Diagnostic cutoff values of synovial fluid biomarkers for acute postoperative prosthetic joint infection: a systematic review and meta-analysis.

Introduction: The assessment of white blood cell (WBC) count and polymorphonuclear cell (PMN) percentage in synovial fluid can help in the diagnosis of acute postoperative peri-prosthetic joint infection (PJI). Their cutoff values, which would differ from those for chronic PJI, have not yet been determined in acute postoperative PJI. The aim of this study was (1) to analyse studies reporting the optimal cutoff values for WBC count and the PMN percentage in synovial fluid and (2) to determine which is the best diagnostic tool for acute postoperative PJI. Methods: We performed a systematic review (SR) of primary studies analysing WBC count and the PMN percentage for diagnosis of acute postoperative PJI. A search was performed in MEDLINE and EMBASE. We studied the risk of bias and quality assessment. We extracted data on cutoff values, sensitivity, specificity, positive and negative predictive value, area under the curve, and accuracy. We calculated the diagnosis odds ratio (DOR), performed the meta-analysis and summarized receiver operating curves (sROCs) for WBC count and the PMN percentage. Results: We included six studies. WBC count showed a DOR of 123.61 (95 % CI: 55.38-275.88), an sROC with an area under the curve (AUC) of 0.96 (SE: 0.009) and a Q index of 0.917. The PMN percentage showed a summary DOR of 18.71 (95 % CI: 11.64-30.07), an sROC with an AUC 0.88 (SE: 0.018) and a Q index of 0.812. Conclusion: We concluded that WBC count and the PMN percentage are useful tests for the diagnosis of acute PJI; WBC is the more powerful of the two. Studies centred on other synovial fluid biomarkers not yet studied could help in this diagnosis.

Changes in Cortisol and in Oxidative/Nitrosative Stress Indicators after ADHD Treatment.

Although ADHD is one of the most prevalent diseases during childhood, we still do not know its precise origin; oxidative/nitrosative stress and the hypothalamic-pituitary-adrenal axis are suggested contributors. Methylphenidate, among others, is the main drug used in ADHD patients, but its effects on relevant markers and structures remain unclear. This study, involving 59 patients diagnosed with ADHD according to DSM-5 criteria, aimed to assess changes in cortisol levels (using cortisol awakening response, CAR) and oxidative/nitrosative status with the treatment. Blood samples before and 3 months after treatment with methylphenidate were used to measure oxidative and inflammatory markers, as well as the endogenous antioxidant activity, while saliva samples tracked cortisol awakening response (CAR). The results showed a treatment-related improvement in the redox profile, with the reduction in advanced oxidation protein products (AOPP), lipid peroxidation (LPO), and nitrite plus nitrate (NOx) levels, and the increase in the enzymatic activities of glutathione reductase (GRd) and catalase (CAT). Moreover, the area under the curve (AUC) of CAR increased significantly, indicating increased reactivity of the HPA axis. These results support, for the first time, the involvement of the endogenous antioxidant system in the pathophysiology of ADHD.

Multiplex real-time PCR FilmArray performance in the diagnosis of meningoencephalitis: lights and shadows.

PURPOSE: We aimed to evaluate the performance of the FilmArray (FA) meningitis/encephalitis (ME) panel. Secondarily, we analyzed the false positive (FP) and false negative (FN) results, as well as the predictive values of the technique, regarding the cerebrospinal fluid (CSF) characteristics. METHODS: FA is a multiplex real-time PCR detecting 14 of the most common ME pathogens in CSF. All FA performed at our hospital (2018-2022) were retrospectively reviewed. FA was compared to conventional techniques and its performance was assessed based on the final diagnosis of the episode. RESULTS: FA was performed in 313 patients with suspicion of ME. Most patients had altered mental status (65.2%) and fever (61%). Regarding CSF characteristics, 49.8% and 53.7% presented high CSF proteins and pleocytosis, respectively. There were 84 (26.8%) positive FA results, mainly for HSV-1 (10.9%), VZV (5.1%), Enterovirus (2.6%), and S. pneumoniae (1.9%). In the 136 cases where both FA and routine methods were performed, there was a 25.7% lack of agreement. We identified 6.6% FN results, but 28.6% FP, mainly due to HSV-1. This resulted in a high negative predictive value (NPV) of 93.4%, but a positive predictive value (PPV) of 73%. Remarkably, PPV as low as 36.9%, and 70.2%, were found in cases without pleocytosis, or lack of high CSF protein levels, respectively. CONCLUSION: FA was associated with high NPV, but frequent FP results and low PPV, particularly for HSV-1, and especially in patients without high CSF protein levels or pleocytosis.

