Executive summary: Guidelines for the diagnosis and treatment of septic arthritis in adults and children, developed by the GEIO (SEIMC), SEIP and SECOT / Resumen ejecutivo: Guía de diagnóstico y tratamiento de la artritis séptica en adultos y niños de GEIO (SEIMC), SEIP y 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.(AU)

La infección de una articulación nativa, generalmente denominada artritis séptica, constituye una urgencia médica por el riesgo de destrucción articular y las consecuentes secuelas. Su diagnóstico requiere un alto nivel de sospecha. Esta guía de diagnóstico y tratamiento de la artritis séptica en niños y adultos está destinada a cualquier médico que atienda pacientes con sospecha de artritis séptica o artritis séptica confirmada. La guía ha sido elaborada por un panel multidisciplinar en el que están representados el Grupo de Estudio de Infecciones Osteoarticulares (GEIO) de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC), la Sociedad Española de Infectología Pediátrica (SEIP) y la Sociedad Española de Cirugía Ortopédica y Traumatología (SECOT); además han participado dos reumatólogos. Las recomendaciones se basan en la evidencia proporcionada por una revisión sistemática de la literatura y, en su defecto, en la opinión de los expertos que han elaborado la presente guía. En el texto completo online se hace una descripción detallada de los antecedentes, métodos, resumen de la evidencia, fundamentos que apoyan cada recomendación y las lagunas de conocimiento existentes.(AU)

What Is the Most Effective Treatment for Periprosthetic Joint Infection After Total Joint Arthroplasty in Patients with Rheumatoid Arthritis?: A Systematic Review.

BACKGROUND: Rheumatoid arthritis (RA) is a risk factor for periprosthetic joint infection (PJI) after total joint arthroplasty (TJA). The purpose of this study was to perform a systematic review comparing the failure rates of debridement, antibiotics, and implant retention (DAIR), one-stage exchange arthroplasty/revision (OSR), and 2-stage exchange arthroplasty/revision (TSR) for RA patients with PJI and identify risk factors in the RA population associated with increased treatment failure rate. METHODS: PubMed, Ovid MEDLINE, and Ovid Embase databases were screened with the terms "rheumatoid arthritis," "total joint arthroplasty," "prosthetic joint infection," and "treatment for PJI" on August 29, 2021. Four hundred ninety-one studies were screened, of which 86 were evaluated. The primary outcome evaluated was failure of surgical treatment for PJI. RESULTS: Ten retrospective cohort studies were included after full-text screening, yielding 401 patients with RA. Additional demographic and PJI management data were obtained for 149 patients. Patients with RA who underwent TSR demonstrated a lower failure rate (26.8%) than both DAIR (60.1%) and OSR (39.2%) (χ2 = 37.463, p < 0.00001). Patients with RA who underwent DAIR had a 2.27 (95% CI, 1.66-3.10) times higher risk of experiencing treatment failure than those who underwent TSR. Among risk factors, there was a significant difference in the C-reactive protein of patients who did vs. did not experience treatment failure (p = 0.02). CONCLUSION: TSR has a higher rate of success in the management of PJI patients with RA compared with DAIR and OSR. The complete removal of the infected prosthesis and delayed reimplantation may lower the treatment failure rate. LEVEL OF EVIDENCE: Level III. See Instructions for Authors for a complete description of levels of evidence.

Impact of a Hospitalist Co-Management Program on Medical Complications and Length of Stay in Neurosurgical Patients.

BACKGROUND: The impact of co-management on clinical outcomes in neurosurgical patients is uncertain. This study aims to describe the implementation of a hospitalist co-management program in a neurosurgery department and its impact on the incidence of complications, mortality, and length of stay. METHODS: The authors used a quasi-experimental study design that compared a historical control period (July-December 2017) to a prospective intervention arm. During the intervention period, patients admitted to a neurosurgery inpatient unit who were older than 65 years, suffered certain conditions, or were admitted from ICUs were included in the co-management program. Two hospitalists joined the surgical staff and intervened in the diagnostic and therapeutical plan of patients, participating in clinical decisions and coordinating patient navigation with neurosurgeons. The incidence of moderate or severe complications measured by the Accordion Severity Grading System, in-hospital mortality, and length of stay of the two cohorts were compared. Multivariate regression was used to adjust for confounders, and the average treatment effect was estimated using inverse probability of treatment weighting. RESULTS: The adjusted incidence of moderate or severe complications was lower among co-managed patients (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.39-0.91). Mortality was unchanged (OR 0.83, 95% CI 0.15-4.17). Length of stay was lower in co-managed patients, with a 1.3-day reduction observed after inverse probability of treatment weighting analysis. CONCLUSION: Hospitalist co-management was associated with a reduced incidence of complications and length of stay in neurosurgical patients, but there was no difference in in-hospital mortality.

