Impact of antibiotic prophylaxis in second-stage surgery in joint prosthesis infection treated with two-stage exchange. A multicenter case-control study.

INTRODUCTION: After two-stage exchange due to prosthetic joint infection (PJI), the new prosthesis carries a high risk of reinfection (RePJI). There isn`t solid evidence regarding the antibiotic prophylaxis in 2nd-stage surgery. The objective of this study is to describe what antibiotic prophylaxis is used in this surgery and evaluate its impact on the risk of developing RePJI. METHODS: Retrospective multicenter case-control study in Spanish hospitals. The study included cases of PJI treated with two-stage exchange and subsequently developed a new infection. For each case, two controls were included, matched by prosthesis location, center, and year of surgery. The prophylaxis regimens were grouped based on their antibacterial spectrum, and we calculated the association between the type of regimen and the development of RePJI using conditional logistic regression, adjusted for possible confounding factors. RESULTS: We included 90 cases from 12 centers, which were compared with 172 controls. The most frequent causative microorganism was Staphylococcus epidermidis with 34 cases (37.8%). Staphylococci were responsible for 50 cases (55.6%), 32 of them (64%) methicillin-resistant. Gram-negative bacilli were involved in 30 cases (33.3%), the most common Pseudomonas aeruginosa. In total, 83 different antibiotic prophylaxis regimens were used in 2nd-stage surgery, the most frequent a single preoperative dose of cefazolin (48 occasions; 18.3%); however, it was most common a combination of a glycopeptide and a beta-lactam with activity against Pseudomonas spp (99 cases, 25.2%). In the adjusted analysis, regimens that included antibiotics with activity against methicillin-resistant staphylococci AND Pseudomonas spp were associated with a significantly lower risk of RePJI (adjusted OR = 0.24; 95% IC: 0.09-0.65). CONCLUSIONS: The lack of standardization in 2nd-satge surgery prophylaxis explains the wide diversity of regimens used in this procedure. The results suggest that antibiotic prophylaxis in this surgery should include an antibiotic with activity against methicillin-resistant staphylococci and Pseudomonas.

Remdesivir for Severe Coronavirus Disease 2019 (COVID-19) Versus a Cohort Receiving Standard of Care.

BACKGROUND: We compared the efficacy of the antiviral agent, remdesivir, versus standard-of-care treatment in adults with severe coronavirus disease 2019 (COVID-19) using data from a phase 3 remdesivir trial and a retrospective cohort of patients with severe COVID-19 treated with standard of care. METHODS: GS-US-540-5773 is an ongoing phase 3, randomized, open-label trial comparing two courses of remdesivir (remdesivir-cohort). GS-US-540-5807 is an ongoing real-world, retrospective cohort study of clinical outcomes in patients receiving standard-of-care treatment (non-remdesivir-cohort). Inclusion criteria were similar between studies: patients had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, were hospitalized, had oxygen saturation ≤94% on room air or required supplemental oxygen, and had pulmonary infiltrates. Stabilized inverse probability of treatment weighted multivariable logistic regression was used to estimate the treatment effect of remdesivir versus standard of care. The primary endpoint was the proportion of patients with recovery on day 14, dichotomized from a 7-point clinical status ordinal scale. A key secondary endpoint was mortality. RESULTS: After the inverse probability of treatment weighting procedure, 312 and 818 patients were counted in the remdesivir- and non-remdesivir-cohorts, respectively. At day 14, 74.4% of patients in the remdesivir-cohort had recovered versus 59.0% in the non-remdesivir-cohort (adjusted odds ratio [aOR] 2.03: 95% confidence interval [CI]: 1.34-3.08, P < .001). At day 14, 7.6% of patients in the remdesivir-cohort had died versus 12.5% in the non-remdesivir-cohort (aOR 0.38, 95% CI: .22-.68, P = .001). CONCLUSIONS: In this comparative analysis, by day 14, remdesivir was associated with significantly greater recovery and 62% reduced odds of death versus standard-of-care treatment in patients with severe COVID-19. CLINICAL TRIALS REGISTRATION: NCT04292899 and EUPAS34303.

Safety and Tolerability of More than Six Days of Tedizolid Treatment.