Executive summary: Guidelines for the diagnosis and treatment of septic arthritis in adults and children, developed by the GEIO (SEIMC), SEIP and SECOT.

Infection of a native joint, commonly referred to as septic arthritis, is a medical emergency because of the risk of joint destruction and subsequent sequelae. Its diagnosis requires a high level of suspicion. These guidelines for the diagnosis and treatment of septic arthritis in children and adults are intended for use by any physician caring for patients with suspected or confirmed septic arthritis. They have been developed by a multidisciplinary panel with representatives from the Bone and Joint Infections Study Group (GEIO) belonging to the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Paediatric Infections (SEIP) and the Spanish Society of Orthopaedic Surgery and Traumatology (SECOT), and two rheumatologists. The recommendations are based on evidence derived from a systematic literature review and, failing that, on the opinion of the experts who prepared these guidelines. A detailed description of the background, methods, summary of evidence, the rationale supporting each recommendation, and gaps in knowledge can be found online in the complete document.

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 .

Cefto Real-Life Study: Real-World Data on the Use of Ceftobiprole in a Multicenter Spanish Cohort.

BACKGROUND: Ceftobiprole is a fifth-generation cephalosporin that has been approved in Europe solely for the treatment of community-acquired and nosocomial pneumonia. The objective was to analyze the use of ceftobiprole medocaril (Cefto-M) in Spanish clinical practice in patients with infections in hospital or outpatient parenteral antimicrobial therapy (OPAT). METHODS: This retrospective, observational, multicenter study included patients treated from 1 September 2021 to 31 December 2022. RESULTS: A total of 249 individuals were enrolled, aged 66.6 ± 15.4 years, of whom 59.4% were male with a Charlson index of four (IQR 2-6), 13.7% had COVID-19, and 4.8% were in an intensive care unit (ICU). The most frequent type of infection was respiratory (55.8%), followed by skin and soft tissue infection (21.7%). Cefto-M was administered to 67.9% of the patients as an empirical treatment, in which was administered as monotherapy for 7 days (5-10) in 53.8% of cases. The infection-related mortality was 11.2%. The highest mortality rates were identified for ventilator-associated pneumonia (40%) and infections due to methicillin-resistant Staphylococus aureus (20.8%) and Pseudomonas aeruginosa (16.1%). The mortality-related factors were age (OR: 1.1, 95%CI (1.04-1.16)), ICU admission (OR: 42.02, 95%CI (4.49-393.4)), and sepsis/septic shock (OR: 2.94, 95%CI (1.01-8.54)). CONCLUSIONS: In real life, Cefto-M is a safe antibiotic, comprising only half of prescriptions for respiratory infections, that is mainly administered as rescue therapy in pluripathological patients with severe infectious diseases.

Increasing of New CA-MRSA Infections Detected in people living with HIV Who Engage in Chemsex in Barcelona: An Ambispective Study.

