Osteoarticular Infections Research Articles

1138. Utility of Methicillin-resistant Staphylococcus aureus Nares Screening in Hospitalized Children With Acute Infectious Disease Syndromes

BackgroundEmpirical antibiotic regimens frequently include treatment for methicillin-resistant Staphylococcus aureus (MRSA). Studies in adults with pneumonia support the use of a negative MRSA nares screening (MNS) to help de-escalate antibiotic therapy. Comparable pediatric data in the literature is scarce. We aimed to evaluate the use of MNS for antibiotic de-escalation in hospitalized children (< 18 years) at a tertiary children’s hospital. MethodsA retrospective chart review was conducted of pediatric inpatients (January 01, 2015 to December 31, 2020) with a presumed infectious diagnosis who had a PCR-based MNS test and a clinical culture (i.e. site of infection or blood) performed as part of their diagnostic work up. Those who were screened >5 days since admission or > 48 hours since start of MRSA-active antimicrobials, and those who had antibiotic treatment withdrawn after 48 hours because of negative cultures were excluded. ResultsA total of 101 children were included with a median age (range) of 2 years (0-17) and about half (n=57, 56.4%) were male. Top three diagnosis groups were skin and soft tissue infections (n=33, 32.7%), toxin-mediated syndromes (n=21, 20.8%), and osteoarticular infections (n=13, 12.9%). Pneumonia accounted for only six (5.9%) patients. The prevalence of nasal MRSA colonization was 6.9% (n=7). The sensitivity of the MNS test to predict a MRSA infection was 42.9% with a specificity of 95.7%. The positive predictive value (PPV) and negative predictive values (NPV) were 42.9% and 95.7%, respectively. In about half (55/95, 57.9%) of patients initiated on anti-MRSA therapy, these agents were discontinued during the admission. A quarter (n=14, 25.5%) were de-escalated based on the negative MNS test alone, and another third (n=21, 38.2%) after negative MNS test and negative culture results became available. ConclusionPediatric providers at this institution have started to use the MNS to help limit anti-MRSA therapy. We noted a high NPV which suggests that MNS may be useful for timely de-escalation of anti-MRSA therapy and thereby a useful antimicrobial stewardship tool for hospitalized children. Prospective studies to evaluate the utility of MNS for the various infectious syndromes are warranted.Disclosures All Authors: No reported disclosures

1150. Pediatric Osteoarticular Infections Caused by Mycobacteria Tuberculosis Complex: A Twenty-Six Year Review of Cases in San Diego, California

BackgroundOsteoarticular infections (OAI) account for 10-20% of extrapulmonary Mycobacteria tuberculosis (MTB) complex infections in children. Given the rarity of MTB OAI, the epidemiology, disease manifestations, and treatment are poorly characterized. We describe 21 children treated for MTB complex OAI over a 26-year period at a tertiary pediatric center in southern California. MethodsWe conducted a retrospective review of children diagnosed with MTB complex OAI and cared for between 31 Dec 1992 to 31 Dec 2018 at a single tertiary care pediatric hospital with close proximity to the United States-Mexico border. ResultsWe identified 21 children with MTB complex OAI during the study period (Table 1). Concurrent pulmonary disease (4.8%), meningitis (9.5%), and intra-abdominal involvement (14.3%) were all observed. MTB complex was identified by culture from operative samples in 15/21 children (71.4%); 8/15 (51.3%) cultures were positive for Mycobacterium bovis. Of the eight cases of vertebral OAI (the most common site), one was culture-positive for M. bovis. Open bone biopsy was the most common procedure for procurement of a tissue sample and had the highest culture yield (Table 2). The median duration of antimicrobial therapy was 52 weeks (IQR 52-58). Successful completion of therapy was documented in 15 children (71.4%). Seven children (33.3%) experienced long term sequelae related to their infection.Table 1. Twenty-one children with Mycobacteria tuberculosis complex osteoarticular infections. Table 2. Surgical sample type and percent positivity. ConclusionAmong the 21 children with MTB complex OAI assessed, 8 of 15 (53.3%) children with a positive tissue culture had M. bovis (intrinsically resistant to pyrazinamide), representing a higher percentage than in previous reports and potentially reflecting its presence in unpasteurized dairy products in the California-Baja region. Local epidemiological trends in endemic MTB complex species should be considered when evaluating and managing MTB complex OAI. Bone biopsy produced the highest culture yield in this study. Given the rarity of this disease, multicenter collaborative studies are needed to improve our understanding of the presentation and management of pediatric MTB complex OAI.Disclosures Vanessa Raabe, MD, MSc, Pfizer (Scientific Research Study Investigator, Other Financial or Material Support, Editorial support)Sanofi (Scientific Research Study Investigator)

