, the combination of suPAR with qSOFA was analyzed in a prospective cohort for early risk detection. At the second part, the double-blind, randomized controlled trial (RCT) SUPERIOR evaluated the efficacy of the suPAR-guided medical intervention. SUPERIOR took place between November 2018 and December 2020. Multivariate stepwise Cox regression was used for the prospective cohort, while univariate and multivariate logistic regression was used for the RCT. Consecutive admissions at the emergency department (ED) with suspected infection, qSOFA 1 and suPAR ≥ 12 ng/mL were allocated to single infusion of placebo or meropenem. The primary endpoint was early deterioration, defined as at least one-point increase of admission Sequential Organ Failure Assessment (SOFA) score the first 24 h. RESULTS: Most of the mortality risk was for patients with qSOFA 2 and 3. Taking the hazard ratio (HR) for death of patients with qSOFA = 1 and suPAR < 12 ng/mL as reference, the HR of qSOFA = 1 and suPAR ≥ 12 ng/mL for 28-day mortality was 2.98 (95% CI 2.11-3.96). The prospective RCT was prematurely ended due to pandemia-related ED re-allocations, with 91 patients enrolled: 47 in the placebo and 44 in the meropenem arm. The primary endpoint was met in 40.4% (n = 19) and 15.9% (n = 7), respectively (difference 24.5% [5.9-40.8]; odds ratio 0.14 [0.04-0.50]). One post hoc analysis showed significant median changes of SOFA score after 72 and 96 h equal to 0 and - 1, respectively. CONCLUSIONS: Combining qSOFA 1 with the biomarker suPAR improves its prognostic performance for unfavorable outcome and can help decision for earlier treatment. Trial registration EU Clinical Trials Register (EudraCT, 2018-001008-13) and Clinical-Trials.gov (NCT03717350). Registered 24 October 2018.

The association between vegetation size and surgical treatment on 6-month mortality in left-sided infective endocarditis.

AIMS: In left-sided infective endocarditis (IE), a large vegetation >10 mm is associated with higher mortality, yet it is unknown whether surgery during the acute phase opposed to medical therapy is associated with improved survival. We assessed the association between surgery and 6-month mortality as related to vegetation size. METHODS AND RESULTS: Patients with definite, left-sided IE (2008-2012) from The International Collaboration on Endocarditis prospective, multinational registry were included. We compared clinical characteristics and 6-month mortality (by Cox regression with inverse propensity of treatment weighting) between patients with vegetation size ≤10 mm vs. >10 mm in maximum length by surgical treatment strategy. A total of 1006 patients with left sided IE were included; 422 with a vegetation size ≤10 mm (median age 66.0 years, 33% women) and 584 (median age 58.4 years, 34% women) patients with a large vegetation >10 mm. Operative risk by STS-IE score was similar between groups. Embolic events occurred in 28.4% vs. 44.3% (P < 0.001), respectively. Patients with a vegetation >10 mm was associated with higher 6-month mortality (25.1% vs. 19.4% for small vegetation, P = 0.035). However, after propensity adjustment, the association with higher mortality persisted only in patients with a large vegetation >10 mm vs. ≤10 mm: hazard ratio (HR) 1.55 (1.27-1.90); but only in patients with large vegetation managed medically [HR 1.86 (1.48-2.34)] rather than surgically [HR 1.01 (0.69-1.49)]. CONCLUSION: Left-sided IE with vegetation size >10 mm was associated with an increased mortality at 6 months in this observational study but was dependent on treatment strategy. For patients with large vegetation undergoing surgical treatment, survival was similar to patients with smaller vegetation size.

Association between the timing of surgery for complicated, left-sided infective endocarditis and survival.