INTRODUCTION: There are no data on community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in the context of the chemsex phenomenon. This study aimed to characterize CA-MRSA-related infections in a cohort of people living with HIV (PLWH) who engage in chemsex. METHODS: At the Hospital Clinic of Barcelona, from February 2018 to January 2022, we analyzed CA-MRSA infections diagnosed in a cohort of PLWH who engage in chemsex. Epidemiological, behavioral and clinical variables were assessed. Mass spectrometry identification and antimicrobial susceptibility testing were performed on MRSA isolates. Pulse field electrophoresis was used to assess the clonality of the MRSA strains. The presence of Panton-Valentine leukocidin was also investigated. RESULTS: Among the cohort of 299 participants who engage in chemsex, 25 (8%) with CA-MRSA infections were identified, 9 at baseline and 16 with incident cases; the cumulative incidence was 5.5% (95% CI: 3.2%, 8.8%). The most common drugs were methamphetamine (96%) and GHB/GBL (92%). Poly-consumption and slamming were reported by 32% and 46%, respectively. CA-MRSA was isolated from the infection sites of 20 participants, and CA-MRSA colonization was confirmed in the remaining 5 persons. Seventy-one percent had used antibiotics in the previous year. All participants presented with skin and soft tissue infections, 28% required hospitalization, and 48% had recurrence. Of the 23 MRSA isolates further studied, 19 (82,6%) belonged to the same clone. Panton-Valentine leukocidin was detected in all isolates. CONCLUSION: PLWH who engage in chemsex may present with CA-MRSA infections. Clinical suspicion and microbiological diagnosis are required to provide adequate therapy, and CA-MRSA prevention interventions should be designed.

Information Delay of Significant Bloodstream Isolates and Patient Mortality: A Retrospective Analysis of 6225 Adult Patients With Bloodstream Infections.

BACKGROUND: Our aim in this study was to evaluate the clinical and prognostic impact of communicating microbiological information in real time for adult patients with bloodstream infections (BSIs). METHODS: We retrospectively reviewed 6225 clinical episodes of bacteremia in a teaching hospital from January 2013 to December 2019. Bacteremia-associated mortality was compared when blood culture results were relayed to the infectious diseases specialist (IDS) in real time and periods when results were relayed the following morning. The impact of information availability using mortality at 30 days was used as the main outcome of the study. RESULTS: The initial analysis (all microorganisms included) did not show an association of mortality and information delay to the IDS (odds ratio [OR], 1.18; 95% confidence interval [CI], .99-1.42). However, information delay of BSIs caused by fast-growing microorganisms such as Enterobacterales was associated with a significant increase in the odds of death at 30 days both in the univariate (OR, 1.76; 95% CI, 1.30-2.38) and multivariate analysis (OR, 2.22; 95% CI, 1.50-3.30). Similar results were found with mortality at 14 days and 7 days in the univariate (OR, 1.54; 95% CI, 1.08-2.20 and OR, 1.56; 95% CI, 1.03-2.37, respectively) and the multivariate analysis (OR, 2.05; 95% CI, 1.27-3.32 and OR, 1.92; 95% CI, 1.09-3.40, respectively). CONCLUSIONS: Information delivered in real time has prognostic relevance and is likely to improve survival of patients with documented BSIs. Future studies should address the prognostic impact of adequate resource allocation (microbiologist/IDS with 24/7 coverage) in BSIs.

Antimicrobials in polymethylmethacrylate: from prevention to prosthetic joint infection treatment: basic principles and risk of resistance.

BACKGROUND: Excellent revisions about antibiotic-loaded bone cement (ALBC) have been recently published. In the present article, we review the principles and limitations of local antibiotic delivery in the context of recent advances in the pathogenesis of prosthetic joint infections (PJI), with particular attention paid to the potential association between ALBC and antimicrobial resistance. MAIN BODY: Recalcitrance of PJI is related to the ability of pathogens to adapt to particular environments present in bone tissue and protect themselves from host immunity in different ways. Accordingly, delivery of high local antimicrobial concentrations using ALBC is needed. Most relevant clinical data showing the efficacy of ALBC for PJI prophylaxis and treatment are reviewed, and we dissected the limitations on the basis of the recent findings from animal models and suggested that aminoglycosides, in particular, could not be the best option. One of the major concerns associated with ALBC is the emergence of resistance because of theoretical prolonged exposure to low antibiotic concentrations. We summarize the mechanisms for the selection of resistant microorganisms, and we critically reviewed the evidence from animal models and clinical data from observational and registry studies and concluded that there is no evidence to support this association. CONCLUSION: While waiting for better evidence from well-designed clinical trials, ALBC shows a beneficial effect as a prophylaxis in arthroplasty, and to avoid the colonization of spacers used for two-stage revision in patients with PJI. Experimental models and clinical evidence suggest the need to achieve high local antimicrobial concentrations to obtain the highest prophylactic and therapeutic effect. The current evidence does not support the risk of increasing resistance with use of ALBC. In the future, it is necessary to evaluate new carriers and different antimicrobials to improve clinical outcomes.

