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[Background] Prosthetic joints are at risk of becoming infected during an episode of bacteremia, especially during Staphylocococcus aureus bacteremia. However, it is unclear how often asymptomatic periprosthetic joint infection (PJI) occurs, and whether additional diagnostics should be considered., [Methods] In this multicenter study, we retrospectively analyzed a cohort of patients with a late acute (hematogenous) PJI between 2005–2015 who had concomitant prosthetic joints in situ. Patients without at least 1 year of follow-up were excluded., [Results] We included 91 patients with a hematogenous PJI and 108 concomitant prosthetic joints. The incident PJI was most frequently caused by Staphylococcus aureus (43%), followed by streptococci (26%) and Gram-negative rods (18%). Of 108 concomitant prosthetic joints, 13 were symptomatic, of which 10 were subsequently diagnosed as a second PJI. Of the 95 asymptomatic prosthetic joints, 1 PJI developed during the follow-up period and was classified as a “missed” PJI at the time of bacteremia with S. aureus (1.1%). Infected prosthetic joints were younger than the noninfected ones in 67% of cases, and prosthetic knees were affected more often than prosthetic hips (78%)., [Conclusions] During an episode of hematogenous PJI, concomitant asymptomatic prosthetic joints have a very low risk of being infected, and additional diagnostic work-up for these joints is not necessary.

Background The objective of this study was to investigate the neutralizing response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoC) during coronavirus disease 2019 (COVID-19) convalescence and after vaccination. Methods COVID-19-convalescent and -naïve individuals were tested for neutralizing activity against SARS-CoV-2 VoC Alpha, Beta, Gamma, and Delta at 1 and 7 months postinfection and 4–6 weeks after BNT162b2 vaccination. Results Vaccination induced a high neutralizing response in naïve individuals. Interestingly, vaccination of convalescent patients induced a boosted response that was able to neutralize all VoC at high titers. Conclusions Vaccination with BNT162b2 induced high levels of neutralization against SARS-CoV-2 VoC in most patients; this is especially beneficial in COVID-19-convalescent individuals.

Place: United States

Background Cutibacterium species are common pathogens in periprosthetic joint infections (PJI). These infections are often treated with β-lactams or clindamycin as monotherapy, or in combination with rifampin. Clinical evidence supporting the value of adding rifampin for treatment of Cutibacterium PJI is lacking. Methods In this multicenter retrospective study, we evaluated patients with Cutibacterium PJI and a minimal follow-up of 12 months. The primary endpoint was clinical success, defined by the absence of infection relapse or new infection. We used Fisher’s exact tests and Cox proportional hazards models to analyze the effect of rifampin and other factors on clinical success after PJI. Results We included 187 patients (72.2% male, median age 67 years) with a median follow-up of 36 months. The surgical intervention was a 2-stage exchange in 95 (50.8%), 1-stage exchange in 51 (27.3%), debridement and implant retention (DAIR) in 34 (18.2%), and explantation without reimplantation in 7 (3.7%) patients. Rifampin was included in the antibiotic regimen in 81 (43.3%) cases. Infection relapse occurred in 28 (15.0%), and new infection in 13 (7.0%) cases. In the time-to-event analysis, DAIR (adjusted hazard ratio [HR] = 2.15, P = .03) and antibiotic treatment over 6 weeks (adjusted HR = 0.29, P = .0002) significantly influenced treatment failure. We observed a tentative evidence for a beneficial effect of adding rifampin to the antibiotic treatment—though not statistically significant for treatment failure (adjusted HR = 0.5, P = .07) and not for relapses (adjusted HR = 0.5, P = .10). Conclusions We conclude that a rifampin combination is not markedly superior in Cutibacterium PJI, but a dedicated prospective multicenter study is needed.

Few studies have assessed the clinical and bacterial characteristics of Pseudomonas aeruginosa (PA) bacteraemic pneumonia (BP) episodes. This study analysed all non-duplicate PA-BP episodes from a tertiary hospital in 2013–2017. Epidemiology, clinical data, antimicrobial therapy and outcomes were recorded. Whole-genome sequencing was performed on PA blood isolates. The impact on early and late overall mortality of host, antimicrobial treatment and pathogen factors was assessed by multivariate logistic regression analysis. Of 55 PA-BP episodes, 32 (58.2%) were caused by extensively drug-resistant (XDR) PA. ST175 (32.7%) and ST235 (25.5%) were the most frequent high-risk clones. β-Lactamases/carbapenemases were detected in 29 isolates, including blaVIM-2 (27.2%) and blaGES type (25.5%) [blaGES-5 (20.0%), blaGES-1 (3.6%) and blaGES-20 (1.8%)]. The most prevalent O-antigen serotypes were O4 (34.5%) and O11 (30.9%). Overall, an extensive virulome was identified in all isolates. Early mortality (56.4%) was independently associated with severe neutropenia (aOR = 4.64, 95% CI 1.11–19.33; P = 0.035) and inappropriate empirical antimicrobial therapy (aOR = 5.71, 95% CI 1.41–22.98; P = 0.014). Additionally, late mortality (67.3%) was influenced by septic shock (aOR = 8.85, 95% CI 2.00–39.16; P = 0.004) and XDR phenotype (aOR = 5.46, 95% CI 1.25–23.85; P = 0.024). Moreover, specific genetic backgrounds [ST235, blaGES, gyrA (T83I), parC (S87L), exoU and O11 serotype] showed significant differences in patient outcomes. Our results confirm the high mortality associated with PA-BP. Besides relevant clinical characteristics and inappropriate empirical therapy, bacteria-specific genetics factors, such as XDR phenotype, adversely affect the outcome of PA-BP.

Dalbavancin (DAL) is a lipoglycopeptide with bactericidal activity against a very wide range of Gram-positive microorganisms. It also has unique pharmacokinetic properties, namely a prolonged half-life (around 181 h), which allows a convenient weekly dosing regimen, and good diffusion in bone tissue. These features have led to off-label use of dalbavancin in the setting of bone and joint infection, including prosthetic joint infections (PJI). In this narrative review, we go over the pharmacokinetic and pharmacodynamic characteristics of DAL, along with published in vitro and in vivo experimental models evaluating its activity against biofilm-embedded bacteria. We also examine published experience of osteoarticular infection with special attention to DAL and PJI.