Superior neutralizing response after first versus second SARS-CoV-2 infection in fully vaccinated individuals.

Currently, the majority of the population has been vaccinated against COVID-19 and/or has experienced SARS-CoV-2 infection either before or after vaccination. The immunological response to repeated episodes of infections is not completely clear. We measured SARS-CoV-2 specific neutralization titers by a pseudovirus assay after BA.1 infection and RBD-specific immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) in a cohort of COVID-19 uninfected and triple vaccinated individuals (breakthrough infection group, BTI) as compared with those previously infected by SARS-CoV-2 (reinfection group, REI) who underwent identical vaccination schedule. SARS-CoV-2 specific neutralizing response after BA.1 infection was significantly higher in the BTI group as compared with the REI. Furthermore, neutralization titers in REI were not significant different from convalescent non reinfected controls. RBD-specific IgG and IgA, but not IgM, were also significantly higher in BTI as compared with REI. Our results show that the first episode of SARS-CoV-2 infection induces a significant increase in neutralizing titers in triple vaccinated individuals and that previous SARS-CoV-2 infection compromise significantly the neutralization response induced by reinfection, even by divergent SARS-CoV-2 variants and at least up to 2 years postinfection, suggesting a fundamental limitation in inducing effective booster through the intranasal route in previously infected individuals.

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.

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.

Early switch from intravenous to oral antibiotic treatment in bone and joint infections.

OBJECTIVES: The timing of the switch from intravenous (i.v.) to oral antibiotic therapy for orthopaedic bone and joint infections (BJIs) is debated. In this narrative article, we discuss the evidence for and against an early switch in BJIs. DATA SOURCES: We performed a PubMed and internet search investigating the association between the duration of i.v. treatment for BJI and remission of infection among adult orthopaedic patients. CONTENT: Among eight randomized controlled trials and multiple retrospective studies, we failed to find any minimal duration of postsurgical i.v. therapy associated with clinical outcomes. We did not find scientific data to support the prolonged use of i.v. therapy or to inform a minimal duration of i.v. THERAPY: Growing evidence supports the safety of an early switch to oral medications once the patient is clinically stable. IMPLICATIONS: After surgery for BJI, a switch to oral antibiotics within a few days is reasonable in most cases. We recommend making the decision on the time point based on clinical criteria and in an interdisciplinary team at the bedside.

Randomized Clinical Trial of the Need for Antibiotic Treatment for Low-Risk Catheter-Related Bloodstream Infection Caused by Coagulase-Negative Staphylococci.

According to clinical guidelines, the management of catheter-related bloodstream infections (CRBSI) due to coagulase-negative staphylococci (CoNS) includes catheter removal and antibiotic treatment for 5 to 7 days. However, in low-risk episodes, it remains uncertain whether antibiotic therapy is necessary. This randomized clinical trial aims to determine whether the non-administration of antibiotic therapy is as safe and effective as the recommended strategy in low-risk episodes of CRBSI caused by CoNS. With this purpose, a randomized, open-label, multicenter, non-inferiority clinical trial was conducted in 14 Spanish hospitals from 1 July 2019 to 31 January 2022. Patients with low-risk CRBSI caused by CoNS were randomized 1:1 after catheter withdrawal to receive/not receive parenteral antibiotics with activity against the isolated strain. The primary endpoint was the presence of any complication related to bacteremia or to antibiotic therapy within 90 days of follow-up. The secondary endpoints were persistent bacteremia, septic embolism, time until microbiological cure, and time until the disappearance of a fever. EudraCT: 2017-003612-39 INF-BACT-2017. A total of 741 patients were assessed for eligibility. Of these, 27 were included in the study; 15 (55.6%) were randomized to the intervention arm (non-antibiotic administration) and 12 (44.4%) to the control arm (antibiotic therapy as per standard practice). The primary endpoint occurred in one of the 15 patients in the intervention group (septic thrombophlebitis) and in no patients in the control group. The median time until microbiological cure was 3 days (IQR 1-3) in the intervention arm and 1.25 days (IQR 0.5-2.62) in the control arm, while the median time until fever resolution was zero days in both arms. The study was stopped due to the insufficient number of recruited patients. These results seem to indicate that low-risk CRBSI caused by CoNS can be managed without antibiotic therapy after catheter removal; efficacy and safety are not affected.