BACKGROUND: In patients with active infective endocarditis (IE), the relationship between timing of surgery and survival is uncertain. The objective was to evaluate clinical characteristics associated with timing of surgery and the association between surgical timing and 6-month survival in complicated, left-sided IE. METHODS: In a prospective, multicenter, observational registry (The International Collaboration on Endocarditis-PLUS, registry from 2008 to 2012), clinical factors associated with timing of surgery during the index hospitalization were determined among 485 adult patients with definite, complicated, left-sided IE who underwent cardiac surgery during their index hospitalization. The relationship between early surgical intervention (<7 days from admission to surgery center) and outcome after surgery was analyzed. The primary end point of the study was 6-month survival. RESULTS: The median time to surgery from admission to surgical center was 7 (interquartile range 2-15) days. Patients who underwent earlier surgery were more likely transferred to the surgical center (74.2% vs 46.4%, P < .001) and had a lower percentage of preexisting heart failure (before IE diagnosis) (6.0% vs 17.3%, P < .001) but higher rate of acute heart failure (53.2% vs 38.4%, P = .001). Variables independently associated with surgery <7 days from admission were patient transfer, acute heart failure, and nonelective surgical status (C-index = 0.84), but predicted operative risk was not. Cox proportional hazards modeling with inverse probability of treatment weighting found that earlier surgery was associated with a trend toward higher 6-month mortality compared with later surgery (hazard ratio = 1.68, 95% CI 0.97-2.96; P = .065), particularly surgery within 2 days of admission or transfer. Mortality was significantly associated with operative risk and complicated IE, including Staphylococcus aureus infection and presence of abscess. CONCLUSIONS: Earlier surgery in IE is strongly associated with acute heart failure and surgical urgency. After adjustment for operative risk and IE complications, earlier surgery <7 days from admission was associated with a trend toward higher 6-month overall mortality compared with surgery later in the index hospitalization.

The Not-So-Good Prognosis of Streptococcal Periprosthetic Joint Infection Managed by Implant Retention: The Results of a Large Multicenter Study.

BACKGROUND.: Streptococci are not an infrequent cause of periprosthetic joint infection (PJI). Management by debridement, antibiotics, and implant retention (DAIR) is thought to produce a good prognosis, but little is known about the real likelihood of success. METHODS.: A retrospective, observational, multicenter, international study was performed during 2003-2012. Eligible patients had a streptococcal PJI that was managed with DAIR. The primary endpoint was failure, defined as death related to infection, relapse/persistence of infection, or the need for salvage therapy. RESULTS.: Overall, 462 cases were included (median age 72 years, 50% men). The most frequent species was Streptococcus agalactiae (34%), and 52% of all cases were hematogenous. Antibiotic treatment was primarily using ß-lactams, and 37% of patients received rifampin. Outcomes were evaluable in 444 patients: failure occurred in 187 (42.1%; 95% confidence interval, 37.5%-46.7%) after a median of 62 days from debridement; patients without failure were followed up for a median of 802 days. Independent predictors (hazard ratios) of failure were rheumatoid arthritis (2.36), late post-surgical infection (2.20), and bacteremia (1.69). Independent predictors of success were exchange of removable components (0.60), early use of rifampin (0.98 per day of treatment within the first 30 days), and long treatments (≥21 days) with ß-lactams, either as monotherapy (0.48) or in combination with rifampin (0.34). CONCLUSIONS.: This is the largest series to our knowledge of streptococcal PJI managed by DAIR, showing a worse prognosis than previously reported. The beneficial effects of exchanging the removable components and of ß-lactams are confirmed and maybe also a potential benefit from adding rifampin.

What is new in the management of skin and soft tissue infections in 2016?

PURPOSE OF REVIEW: Skin and soft tissue infections (SSTIs) are the most frequent infectious cause of referrals to emergency departments and hospital admissions in developed world, contributing to significant morbidity and healthcare expenditures. We sought to review recent literature covering epidemiology and management of SSTIs. RECENT FINDINGS: Incidence trends of SSTIs were increasing worldwide with Staphylococcus aureus and streptococci predominating and methicillin-resistant S. aureus (MRSA) posing additional challenges, because of high rates of treatment failure and relapse. Development of new antimicrobials was associated with an appraisal of regulatory definitions and endpoints. Prediction of clinical response can be very tricky, because of variable risk factors for recurrence or treatment failure, depending mostly on the host. Precise indications for new antimicrobials should be established; their integration into clinical practice algorithms may serve reduction of unnecessary admissions, overtreatment and total costs. SUMMARY: New antimicrobials with activity against MRSA have been recently launched. Long-acting agents, mainly oritavancin and dalbavancin, provide the opportunity of single-dose treatment and early discharge. Further outpatient treatment options include new per os antibiotics such as oxazolidinones. Validated assessment tools are urgently needed to support decision-making toward rational resource utilization and delivery of optimal treatment.

Association between surgical indications, operative risk, and clinical outcome in infective endocarditis: a prospective study from the International Collaboration on Endocarditis.