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

A subgroup of patients with SARS-CoV-2 infection was thought to have developed cytokine release syndrome and were treated with tocilizumab; however, a significant percentage of patients evolved. This study aimed to determine the usefulness of anakinra as a rescue treatment for patients with tocilizumab-refractory COVID-19 disease. A prospective cohort of patients with COVID-19 pneumonia who received anakinra as salvage therapy after failure of tocilizumab were compared (1:1) with selected controls in a historical cohort of patients treated with tocilizumab. Cases and controls were matched by age, comorbidities, pulse oximetry oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) ratio at baseline, and time elapsed since the initiation of treatment with tocilizumab. The primary outcome was the improvement in clinical status measured by a 6-point ordinal scale, from baseline to day 21. The study included 20 cases and 20 controls (mean age 65.3 ± 12.8 years, 65% males). No differences were found in the clinical improvement rates at 7, 14 and 21 days of follow-up. The in-hospital mortality rate for patients receiving anakinra was 55% vs. 45% in the control group (P = 0.527). Treatment with anakinra was not useful in improving the prognosis of patients with tocilizumab-refractory severe COVID-19. This work was supported by Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (COV20/00181) — co‐financed by European Development Regional Fund “A way to achieve Europe”. M.F.R. holds a research contract “Miguel Servet” (CP18/00073) from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III. Sí

The aim of our study was to elucidate if SARS-CoV-2 viral load on admission, measured by real-time reverse transcriptase–polymerase chain reaction (rRT-PCR) cycle threshold (Ct) value on nasopharyngeal samples, was a marker of disease severity. All hospitalized adult patients with a diagnosis of SARS-CoV-2 infection by rRT-PCR performed on a nasopharingeal sample from March 1 to March 18 in our institution were included. The study population was divided according to the Ct value obtained upon admission in patients with high viral load (Ct 30). Demographic, clinical and laboratory variables of the different groups were analyzed to assess the influence of viral load on the development of respiratory failure during admission. Overall, 455 sequential patients were included. The median Ct value was 28 (IQR: 24–32). One hundred and thirty patients (28.6%) had a high viral load, 175 (38.5%) an intermediate viral load and 150 (33%) a low viral load. Advanced age, male sex, presence of cardiovascular disease and laboratory markers such as lactate dehydrogenase, lymphocyte count and C-reactive protein, as well as a high viral load on admission, were predictive of respiratory failure. A Ct value

El presente estudio retrospectivo observacional tiene como objetivo analizar la utilidad de las escalas SOFA (Sequential Organ Failure Assessment), qSOFA (Quick SOFA), NEWS (National Early Warning Score ) y Quick NEWS para predecir el fallo respiratorio y la muerte en pacientes con COVID-19 atendidos fuera de la Unidad de Cuidados Intensivos (UCI). Se incluyeron 237 adultos con COVID-19 hospitalizados seguidos durante un mes o hasta su fallecimiento. El fallo respiratorio se definió como un cociente PaO2/FiO2 ≤ 200 mmHg o la necesidad de ventilación mecánica. Setenta y siete pacientes (32,5%) desarrollaron fallo ventilatorio; 29 (12%) precisaron ingreso en UCI, y 49 fallecieron (20,7%). La discriminación del fallo ventilatorio fue algo mayor con la puntuación NEWS, seguida de la SOFA. En cuanto a la mortalidad, la puntuación SOFA fue más exacta que las otras escalas. En conclusión, las escalas de sepsis son útiles para predecir el fallo respiratorio y la muerte en COVID-19. Una puntuación ≥ 4 en la escala NEWS sería el mejor punto de corte para predecir fallo respiratorio.

[Background]: Linezolid has good penetration to the meninges and could be an alternative for treatment of Staphylococcus aureus meningitis. We assessed the efficacy and safety of linezolid therapy for this infection., [Methods]: Retrospective multicenter cohort study of 26 adults treated with linezolid, derived from a cohort of 350 cases of S. aureus meningitis diagnosed at 11 university hospitals in Spain (1981-2015)., [Results]: There were 15 males (58%) and mean age was 47.3 years. Meningitis was postoperative in 21 (81%) patients. The infection was nosocomial in 23 (88%) cases, and caused by methicillin-resistant S. aureus in 15 cases and methicillin-susceptible S. aureus in 11. Linezolid was given as empirical therapy in 10 cases, as directed therapy in 10, and due to failure of vancomycin in 6. Monotherapy was given to 16 (62%) patients. Median duration of linezolid therapy was 17 days (IQR 12-22 days) with a daily dose of 1,200 mg in all cases. The clinical response rate to linezolid was 69% (18/26) and microbiological response was observed in 14 of 15 cases evaluated (93%). Overall 30-day mortality was 23% and was directly associated with infection in most cases. When compared with the patients of the cohort, no significant difference in mortality was observed between patients receiving linezolid or vancomycin for therapy of methicillin-resistant S. aureus meningitis (9% vs. 20%; p = .16) nor between patients receiving linezolid or cloxacillin for therapy of methicillin-susceptible S. aureus meningitis (20% vs 14%; p = .68). Adverse events appeared in 14% (3/22) of patients, but linezolid was discontinued in only one patient., [Conclusions]: Linezolid appears to be effective and safe for therapy of S. aureus meningitis. Our findings showed that linezolid may be considered an adequate alternative to other antimicrobials in meningitis caused by S. aureus.

Background: Passive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19 for which evidence from controlled clinical trials is lacking. Methods: We conducted a multi-center, randomized clinical trial in patients hospitalized for COVID-19. All patients received standard of care treatment, including off-label use of marketed medicines, and were randomized 1:1 to receive one dose (250-300 mL) of CP from donors with IgG anti-SARS-CoV-2. The primary endpoint was the proportion of patients in categories 5, 6 or 7 of the COVID-19 ordinal scale at day 15. Results: The trial was stopped after first interim analysis due to the fall in recruitment related to pandemic control. With 81 patients randomized, there were no patients progressing to mechanical ventilation or death among the 38 patients assigned to receive plasma (0%) versus 6 out of 43 patients (14%) progressing in control arm. Mortality rates were 0% vs 9.3% at days 15 and 29 for the active and control groups, respectively. No significant differences were found in secondary endpoints. At inclusion, patients had a median time of 8 days (IQR, 6-9) of symptoms and 49,4% of them were positive for anti-SARS-CoV-2 IgG antibodies. Conclusions: Convalescent plasma could be superior to standard of care in avoiding progression to mechanical ventilation or death in hospitalized patients with COVID-19. The strong dependence of results on a limited number of events in the control group prevents drawing firm conclusions about CP efficacy from this trial. (Funded by Instituto de Salud Carlos III; NCT04345523). This research is funded by the Government of Spain, Ministry of Science and Innovation, Instituto de Salud Carlos III, grant number COV20/00072 (Royal Decree-Law 8/2020, of 17 March, on urgent extraordinary measures to deal with the economic and social impact of COVID-19), co-financed by the European Regional Development Fund (FEDER) ‘‘A way to make Europe’’ and supported by SCReN (Spanish Clinical Research Network), ISCIII, project PT17/0017/0009. Clinical trial insurance coverage was kindly donated by MARCH RS Correduría de Seguros y Reaseguros. Mikel Mancheño-Losa holds a "Río Hortega" research contract (expte. CM19/00226 No

Background Staphylococcus aureus is the leading cause of prosthetic joint infection (PJI). Beyond the antibiogram, little attention has been paid to the influence of deep microbiological characteristics on patient prognosis. Our aim was to investigate whether microbiological genotypic and phenotypic features have a significant influence on infection pathogenesis and patient outcome. Methods A prospective multicenter study was performed, including all S. aureus PJIs (2016–2017). Clinical data and phenotypic (agr functionality, β-hemolysis, biofilm formation) and genotypic characteristics of the strains were collected. Biofilm susceptibility to antimicrobials was investigated (minimal biofilm eradication concentration [MBEC] assay). Results Eighty-eight patients (39.8% men, age 74.7 ± 14.1 years) were included. Forty-five had early postoperative infections (EPIs), 21 had chronic infections (CPIs), and 19 had hematogenous infections (HIs). Twenty (22.7%) were caused by methicillin-resistant S. aureus. High genotypic diversity was observed, including 16 clonal complexes (CCs), with CC5 being the most frequent (30.7%). agr activity was greater in EPI than CPI (55.6% vs 28.6%; P = .041). Strains causing EPI were phenotypically and genotypically similar, regardless of symptom duration. Treatment failure (36.5%) occurred less frequently among cases treated with implant removal. In cases treated with debridement and implant retention, there were fewer failures among those who received combination therapy with rifampin. No genotypic or phenotypic characteristics predicted failure, except vancomycin minimal inhibitory concentration ≥1.5 mg/L (23.1% failure vs 3.4%; P = .044). MBEC50 was >128 mg/L for all antibiotics tested and showed no association with prognosis. Conclusions S. aureus with different genotypic backgrounds is capable of causing PJI, showing slight differences in clinical presentation and pathogenesis. No major microbiological characteristics were observed to influence the outcome, including MBEC.

