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.

High Rate of Undetected Infections in Failed Osteosynthesis of Pertrochanteric Fractures.

OBJECTIVE: The objective of this study was to assess the incidence of infection in patients with cutout after proximal femur fracture (PFF) osteosynthesis. DESIGN: Retrospective cohort study. SETTING: Third-level trauma center. PATIENT SELECTION CRITERIA: Patients presenting with a cutout following PFF (OTA/AO 31A) osteosynthesis, between January 2007 and December 2020. OUTCOME MEASUREMENTS AND COMPARISONS: The primary outcome was infection according to the European Bone and Joint Infection Society criteria. RESULTS: Sixty-seven patients presenting with a cutout were included, with mean age of 83.3 years (range 63-96), and 51 (76.1%) were women. Of all cases, 16 (24.7%) presented a concomitant infection. The presence of concomitant infection was suspected preoperatively in only 3 of the cases. A subgroup analysis was performed between the cases with infection and those without infection, the groups being comparable in terms of demographic data and postoperative radiological criteria. Patients with underlying infection had a higher rate of surgical wound complication (56.3% vs. 22%, P = 0.014) and higher rates of leukocytosis (11.560 vs. 7.890, P = 0.023). CONCLUSION: Faced with a cutout after osteosynthesis of a PFF, underlying infection should be considered as a possible etiological factor. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Safety and efficacy of favipiravir in COVID-19 patients with pneumonia. A randomized, double-blind, placebo-controlled study (FAVID).

PURPOSE: To design a randomized clinical trial to assess the efficacy and safety of favipiravir in patients with COVID-19 disease with pneumonia. METHODS: A randomized, double blind, placebo-controlled clinical trial of favipiravir in patients with COVID-19 pneumonia was conducted in three Spanish sites. Randomization 1:1 to favipiravir or placebo (in both groups added to the Standard of Care) was performed to treat the patients with COVID-19 pneumonia. The primary endpoint was "time to clinical improvement," measured as an improvement for ≥ two categories on a 7-point WHO ordinal scale in an up to 28 days' time frame. RESULTS: Forty-four patients were randomized (23 in the favipiravir group and 21 in the placebo group). The median time to clinical improvement was not different between the favipiravir and the placebo arms (10 days for both groups) and none of the secondary endpoints showed significant differences between arms. The proportion of adverse events (both serious and non-serious) was statistically different between the favipiravir group (68.29%) and the placebo group (31.7%) (p = 0.019), but there was insufficient statistical evidence to correlate the degree of severity of the events with the treatment group. CONCLUSIONS: Favipiravir administered for ten days to patients with COVID-19 and pneumonia did not improve outcomes compared with placebo. Although this is an underpowered negative study, efficacy results align with other randomized trials. However, in the present study, the non-serious adverse events were more frequent in the favipiravir group.

Colistin plasma concentrations are not associated with better clinical outcomes in patients with pneumonia caused by extremely drug-resistant Pseudomonas aeruginosa.

IMPORTANCE: In some cases, colistin is the only treatment option for infections caused by the very drug-resistant Pseudomonas aeruginosa. However, in the past decade, there have been questions concerning its pharmacokinetics and concentration at the site of infection. In this scenario, its use in a difficult-to-treat infection like pneumonia is currently debatable. This is a clinical pharmacokinetic study of colistin in patients with multidrug-resistant P. aeruginosa pneumonia. Our findings demonstrate that colistin exposure is associated with worse clinical outcomes rather than better clinical outcomes, implying that other therapeutic options should be explored in this clinical setting.

Should We Use Rifampicin in Periprosthetic Joint Infections Caused by Staphylococci When the Implant Has Been Exchanged? A Multicenter Observational Cohort Study.