Pseudomonas aeruginosa Bloodstream Infection, Resistance, and Mortality: Do Solid Organ Transplant Recipients Do Better or Worse?

BACKGROUND: The prevalence of antimicrobial resistance of Pseudomonas aeruginosa (P. aeruginosa) in solid organ transplant (SOT) recipients is higher than that of the general population. However, the literature supporting this statement is scarce. Identifying patients at risk of carbapenem resistance (CR) is of great importance, as CR strains more often receive inappropriate empiric antibiotic therapy, which is independently associated with mortality in bloodstream infections (BSIs). METHODS: We prospectively recorded data from all consecutive BSIs from January 1991 to July 2019 using a routine purpose-designed surveillance database. The following variables were included: age, sex, type of transplant, use of vascular and urinary catheters, presence of neutropenia, period of diagnosis, treatment with steroids, origin of BSI, source of bacteremia, septic shock, ICU admission, mechanical ventilation, previous antibiotic treatment, treatment of bacteremia, and 30-day all-cause mortality. RESULTS: We identified 2057 episodes of P. aeruginosa BSI. Of these, 265 (13%) episodes corresponded to SOT recipients (130 kidney transplants, 105 liver, 9 hearts, and 21 kidney-pancreas). Hematologic malignancy [OR 2.71 (95% CI 1.33-5.51), p = 0.006] and prior carbapenem therapy [OR 2.37 (95% CI 1.46-3.86), p < 0.001] were associated with a higher risk of having a CR P. aeruginosa BSI. Age [OR 1.03 (95% CI 1.02-1.04) p < 0.001], urinary catheter [OR 2.05 (95% CI 0.37-3.06), p < 0.001], shock at onset [OR 6.57 (95% CI 4.54-9.51) p < 0.001], high-risk source [OR 4.96 (95% CI 3.32-7.43) p < 0.001], and bacteremia caused by CR strains [OR 1.53 (95% CI 1.01-2.29) p = 0.036] were associated with increased mortality. Correct empirical therapy was protective [OR 0.52 (95% CI 0.35-0.75) p = 0.001]. Mortality at 30 days was higher in non-SOT patients (21% vs. 13%, p = 0.002). SOT was not associated with a higher risk of having a CR P. aeruginosa BSI or higher mortality. CONCLUSIONS: In our cohort of 2057 patients with P. aeruginosa BSIs, hematologic malignancies and previous carbapenem therapy were independently associated with a risk of presenting CR P. aeruginosa BSI. Age, urinary catheter, high-risk source, bacteremia caused by carbapenem-resistant strains, and severity of the infection were independently associated with mortality, whereas correct empirical therapy was a protective factor. An increasing trend in the resistance of P. aeruginosa was found, with >30% of the isolates being resistant to carbapenems in the last period. SOT was not associated with a higher risk of carbapenem-resistant BSIs or higher mortality.

Qualitative Subgenomic RNA to Monitor the Response to Remdesivir in Hospitalized Patients With Coronavirus Disease 2019: Impact on the Length of Hospital Stay and Mortality.