Coronavirus Disease 2019 (COVID-19) pandemic has implacably stricken on the wellness of many countries and their health-care systems. The aim of the present study is to analyze the clinical characteristics of the initial wave of patients with COVID-19 attended in our center, and to identify the key variables predicting the development of respiratory failure. Prospective design study with concurrent data retrieval from automated medical records of all hospitalized adult patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rRT-PCR assay performed on respiratory samples from March 2nd to 18th, 2020. Patients were followed up to May 1st, 2020 or death. Respiratory failure was defined as a PaO2/FiO2 ratio ≤ 200 mm Hg or the need for mechanical ventilation (either non-invasive positive pressure ventilation or invasive mechanical ventilation). We included 521 patients of whom 416 (81%) had abnormal Chest X-ray on admission. Median age was 64.6 ± 18.2 years. One hundred eighty-one (34.7%) developed respiratory failure after a median time from onset of symptoms of 9 days (IQR 6–11). In-hospital mortality was 23.8% (124/521). The modeling process concluded into a logistic regression multivariable analysis and a predictive score at admission. Age, peripheral pulse oximetry, lymphocyte count, lactate dehydrogenase and C-reactive protein were the selected variables. The model has a good discriminative capacity with an area under the ROC curve of 0.85 (0.82–0.88). The application of a simple and reliable score at admission seems to be a useful tool to predict respiratory failure in hospitalized COVID-19 patients. Supplementary Information The online version contains supplementary material available at 10.1007/s11739-021-02748-2.

Recent studies have demonstrated improved survival when the management of Staphylococcus aureus bloodstream infection (BSI) is compliant with evidence-based therapeutic interventions. Whether this effect extends to low-risk sources, such as catheter-related BSI, remains unclear.We retrospectively included 225 episodes of methicillin-sensitive S. aureus catheter-related BSI diagnosed in our centre during two non-consecutive periods: 2002-2004 (first period (101 episodes)) and 2009-2013 (second period (124 episodes)). We evaluated the adherence (percentage of compliance = (no. of interventions performed/no. of interventions recommended) × 100) to the following bundle: early catheter removal (≤72 hours), early initiation of appropriate antibiotic therapy, adequate sampling of follow-up blood cultures, transthoracic echocardiography (TTE) during hospitalization and adequate duration of therapy.Patients in the second period had a higher burden of comorbidities and more severe underlying conditions. All-cause 30-day mortality was 9.3%, with a significant difference between the first and second periods (13.9% versus 5.6%; p value = .035). Bundle adherence was significantly higher in the second period, particularly for follow-up blood cultures (26.7% versus 48.4%; p value = .001), performance of TTE (45.5% versus 84.7%; p value .001) and appropriate duration of therapy (34.7% versus 50.0%; p value = .022). Bundle adherence ≥ 55% was associated with lower 30-day mortality (hazard ratio: 0.31; 95% confidence interval: 0.13-0.76). This effect remained significant across propensity score-based models adjusted for septic shock, study period and underlying conditions.There was a survival benefit in adhering to a bundle of evidence-based interventions in the specific setting of catheter-related BSI due to methicillin-sensitive S. aureus.

Resumen Las mordeduras producidas por animales y por seres humanos suponen un motivo de consulta no infrecuente. Tienen un mayor riesgo de infeccion las producidas por gatos y seres humanos, las heridas extensas o profundas, las que afectan a la cara y a las manos o que estan proximas a las articulaciones, y aquellas con retraso en la atencion medica o infringidas a pacientes inmunodeprimidos. Los microorganismos responsables son los habituales de la flora bacteriana bucal de los animales. El tratamiento inicial implica una evaluacion cuidadosa de los danos y del riesgo de infeccion, el lavado de la herida y la elevacion del miembro. En los casos con riesgo de infeccion debe considerarse un curso corto de antibioticos profilacticos. Es importante, asimismo, la reevaluacion de la herida a corto plazo. En los casos de infeccion asociada, debe incidirse en la limpieza de la herida, la escision de tejido necrotico y cuerpos extranos y un curso mas prolongado de antibioticos.

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 β-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 β-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 β-lactams are confirmed and maybe also a potential benefit from adding rifampin.

We have explored the relationship of phenotypic (antibiogram, β-haemolysis, agr functionality, biofilm formation) and genotypic characteristics on the prognosis of 18 cases of methicillin-resistant S. aureus prosthetic joint infection (2005-2015). All isolates belonged to CC5, and had agr type II. This pilot study suggests that phage-borne genes belonging to the immune evasion cluster (chp, sak and scn) were more frequent among episodes with treatment failure (80.0 vs. 37.5%).

Whether multidrug resistance (MDR) is associated with mortality in patients with Pseudomonas aeruginosa bloodstream infections (BSI) remains controversial. Here, we explored the prognostic factors of P. aeruginosa BSI with emphasis on antimicrobial resistance and virulence. All P. aeruginosa BSI episodes in a 5-year period were retrospectively analyzed. The impact in early (5-day) and late (30-day) crude mortality of host, antibiotic treatment, and pathogen factors was assessed by multivariate logistic regression analysis. Of 243 episodes, 93 (38.3%) were caused by MDR-PA. Crude 5-day (20%) and 30-day (33%) mortality was more frequent in patients with MDR-PA (34.4% versus 11.3%, P < 0.001 and 52.7% versus 21.3%, P < 0.001, respectively). Early mortality was associated with neutropenia (adjusted odds ratio [aOR], 9.21; 95% confidence interval [CI], 3.40 to 24.9; P < 0.001), increased Pitt score (aOR, 2.42; 95% CI, 1.34 to 4.36; P = 0.003), respiratory source (aOR, 3.23; 95% CI,2.01 to 5.16; P < 0.001), inadequate empirical therapy (aOR, 4.57; 95% CI, 1.59 to 13.1; P = 0.005), shorter time to positivity of blood culture (aOR, 0.88; 95% CI, 0.80 to 0.97; P = 0.010), an exoU-positive genotype (aOR, 3.58; 95% CI, 1.31 to 9.79; P = 0.013), and the O11 serotype (aOR, 3.64; 95% CI, 1.20 to 11.1; P = 0.022). These risk factors were similarly identified for late mortality, along with an MDR phenotype (aOR, 2.18; 95% CI, 1.04 to 4.58; P = 0.040). Moreover, the O11 serotype (15.2%, 37/243) was common among MDR (78.4%, 29/37) and exoU-positive (89.2%, 33/37) strains. Besides relevant clinical variables and inadequate empirical therapy, pathogen-related factors such as an MDR phenotype, an exoU-positive genotype, and the O11 serotype adversely affect the outcome of P. aeruginosa BSI.