Background: Previous studies demonstrated the efficacy of a rifampicin-based regimen in the treatment of acute staphylococcal periprosthetic joint infections (PJIs) treated with surgical debridement. However, evidence is lacking to support the use of rifampicin in cases where the implant is exchanged during revision. Methods: We included all consecutive cases of staphylococcal PJIs treated from January 2013 to December 2018 with revision surgery in this international, retrospective, multicenter observational cohort study. PJI was defined according to the European Bone and Joint Infection Society diagnostic criteria. A relapse or reinfection during follow-up, the need for antibiotic suppressive therapy, the need for implant removal, and PJI-related death were defined as clinical failure. Cases without reimplantation or with follow-up <12 months were excluded. Results: A total of 375 cases were included in the final analysis, including 124 1-stage exchanges (33.1%) and 251 2-stage exchanges (66.9%). Of those, 101 cases failed (26.9%). There was no statistically significant difference in failure of patients receiving rifampicin (22.5%, 42/187) and those not receiving rifampicin (31.4%, 59/188; P = .051). A subanalysis of chronic PJIs treated by 2-stage exchange arthroplasty demonstrated a lower failure rate in cases treated with rifampicin (15%) compared with the no-rifampicin group (35.5%; P = .005). In this subgroup, the use of rifampicin and an antibiotic holiday of >2 weeks were independent predictors of clinical success (odds ratio [OR], 0.36; 95% CI, 0.15-0.88; and OR, 0.19; 95% CI, 0.04-0.90; respectively). Conclusions: Combination treatment with rifampicin increases treatment success in patients with chronic staphylococcal PJI treated with 2-stage exchange arthroplasty.

Incidence, functional outcomes and cure rate of hematogenous infection in a 2,498 Total Knee Arthroplasties cohort.

PURPOSE: The primary aim of the present study is to report the late acute hematogenous (LAH) prosthetic joint infection (PJI) cure rate following Total knee arthroplasty (TKA) treated by means of debridement, antibiotics, and implant retention (DAIR) in a long-term follow-up. The secondary purpose is to report the functional outcomes at that follow-up and to compare them with a non-infected group. MATERIAL AND METHODS: This study cohort consists of 2,498 TKA performed from September 2005 to April 2010 that had a minimum follow-up of 10 years. The diagnosis of PJI and classification into LAH was done in accordance with the Zimmerli criteria. The primary outcome was the failure rate, defined as death before the end of antibiotic treatment, a further surgical intervention for treatment of infection, life-long antibiotic suppressive treatment or chronic infection. The Knee Society Score (KSS) was used to evaluate clinical outcomes. RESULTS: Ten patients were diagnosed with acute hematogenous PJI during the study period (0.4%). All of them were managed with DAIR, which was performed by a knee surgeon and/or PJI surgeon. The failure rate was 0% at the 8.5-year (SD, 2.4) follow-up mark. The KSS score was 82.1 vs. 84.1 (p n.s.) at final follow-up. CONCLUSION: Although the literature suggests that TKA DAIR for LAH periprosthetic joint infection is associated with high rates of failure, the results presented here suggest a high cure rate with good functional outcomes. LEVEL OF EVIDENCE: Level II, prospective cohort study.

Is an isolated positive sonication fluid culture in revision arthroplasties clinically relevant?

OBJECTIVES: The aim of this study was to investigate the clinical relevance of an isolated positive sonication fluid culture (SFC) in patients who underwent revision surgery of a prosthetic joint. We hypothesized that cases with a positive SFC have a higher rate of infection during follow-up compared with controls with a negative SFC. METHODS: This retrospective multicentre observational study was performed within the European Study Group of Implant-Associated Infections. All patients who underwent revision surgery of a prosthetic joint between 2013 and 2019 and had a minimum follow-up of 1 year were included. Patients with positive tissue cultures or synovial fluid cultures were excluded from the study. RESULTS: A total of 95 cases (positive SFC) and 201 controls (negative SFC) were included. Infection during follow-up occurred in 12 of 95 cases (12.6%) versus 14 of 201 controls (7.0%) (p = 0.125). In all, 79.8% of cases were with treated with antibiotics (76/95). Of the non-treated cases, 89% (17/19) had a positive SFC with a low virulent microorganism. When solely analysing patients who were not treated with antibiotics, 16% of the cases (3/19) had an infection during follow-up versus 5% of the controls (9/173) (p = 0.08). DISCUSSION: Although not statistically significant, infections were almost twice as frequent in patients with an isolated positive SFC. These findings require further exploration in larger trials and to conclude about the potential benefit of antibiotic treatment in these cases.

Description of reinfection of joint prosthesis after 2-stage replacement (infection of the 2nd stage prosthesis): A multicenter study.