BACKGROUND: Use of surgery for the treatment of infective endocarditis (IE) as related to surgical indications and operative risk for mortality has not been well defined. METHODS AND RESULTS: The International Collaboration on Endocarditis-PLUS (ICE-PLUS) is a prospective cohort of consecutively enrolled patients with definite IE from 29 centers in 16 countries. We included patients from ICE-PLUS with definite left-sided, non-cardiac device-related IE who were enrolled between September 1, 2008, and December 31, 2012. A total of 1296 patients with left-sided IE were included. Surgical treatment was performed in 57% of the overall cohort and in 76% of patients with a surgical indication. Reasons for nonsurgical treatment included poor prognosis (33.7%), hemodynamic instability (19.8%), death before surgery (23.3%), stroke (22.7%), and sepsis (21%). Among patients with a surgical indication, surgical treatment was independently associated with the presence of severe aortic regurgitation, abscess, embolization before surgical treatment, and transfer from an outside hospital. Variables associated with nonsurgical treatment were a history of moderate/severe liver disease, stroke before surgical decision, and Staphyloccus aureus etiology. The integration of surgical indication, Society of Thoracic Surgeons IE score, and use of surgery was associated with 6-month survival in IE. CONCLUSIONS: Surgical decision making in IE is largely consistent with established guidelines, although nearly one quarter of patients with surgical indications do not undergo surgery. Operative risk assessment by Society of Thoracic Surgeons IE score provides prognostic information for survival beyond the operative period. S aureus IE was significantly associated with nonsurgical management.

When and how to operate on spondylodiscitis: a report of 13 patients.

PURPOSE: Conflicting reports exist regarding the surgical indications, timing, approach, staged or not operation, and spinal instrumentation for patients with spondylodiscitis. Therefore, we performed this study to evaluate the outcome of a series of patients with spondylodiscitis aiming to answer when and how to operate on these patients. MATERIALS AND METHODS: We retrospectively studied the files of 153 patients with spondylodiscitis treated at our institution from 2002 to 2012. The approach included MR imaging of the infected spine, isolation of the pathogen with blood cultures and/or biopsy, and further conservative or surgical treatment. The mean follow-up was 6 years (range 1-13 years). We evaluated the indications, timing (when), and methods (how) for surgical treatment, and the clinical outcome of these patients. RESULTS: Orthopedic surgical treatment was necessary for 13 of the 153 patients (8.5 %). These were patients with low access to healthcare systems because of low socioeconomic status, third-country migrants, prisoners or intravenous drug use, patients in whom a bacterial isolate documentation was necessary, and patients with previous spinal operations. The most common pathogen was Mycobacterium tuberculosis. The surgical indications included deterioration of the neurological status (11 patients), need for bacterial isolate (10 patients), septicemia due to no response to antibiotics (five patients), and/or spinal instability (three patients). An anterior vertebral approach was more commonly used. Nine of the 13 patients had spinal instrumentation in the same setting. Improvement or recovery of the neurological status was observed postoperatively in all patients with preoperative neurological deficits. Postoperatively, two patients deceased from pulmonary infection and septicemia, and heart infarction. At the last follow-up, patients who were alive were asymptomatic; ten patients were neurologically intact, and one patient experienced paraparesis. Imaging showed spinal fusion, without evidence of recurrent spondylodiscitis. Complications related to the spinal instrumentation were not observed in the respective patients. CONCLUSIONS: Conservative treatment is the standard for spondylodiscitis. Physicians should be alert for Mycobacterium tuberculosis spondylitis because of the low access to healthcare systems of patients with low social and economic status. Surgical indications include obtaining tissue sample for diagnosis, occurrence or progression of neurological symptoms, failure of conservative treatment, large anterior abscesses, and very extensive disease. Thorough debridement of infected tissue and spinal stability is paramount. The anterior approach provides direct access and improved exposure to the most commonly affected part of the spine. Spinal instrumentation is generally recommended for optimum spinal stability and fusion, without any implant-related complications.

Impact of early valve surgery on outcome of Staphylococcus aureus prosthetic valve infective endocarditis: analysis in the International Collaboration of Endocarditis-Prospective Cohort Study.

BACKGROUND: The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis-Prospective Cohort Study. METHODS: Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. RESULTS: EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39-1.15]; P = .15). CONCLUSIONS: In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE.

Candida infective endocarditis: an observational cohort study with a focus on therapy.