Background: Coronavirus Disease 2019 (COVID-19) pandemic has implacably stricken on the wellness of many countries and their health-care systems. The aim of the present study is analyze the clinical characteristics of the initial wave of patients with COVID-19 attended in our center, and to identify the key variables predicting the development of respiratory failure. Methods: We retrospectively recruited all hospitalized adult patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rRT-PCR assay performed on respiratory samples from March 2nd to 18th, 2020. Patients were followed up to May 1st, 2020 or death. Respiratory failure was defined as a PaO2/FiO2 ratio ≤200 mm Hg or the need for mechanical ventilation (either non-invasive positive pressure ventilation or invasive mechanical ventilation). Findings: We included 521 patients of whom 416 (81%) had abnormal Chest X-ray on admission. Median age was 64·6 ± 18·2 years, with 317 patients (60.8%) over 60 years. One hundred eighty-one (34·7%) developed respiratory failure after a median time from onset of symptoms of 9 days (IQR: 6-11) and the in-hospital mortality was 23·8% (124/521). The modelling process concluded into a logistic regression multivariable analysis and a predictive score at admission. Age, peripheral pulse oximetry, lymphocyte count, lactate dehydrogenase and C-reactive protein were the selected variables. The model has a good discriminative capacity with an area under the ROC curve of 0·85 (0·82-0·88). Interpretation: The application of a simple and reliable score at admission seems to be a useful tool to predict respiratory failure in hospitalized COVID-19 patients. Funding: This study was supported by the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (COVID-19 research call COV20/00181) — co‐ financed by the European Development Regional Fund “A way to achieve Europe”. Mikel Mancheno-Losa was supported by a Research Contract “Rio Hortega” from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (CM19/00226). Mario Fernandez-Ruiz holds a research contract “Miguel Servet” from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (CP 18/00073). Declaration of Interests: The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript. Ethics Approval Statement: The protocol was approved by the Hospital 12 de Octubre Clinical Research Ethics Committee (reference 20/117) and granted a waiver of informed consent due to its retrospective observational design.

Multidrug-resistant (MDR) Pseudomonas aeruginosa represents a major clinical concern. The interplay between antimicrobial resistance and virulence of P. aeruginosa was investigated in in vitro and in vivo studies. Thirty-eight well-characterized (21 MDR and 17 non-MDR) P. aeruginosa strains from patients with bacteraemia were analysed. Resistance phenotype, carbapenemase production, clonal relatedness, type III secretion system genotype, O-antigen serotype, cytotoxicity (ability to lyse cells) on A549 cells, and virulence (lethality in nematodes) in a Caenorhabditis elegans model were investigated. MDR strains showed lower cytotoxicity (35.4 ± 21.30% vs. 45.0 ± 18.78 %; P = 0.044) and virulence (66.7% vs. 100%; P = 0.011) than non-MDR strains. However, the pathogenicity of MDR high-risk clones varied broadly, with ST235 and ST175 clones being the most and least cytotoxic (51.8 ± 10.59% vs. 11.0 ± 1.25%; P < 0.0001) and virulent ([100% vs. 73.1; P = 0.075] and [0% vs. 93.9%; P < 0.0001], respectively). The pathogenicity of the ST235 clone was similar to that of non-MDR strains, and its ability to lyse cells and high virulence were related with the exoU-positive genotype. Furthermore, the O11 serotype was more frequent among the ST235 clone and exoU-positive genotype strains and was also essential for the pathogenicity of P. aeruginosa. Our data suggest that the pathogenicity of MDR high-risk clones is the result not only of the resistance phenotype but also of the virulence genotype. These findings have implications for the clinical management of patients and infection control programmes.

Dalbavancin is a lipoglycopeptide with potent activity against Gram-positive microorganisms, a long half-life, a favorable safety profile, and a high concentration in bone, which makes it an interesting alternative for treatment of osteoarticular infections. We performed a multicentric retrospective study of all patients with an osteoarticular infection (septic arthritis, spondylodiscitis, osteomyelitis, or orthopedic implant-related infection) treated with at least one dose of dalbavancin between 2016 and 2017 in 30 institutions in Spain. In order to evaluate the response, patients with or without an orthopedic implant were separated. A total of 64 patients were included. Staphylococcus epidermidis and Staphylococcus aureus were the most frequent microorganisms. The reasons for switching to dalbavancin were simplification (53.1%), adverse events (25%), or failure (21.9%). There were 7 adverse events, and no patient had to discontinue dalbavancin. In 45 cases, infection was related to an orthopedic implant. The implant material was retained in 23 cases, including that in 15 (65.2%) patients that were classified as cured and 8 (34.8%) that presented improvement. In 21 cases, the implants were removed, including those in 16 (76.2%) cases that were considered successes, 4 (19%) cases were considered improved, and 1 (4.8%) case that was considered a failure. Among the 19 cases without implants, 14 (73.7%) were considered cured, 3 (15.8%) were considered improved, and 2 (10.5%) were considered failures. The results show that dalbavancin is a well-tolerated antibiotic, even when 2 doses are administered, and is associated with a high cure rate. These are preliminary data with a short follow-up; therefore, it is necessary to gain more experience and, in the future, to establish the most appropriate dose and frequency., This study was supported by the Bone and Joint Infection Study Group (SGR 253) of the Agència de Gestió d’Ajuts Universitaris I de Recerca (AGAUR) and by the Red Española de Investigación en Patología Infecciosa (REIPI). L. Morata is the recipient of a Rio-Hortega grant (CM 15/00129) from the Instituto de Salud Carlos III.

Background Staphylococcus aureus may invade and persist intracellularly in prosthetic joint infections (PJIs). Despite optimized treatments with levofloxacin plus rifampin, the intracellular reservoir may lead to infection relapse. This study assessed the intracellular activity of levofloxacin and rifampin in an in-vitro model of human osteoblastic infection. Methods Ten meticillin-susceptible S. aureus strains were used to infect osteoblastic MG63 cells. Osteoblasts were challenged with rifampin and levofloxacin at cortical and cancellous bone concentrations. Efficacy was measured as the intracellular counts of colony-forming units (log10CFU) compared with untreated controls. The emergence of small colony variants (SCVs) was determined, and the results were stratified according to the patient's prognosis (six cured and four with persistence/relapse). Results All regimes led to a significant decrease in CFU count compared with controls (1–2 log10CFU). Levofloxacin was the most effective treatment at both cortical and cancellous bone concentrations (-2.4 to -1.9 log10CFU, respectively). The addition of rifampin to levofloxacin did not improve performance (-1.9 log10CFU for cortical concentration and -1.8 log10 CFU for cancellous concentration). An increase in SCVs was observed in the presence of rifampin. The efficacy of antimicrobials was higher and the formation of SCVs was lower against strains belonging to PJIs with a favourable outcome. Conclusions Levofloxacin plus rifampin had good intracellular activity against S. aureus. However, from the intracellular perspective, the addition of rifampin to levofloxacin showed no benefit but could account for an increased number of SCVs.