BACKGROUND: There is no reliable microbiological marker to guide the indication and the response to antiviral treatment in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the dynamics of subgenomic RNA (sgRNA) in patients with COVID-19 before and after receiving treatment with remdesivir. METHODS: We included consecutive patients admitted for COVID-19 who received remdesivir according to our institutional protocol and accepted to participate in the study. A nasopharyngeal swab for quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was collected at baseline and after 3 and 5 days of treatment with remdesivir. Genomic and sgRNA were analyzed in those samples and main comorbidities and evolution were collected for the analyses. The main outcomes were early discharge (≤10 days) and 30-day mortality. RESULTS: A total of 117 patients were included in the study, of whom 24 had a negative sgRNA at baseline, with 62.5% (15/24) receiving early discharge (≤10 days) and no deaths in this group. From the 93 remaining patients, 62 had a negative sgRNA at day 5 with 37/62 (59.6%) with early discharge and a mortality rate of 4.8% (3/62). In the subgroup of 31 patients with positive sgRNA after 5 days of remdesivir, the early discharge rate was 29% (9/31) and the mortality rate was 16.1% (5/31). In multivariable analyses, the variables associated with early discharge were negative sgRNA at day 3 and not needing treatment with corticosteroids or intensive care unit admission. CONCLUSIONS: Qualitative sgRNA could help in monitoring the virological response in patients who receive remdesivir. Further studies are needed to confirm these findings.

Do Cultures Obtained During Primary THA Predict the Likelihood of Revision?

BACKGROUND: There can be unexpectedly positive culture results during elective hip arthroplasty, but the degree to which these are associated with an increased risk of subsequent premature revision is not known. QUESTION/PURPOSE: Are unexpectedly positive culture results obtained during elective THA associated with an increased likelihood of revision within 5 years of the procedure? METHODS: Between March 2007 and March 2011, the hip unit at our institution performed elective primary THA in 829 patients. We systematically collected three samples in 52% (428 of 829) of the interventions. Of those, 26 patients were excluded because of sampling errors; 94% (402 of 428) had samples that were collected systematically and were eligible for the study. We only considered one hip randomly in bilateral procedures (4% [15 of 428]); patients presenting with acute (< 3 months) periprosthetic joint infection undergoing open debridement (4% [16 of 402]) and patients who died before 5 years of follow-up (2% [seven of 402]) were excluded from the study, leaving 91% (364 of 402) eligible for analysis in this retrospective study of a previous prospective trial. No patient included in the final analysis was lost to follow-up within 5 years from the index surgery. The patient group consisted of 52% (188 of 364) women, with a mean ± SD age of 64.8 ± 13.9 years. RESULTS: Positives culture results were associated with a higher risk of revision within 5 years of the index surgery. The proportion of revision surgery was higher in the group with positive culture results than in those with negative results (10% [eight of 77] versus 2% [seven of 290]; p = 0.01). The difference was mainly attributable to a higher proportion of aseptic loosening in those with positive culture results than in those with negative results (8% [six of 74] versus 1% [four of 290]; p = 0.01). After a multivariable analysis, the only independent variable associated with 5-year revision surgery was the presence of positive results during THA (odds ratio 4.9 [95% confidence interval 1.72 to 13.99]). CONCLUSION: Our findings suggest that bacterial contamination during THA is associated with an increased likelihood of early revision. This higher risk of revision is mainly because of presumed aseptic loosening; thus, efforts should focus on the need to rule out infection. These results not only open new questions that should be answered in new prospective and well-designed studies, but also may help to better select patients to obtain a more favorable outcome after THA. LEVEL OF EVIDENCE: Level III, therapeutic study.

Impact of adherence to individual quality-of-care indicators on the prognosis of bloodstream infection due to Staphylococcus aureus: a prospective observational multicentre cohort.

OBJECTIVES: To analyse the adherence and impact of quality-of-care indicators (QCIs) in the management of Staphylococcus aureus bloodstream infection in a prospective and multicentre cohort. METHODS: Analysis of the prospective, multicentre international S. Aureus Collaboration cohort of S. Aureus bloodstream infection cases observed between January 2013 and April 2015. Multivariable analysis was performed to evaluate the impact of adherence to QCIs on 90-day mortality. RESULTS: A total of 1784 cases were included. Overall, 90-day mortality was 29.9% and mean follow-up period was 118 days. Adherence was 67% (n = 1180/1762) for follow-up blood cultures, 31% (n = 416/1342) for early focus control, 77.6% (n = 546/704) for performance of echocardiography, 75.5% (n = 1348/1784) for adequacy of targeted antimicrobial therapy, 88.6% (n = 851/960) for adequacy of treatment duration in non-complicated bloodstream infections and 61.2% (n = 366/598) in complicated bloodstream infections. Full bundle adherence was 18.4% (n = 328/1784). After controlling for immortal time bias and potential confounders, focus control (adjusted hazard ratio = 0.76; 95% CI, 0.59-0.99; p 0.038) and adequate targeted antimicrobial therapy (adjusted hazard ratio = 0.75; 95% CI, 0.61-0.91; p 0.004) were associated with low 90-day mortality. DISCUSSION: Adherence to QCIs in S. Aureus bloodstream infection did not reach expected rates. Apart from the benefits of application as a bundle, focus control and adequate targeted therapy were independently associated with low mortality.