INTRODUCTION: Two-stage exchange is the gold standard in the surgical management of prosthetic joint infection (PJI). However, perioperative reinfections (RePJI) can occur to newly inserted prosthesis, which highlights the importance of an adequate antibiotic prophylaxis, although there is scarce evidence in this field. Our objective was to evaluate the characteristics of RePJI, its prognosis and the antibiotic prophylaxis that is commonly used in second-stage surgery. METHODS: Multicentric retrospective observational study in Spanish hospitals including patients with RePJI between 2009 and 2018. RESULTS: We included 92 patients with RePJI from 12 hospitals. The most frequent isolated microorganism was Staphylococcus epidermidis in 35 cases (38.5%); 61.1% of staphylococci were methiciliin-resistant. In 12 cases (13%), the same microoganism causing the primary PJI was isolated in RePJI. When comparing with the microbiology of primary PJI, there were more cases caused by Gram-negative bacteria (the most frequent was Pseudomonas spp.) and less by Gram-positive bacteria. Failure occured in 69 cases (75%). There were 43 different courses of antibiotic prophylaxis after the second-stage surgery; the most frequent was a unique preoperative cefazolin dose, but most patients received prophylaxis before and after the second-stage surgery (61 cases). CONCLUSIONS: The most frequent microorganisms in RePJI are coagulase-negative staphylococci, although Gram-negative bacteria, especially Pseudomonas spp. are also common. There is a significant heterogeneity in antibiotic prophylaxis for a second-stage surgery. ReIPJI treatment has a high failure rate.

Therapeutic Drug Monitoring of Vancomycin Concentrations for the Management of Bone and Joint Infections: An Urgent Need.

Vancomycin is used for the treatment of bone and joint infections (BJI), but scarce information is available about its pharmacokinetic/pharmacodynamic (PK/PD) characteristics. We aimed to identify the risk factors associated with the non-achievement of an optimal PK/PD target in the first therapeutic drug monitoring (TDM). Methods: A retrospective study was conducted in a tertiary hospital from January 2020 to January 2022. Patients with BJI and TDM of vancomycin on day 2 of treatment were included. Initial vancomycin fixed doses (1 g every 8 h or 12 h) was decided by the responsible doctors. According to TDM results, dosage adjustments were performed. An AUC24h/MIC < 400 mg × h/L, between 400 and 600 mg × h/L and >600 mg × h/L, were defined as suboptimal, optimal and supratherapeutic, respectively. Patients were grouped into these three categories. Demographic, clinical and PK characteristics were compared between groups. Nephrotoxicity at the end of treatment was assessed. Results: A total of 94 patients were included: 22 (23.4%), 42 (44.7%) and 30 (31.9%) presented an infratherapeutic, optimal and supratherapeutic PK/PD targets, respectively. A younger age and initial vancomycin dose <40 mg/kg/day were predictive factors for achieving a suboptimal PK/PD target, while older age, higher serum-creatinine and dose >40 mg/kg/day were associated with overexposure. The nephrotoxicity rate was 22.7%. More than 50% of patients did not achieve an optimal PK/PD. Considering age, baseline serum-creatinine and body weight, TDM is required to readily achieve an optimal and safe exposure.

Evaluation of the host immune response assay SeptiCyte RAPID for potential triage of COVID-19 patients.

Tools for the evaluation of COVID-19 severity would help clinicians with triage decisions, especially the decision whether to admit to ICU. The aim of this study was to evaluate SeptiCyte RAPID, a host immune response assay (Immunexpress, Seattle USA) as a triaging tool for COVID-19 patients requiring hospitalization and potentially ICU care. SeptiCyte RAPID employs a host gene expression signature consisting of the ratio of expression levels of two immune related mRNAs, PLA2G7 and PLAC8, measured from whole blood samples. Blood samples from 146 adult SARS-CoV-2 (+) patients were collected within 48 h of hospital admission in PAXgene blood RNA tubes at Hospital del Mar, Barcelona, Spain, between July 28th and December 1st, 2020. Data on demographics, vital signs, clinical chemistry parameters, radiology, interventions, and SeptiCyte RAPID were collected and analyzed with bioinformatics methods. The performance of SeptiCyte RAPID for COVID-19 severity assessment and ICU admission was evaluated, relative to the comparator of retrospective clinical assessment by the Hospital del Mar clinical care team. In conclusion, SeptiCyte RAPID was able to stratify COVID-19 cases according to clinical severity: critical vs. mild (AUC = 0.93, p < 0.0001), critical vs. moderate (AUC = 0.77, p = 0.002), severe vs. mild (AUC = 0.85, p = 0.0003), severe vs. moderate (AUC = 0.63, p = 0.05). This discrimination was significantly better (by AUC or p-value) than could be achieved by CRP, lactate, creatine, IL-6, or D-dimer. Some of the critical or severe cases had "early" blood draws (before ICU admission; n = 33). For these cases, when compared to moderate and mild cases not in ICU (n = 37), SeptiCyte RAPID had AUC = 0.78 (p = 0.00012). In conclusion, SeptiCyte RAPID was able to stratify COVID-19 cases according to clinical severity as defined by the WHO COVID-19 Clinical Management Living Guidance of January 25th, 2021. Measurements taken early (before a patient is considered for ICU admission) suggest that high SeptiScores could aid in predicting the need for later ICU admission.