The optimal approach following the isolation of Staphylococcus aureus from an intravascular catheter tip in the absence of concomitant bacteremia remains unclear. We aimed to determine the rate of delayed complications in these patients. We performed a retrospective observational study (during the period 2002–2012) including patients with a catheter tip culture yielding S. aureus. Patients were followed up for ≥6 months. The primary endpoint was the occurrence of delayed staphylococcal complications (either bacteremia and/or metastatic distant infections). A total of 113 patients were included (75 % male, median age 61 years): 46 and 67 with negative and positive blood cultures, respectively. We found a lower rate of delayed staphylococcal complications in cases with no bacteremia within 48 h since catheter removal than in cases of confirmed S. aureus catheter-related bacteremia (0.0 % vs. 25.4 %; p-value

Biofilm is an adaptive bacterial strategy whereby microorganisms become encased in a complex glycoproteic matrix. The low concentration of oxygen and nutrients in this environment leads to heterogeneous phenotypic changes in the bacteria, with antimicrobial tolerance being of paramount importance. As with other antibiotics, the activity of colistin is impaired by biofilm-embedded bacteria. Therefore, the recommendation for administering high doses in combination with a second drug, indicated for planktonic infections, remains valid in this setting. Notably, colistin has activity against metabolically inactive biofilm-embedded cells located in the inner layers of the biofilm structure. This is opposite and complementary to the activity of other antimicrobials that are able to kill metabolically active cells in the outer layers of the biofilm. Several experimental models have shown a higher activity of colistin when used in combination with other agents, and have reported that this can avoid the emergence of colistin-resistant subpopulations. Most experience of colistin in biofilm-associated infections comes from patients with cystic fibrosis, where the use of nebulized colistin allows high concentrations to reach the site of the infection. However, limited clinical experience is available in other scenarios, such as osteoarticular infections or device-related central nervous system infections caused by multi-drug resistant microorganisms. In the latter scenario, the use of intraventricular or intrathecal colistin also permits high local concentrations and good clinical results. Overall, the efficacy of intravenous colistin seems to be poor, but its association with a second antimicrobial significantly increases the response rate. Given its activity against inner bioflm-embedded cells, its possible role in combination with other antibiotics, beyond last-line therapy situations, should be further explored.

Objectives Septic arthritis is associated with significant case fatality and morbidity. Staphylococcus aureus is the most common cause of arthritis. We aimed to analyze the microbiological features of S. aureus causing native arthritis and to investigate their influence on the clinical outcome of the infection. Patients and methods We conducted a retrospective study including all episodes of S. aureus native arthritis between 2005–2015. Phenotypic (antimicrobial susceptibility, β-hemolysis, agr functionality, biofilm formation) and genotypic characteristics (pulsed-field gel electrophoresis, DNA microarrays) were investigated. The primary endpoint was microbiological failure of treatment, including infection relapse, persistence, or attributable death. Results Twenty-nine patients were included (65.5% of men, mean age: 59): seven (24.1%) patients presenting with methicillin-resistant S. aureus (MRSA) native arthritis and 19 with methicillin-susceptible S. aureus (MSSA) native arthritis. Treatment failure occurred in seven (26.9%) patients (4/7 patients [57.1%] among MRSA infections vs. 3/19 [15.8%] among MSSA infections). The persistence rate was similar in MRSA and MSSA infections (1/7 vs. 3/19). However, the case fatality was significantly higher in patients with MRSA infection (3/7 vs. 0/19). The most frequent clonal complex (CC) was CC5 (38.1%). MSSA showed higher genetic variability (nine CCs) versus MRSA (3 CCs). Conclusions Beyond methicillin resistance, we did not find phenotypic or genotypic factors associated with the poor outcome of S. aureus native arthritis. CC5 was the major CC, showing the higher genetic variability of MSSA versus MRSA.

We describe a case of a 60-year old male who developed an acute prosthetic joint infection (PJI) of the knee, secondary to erysipelas of the lower leg due to beta-hemolytic Group G streptococci. As it is unknown how often this phenomenon occurs in patients with prosthetic implants and which patients are most prone to develop this complication, we analyzed: i) the incidence of the development of a PJI in these patients and ii) the clinical characteristics of streptococcal PJI during an episode of erysipelas/cellulitis. Based on a retrospective analysis of patients with a prosthetic implant in situ presenting at the emergency department with erysipelas/cellulitis, 1 out of 10 patients developed a PJI. An additional analysis within a multicenter cohort on streptococcal PJI demonstrated in 22 patients that a secondary PJI due to erysipelas/cellulitis mostly develops in young implants (

Objective To analyze the clinical features, microbiological spectrum, diagnostic procedures and outcomes in native joint pyogenic arthritis among non-intravenous drug users. Methods We collected all microbiologically proved cases of infectious arthritis at our hospital between 1992 and 2013. Patients with prosthetic joint infection were excluded, as were patients with non-pyogenic arthritis and intravenous drug users. Results We identified 268 patients; the mean age was 61 ± 14.7 years and 62% were men. The incidence increased over the period of study. In 188 patients (70%), one or more underlying medical illnesses were found. The mean symptom duration was 8.9 ± 9.5 days. Globally, 311 affected joints were found, 232 (75%) involving peripheral joints and 79 (25%) axial joints. Staphylococci (55%) and Streptococci (29%) were the predominant microorganisms. Blood cultures were positive in 78% (173/223) of the cases. In 81 patients (30%), one or more concomitant infectious processes were found. Antimicrobial therapy was prescribed 4–8 weeks in most cases, and surgical drainage was performed in 65% of patients. Four patients relapsed and 23 (8%) died. Conclusions The prevalence of pyogenic native joint arthritis in non-intravenous drug users is increasing, frequently affecting old patients with underlying medical conditions. Although large joints are the most frequently compromised, the involvement of axial joints is a relevant feature that has not been recognized in other series. Staphylococci and Streptococci are the main causative agents. Bacteremia and concomitant infectious processes are frequent complications. Diagnostic delay and mortality continue to be important concerns.

Predictors of mortality and the impact of multidrug resistance and virulence on patients with Pseudomonas aeruginosa (PA) bacteraemia were evaluated. Patients with PA bacteraemia in a 12-month period were retrospectively analysed. Carbapenemase production, molecular typing and identification of virulence factor ExoU were carried out. The activity of ceftolozane-tazobactam and ceftazidime-avibactam was also investigated. The primary endpoint was 30-day crude mortality. Of 64 patients with bacteraemia, 24 (37.5%) were caused by extensively drug-resistant PA (XDR-PA): 10 (41.7%) cases involved the VIM-2 carbapenemase-producing ST175 clone, 11 (45.8%) the GES-5 carbapenemase-producing ST235 clone, and 3 (12.5%) were non-carbapenemase producers. The exoU genotype was detected in all ST235 strains and in 6 (15%) of the non-XDR isolates. Ceftazidime-avibactam (58.3%) showed greater activity than ceftolozane-tazobactam (12.5%) against XDR-PA isolates, particularly in GES-5 producers (100%). The 30-day crude mortality rate in patients with XDR-PA bacteraemia was higher than in cases caused by susceptible strains (62.5% vs. 30%; P=0.02). Multivariate analysis showed that independent risk factors associated with 30-day crude mortality were Pitt score ≥2 (OR, 42.31; 95% CI, 4.88-366.7; P=0.001) and respiratory source of bacteraemia (OR, 49.13; 95% CI 3.89-620.5; P=0.003). Stratified analysis adjusting for respiratory source revealed a non-significant trend towards higher mortality in patients with bacteraemia caused by the ST235 clone and exoU-producing isolates. These data support the notion that the XDR phenotype associated with the GES-5 carbapenemase-producing ST235 clone and the exoU-positive genotype adversely affects the outcome of patients with PA bacteraemia, particularly those with respiratory tract infections and a severe clinical presentation.