Dalbavancin in clinical practice in Spain: a 2†year retrospective study.

Objectives: Dalbavancin is approved for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) in adults. Its unique pharmacokinetic properties allow daily dosing to be avoided. The objective was to describe the sociodemographic and clinical characteristics of patients treated with dalbavancin in Spain, and to evaluate its effectiveness and safety in real-world settings. Patients and methods: This non-interventional, retrospective, observational and multicentre study included patients who received at least one dose between 2018 and 2019 in seven Spanish hospitals. Results: In total, 187 patients were included. The most common comorbidities were cardiovascular disease (27.4%) and diabetes mellitus (23.5%). Dalbavancin was used to treat osteoarticular infections (28.3%), ABSSSIs (22.5%), cardiovascular infections (20.9%) and catheter-related infections (18.2%). The most prevalent pathogens were Staphylococcus aureus (34.2%), CoNS (32.6%), and enterococci (12.8%). The main reason for use was early hospital discharge (65.8%). Most patients were treated with 1500 mg in a single dose (35.3%) and the median duration of treatment was 2 weeks. The treatment was clinically successful in 91.4% of cases. Six patients (3.2%) reported adverse events. Physicians agreed on the potential reduction of hospitalization days (85.3%). A subanalysis of patient characteristics and type of pathogen showed similar results in terms of efficacy and safety. Conclusions: Dalbavancin seems to be effective and safe as second-line treatment in severe Gram-positive infections. It improves treatment adherence and allows outpatient management. Furthermore, the effectiveness and safety profile are maintained against diverse microorganisms in Gram-positive infections and regardless of the patients' comorbidities at baseline, or age.

Clinical usefulness of quantifying microbial load from diabetic foot ulcers: A multicenter cohort study.

AIMS: To evaluate if microbial load from diabetic foot ulcers (DFUs) can help in predicting outcomes. METHODS: A multicenter prospective cohort study was performed in an outpatient setting (September 1, 2017-January 31, 2019) in diabetic patients with DFU.Quantitative cultures from DFU tissue biopsies at a baseline visit were obtained; high and low microbial loads were defined as ≥6logCFU/mL and <6logCFU/mL, respectively. Diagnosis of DFU infection was made and managed according to established guidelines. The outcome was evaluated at 6 month-visit as failure (persistence/new infection/amputation) or cure. RESULTS: Out of 65 patients, 52 (80%) had long-standing DFUs (≥4 weeks), with high microbial load in 19 (29%).DFU infection (n = 24, 37%) was not associated with high microbial load in all patients but those with shorter DFU duration.Treatment failure occurred in 20/57 (35%) patients; high DFU microbial load was associated with worse outcome (n = 9/20, 45% failure rate, adjusted OR4.69; 95% CI, 1.22-18.09; p = 0.03),mainly due to the subgroup of patients with high microbial load and long-stand DFUs. CONCLUSIONS: Since patients with high microbial load had a worse outcome, quantitative cultures from DFUs can identify patients who would benefit from antibiotic therapy.

Impact of SARS-CoV-2 viral load and duration of symptoms before hospital admission on the mortality of hospitalized COVID-19 patients.