An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients.

Background: Whilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings. Methods: Here, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries. Results: Our analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61-0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population. Conclusions: Although clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome. Funding: Bronner P. Gonçalves, Peter Horby, Gail Carson, Piero L. Olliaro, Valeria Balan, Barbara Wanjiru Citarella, and research costs were supported by the UK Foreign, Commonwealth and Development Office (FCDO) and Wellcome [215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z]; and Janice Caoili and Madiha Hashmi were supported by the UK FCDO and Wellcome [222048/Z/20/Z]. Peter Horby, Gail Carson, Piero L. Olliaro, Kalynn Kennon and Joaquin Baruch were supported by the Bill & Melinda Gates Foundation [OPP1209135]; Laura Merson was supported by University of Oxford's COVID-19 Research Response Fund - with thanks to its donors for their philanthropic support. Matthew Hall was supported by a Li Ka Shing Foundation award to Christophe Fraser. Moritz U.G. Kraemer was supported by the Branco Weiss Fellowship, Google.org, the Oxford Martin School, the Rockefeller Foundation, and the European Union Horizon 2020 project MOOD (#874850). The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views of the European Commission. Contributions from Srinivas Murthy, Asgar Rishu, Rob Fowler, James Joshua Douglas, François Martin Carrier were supported by CIHR Coronavirus Rapid Research Funding Opportunity OV2170359 and coordinated out of Sunnybrook Research Institute. Contributions from Evert-Jan Wils and David S.Y. Ong were supported by a grant from foundation Bevordering Onderzoek Franciscus; and Andrea Angheben by the Italian Ministry of Health "Fondi Ricerca corrente-L1P6" to IRCCS Ospedale Sacro Cuore-Don Calabria. The data contributions of J.Kenneth Baillie, Malcolm G. Semple, and Ewen M. Harrison were supported by grants from the National Institute for Health Research (NIHR; award CO-CIN-01), the Medical Research Council (MRC; grant MC_PC_19059), and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE) (award 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award IS-BRC-1215-20013), and NIHR Clinical Research Network providing infrastructure support. All funders of the ISARIC Clinical Characterisation Group are listed in the appendix.

Acute Hematogenous Periprosthetic Hip Infection by Gemella morbillorum, Successfully Treated with Debridement, Antibiotics and Implant Retention: A Case Report and Literature Review of Osteoarticular Gemella morbillorum Infections.

Gemella morbillorum is a facultative anaerobic, catalase-negative and non-spore forming Gram-positive cocci. It can be found as part of the normal oropharyngeal flora, in the gastrointestinal tract and the female genital tract. However, it can be a causal agent of infections such as endocarditis, meningitis or brain abscesses, and very rarely can cause osteoarticular infections. Herein, a case report of an acute hematogenous prosthetic hip infection caused by Gemella morbillorum, successfully treated with a DAIR and beta-lactam antibiotic therapy, is presented. We provide a literature review of the other orthopedic-related infections caused by this microorganism.

Comparative efficacy of dalbavancin alone and with rifampicin against in vitro biofilms in a pharmacodynamic model with methicillin-resistant Staphylococcus aureus.