Antimicrobial resistance in Gram-negative bacilli in Spain: an experts’ view / Resistencia a antimicrobianos en bacilos gramnegativos en España: una visión de expertos

Background: Antibiotic resistance in Gram-negative bacilli poses a serious problem for public health. In hospitals, in addition to high mortality rates, the emergence and spread of resistance to practically all antibiotics restricts therapeutic options against serious and frequent infections. Objectives: The aim of this work is to present the views of a group of experts on the following aspects regarding resistance to antimicrobial agents in Gram-negative bacilli: 1) the current epidemiology in Spain, 2) how it is related to local clinical practice and 3) new therapies in this area, based on currently available evidence. Methodology: After reviewing the most noteworthy evidence, the most relevant data on these three aspects were presented at a national meeting to 99 experts in infectious diseases, clinical microbiology, internal medicine, intensive care medicine, anaesthesiology and hospital pharmacy. Results and conclusions: Subsequent local debates among these experts led to conclusions in this matter, including the opinion that the approval of new antibiotics makes it necessary to train the specialists involved in order to optimise how they use them and improve health outcomes; microbiology laboratories in hospitals must be available throughout a continuous timetable; all antibiotics must be available when needed and it is necessary to learn to use them correctly; and the Antimicrobial Stewardship Programs (ASP) play a key role in quickly allocating the new antibiotics within the guidelines and ensure appropriate use of them. (AU)

Contexto: La resistencia a los antibióticos en bacilos gramnegativos representa un grave problema de salud pública. En el hospital, además de unas elevadas tasas de mortalidad, la aparición y propagación de resistencias a la práctica totalidad de los antibióticos limita las opciones terapéuticas frente a infecciones graves y frecuentes. Objetivos: Este trabajo tiene por objetivo dar a conocer la visión de un grupo de expertos en los siguientes aspectos respecto a la resistencia a agentes antimicrobianos en bacilos gramnegativos: 1) la epidemiología actual en España, 2) su relación con la práctica clínica local y 3) las novedades terapéuticas en este ámbito, fundamentada en la evidencia actualmente disponible. Metodología: Tras la revisión de la evidencia más destacada, los datos más relevantes de estos 3 aspectos fueron presentados en una reunión nacional ante 99 expertos en enfermedades infecciosas, microbiología clínica, medicina interna, medicina intensiva, anestesiología y farmacia hospitalaria. Resultados y conclusiones: De debates locales posteriores entre estos expertos se extrajeron conclusiones al respecto entre las que se destacan que la aprobación de nuevos antibióticos hace necesaria la formación de los especialistas implicados para optimizar su uso y mejorar los resultados en salud; los laboratorios de Microbiología de los hospitales deben estar disponibles en horario continuado; todos los antibióticos deben estar disponibles para cuando sean necesarios y se debe aprender a usarlos de forma correcta; y los Programas de Optimización del Uso de Antimicrobianos (PROA) desempeñan una labor clave en ubicar de forma ágil los nuevos antibióticos en las guías y asegurar un uso apropiado de los mismos. (AU)

Cross neutralization of SARS-CoV-2 omicron subvariants after repeated doses of COVID-19 mRNA vaccines.

We have measured the humoral response to messenger RNA (mRNA) vaccines in COVID-19 naïve and convalescent individuals. Third doses of mRNA COVID-19 vaccines induced a significant increase in potency and breadth of neutralization against SARS-CoV-2 variants of concern (VoC) including Omicron subvariants BA.1, BA.2, and BA.2.12.1, that were cross-neutralized at comparable levels and less for BA.4/5. This booster effect was especially important in naïve individuals that only after the third dose achieved a level that was comparable with that of vaccinated COVID-19 convalescents except for BA.4/5. Avidity of RBD-binding antibodies was also significantly increased in naïve individuals after the third dose, indicating an association between affinity maturation and cross neutralization of VoC. These results suggest that at least three antigenic stimuli by infection or vaccination with ancestral SARS-CoV-2 sequences are required to induce high avidity cross-neutralizing antibodies. Nevertheless, the circulation of new subvariants such as BA.4/5 with partial resistance to neutralization will have to be closely monitored and eventually consider for future vaccine developments.