PURPOSE: Assess the impact of viral load estimated by cycle threshold (Ct) of reverse transcription real time-polymerase chain reaction (rRT-PCR) and the days from symptoms onset on mortality in hospitalized patients with COVID19. METHODS: Retrospective observational study of 782 patients with a positive rRT-PCR from a nasopharyngeal swab was performed within the first 24 h from admission. Demographic data, clinical manifestations and laboratory parameters were collected. Uni- and multivariate analyses were performed to identify factors associated with mortality at 60 days. RESULTS: Ct was divided into three groups and the mortality rate decreased from 27.3 to 20.7% and 9.8% for Ct values of ≤ 20, 21-25 and > 25, respectively (P = 0.0001). The multivariate analysis identified as predictors of mortality, a Ct value < 20 (OR 3.13, CI 95% 1.38-7.10), between 21-25 (OR 2.47, CI 95% 1.32-4.64) with respect to a Ct value > 25. Days from symptoms onset is a variable associated with mortality as well (DSOA) ≤ 6 (OR 1.86, CI 95% 1.00-3.46), among other factors. Patients requiring hospital admission within 6 DSOA with a Ct value ≤ 25 had the highest mortality rate (28%). CONCLUSIONS: The inclusion of Ct values and DSOA in the characterization of study populations could be a useful tool to evaluate the efficacy of antivirals.

Clinical Presentation and Outcome of COVID-19 in a Latin American Versus Spanish Population: Matched Case-Control Study.

INTRODUCTION: Increased mortality has been reported in the Latin American population. The objective is to compare the clinical characteristics and outcome of Latin American and Spanish populations in a cohort of patients hospitalized with COVID-19 during the first year of the pandemic. METHODS: We retrospectively analysed all the Latin American patients (born in South or Central America) hospitalized in our centre from February 2020 to February 2021 and compared them with an age- and gender-matched group of Spanish subjects. Variables included were demographics, co-morbidities, clinical and analytical parameters at admission and treatment received. The primary outcomes were ICU admission and mortality at 60 days. A conditional regression analysis was performed to evaluate the independent baseline predictors of both outcomes. RESULTS: From the 3216 patients in the whole cohort, 216 pairs of case-controls (Latin American and Spanish patients, respectively) with same age and gender were analysed. COPD was more frequent in the Spanish group, while HIV was more prevalent in the Latin American group. Other co-morbidities showed no significant difference. Both groups presented with similar numbers of days from symptom onset, but the Latin American population had a higher respiratory rate (21 vs. 20 bpm, P = 0.041), CRP (9.13 vs. 6.22 mg/dl, P = 0.001), ferritin (571 vs. 383 ng/ml, P = 0.012) and procalcitonin (0.10 vs. 0.07 ng/ml, P = 0.020) at admission and lower cycle threshold of PCR (27 vs. 28.8, P = 0.045). While ICU admission and IVM were higher in the Latin American group (17.1% vs. 13% and 9.7% vs. 5.1%, respectively), this was not statistically significant. Latin American patients received remdesivir and anti-inflammatory therapies more often, and no difference in the 60-day mortality rate was found (3.2% for both groups). CONCLUSION: Latin American patients with COVID-19 have more severe disease than Spanish patients, requiring ICU admission, antiviral and anti-inflammatory therapies more frequently. However, the mortality rate was similar in both groups.

Impact of neutropenia on clinical manifestations and outcome of Staphylococcus aureus bloodstream infection: a propensity score-based overlap weight analysis in two large, prospectively evaluated cohorts.

OBJECTIVES: This study aimed to investigate whether neutropenia influenced mortality and long-term outcomes of Staphylococcus aureus bloodstream (SAB) infection. METHODS: Data from two prospective, multicentre cohort studies (INSTINCT and ISAC) conducted at 20 tertiary care hospitals in six countries between 2006 and 2015 were analyzed. Neutropenic and severely neutropenic patients (defined by proxy of total white blood cell count <1000/µl and <500/µl, respectively, at onset of SAB infection) were compared with a control group using a propensity score model and overlapping weights to adjust for baseline characteristics. Overall survival and time to SAB infection-related late complications (SAB infection recurrence, infective endocarditis, osteomyelitis, or other deep-seated manifestations) were analyzed with Cox regression and competing risk analyses, respectively. RESULTS: Of the 3187 included patients, 102 were neutropenic and 70 severely neutropenic at the time of SAB infection onset. Applying overlap weights yielded two groups of 83 neutropenic and 220 nonneutropenic patients, respectively. The baseline characteristics of these groups were exactly balanced. In the Cox regression analysis, we observed no significant difference in survival between the two groups (death during follow up: 36.1% in neutropenic vs. 30.6% in nonneutropenic patients; hazard ratio (HR): 1.21; 95% CI, 0.79-1.83). This finding remained unchanged when we considered severely neutropenic patients (HR: 1.08; 95% CI, 0.60-1.94). A competing risk analysis showed a cause-specific HR of 0.39 (95% CI, 0.11-1.39) for SAB infection-related late complications in neutropenic patients. DISCUSSION: Neutropenia was not associated with a higher survival rate during follow up. The lower rate of SAB infection-related late complications in neutropenic patients should be validated in other cohorts.