BACKGROUND: The anti-biofilm efficacy of dalbavancin (DAL) has been evaluated in static models. The comparative activity of DAL alone and with rifampicin (RIF) against biofilm-embedded methicillin-resistant Staphylococcus aureus (MRSA) was evaluated using an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model. METHODS: Two MRSA strains (HUB-4, HUB-5) were evaluated with the Calgary Device System and the dynamic CDC-Biofilm Reactor over 144 h. Dosage regimens simulated the human PK of DAL (1500 mg, single dose), vancomycin (VAN) (1000 mg/12 h) and linezolid (LZD) (600 mg/12 h), alone and with RIF (600 mg/24 h). Efficacy was evaluated by assessing log10CFU/mL changes (ΔlogCFU/mL) and screening for resistance was conducted. RESULTS: The minimal biofilm inhibitory/eradication concentrations of DAL were 0.25/16 mg/L (HUB-4) and 0.25/8 mg/L (HUB-5). In the PK/PD analysis, DAL alone showed limited efficacy but no development of resistance. Adding RIF improved the activities of DAL, VAN, and LZD, but RIF-resistant strains appeared over time in all cases. DAL-RIF was bactericidal against HUB-4 in the absence of resistance at 72 h and 144 h (ΔlogCFU/mL: -3.54±0.83, -4.32±0.12, respectively), an effect that was only achieved by LZD-RIF at 144 h (-3.33 ± 0.66). DAL-RIF activity against HUB-5 was impaired by RIF resistance to a greater extent than other combinations and this combination had no bactericidal effect. CONCLUSIONS: The anti-biofilm efficacy of DAL was improved significantly by adding RIF. Although DAL resistance did not occur, RIF resistance appeared in all combination therapies and decreased their efficacy over time. DAL-RIF in vitro treatment appears to be a promising anti-biofilm therapy, but further studies are needed to evaluate the efficacy and risk of resistance in vivo.

Comparison of Hospitalized Coronavirus Disease 2019 and Influenza Patients Requiring Supplemental Oxygen in a Cohort Study: Clinical Impact and Resource Consumption.

BACKGROUND: To compare clinical characteristics, outcomes, and resource consumption of patients with coronavirus disease 2019 (COVID-19) and seasonal influenza requiring supplemental oxygen. METHODS: Retrospective cohort study conducted at a tertiary-care hospital. Patients admitted because of seasonal influenza between 2017 and 2019, or with COVID-19 between March and May 2020 requiring supplemental oxygen were compared. Primary outcome: 30-day mortality. Secondary outcomes: 90-day mortality and hospitalization costs. Attempted sample size to detect an 11% difference in mortality was 187 patients per group. RESULTS: COVID-19 cases were younger (median years of age, 67; interquartile range [IQR] 54-78 vs 76 [IQR 64-83]; P < .001) and more frequently overweight, whereas influenza cases had more hypertension, immunosuppression, and chronic heart, respiratory, and renal disease. Compared with influenza, COVID-19 cases had more pneumonia (98% vs 60%, <.001), higher Modified Early Warning Score (MEWS) and CURB-65 (confusion, blood urea nitrogen, respiratory rate, systolic blood pressure, and age >65 years) scores and were more likely to show worse progression on the World Health Organization ordinal scale (33% vs 4%; P < .001). The 30-day mortality rate was higher for COVID-19 than for influenza: 15% vs 5% (P = .001). The median age of nonsurviving cases was 81 (IQR 74-88) and 77.5 (IQR 65-84) (P = .385), respectively. COVID-19 was independently associated with 30-day (hazard ratio [HR], 4.6; 95% confidence interval [CI], 2-10.4) and 90-day (HR, 5.2; 95% CI, 2.4-11.4) mortality. Sensitivity and subgroup analyses, including a subgroup considering only patients with pneumonia, did not show different trends. Regarding resource consumption, COVID-19 patients had longer hospital stays and higher critical care, pharmacy, and complementary test costs. CONCLUSIONS: Although influenza patients were older and had more comorbidities, COVID-19 cases requiring supplemental oxygen on admission had worse clinical and economic outcomes.

Should all patients with a culture-negative periprosthetic joint infection be treated with antibiotics? : a multicentre observational study.

AIMS: The aim of this study was to analyze the prevalence of culture-negative periprosthetic joint infections (PJIs) when adequate methods of culture are used, and to evaluate the outcome in patients who were treated with antibiotics for a culture-negative PJI compared with those in whom antibiotics were withheld. METHODS: A multicentre observational study was undertaken: 1,553 acute and 1,556 chronic PJIs, diagnosed between 2013 and 2018, were retrospectively analyzed. Culture-negative PJIs were diagnosed according to the Muskuloskeletal Infection Society (MSIS), International Consensus Meeting (ICM), and European Bone and Joint Society (EBJIS) definitions. The primary outcome was recurrent infection, and the secondary outcome was removal of the prosthetic components for any indication, both during a follow-up period of two years. RESULTS: None of the acute PJIs and 70 of the chronic PJIs (4.7%) were culture-negative; a total of 36 culture-negative PJIs (51%) were treated with antibiotics, particularly those with histological signs of infection. After two years of follow-up, no recurrent infections occurred in patients in whom antibiotics were withheld. The requirement for removal of the components for any indication during follow-up was not significantly different in those who received antibiotics compared with those in whom antibiotics were withheld (7.1% vs 2.9%; p = 0.431). CONCLUSION: When adequate methods of culture are used, the incidence of culture-negative PJIs is low. In patients with culture-negative PJI, antibiotic treatment can probably be withheld if there are no histological signs of infection. In all other patients, diagnostic efforts should be made to identify the causative microorganism by means of serology or molecular techniques. Cite this article: Bone Joint J 2022;104-B(1):183-188.