A desirability of outcome ranking (DOOR) for periprosthetic joint infection - a Delphi analysis.

Background: Treatment outcomes in studies on prosthetic joint infection are generally assessed using a dichotomous outcome relating to treatment success or failure. These outcome measures neither include patient-centred outcome measures including joint function and quality of life, nor do they account for adverse effects of treatment. A desirability of outcome ranking (DOOR) measure can include these factors and has previously been proposed and validated for other serious infections. We aimed to develop a novel DOOR for prosthetic joint infections (PJIs). Methods: The Delphi method was used to develop a DOOR for PJI research. An international working group of 18 clinicians (orthopaedic surgeons and infectious disease specialists) completed the Delphi process. The final DOOR comprised the dimensions established to be most important by consensus with > 75  % of participant agreement. Results: The consensus DOOR comprised four main dimensions. The primary dimension was patient-reported joint function. The secondary dimensions were infection cure and mortality. The final dimension of quality of life was selected as a tie-breaker. Discussion: A desirability of outcome ranking for periprosthetic joint infection has been proposed. It focuses on patient-centric outcome measures of joint function, cure and quality of life. This DOOR provides a multidimensional assessment to comprehensively rank outcomes when comparing treatments for prosthetic joint infection.

Rates and Predictors of Treatment Failure in Staphylococcus aureus Prosthetic Joint Infections According to Different Management Strategies: A Multinational Cohort Study-The ARTHR-IS Study Group.

INTRODUCTION: Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome. METHODS: A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016. The outcome variable was TF, including related mortality, clinical failure and functional loss both after the initial surgical procedure and after all procedures at 18 months. Predictors of TF were identified by logistic regression. Landmark analysis was used to avoid immortal time bias with rifampicin when debridement, antibiotics and implant retention (DAIR) was performed. RESULTS: One hundred twenty cases of SA-PJI were included. TF rates after the first and all surgical procedures performed were 32.8% and 24.2%, respectively. After all procedures, functional loss was 6.0% for DAIR and 17.2% for prosthesis removal. Variables independently associated with TF for the first procedure were Charlson ≥ 2, haemoglobin < 10 g/dL, bacteraemia, polymicrobial infection and additional debridement(s). For DAIR, TF was also associated with a body mass index (BMI) > 30 kg/m2 and delay of DAIR, while rifampicin use was protective. For all procedures, the variables associated with TF were haemoglobin < 10 g/dL, hip fracture and additional joint surgery not related to persistent infection. CONCLUSIONS: TF remains common in SA-PJI. Functional loss accounted for a substantial proportion of treatment failures, particularly after prosthesis removal. Use of rifampicin after DAIR was associated with a protective effect. Among the risk factors identified, anaemia and obesity have not frequently been reported in previous studies. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov, registration no. NCT03826108.

Staphylococcus aureus is one of the most virulent bacteria and frequently causes prosthetic joint infections.Knowledge of the treatment of this type of infection has advanced in recent years, and treatment guidelines have led to improved management. Typically, the successful treatment of these infections has been determined by clinical cure, that is, the symptoms of infection have disappeared, but has not taken into account loss of function (such as significant difficulties walking), which is critical for the patient's quality of life. Our aim in this study was to evaluate the success of current management strategies for S. aureus prosthetic joint infection, including recovery of functionality, and the factors that predict why some of these infections are not cured, to identify areas for improvement.In a multinational cohort of 128 patients with S. aureus prosthetic joint infection, rates of treatment failure were found to be high, with significant rates of loss of function, especially when the prosthesis needed to be removed. Loss of function was less frequent when the infection was initially treated with surgical cleaning without removal of the prosthesis, even when this procedure failed at first. We found that anaemia and obesity were associated with lower treatment success, and that the probability of treatment success increased when surgical cleaning without prosthesis removal was performed early, and when the antibiotic rifampicin was used in combination with another antibiotic.

Strain-to-strain variability among Staphylococcus aureus causing prosthetic joint infection drives heterogeneity in response to levofloxacin and rifampicin.