Candida infective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different antifungal treatment regimens for Candida infective endocarditis. This prospective cohort study was based on 70 cases of Candida infective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high, with 36% mortality in the hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A subgroup analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this subgroup, 11 patients received amphotericin B-based therapy and 14 received echinocandin-based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality rates were similar between the two groups. In conclusion, Candida infective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as amphotericin B-based therapy in the small subgroup analysis.

Promoting prudent use of antibiotics: the experience from a multifaceted regional campaign in Greece.

BACKGROUND: Antibiotic resistance, a major public health problem, has been linked to antibiotic consumption. In Greece both consumption and resistance rates are among the highest in Europe. A multifaceted campaign targeting both physicians and parents of school children was implemented for the first time in order to educate the public and update doctors, aiming to promote judicious use of antibiotics and hopefully decrease its consumption. METHODS: The programme consisted of a public education campaign and academic detailing of primary care physicians in the district of Corinth in Peloponnese. The experience and perceptions of parents were recorded in the meetings in the form of course evaluation and assessment, anonymous questionnaires. The use of Rapid Antigen Detection Test (RADT) for streptococcal pharyngitis by primary care physicians was also assessed by use of anonymous questionnaires. Antibiotic consumption was compared before and after the programme between the district of Corinth and the other districts of Peloponnese, as well as at a national level. RESULTS: Antibiotic consumption remained unaltered at 26 Defined daily doses per 1000 Inhabitants per Day (DID) in accordance with the trend in other regions and at a national level. However, the utilization of Amoxycillin and Penicillin was increased by 34.3%, while the use of other antimicrobial classes including macrolides, cephalosporins and fluoroquinolones decreased by 6.4-21.9%. The use of RADT did not lead to a significantly decreased antimicrobial consumption. CONCLUSIONS: A multifaceted educational programme targeting both the general public and primary care physicians was associated with rationalization in the choice of antimicrobial. A reduction in the total antimicrobial consumption was not achieved.

Strontium ranelate improves delayed healing of osteolytic lesions of the jaw in a man with chronic osteomyelitis. Case report.

We report the case of a man with osteolytic lesions of the right mandible due to chronic osteomyelitis, with delayed healing after six months of antibiotic therapy. The patient received off-label therapy with strontium ranelate, with significant radiological improvement of his condition after 3 months.

Foot Osteomyelitis Caused by Multidrug- and Extensively Drug-Resistant Gram-Negative Bacteria.

There are scarce data regarding foot osteomyelitis (FO) caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB). This study investigates the causative organisms, the diagnostic and therapeutic approach and the outcome of these infections. All patients with FO caused by MDR and/or XDR GNB who received treatment in the Department of osseous infectious diseases of the "Attikon" University Hospital of Athens, Greece, were recorded and evaluated during a six-year-period. Seventeen patients, of which 64.7% females, with a mean age of 54.06 years were studied. There were nine cases with diabetic (DFO), and 76.5% of patients reported previous use of antimicrobials. Pathogens were isolated from soft-tissue biopsies or intra-operative tissue samples (n=12) and/or affected bone samples (n=5). In most cases, E. coli and P. aeruginosa were isolated (each 29.4%), followed by P. mirabilis (11.7%), while polymicrobial infection was detected in nine patients (53%). Most cases were given antimicrobial monotherapy (88.2%) with a mean duration of 90.05 days, while surgery significantly promoted cure of the infection. Foot and DFO cases represent a challenging to treat disease, requiring a multidisciplinary approach. Surgical treatment remains the cornerstone of treatment, while it is of utmost importance to isolate the causative organisms. MDR and XDR GNB represent an emerging threat and more data are needed to better understand these infections.

Intraparenchymal Lung Abscess Complicating a Primary COVID-19 Infection in a Patient with Waldenström's Macroglobulinemia: A Case Report.

Intraparenchymal lung abscess development associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a rare complication, with only half a dozen primary cases having been reported in the literature. We present the case of a patient with Waldenström's macroglobulinemia who developed a lung abscess subsequent to a primary SARS-CoV-2 infection. We present a 63-year-old male patient with SARS-CoV-2 infection and a history of Waldenström's macroglobulinemia who developed a cavitating intraparenchymal lung abscess with an air-fluid level in his right lower lobe two weeks following admission to hospital. The patient became septic and developed acute respiratory failure requiring mechanical ventilation and intensive care. He was managed with broad-spectrum antibiotic therapy and aspiration drainage, but unfortunately due to his severe clinical condition died 20 days after his initial admission. The development of a lung abscess in patients with COVID-19, although rare, can be quite compromising and even prove fatal, especially in immunocompromised patients. Clinicians should be aware of this potential complication.