Implant Removal in the Management of Prosthetic Joint Infection by Staphylococcus aureus: Outcome and Predictors of Failure in a Large Retrospective Multicenter Study.

OBJECTIVES: To compare the characteristics and outcomes of cases with acute prosthetic joint infection (PJI; early post-surgical or hematogenous) by Staphylococcus aureus managed with implant removal (IRm) or debridement and retention (DAIR). To analyze the outcomes of all cases managed with IRm (initially or after DAIR failure). METHODS: Retrospective, multicenter, cohort study of PJI by S. aureus (2003-2010). Overall failure included mortality within 60 days since surgery and local failure due to staphylococcal persistence/relapse. RESULTS: 499 cases, 338 initially managed with DAIR, 161 with IRm. Mortality was higher in acute PJI managed initially with IRm compared to DAIR, but not associated with the surgical procedure, after propensity score matching. Underlying conditions, hemiarthroplasty, and methicillin-resistant S. aureus were risk factors for mortality. Finally, 249 cases underwent IRm (88 after DAIR failure); overall failure was 15.6%. Local failure (9.3%) was slightly higher in cases with several comorbidities, but independent of previous DAIR, type of IRm, and rifampin treatment. CONCLUSIONS: In a large multicenter study of S. aureus PJI managed with IRm, failure was low, but mortality significant, especially in cases with acute PJI and underlying conditions, but not associated with the IRm itself. Rifampin efficacy was limited in this setting.

In vitro pharmacokinetics/pharmacodynamics of continuous ceftazidime infusion alone and in combination with colistin against Pseudomonas aeruginosa biofilm.

OBJECTIVES: The pharmacokinetics/pharmacodynamics of continuous infusion (CI) beta-lactams for Pseudomonas aeruginosa biofilm infections has not been defined. This study evaluated the efficacy of several dosage regimens of CI ceftazidime, with or without colistin, an antibiotic with a potential antibiofilm effect, against biofilm-embedded P. aeruginosa. METHODS: Mature biofilms of the reference strain PAO1 and the clinical isolate HUB8 (both ceftazidime- and colistin-susceptible) were investigated over 54h using a dynamic CDC biofilm reactor. CI dosage regimens were ceftazidime monotherapy (4, 10, 20 and 40 mg/L), colistin monotherapy (3.50 mg/L), and combinations of colistin and ceftazidime (4 or 40 mg/L). Efficacy was evaluated by changes in log10colony-forming units (cfu)/mL and confocal microscopy. RESULTS: At 54 h, the antibiofilm activity of ceftazidime monotherapies was slightly higher for ceftazidime 20 mg/L (-2.84 log10cfu/mL) and 40 mg/L (-3.05) against PAO1, but no differences were seen against HUB8. Ceftazidime-resistant colonies emerged with 4 mg/L regimens in both strains and with other regimens in PAO1. Colistin monotherapy had significant antibiofilm activity against HUB8 (-3.07), but lower activity against PAO1 (-1.12), and colistin-resistant strains emerged. Combinations of ceftazidime and colistin had higher antibiofilm activity at 54 h compared with each monotherapy, and prevented the emergence of resistance to both antibiotics; higher antibiofilm activity was observed with ceftazidime 40 mg/L plus colistin compared with ceftazidime 4 mg/L plus colistin (-4.19 vs. -3.10 PAO1; -4.71 vs. -3.44 HUB8). CONCLUSIONS: This study demonstrated that, with %T>MIC=100%, CI ceftazidime displayed concentration-dependent antibiofilm activity against P. aeruginosa biofilm, particularly in combination with colistin. These results support the use of high-dosage regimens of CI ceftazidime with colistin against biofilm-associated infections with ceftazidime-susceptible P. aeruginosa.