INTRODUCTION: Levofloxacin and rifampicin are the preferred treatment for prosthetic joint infection (PJI) caused by Staphylococcus aureus, especially when managed with implant retention (DAIR). However, a significant variability of success has been reported, which could be related to intrinsic characteristics of the microorganism. Our aim was to evaluate the variability in the anti-biofilm response to levofloxacin and rifampicin in a clinical collection of S. aureus. MATERIAL AND METHODS: Eleven levofloxacin- and rifampicin-susceptible S. aureus isolates causing PJI managed with DAIR were included. Levofloxacin, rifampicin and levofloxacin + rifampicin were tested in an in vitro static biofilm model in microtitre plates, where 48 h biofilms were challenged with antimicrobials during 24 h. Additionally, two genetically similar strains were tested in the CDC Biofilm Reactor, where 48 h biofilms were treated during 56 h. Antimicrobial activity was assessed by viable biofilm-embedded cells recount, and by crystal violet staining. RESULTS: All antimicrobial regimens showed significant anti-biofilm activity, but a notable scattering in the response was observed across all strains (inter-strain coefficient of variation for levofloxacin, rifampicin and levofloxacin + rifampicin of 22.8%, 35.8% and 34.5%, respectively). This variability was tempered with the combination regimen when tested in the biofilm reactor. No correlation was observed between the minimal biofilm eradicative concentration and the antimicrobial activity. Recurrent S. aureus isolates exhibited higher biofilm-forming ability compared with strains from resolved infections (7.6 log10 cfu/cm2±0.50 versus 9.0 log10 cfu±0.07). CONCLUSIONS: Significant variability may be expected in response to levofloxacin and rifampicin among biofilm-embedded S. aureus. A response in the lower range, together with other factors of bad prognosis, could be responsible of treatment failure.

Microbiological and Molecular Features Associated with Persistent and Relapsing Staphylococcus aureus Prosthetic Joint Infection.

BACKGROUND: Persistent and relapsing prosthetic joint infection (PJI) due to Staphylococcus aureus presents a clinical challenge. This study aimed to provide an extensive description of phenotypic and genomic changes that could be related to persistence or relapse. METHODS: Initial and second S. aureus isolates from 6 cases of persistent and relapsing PJI, along with clinical isolates from 8 cases, with favorable outcome were included. All isolates were studied by phenotypic and genotypic approaches. RESULTS: Recurrent S. aureus isolates exhibited a significant increase in adhesive capacity, invasion and persistence compared to resolved isolates. No association was found for the presence or absence of certain genes with the persistence or relapse of PJI. All sequential isolates showed identical sequence type (ST). Resistance gene loss during the infection and a great diversity of variants in different virulence genes between the pair of strains, mainly in genes encoding adhesins such as fnbA, were observed. CONCLUSIONS: S. aureus-caused relapse and persistence PJI is associated with bacterial phenotypical and genotypical adaptation. The main paths of adaptation were persistence in the intracellular compartment, and the loss of antibiotic resistance genes and variant acquisition, especially in genes encoding adhesins.

Clinical impact of time-to-positivity of blood cultures on mortality in patients with Pseudomonas aeruginosa bacteremia.

OBJECTIVES: To investigate the impact of the time-to-positivity of blood cultures (TTP) on 30-day mortality in patients with Pseudomonas aeruginosa bacteremia. METHODS: All nonduplicated episodes of P. aeruginosa monomicrobial bacteremia in adult patients from January 2013 to February 2020 were analysed. Epidemiological and clinical data were collected. TTP of blood cultures for P. aeruginosa isolates was automatically recorded. Multivariate analysis identified factors predicting 30-day overall mortality. RESULTS: A total of 328 patients were identified. The median TTP for P. aeruginosa isolates was 15 h (interquartile range [IQR] 12-18 h). All multidrug-resistant and extensively drug-resistant (MDR/XDR) episodes were positive within the first 36 h. The 30-day mortality rate was 32.3%. The best cut-off value of the TTP for predicting mortality was 16 h (area under the receiver operating characteristic curve 0.62, 95% confidence interval [CI] 0.56-0.67, P = 0.001). The 30-day mortality rate was significantly higher in the TTP ≤16 h group (41.0% vs. 19.5%, P < 0.001). In a multivariate analysis, severe neutropenia (adjusted odds ratio [aOR] 2.67, 95% CI 1.4-5.09, P = 0.002), septic shock (aOR 3.21, 95% CI 1.57-5.89, P < 0.001), respiratory source (aOR 4.37, 95% CI 2.24-8.52, P < 0.001), nosocomial acquisition (aOR 1.99, 95% CI 1.06-3.71, P = 0.030), TTP ≤16 h (aOR 2.27, 95% CI 2.12-4.25, P = 0.010), and MDR/XDR phenotype (aOR 2.54, 95% CI 1.38-4.67, P = 0.002) were independently associated with 30-day mortality. CONCLUSIONS: A short TTP (≤16 h) was independently associated with increased 30-day mortality. After local validation, this routinely available microbiological parameter might be useful for guiding empirical antipseudomonal therapies and supporting the close monitoring of patients with P. aeruginosa bacteremia.