Background: Late acute (LA) periprosthetic joint infections (PJI) treated with surgical debridement and implant retention (DAIR) have a high failure rate. Therefore, we evaluated treatment outcome in LA PJIs treated with DAIR versus implant removal. Methods: In a large multicenter study, LA PJIs of the hip and knee were retrospectively evaluated. Failure was defined as: PJI related death, prosthesis removal or the need for suppressive antibiotic therapy. LA PJI was defined as acute symptoms

The management of periprosthetic joint infections is a challenging issue, needing a combined medical and surgical approach. The presence of antibiotic-tolerant biofilm-embedded bacteria will demand a sophisticated antimicrobial treatment, influenced by the surgical treatment chosen. In this regard, the main surgical alternatives are curative attempt with prosthesis retention, curative attempt with prosthesis removal and palliative treatment with prosthesis retention. The choice for one of these depends on the patient’s baseline condition, the aetiology of the infection and the clinical presentation. Acute cases with periprosthetic soft tissue in good condition, a soundly fixed prosthesis, and caused by microorganisms susceptible to antibiotics with a good anti-biofilm profile, can be managed by debridement and prosthesis retention. Chronic cases or episodes not meeting these conditions should be managed with prosthesis removal and submitted to a one- or two-step exchange procedure or to joint arthrodesis. Alternatively, patients with significant comorbidities precluding aggressive surgical approaches and with stable and free-pain prosthesis could be managed with long-term suppressive antibiotics. For staphylocococci, rifampin plus levofloxacin is the treatment of choice. Other alternative rifampin-based combinations may be also suitable for treating these infections. In the case of Gram-negative bacilli, ciprofloxacin is recommended as the first-line treatment. For enterococci and streptococci, β-lactams are the preferred treatment, and some evidence suggests the benefits of adding rifampin. Further research is needed to find alternative treatments when these are not available.

The role of Streptococcus species as an aetiological microorganism of vertebral osteomyelitis (VO) is considered to be of little relevance. We aimed to describe a large number of cases of streptococcal vertebral osteomyelitis (SVO), to analyze the clinical features associated with different Streptococcus species, and to compare them with a cohort of patients with VO caused by Staphylococcus aureus. An incidence study and a retrospective, multicenter, observational clinical study of cases of SVO (1991–2011) were performed. Statistical comparison of SVO by different species and between them and staphylococcal VO was carried out. Over the whole period there was an increasing incidence in the number of VOs and SVOs per year (p

BACKGROUND AND AIMS. In cirrhotic patients with spontaneous bacterial peritonitis (SBP) higher polymorphonuclear (PMN) count in ascitic fluid have been reported in infections caused by Gram-negative bacilli (GNB) as opposed to Gram-positive cocci (GPC). However, the influence of other associated factors on the PMN count, such as the specific microorganism causing the episode of SBP, has not been well established. METHODS. Retrospective observational study of 194 episodes of positive ascitic and/or blood culture SBP in 159 patients with liver cirrhosis (2001-2009). Parameters associated with PMN count in ascitic fluid at diagnosis were evaluated. RESULTS. The multivariate analysis (model 1) showed that a virulent etiology of the infection [coefficient 3.941 (95% confidence interval (95 CI): 0.421-7.461)] and the model for end-stage liver disease (MELD) score [coefficient 0.196 (95 CI: 0.007-0.384)] were positively associated with the PMN count in ascites, while a nosocomial acquisition was inversely associated [coefficient -3.546 (95 CI: -6.855 - -0.238)]. A nonsignificant trend toward higher PMN count was found in GNB versus GPC, but there were differences between groups of microorganisms: pyogenic streptococci [median (p25-p75): 3211 (1615-8004)], Enterobacteriaceae [2958 (917-7690)], Vibrionaceae [9215 (375-17280)], nonfermenting GNB [1384 (565-3865)], viridans group streptococci [1044 (503-2354)] and enterococci [1050 (476-4655)](p = 0.005). No clear cut-offs of ascitic PMN count predicting a particular etiology could be calculated out of these data. CONCLUSIONS. In cirrhotic patients with SBP, the causing microorganism, the place of acquisition of the infection and the host liver condition were the main factors determining PMN count in ascitic fluid. Third-generation cephalosporin resistance was associated with low PMN count probably because this group included bacteria with inherent low virulence.

Linezolid may be an interesting alternative for prosthetic joint infection (PJI) due to its bioavailability and its antimicrobial spectrum. However, experience in this setting is scarce. The aim of the study was to assess linezolid's clinical and microbiological efficacy, and also its tolerance. This was a prospective, multicenter, open-label, non-comparative study of 25 patients with late-chronic PJI caused by Gram-positive bacteria managed with a two-step exchange procedure plus 6 weeks of linezolid. Twenty-two (88%) patients tolerated linezolid without major adverse effects, although a global decrease in the platelet count was observed. Three patients were withdrawn because of major toxicity, which reversed after linezolid stoppage. Among patients who completed treatment, 19 (86%) demonstrated clinical and microbiological cure. Two patients presented with clinical and microbiological failure, and one showed clinical cure and microbiological failure. In conclusion, linezolid showed good results in chronic PJI managed with a two-step exchange procedure. Tolerance seems acceptable, though close surveillance is required.

[EN] The incidence of prosthetic joint infection (PJI) is expected to increase in the coming years. PJI has serious consequences for patients, and high costs for the health system. The complexity of these infections makes it necessary to organize the vast quantity of information published in the last several years. The indications for the choice of a given surgical strategy and the corresponding antimicrobial therapy are specifically reviewed. The authors selected clinically relevant questions and then reviewed the available literature in order to give recommendations according to a pre-determined level of scientific evidence. The more controversial aspects were debated, and the final composition was agreed at an ad hoc meeting. Before its final publication, the manuscript was made available online in order that all SEIMC members were able to read it and make comments and suggestions., [ES] Se prevé un incremento de la incidencia de infección de las prótesis articulares (IPA) en los próximos años. Las IPA plantean graves consecuencias para los pacientes y un alto coste el sistema sanitario. La complejidad de estas infecciones hace que sea necesario organizar la inmensa cantidad de información publicada en los últimos años. En estas guías se revisan específicamente las indicaciones para la elección de una estrategia quirúrgica dada y el tratamiento antimicrobiano correspondiente. Los autores seleccionaron las preguntas clínicamente relevantes y revisaron la literatura disponible con el fin de proporcionar recomendaciones de acuerdo con un grado de evidencia científica predeterminada. Los aspectos más controvertidos fueron debatidos y la redacción final se acordó en una reunión ad hoc. Antes de su publicación, el manuscrito estuvo abierto a comentarios y sugerencias de los miembros de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica.