Real life treatment experience and outcome of consecutively hospitalised patients with SARS-CoV-2 pneumonia by Omicron-1 vs Delta variants.

BACKGROUND: Omicron-1 COVID-19 is less invasive in the general population than previous viral variants. However, clinical course and outcome of hospitalised patients with SARS-CoV-2 pneumonia during the shift of the predominance from Delta to Omicron variants are not fully explored. METHODS: During January 2022 consecutively hospitalised patients with SARS-CoV-2 pneumonia were analysed. SARS-CoV-2 variants were identified by a 2-step pre-screening protocol and randomly confirmed by whole genome sequencing analysis. Clinical, laboratory and treatment data split by type of variant were analysed along with logistic regression of factors associated to mortality. RESULTS: 150 patients [mean age (SD) 67.2(15.8) years, male 54%] were analysed. Compared to Delta (n = 46), Omicron-1 patients (n = 104) were older [mean age (SD): 69.5(15.4) vs 61.9(15.8) years, p = 0.007], with more comorbidities (89.4% vs 65.2%, p = 0.001), less obesity (BMI >30Kg/m2 in 24% vs 43.5%, p = 0.034) but higher vaccination rates for COVID-19 (52.9% vs 8.7%, p < 0.001). Severe pneumonia (48.7%), pulmonary embolism (4.7%), need for invasive mechanical ventilation (8%), administration of dexamethasone (76%) and 60-day mortality (22.6%) did not significantly differ. Severe SARS-CoV-2 pneumonia independently predicted mortality [OR 8.297 (CI95% 2.080-33.095), p = 0.003]. Remdesivir administration (n = 135) was protective from death both in unadjusted and adjusted models [OR 0.157 (CI95% 0.026-0.945), p = 0.043. CONCLUSIONS: In a COVID-19 department the severity of pneumonia that did not differ between Omicron-1 and Delta variants predicted mortality whilst remdesivir remained protective in all analyses. Death rates did not differ between SARS-CoV-2 variants. Vigilance and consistency with prevention and treatment guidelines for COVID-19 is mandatory regardless of the predominant SARS-CoV-2 variant.

Guideline for management of septic arthritis in native joints (SANJO).

This clinical guideline is intended for use by orthopedic surgeons and physicians who care for patients with possible or documented septic arthritis of a native joint (SANJO). It includes evidence and opinion-based recommendations for the diagnosis and management of patients with SANJO.

Pan-Echinocandin Resistant C. parapsilosis Harboring an F652S Fks1 Alteration in a Patient with Prolonged Echinocandin Therapy.

The isolation of a pan-echinocandin-resistant Candida parapsilosis strain (anidulafungin, caspofungin, micafungin and rezafungin EUCAST MICs > 8 mg/L) from urine of a patient following prolonged exposure to echinocandins (38 days of micafungin followed by 16 days of anidulafungin) is described. The isolate harbored the novel alteration F652S in the hotspot 1 region of fks1. Isogenic C. parapsilosis bloodstream isolates collected up to 1.5 months earlier from the same patient were susceptible to echinocandins (anidulafungin, caspofungin and micafungin EUCAST MICs 1−2, 1 and 1 mg/L, respectively) and contained wild-type FKS1 sequences. This is the first report of pan-echinocandin resistance in C. parapsilosis associated with an aminoacid change in hotspot 1 region of fks1.

Bloodstream Infections in a COVID-19 Non-ICU Department: Microbial Epidemiology, Resistance Profiles and Comparative Analysis of Risk Factors and Patients' Outcome.