Genomic Analysis of Ceftazidime/Avibactam-Resistant GES-Producing Sequence Type 235 Pseudomonas aeruginosa Isolates.

The emergence of ceftazidime/avibactam (CZA) resistance among Guiana extended-spectrum ß-lactamase (GES)-producing Pseudomonas aeruginosa isolates has rarely been described. Herein, we analyze the phenotypic and genomic characterization of CZA resistance in different GES-producing P. aeruginosa isolates that emerged in our institution. A subset of nine CZA-resistant P. aeruginosa isolates was analyzed and compared with thirteen CZA-susceptible isolates by whole-genome sequencing (WGS). All CZA-resistant isolates belonged to the ST235 clone and O11 serotype. A variety of GES enzymes were detected: GES-20 (55.6%, 5/9), GES-5 (22.2%, 2/9), GES-1 (11.1%, 1/9), and GES-7 (11.1%, 1/9). WGS revealed the presence of two mutations within the blaGES-20 gene comprising two single-nucleotide substitutions, which caused aspartic acid/serine and leucine/premature stop codon amino acid changes at positions 165 (D165S) and 237 (L237X), respectively. No major differences in the mutational resistome (AmpC, OprD porin, and MexAB-OprM efflux pump-encoding genes) were found among CZA-resistant and CZA-susceptible isolates. None of the mutations that have been previously demonstrated to cause CZA resistance were observed. Different mutations within the blaGES-20 gene were documented in CZA-resistant GES-producing P. aeruginosa isolates belonging to the ST235 clone in our institution. Although further analysis should be performed, according to our results, other resistance mechanisms might be involved in CZA resistance.

Preoperative and perioperative risk factors, and risk score development for prosthetic joint infection due to Staphylococcus aureus: a multinational matched case-control study.

OBJECTIVES: We aim to identify the preoperative and perioperative risk factors associated with post-surgical Staphylococcus aureus prosthetic joint infections (PJI) and to develop and validate risk-scoring systems, to allow a better identification of high-risk patients for more efficient targeted interventions. METHODS: We performed a multicenter matched case-control study of patients who underwent a primary hip and knee arthroplasty from 2014 to 2016. Two multivariable models by logistic regression were performed, one for the preoperative and one for perioperative variables; predictive scores also were developed and validated in an external cohort. RESULTS: In total, 130 cases and 386 controls were included. The variables independently associated with S. aureus-PJI in the preoperative period were (adjusted OR; 95% CI): body mass index >30 kg/m2 (3.0; 1.9 to 4.8), resident in a long-term care facility (2.8; 1.05 to 7.5), fracture as reason for arthroplasty (2.7; 1.4 to 5.03), skin disorders (2.5; 0.9 to 7.04), previous surgery in the index joint (2.4; 1.3 to 4.4), male sex (1.9; 1.2 to 2.9) and American Society of Anesthesiologists index score 3 to 4 (1.8; 1.2 to 2.9). The area under the receiver operating characteristic curve was 0.73 (95% CI 0.68 to 0.78). In perioperative model, the risk factors were the previous ones plus surgical antibiotic prophylaxis administered out of the first 60 minutes before incision (5.9; 2.1 to 16.2), wound drainage for >72 hours after arthroplasty (4.5; 1.9 to 19.4) and use of metal bearing material versus ceramic (1.9; 1.1 to 3.3). The area under the receiver operating characteristic curve was 0.78 (95% CI 0.72 to 0.83). The predictive scores developed were validated in the external cohort. DISCUSSION: Predictive scores for S. aureus-PJI were developed and validated; this information would be useful for implementation of specific preventive measures.