Background Little is known regarding the optimal treatment of ventriculoperitoneal (VP) shunt infections in adults. Our aim was to assess the efficacy of treatment strategies and to identify factors that predict failure. Methods Retrospective, observational study of patients aged ≥12 years with VP shunt infections (1980 -2014). Therapeutic approaches were classified under 4 headings: only antibiotics (OA), one-stage shunt replacement (OSSR), two-stage shunt replacement (TSSR), and shunt removal without replacement (SR). The primary endpoint was failure of the treatment strategy, defined as the absence of definite cerebrospinal fluid (CSF) sterilization or related mortality. The parameters that predicted failure were analyzed using logistic regression. Results Of 108 episodes (51% male, median age 50 years), 86 were analyzed. Intravenous antibiotics were administered for a median of 19 days. Eighty episodes were treated using strategies that combined antibiotic and surgical treatment (37 TSSR, 24 SR, 19 OSSR) and 6 with OA. Failure occurred in 30% of episodes, mostly due to lack of CSF sterilization in OSSR and OA groups. Twelve percent died of related causes and 10% presented superinfection of the CSF temporary drainage/externalized peritoneal catheter. TSSR was the most effective strategy when VP shunt replacement was attempted. The only independent risk factor that predicted failure was retention of the VP shunt, regardless of the strategy. Conclusions This is the largest series of VP shunt infections in adults reported to date. VP shunt removal, particularly TSSR when the patient is shunt dependent, remains the optimal choice of treatment and does not increase morbidity.

Levofloxacin plus rifampicin (L+R) is the treatment of choice for acute staphylococcal prosthetic joint infection (PJI) managed with debridement and implant retention (DAIR). Long courses have been empirically recommended, but some studies have suggested that shorter treatments could be as effective. Our aim was to prove that a short treatment schedule was non-inferior to the standard long schedule. An open-label, multicentre, randomised clinical trial (RCT) was performed. Patients with an early post-surgical or haematogenous staphylococcal PJI, managed with DAIR and initiated on L+R were randomised to receive 8 weeks of treatment (short schedule) versus a long schedule (3 months or 6 months for hip or knee prostheses, respectively). The primary endpoint was cure rate. From 175 eligible patients, 63 were included (52% women; median age, 72 years): 33 patients (52%) received the long schedule and 30 (48%) received the short schedule. There were no differences between the two groups except for a higher rate of polymicrobial infection in the long-schedule group (27% vs. 7%; P = 0.031). Median follow-up was 540 days. In the intention-to-treat analysis, cure rates were 58% and 73% in patients receiving the long and short schedules, respectively (difference −15.7%, 95% CI −39.2% to 7.8%). Forty-four patients (70%) were evaluable per-protocol: cure rates were 95.0% and 91.7% for the long and short schedules, respectively (difference 3.3%, 95% CI −11.7% to 18.3%). This is the first RCT suggesting that 8 weeks of L+R could be non-inferior to longer standard treatments for acute staphylococcal PJI managed with DAIR.

Background. Several series predicting the prognosis of staphylococcal prosthetic joint infection (PJI) managed with debridement, antibiotics, and implant retention (DAIR) have been published, but some of their conclusions are controversial. At present, little is known regarding the efficacy of the different antibiotics that are used or their ability to eliminate methicillin-resistant S. aureus (MRSA) infection. Methods. This was a retrospective, multicenter, observational study of cases of PJI by S. aureus that were managed with DAIR (2003–2010). Cases were classified as failures when infection persistence/relapse, death, need for salvage therapy, or prosthesis removal occurred. The parameters that predicted failure were analyzed with logistic and Cox regression. Results. Out of 345 episodes (41% men, 73 years), 81 episodes were caused by MRSA. Fifty-two were hematogenous, with poorer prognoses, and 88% were caused by methicillin-susceptible S. aureus (MSSA). Antibiotics were used for a median of 93 days, with similar use of rifampin-based combinations in MSSA- and MRSA-PJI. Failure occurred in 45% of episodes, often early after debridement. The median survival time was 1257 days. There were no overall prognostic differences between MSSA- and MRSA-PJI, but there was a higher incidence of MRSA-PJI treatment failure during the period of treatment (HR 2.34), while there was a higher incidence of MSSA-PJI treatment failure after therapy. Rifampin-based combinations exhibited an independent protective effect. Other independent predictors of outcome were polymicrobial, inflammatory, and bacteremic infections requiring more than 1 debridement, immunosuppressive therapy, and the exchange of removable components of the prosthesis. Conclusions. This is the largest series of PJI by S. aureus managed with DAIR reported to date. The success rate was 55%. The use of rifampin may have contributed to homogenizing MSSA and MRSA prognoses, although the specific rifampin combinations may have had different efficacies.

Despite the use of daptomycin alone at high doses (greater than 6 mg/kg of body weight/day) against difficult-to-treat infections, clinical failures and resistance appeared. Recently, the combination daptomycin-cloxacillin showed enhanced efficacy in clearing bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA). The aim of this study was to evaluate the efficacy of daptomycin at usual and high doses (equivalent to 6 and 10 mg/kg/day in humans, respectively) in combination with cloxacillin in a rat tissue cage infection model by MRSA and to compare its efficacy to that of daptomycin-rifampin. We used MRSA strain ATCC BAA-39. In the log- and stationary-phase kill curves, daptomycin-cloxacillin improved the bactericidal activity of daptomycin, especially in log phase. For in vivo studies, therapy was administered intraperitoneally for 7 days with daptomycin at 100 mg/kg/day and 45/mg/kg/day (daptomycin 100 and daptomycin 45), daptomycin 100-cloxacillin at 200 mg/kg/12 h, daptomycin 45-cloxacillin, and daptomycin 100-rifampin at 25 mg/kg/12 h. Daptomycin-rifampin was the best therapy ( P < 0.05). Daptomycin 45 was the least effective treatment and did not protect against the emergence of resistant strains. There were no differences between the two dosages of daptomycin plus cloxacillin in any situation, and both protected against resistance. The overall effect of the addition of cloxacillin to daptomycin was a significantly greater cure rate (against adhered bacteria) than that for daptomycin alone. In conclusion, daptomycin-cloxacillin enhanced modestly the in vivo efficacy of daptomycin alone against foreign-body infection by MRSA and was less effective than daptomycin plus rifampin. The benefits of adding cloxacillin to daptomycin should be especially evaluated against infections by rifampin-resistant MRSA and for protection against the emergence of daptomycin nonsusceptibility.

Background & Aims The recent emergence of third-generation cephalosporin resistance in spontaneous bacterial peritonitis is of great concern, although neither the risk factors for resistance nor its real impact on mortality have been well defined. Methods We conducted a retrospective study of all spontaneous bacterial peritonitis episodes with positive blood and/or ascitic culture at our center (2001–2009). Episodes were classified according to the place of acquisition: community, healthcare system, or nosocomial. Results Two hundred and forty-six episodes were analyzed in 200 patients (150 males, 57.3years): 34.6% community-acquired, 38.6% healthcare system-acquired, and 26.8% nosocomially-acquired. Third-generation cephalosporin resistance occurred in 21.5% (7.1% community-acquired, 21.1% healthcare system-acquired, 40.9% nosocomially-acquired). These resistant cases were categorized as extended-spectrum β-lactamase-producing Gram-negative bacilli, other resistant Gram-negative bacilli, and Enterococci . Risk factors for resistance were previous use of cephalosporins, diabetes mellitus, upper gastrointestinal bleeding, nosocomial acquisition, and a low polymorphonuclear count in ascites. Regarding third-generation cephalosporin resistance, adequate empirical treatment was 80.7%. Independent predictors of mortality were nosocomial acquisition, poor hepato-renal function, immunosuppressive therapy, a marked inflammatory response during the episode and either third-generation cephalosporin-resistance or low rates of adequate empirical treatment. Conclusions The risk of third-generation cephalosporin resistance was particularly high in nosocomially-acquired episodes of spontaneous bacterial peritonitis, but also occurred in healthcare system-acquired cases. The extent of resistance and the adequacy of empirical antibiotics had a significant effect on mortality along with the patient's hepato-renal function. These data can help determine the most suitable empirical antimicrobial treatments in these patients.