Tedizolid has demonstrated its efficacy and safety in clinical trials; however, data concerning its tolerability in long-term treatments are scarce. The aim of the study was to assess the indications and to describe the long-term safety profile of tedizolid. A multicentric retrospective study of patients who received tedizolid for more than 6 days was conducted. Adverse events (AEs) were identified from patients' medical records and laboratory data. The World Health Organization causality categories were used to discern AEs that were probably associated with tedizolid. Eighty-one patients, treated with tedizolid 200 mg once daily for a median (interquartile range [IQR]) duration of 28 (14 to 59) days, were included; 36 (44.4%) had previously received linezolid. The most common reasons for selecting tedizolid were to avoid linezolid potential toxicities or interactions (53.1%) or due to previous linezolid-related toxicities (27.2%). The most common indications were off-label, including prosthetic joint infections, osteomyelitis, and respiratory infections (77.8%). Overall, 9/81 patients (11.1%) experienced a probably associated AE. Two patients (2.5%) developed gastrointestinal disorders, 1 (1.2%) developed anemia, and 6 developed thrombocytopenia (7.4%) after a median (IQR) duration of treatment of 26.5 (17 to 58.5) days. Four (5%) patients discontinued tedizolid due to AEs. Among 23 patients with chronic renal failure (CRF), the rate of myelotoxicity was 17.4%, and only 8.7% had to stop tedizolid; 20 out of 22 with previous linezolid-associated toxicity had no AE. Long-term tedizolid treatments had good tolerance with rates of gastrointestinal AE and hematological toxicity lower than those reported with linezolid, particularly in patients with CRF and in those with a history of linezolid-associated toxicity.

Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial.

Importance: Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is unknown. Objective: To determine the efficacy of 5 or 10 days of remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment. Design, Setting, and Participants: Randomized, open-label trial of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (pulmonary infiltrates and room-air oxygen saturation >94%) enrolled from March 15 through April 18, 2020, at 105 hospitals in the United States, Europe, and Asia. The date of final follow-up was May 20, 2020. Interventions: Patients were randomized in a 1:1:1 ratio to receive a 10-day course of remdesivir (n = 197), a 5-day course of remdesivir (n = 199), or standard care (n = 200). Remdesivir was dosed intravenously at 200 mg on day 1 followed by 100 mg/d. Main Outcomes and Measures: The primary end point was clinical status on day 11 on a 7-point ordinal scale ranging from death (category 1) to discharged (category 7). Differences between remdesivir treatment groups and standard care were calculated using proportional odds models and expressed as odds ratios. An odds ratio greater than 1 indicates difference in clinical status distribution toward category 7 for the remdesivir group vs the standard care group. Results: Among 596 patients who were randomized, 584 began the study and received remdesivir or continued standard care (median age, 57 [interquartile range, 46-66] years; 227 [39%] women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes), and 533 (91%) completed the trial. Median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group. On day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P = .02). The clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P = .18 by Wilcoxon rank sum test). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care. Conclusions and Relevance: Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment. Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT04292730.

Measuring Outcomes: Pain and Quality of Life 48 Months After Acute Postoperative Total Knee Prosthetic Joint Infection.

BACKGROUND: Measuring HRQOL is simple, inexpensive, permits the health status to be measured over time, and is useful to compare or initiate treatments and evaluate results, facilitating homogenization in patient inclusion. OBJECTIVES: To evaluate disease-specific and generic HRQOL and influence of associated factors in patients undergoing open debridement for acute postsurgical knee prosthetic joint infection after TKR at 12 and 48 months after completing antibiotic treatment and considered cured of infection. METHODS: Health-related quality-of-life measures were administered at baseline (WOMAC) and 12 and 48 months (WOMAC and SF-36) in patients with prosthesis retention, no symptoms of infection, and CRP (≤ 1 mg/dL). RESULTS: Thirty patients were included, and 24 were evaluated at 48 months. WOMAC scores improved significantly (P < 0.01) at 12 and 48 months. The effect size was 0.72 for stiffness, 2.01 for pain, and 2.15 for function. At 48 months, improvements were greater (P < 0.02) except for stiffness. The most frequently isolated microorganisms were Staphylococcus aureus (14 patients) and coagulase-negative staphylococci (9 patients). SF-36 physical role, bodily pain, emotional role, and mental health dimension scores at 12 and 48 months were significantly worse in patients with isolates of Staphylococcus aureus (P < 0.05). CONCLUSIONS: Health-related quality-of-life measures detected significant differences in outcomes in patients infected by S. aureus compared with patients infected by other microorganisms. HRQOL measures may provide useful complementary information on outcomes after acute postoperative infection.