Background: Bloodstream infections (BSI) caused by highly resistant pathogens in non-ICU COVID-19 departments pose important challenges. Methods: We performed a comparative analysis of incidence and microbial epidemiology of BSI in COVID-19 vs. non-COVID-19, non-ICU departments between 1 September 2020-31 October 2021. Risk factors for BSI and its impact on outcome were evaluated by a case-control study which included COVID-19 patients with/without BSI. Results: Forty out of 1985 COVID-19 patients developed BSI. The mean monthly incidence/100 admissions was 2.015 in COVID-19 and 1.742 in non-COVID-19 departments. Enterococcus and Candida isolates predominated in the COVID-19 group (p < 0.001 and p = 0.018, respectively). All Acinetobacter baumannii isolates were carbapenem-resistant (CR). In the COVID-19 group, 33.3% of Klebsiella pneumoniae was CR, 50% of Escherichia coli produced ESBL and 19% of Enterococcus spp. were VRE vs. 74.5%, 26.1% and 8.8% in the non-COVID-19 group, respectively. BSI was associated with prior hospitalization (p = 0.003), >2 comorbidities (p < 0.001), central venous catheter (p = 0.015), severe SARS-CoV-2 pneumonia and lack of COVID-19 vaccination (p < 0.001). In the multivariate regression model also including age and multiple comorbidities, only BSI was significantly associated with adverse in-hospital outcome [OR (CI95%): 21.47 (3.86−119.21), p < 0.001]. Conclusions: BSI complicates unvaccinated patients with severe SARS-CoV-2 pneumonia and increases mortality. BSI pathogens and resistance profiles differ among COVID-19/non-COVID-19 departments, suggesting various routes of pathogen acquisition.

Osteosynthesis-associated infection of the lower limbs by multidrug-resistant and extensively drug-resistant Gram-negative bacteria: a multicentre cohort study.

Purpose: The purpose of this study was the clinical and therapeutic assessment of lower-limb osteosynthesis-associated infection (OAI) by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), which have been poorly studied to date. Methods: A prospective multicentre observational study was conducted on behalf of ESGIAI (the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group on Implant-Associated Infections). Factors associated with remission of the infection were evaluated by multivariate and Cox regression analysis for a 24-month follow-up period. Results: Patients ( n = 57 ) had a history of trauma (87.7 %), tumour resection (7 %) and other bone lesions (5.3 %). Pathogens included Escherichia coli ( n = 16 ), Pseudomonas aeruginosa ( n = 14 ; XDR 50 %), Klebsiella spp. ( n = 7 ), Enterobacter spp. ( n = 9 ), Acinetobacter spp. ( n = 5 ), Proteus mirabilis ( n = 3 ), Serratia marcescens ( n = 2 ) and Stenotrophomonas maltophilia ( n = 1 ). The prevalence of ESBL (extended-spectrum ß -lactamase), fluoroquinolone and carbapenem resistance were 71.9 %, 59.6 % and 17.5 % respectively. Most patients ( n = 37 ; 64.9 %) were treated with a combination including carbapenems ( n = 32 ) and colistin ( n = 11 ) for a mean of 63.3 d. Implant retention with debridement occurred in early OAI (66.7 %), whereas the infected device was removed in late OAI (70.4 %) ( p = 0.008 ). OAI remission was achieved in 29 cases (50.9 %). The type of surgery, antimicrobial resistance and duration of treatment did not significantly influence the outcome. Independent predictors of the failure to eradicate OAI were age > 60  years (hazard ratio, HR, of 3.875; 95 % confidence interval, CI95 %, of 1.540-9.752; p = 0.004 ) and multiple surgeries for OAI (HR of 2.822; CI95 % of 1.144-6.963; p = 0.024 ). Conclusions: Only half of the MDR/XDR GNB OAI cases treated by antimicrobials and surgery had a successful outcome. Advanced age and multiple surgeries hampered the eradication of OAI. Optimal therapeutic options remain a challenge.

Development and validation of SCOPE score: A clinical score to predict COVID-19 pneumonia progression to severe respiratory failure.

Most patients infected with SARS-CoV-2 (COVID-19) experience mild, non-specific symptoms, but many develop severe symptoms associated with an excessive inflammatory response. Elevated plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) provide early warning of progression to severe respiratory failure (SRF) or death, but access to suPAR testing may be limited. The Severe COvid Prediction Estimate (SCOPE) score, derived from circulating concentrations of C-reactive protein, D- dimers, interleukin-6, and ferritin among patients not receiving non-invasive or invasive mechanical ventilation during the SAVE-MORE study, offers predictive accuracy for progression to SRF or death within 14 days comparable to that of a suPAR concentration of ≥6 ng/mL (area under receiver operator characteristic curve 0.81 for both). The SCOPE score is validated in two similar independent cohorts. A SCOPE score of 6 or more is an alternative to suPAR for predicting progression to SRF or death within 14 days of hospital admission for pneumonia, and it can be used to guide treatment decisions.