Objectives To assess the clinical features, risk factors, molecular epidemiology and outcome of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) bacteraemia in hospitalized cancer patients. Methods Episodes of ESBL-EC bacteraemia were compared with a susceptible control group in a 3 year prospective study. ESBL-EC strains were studied by PCR and isoelectric focusing, and molecular typing was performed by PFGE. Results Out of 531 episodes of bacteraemia, 135 were caused by E. coli. Seventeen of these cases involved ESBL-EC-producing strains (12.6%). In the multivariate analysis, female gender [odds ratio (OR) 3.43; 95% confidence interval (CI) 1.03-11.4] and previous antibiotic therapy (OR 3.22; 95% CI 1.00-10.3) were found to be independent risk factors for ESBL acquisition. An analysis of ESBL-EC isolates revealed a polyclonal distribution with CTX-M predominance (59%). Patients with ESBL-EC bacteraemia were more likely to have received an inadequate empirical antibiotic therapy (65% versus 6%; P = 0.000), and the time to adequate therapy was longer in this group (0 versus 1.50 days; P = 0.000). The overall mortality rate was 22%, ranging from 20% to 35% (P = 0.20). Risk factors for mortality were solid tumour (OR 19.41; 95% CI 4.66-80.83), corticosteroid therapy (OR 3.04 95% CI 1.05-8.81) and intensive care unit admission (OR 248.24, 95% CI 18.49-3332.14). In neutropenic patients, ESBL-EC bacteraemia was associated with poorer outcome and a higher overall mortality rate (37.5% versus 6.5%; P = 0.01). Conclusions In our centre, ESBL-EC bacteraemia is frequent among cancer patients, especially in those exposed to antibiotic pressure. All ESBL-EC strains were unrelated and most of them carried a CTX-M group enzyme. Patients with ESBL-EC bacteraemia received inadequate empirical antibiotic therapy more frequently than patients carrying a susceptible strain, but significant differences in mortality could not be demonstrated.

Serious Enterococcus faecalis infections usually require combination therapy to achieve a bactericidal effect. In orthopedic infections, the prognosis of enterococcal etiology is considered poor, and the use of aminoglycosides is questioned. The ampicillin-ceftriaxone combination has recently been accepted as alternative therapy for enterococcal endocarditis. After one of our patients with endocarditis and vertebral osteomyelitis was cured with ampicillin-ceftriaxone, we started a pilot study of orthopedic infections. Patients with infections due to E. faecalis (with two or more surgical samples or blood cultures) diagnosed during 2005 to 2008 were recruited. Polymicrobial infections with ampicillin- and ceftriaxone-resistant microorganisms were excluded. Patients received ampicillin (8 to 16 g/day)-ceftriaxone (2 to 4 g/day) and were followed up prospectively. Of 31 patients with E. faecalis infections, 10 received ampicillin-ceftriaxone. Including the first patient, 11 patients were treated with ampicillin-ceftriaxone: 3 with prosthetic joint infections, 3 with instrumented spine arthrodesis device infections, 2 with osteosynthesis device infections, 1 with foot osteomyelitis, and 2 with vertebral osteomyelitis and endocarditis. Six infections (55%) were polymicrobial. All cases except the vertebral osteomyelitis ones required surgery, with retention of foreign material in six cases. Ampicillin-ceftriaxone was given for 25 days (interquartile range, 15 to 34 days), followed by amoxicillin (amoxicilline) being given to seven patients (64%). One patient with endocarditis died within 2 weeks (hemorrhagic stroke) and was not evaluable. For one patient with prosthesis retention, the infection persisted; 9/10 patients (90%) were cured, but 1 patient was superinfected. Follow-up was for 21 months (interquartile range, 14 to 36 months). Ampicillin-ceftriaxone may be a reasonable synergistic combination to treat orthopedic infections due to E. faecalis . Our experience, though limited, shows good outcomes and tolerability and may provide a basis for further well-designed comparative studies.

Objectives In the era of emergence of MDR Pseudomonas aeruginosa, osteoarticular infections (OIs) add more difficulties to its treatment. The role of β-lactams (BLs) is questioned and older drugs need to be reconsidered. The objective of this study was to describe our experience in the management of OIs caused by MDR P. aeruginosa and evaluate different therapeutic options. Methods This was a retrospective analysis of a prospectively collected cohort (2004-13) of patients with OI caused by MDR P. aeruginosa. We created two groups: (i) Group A (more difficult to treat), prosthetic joint infections (PJIs) and osteoarthritis (OA) managed with device retention; and (ii) Group B (less difficult to treat), OA managed without device retention. Antibiotic treatment was administered according to clinician criteria: monotherapy/combined therapy; and BL used by intermittent bolus (IB)/continuous infusion. Results Of 34 patients, 15 (44.1%) had PJI and 19 (55.9%) had OA (8 related to an orthopaedic device). Twenty-three cases (68%) were caused by XDR P. aeruginosa. The initial management included removal of an orthopaedic device in 14 cases, together with antibiotic [alone, 19 (55.9%; 4 colistin, 14 BL-IB and 1 BL continuous infusion); and in combination, 15 (44.1%; 5 BL-IB and 10 BL continuous infusion)]. The overall cure rate was 50% (39% and 63% in Groups A and B, respectively), ranging from 31.6% with monotherapy to 73.3% with combined therapy (P = 0.016), with special interest within Group A (cure rate with combined therapy 71.4%, P = 0.049). After rescue therapy, which included removal of remaining devices, the cure rate reached 85.3%. Conclusions We suggest that the BL/colistin combination is an optimized therapy for OI caused by MDR P. aeruginosa, together with an appropriate surgical treatment.

Bacteremia and infective endocarditis caused by Staphylococcus aureus are common and severe diseases. Optimization of treatment is fundamental in the prognosis of these infections. The high rates of treatment failure and the increasing interest in the influence of vancomycin susceptibility in the outcome of infections caused by both methicillin-susceptible and -resistant isolates have led to research on novel therapeutic schemes. The interest in the new antimicrobials with activity against methicillin-resistant staphylococci has been extended to susceptible strains, which still carry the most important burden of infection. New combinations of antimicrobials have been investigated in experimental and clinical studies, but their role is still being debated. Also, the appropriateness of the initial empirical therapy has acquired relevance in recent years. The aim of this guideline is to update the 2009 guidelines and to provide an ensemble of recommendations in order to improve the treatment of staphylococcal bacteremia and infective endocarditis, in accordance with the latest published evidence.