Clinical outcomes by supplemental oxygen use in remdesivir-treated, hospitalised adults with COVID-19.

BACKGROUND: Clinical trials show different effects of remdesivir on clinical outcomes relative to COVID-19 severity at hospital admission; in Europe, there are few real-world data. METHODS: A multicentre, multinational retrospective cohort study in adult patients hospitalised with PCR-confirmed COVID-19 was conducted to understand remdesivir clinical use in different countries and to describe outcomes for patients receiving remdesivir stratified by oxygen use. Primary endpoints were all-cause mortality at day 28 and hospitalisation duration. Patients were categorised by baseline disease severity: no supplemental oxygen (NSO); low flow oxygen ≤ 6 litres (l)/minute (LFO); high flow oxygen > 6 l/minute (HFO). RESULTS: Four hundred and forty-eight (448) patients (72 [16.1%] HFO; 295 [65.8%] LFO; 81 (18.1%] NSO) were included; median age was 65 years and 64% were male. Mortality was higher in patients on HFO (rate 23.6%) compared to LFO (10.2%; p = 0.001) or NSO (6.2%; p = 0.002). Duration of hospitalisation was longer in patients on HFO (13 days) compared to LFO (9 days; p = 0.003) and NSO (9 days; p = 0.021). Patients who initiated remdesivir ≥ 2 days compared to within a day of hospitalisation had a 4.2 times higher risk of death, irrespective of age, sex, comorbidities, and oxygen support at baseline. Requirement for mechanical ventilation/ECMO and readmission within 28 days of discharge was similar across groups. Remdesivir use and outcomes differed by country. CONCLUSIONS: A higher mortality rate and duration of hospitalisation was seen in remdesivir-treated COVID-19 patients on HFO compared to LFO and NSO. Initiation of remdesivir upon admission as opposed to delayed initiation has a mortality benefit. CLINICAL TRIALS REGISTRATION: NCT04847622.

Necrotizing fasciitis: Usefulness of the LRINEC score in a third-level hospital.

AIM: To review patients seen in the emergency room, diagnosed with necrotizing fasciitis (NF) and the correlation of such complications with the Laboratory Risk Indicator for Necrotizing fasciitis scale (LRINEC). The purpose of this study is to assess the use of the LRINEC score for early diagnosis of NF and its prognostic use in a consecutive series of cases treated at our hospital. METHODS: Retrospective observational study including patients with a diagnosis of NF in the emergency room of a tertiary hospital over 11 years. The results are shown as median, interquartile range and absolute range for quantitative variables. In the case of qualitative variables, the results are shown as absolute and relative frequency. The comparison between the categories of the LRINEC scale was performed through a post-hoc comparison from a non-parametric rank-ANOVA analysis. Comparisons between LRINEC groups in the qualitative variables were performed using Fisher's exact test. RESULTS: A total of 45 patients with a mean age of 51 years were identified. There was a 20% mortality rate (9 cases). The highest mortality rate was registered in the high-risk group (LRINEC greater than 8) with 4 deceased individuals (44.44%), while in the low and moderate-risk groups, 3 and 2 deceased individuals (33% and 22%) were registered, respectively, without considering this result statistically significant (p=0.811). There was an amputation rate of 15.6% (7 cases). The average LRINEC score was greater in the cases that required amputation 9 (95% CI 7; 13) in comparison to the other patients, 6 (95% CI 5; 8), p=0.044. The average hospital stay lasted 32.5 days (95% CI: 25; 40); 30 days in the low-risk group, 41 days in the moderate-risk group and 40 days in the high-risk group. Mortality was associated to a smaller number of interventions (p=0.005) and was preceded by septic shock in all cases. CONCLUSIONS: The LRINEC score may be useful to aid diagnosis. However, clinical suspicion is the most important in diagnosis. A LRINEC low score does not exclude NF. In this retrospective series, 35.71% of cases presented a low LRINEC score, making the rate of false negatives high. In view of these results, The LRINEC score cannot be used as a prognostic value since an initial low score does not rule out serious evolution.