Clinical Features Associated with Strongyloidiasis in Migrants and the Potential Impact of Immunosuppression: A Case Control Study.

Strongyloides stercoralis is a widely distributed nematode more frequent in tropical areas and particularly severe in immunosuppressed patients. The aim of this study was to determine factors associated with strongyloidiasis in migrants living in a non-endemic area and to assess the response to treatment and follow-up in those diagnosed with the infection. We performed a multicenter case-control study with 158 cases and 294 controls matched 1:2 by a department service. Participants were recruited simultaneously at six hospitals or clinics in Spain. A paired-match analysis was then performed looking for associations and odds ratios in sociodemographic characteristics, pathological background, clinical presentation and analytical details. Cases outcomes after a six-month follow-up visit were also registered and their particularities described. Most cases and controls came from Latin America (63%-47%) or sub-Saharan Africa (26%-35%). The number of years residing in Spain (9.9 vs. 9.8, p = 0.9) and immunosuppression status (30% vs. 36.3%, p = 0.2) were also similar in both groups. Clinical symptoms such as diffuse abdominal pain (21% vs. 13%, p = 0.02), and epigastralgia (29% vs. 18%, p < 0.001); along with a higher eosinophil count (483 vs. 224 cells/mL in cases and controls, p < 0.001) and the mean total Immunoglobulin E (IgE) (354 U/L vs. 157.9 U/L; p < 0.001) were associated with having strongyloidiasis. Finally, 98.2% percent of the cases were treated with ivermectin in different schedules, and 94.5% met the cure criteria at least six months after their first consultation. Abdominal pain, epigastralgia, eosinophilia, increased levels of IgE and Latin American origin remain the main features associated with S. stercoralis infection, although this association is less evident in immunosuppressed patients. The appropriate follow-up time to evaluate treatment response based on serology titers should be extended beyond 6 months if the cure criteria are not achieved.

Efficacy and Therapeutic Drug Monitoring of Continuous Beta-Lactam Infusion for Osteoarticular Infections Caused by Fluoroquinolone-Resistant Pseudomonas aeruginosa: A Prospective Cohort Study.

BACKGROUND AND OBJECTIVES: Osteoarticular infections (OIs) caused by fluoroquinolone-resistant Pseudomonas aeruginosa, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, have poor outcomes. We evaluated the outcomes of an optimized strategy of continuous beta-lactam infusion (BL-CI) guided by therapeutic drug monitoring (TDM) for OIs caused by fluoroquinolone-resistant P. aeruginosa. METHODS: A prospective observational study of patients with P. aeruginosa OIs in a hospital-based BL-CI program (2016-2018) was carried out. TDM targeting free BL concentrations in plasma (fCss) of at least 3-4 × MIC was performed. We compared failure rates between patients with OIs caused by fluoroquinolone-resistant strains who were treated with BL-CI, with or without colistin, and patients with OIs caused by fluoroquinolone-susceptible strains who were treated with ciprofloxacin. RESULTS: Fifty-two patients were included in the study, 19 (36.5%) of whom had OIs caused by fluoroquinolone-resistant P. aeruginosa (13 (68.4%) MDR/XDR strains; 11 (57.9%) device-related infections). The median duration of BL-CI was 36 days; ten patients (52.6%) received BL-colistin combinations. Eighty-two samples were utilized in the TDM, and most patients were found to have a median fCss of 3-10 × MIC; 17 dose adjustments were performed and eight patients needed dose decreases, five of which were due to chronic kidney disease or acute kidney injury (AKI). BL-CI was well tolerated, with the most frequent adverse event being AKI. Failure occurred to 4 patients (21.1%), which was similar to the failure rate of patients with OIs caused by fluoroquinolone-susceptible P. aeruginosa treated with ciprofloxacin (5/30 [16.7%]) (p = 0.699). TDM was also used in the initial BL treatment of patients with OIs caused by susceptible strains before those patients were switched to treatment with ciprofloxacin alone (33 patients, 110 samples, 19 dose adjustments). CONCLUSIONS: BL-CI used with/without colistin and supported by TDM may be an alternative and effective treatment option for OIs caused by fluoroquinolone-resistant P. aeruginosa, where limited available therapeutic options exist, especially in the setting of multidrug resistance. Future research should elucidate whether this strategy can produce outcomes similar to those of patients treated for OIs caused by fluoroquinolone-susceptible strains.