C-reactive protein cut-off for early tocilizumab and dexamethasone prescription in hospitalized patients with COVID-19.

Dexamethasone and tocilizumab have been associated with reduction in mortality, however, the beneficial effect is not for all patients and the impact on viral replication is not well defined. We hypostatized that C-reactive protein (CRP) could help in the identification of patients requiring anti-inflammatory therapy. Patients admitted for > 48 h in our hospital for a confirmed or suspected infection by SARS-CoV-2 from February 2020 to February 2021 were retrospectively evaluated. The primary outcome was mortality at 30 days. Demographics and the most relevant variables related with the outcome were included. CRP was stratified by percentiles. Univariate and multivariate analysis were performed. A total of 3218 patients were included with a median (IQR) age of 66 (74-78) years and 58.9% were males. The rate of intensive care unit admission was 24.4% and the 30-day mortality rate was 11.8%. Within the first 5 days from admission, 1018 (31.7%) patients received dexamethasone and 549 tocilizumab (17.1%). The crude analysis showed a mortality reduction in patients receiving dexamethasone when CRP was > 13.75 mg/dL and > 3.5 mg/dL for those receiving tocilizumab. Multivariate analysis identified the interaction of CRP > 13.75 mg/dL with dexamethasone (OR 0.57; CI 95% 0.37-0.89, P = 0014) and CRP > 3.5 mg/dL with tocilizumab (0.65; CI95%:0.44-0.95, P = 0.029) as independent predictors of mortality. Our results suggest that dexamethasone and tocilizumab are associated with a reduction in mortality when prescribed to patients with a certain inflammatory activity assessed by C-reactive protein.

Bacterial co-infection at hospital admission in patients with COVID-19.

OBJECTIVES: We described the current incidence and risk factors of bacterial co-infection in hospitalized patients with COVID-19. METHODS: Observational cohort study was performed at the Hospital Clinic of Barcelona (February 2020-February 2021). All patients with COVID-19 who were admitted for >48 hours with microbiological sample collection and procalcitonin (PCT) determination within the first 48 hours were included. RESULTS: A total of 1125 consecutive adults met inclusion criteria. Co-infections were microbiologically documented in 102 (9.1%) patients. Most frequent microorganisms were Streptococcus pneumoniae (79%), Staphylococcus aureus (6.8%), and Haemophilus influenzae (6.8%). Test positivity was 1% (8/803) for blood cultures, 10.1% (79/780) for pneumococcal urinary antigen test, and 11.4% (15/132) for sputum culture. Patients with PCT higher than 0.2, 0.5, 1, and 2 ng/mL had significantly more co-infections than those with lower levels (p=0.017, p=0.031, p<0.001, and p<0.001, respectively). In multivariate analysis, oxygen saturation ≤94% (OR 2.47, CI 1.57-3.86), ferritin levels <338 ng/mL (OR 2.63, CI 1.69-4.07), and PCT higher than 0.2 ng/mL (OR 1.74, CI 1.11-2.72) were independent risk factors for co-infection at hospital admission owing to COVID-19. CONCLUSIONS: Bacterial co-infection in patients hospitalized for COVID-19 is relatively common. However, clinicians could spare antibiotics in patients with PCT values <0.2, especially with high ferritin values and oxygen saturation >94%.