[Listeria monocytogenes infection in a total knee arthroplasty]. / Infección por Listeria monocytogenes de una prótesis total de rodilla.

BACKGROUND: Acute blood borne prosthetic infections occur in patients with an asymptomatic prosthesis that, after an infection involving bacteremia, produces bacterial implantation in the prosthesis and causes an acute infection. This type of infection is usually caused by gram positive cocci, Streptococci and Staphylococci. We present the clinical case of a patient without a history of immunodeficiency, who had an acute blood borne knee prosthetic infection caused by Listeria monocytogenes. METHODS: The diagnosis of infection was made based on the clinical data, blood tests and the positive culture of an arthrocentesis. A prosthetic exchange was performed in two stages. RESULTS: After the revision arthroplasty, the patient was still infection free at the 24-month followup. CONCLUSIONS: This type of infection is rare, with very few cases published in the literature, and without a defined treatment modality. The two-stage prosthetic exchange is a valid alternative in prosthetic infections caused by this microorganism and avoids suppressive antibiotic therapy.

Determinación de linezolid en plasma mediante cromatografía líquida de alta resolución para la monitorización terapéutica en pacientes / Determination of linezolid in human plasma by high-performance liquid chromatography for therapeutic drug monitoring

Introducción. Linezolid es un antibiótico sintético de un nuevo grupo, las oxazolidinonas, con espectro de actividad para grampositivos. Está indicado en infecciones de piel y tejidos blandos e infecciones nosocomiales adquiridas en la comunidad así como infecciones causadas por Staphylococcus aureus y Enterococus meticilin y vancomicin-resistentes, respectivamente. El objetivo de este trabajo es desarrollar y evaluar un método de cromatografía líquida de alta resolución (HPLC) para la monitorización de niveles plasmáticos de linezolid en muestras de pacientes. Material y métodos. Se utilizó como fase móvil una mezcla de acetonitrilo y agua con flujo isocrático de 1mL y una columna corta C18. La detección se realizó en un detector ultravioleta/visible a 254nm. El tratamiento de la muestra fue por precipitación de proteínas con ácido tricloroacético y posterior inyección del sobrenadante. Resultados. El método fue lineal y validado para un intervalo de 0,25 a 20mg/L. La precisión intra e interensayo (CV) fue inferior al 1% y 1,6%, respectivamente. La exactitud osciló entre -4,3% y 0,4%. La recuperación media fue superior al 82%. No se encontraron interferencias con otros fármacos habitualmente utilizados en la terapia combinada con linezolid. Tampoco se detectaron interferencias endógenas de la propia matriz biológica. Conclusiones. El método descrito para cuantificar linezolid en muestras de plasma es sensible, reproducible, específico, rápido y requiere poca muestra, por lo que le hace adecuado para la monitorización terapéutica (AU)

Introduction. Linezolid is a synthetic antibiotic of the group of the oxazolidinones with Gram positive spectrum of activity. It is indicated in skin and soft tissue infections, community-acquired nosocomial infections and infections caused by methicillin-resistant and vancomycin-resistant Staphylococcus aureus and Enterococcus, respectively. The aim of this work is to develop and evaluate a high pressure (HPLC) method for the monitoring of plasma levels of linezolid in patients samples. Materials and methods. The mobile phase consisted of a mixture of acetonitrile and water with a flow rate of 1mL/min and a short C18 column. An ultraviolet/visible detector at 254nm was used to detect the peaks. Sample treatment consisted of precipitation of plasma proteins with trichloroacetic acid and then injection of the supernatant. Results. The method was linear and validated from 0,25 to 20mg/L. The within-day and between-day coefficient of variation (CV) was less 1% and 1,6%, respectively. The accuracy varied between −4,3% and 0,4%. The average recovery was greater than 82%. No interferences were found with other drugs habitually used in the therapy combined with linezolid. Endogenous interferences of the biological matrix were not detected. Conclusions. The method described to quantify linezolid in plasma samples is sensitive, reproducible, specific, rapid and needs very little sample, which makes it suitable for therapeutic drug monitoring (AU)