244. Risk Factors Associated with Complications/Sequelae in Pediatric Patients with Osteomyelitis

BackgroundOsteoarticular infections are serious invasive pathologies in the pediatric population. They have high morbidity, especially if antimicrobial treatment is inadequate and late. Based on pediatric series patients with osteomyelitis require prolonged antibiotic schemes, long stay and high hospital costs, multiple surgical procedures and develop short and long-term sequelae. MethodsA retrospective, observational, longitudinal and analytical study was conducted in patients under 17 years of age diagnosed with osteomyelitis at the National Institute of Pediatrics from January 2009 to January 2019. Demographic information, clinical presentation, microbiological, treatment and six-month follow-up were recorded. ResultsA total of 109 patients were included, 57 (52%) males with median age of 98 (1-205) months with predominance in previous healthy (66%). By temporality, the chronic form predominated in 72%. The history of trauma was identified in 26% and fracture 19%. The most affected bone was femur 26%. Blood culture was performed in 55%, secretion culture in 52.2% with isolation in 56%. Methicillin-susceptible Staphylococcus aureus (MSSA) was the main agent identified. Complications occurred in 37%, the most frequent was surgical wound infection in 13% followed by fracture 11%. Risk factors for complications were chronic osteomyelitis RR 5.7 (CI 1.8-17.9), Sepsis/Shock RR 3.8 (CI 1.08-13-8) and MSSA infections RR 2.7 (CI 1.01-7.5); Risk factors for surgical site infection included initial fracture RR 3.5 (CI 1-11), local ulcer RR 4.2 (CI 1.3-13.06) and MSSA infection RR 5.9 (CI 1.8-19.4). Risk factors for limitation to movement included chronic osteomyelitis RR 4.87 (CI 1.6-14), fever RR 2.5 (CI 1.15-5.5), Sepsis/shock RR 5.3 (CI 1.3-20) (p 0.013) and MSSA infection RR 4.1 (CI 1.4-11.9).ConclusionOsteomyelitis is still a health problem in our country. The diagnosis of osteomyelitis may be challenging as lack of suspicion often leads to delayed diagnosis. Knowledge of the risk factors for complications in pediatric patients could be useful to give early and proper antibiotic and surgical treatment. It is a priority to have a multidisciplinary team for the diagnosis and treatment of osteoarticular infections. Disclosures All Authors: No reported disclosures

983. Outcomes of Candida Bone and Joint Infections in Eight Patients from a Phase 3 Open-label Study (FURI)

Abstract Background Candida osteoarticular infections are often preceded by candidemia with the intervertebral discs and knee joints the most common area for candidemic seeding. Candida osteomyelitis has significant morbidity and diagnosis is often delayed difficult to treat. Treatment courses are usually long and there are limited oral options available for patients who have an azole-resistant infection. Oral ibrexafungerp is an investigational broad-spectrum glucan synthase inhibitor antifungal with activity against Candida and Aspergillus species, including azole- and echinocandin-resistant strains. A Phase 3 open-label, single-arm study of ibrexafungerp (FURI; NCT03059992) is ongoing for the treatment of patients with fungal disease refractory or who intolerant of to standard of care antifungal therapy. Table 1. FURI Bone and Joint Infection Outcomes Methods FURI subjects were eligible for enrollment if they have proven or probable, severe mucocutaneous candidiasis, invasive candidiasis or invasive aspergillosis and documented evidence of failure to, intolerance to, or toxicity related to a currently approved standard-of-care antifungal treatment or can not receive approved oral antifungal options (e.g., susceptibility of the organism) or a continued IV antifungal therapy is clinically undesirable or unfeasible. Results An independent Data Review Committee (DRC) provided an assessment of treatment response for a total 74 subjects enrolled in the FURI study from 22 centers in US, UK and EU treated with ibrexafungerp for mucocutaneous or invasive fungal infections from 2016- 2020. There were 8 subjects out of the 74 subjects who were diagnosed with various bone and joint infections, 5 subjects with spondylodiscitis, 1 subject with a knee/prosthetic joint infection and 2 subjects with bone infections, one of the tibia and one of the zygomatic arch. Table 1 shows outcomes for this patient group, five (75%) patients had a clinical benefit (complete or partial response and stable response), one (12.5%) had progression of disease and one patient was indeterminate. The median days of therapy for this group was 210.5 days. Conclusion Analysis of 8 subjects from the FURI study indicates that oral ibrexafungerp provides a promising therapeutic response in option for patients with bone and/or joint infections. Disclosures Caryn Morse, MD, Chimerix (Scientific Research Study Investigator)Covis Pharma (Scientific Research Study Investigator)Gilead Sciences Inc. (Scientific Research Study Investigator)Ridgeback Biotherapeutics (Scientific Research Study Investigator)Roche (Scientific Research Study Investigator)SCYNEXIS, Inc. (Scientific Research Study Investigator)Theratechnologies (Advisor or Review Panel member)Viiv (Advisor or Review Panel member) Oliver Cornely, Prof., Actelion (Consultant, Grant/Research Support)Al-Jazeera Pharmaceuticals (Consultant)Allecra Therapeutics (Consultant)Amplyx (Consultant, Grant/Research Support)Astellas (Consultant, Grant/Research Support)Basilea (Consultant, Grant/Research Support)Biocon (Consultant)Biosys (Consultant)Cidara (Consultant, Grant/Research Support)CoRe Consulting (Consultant)Da Volterra (Consultant, Grant/Research Support)DFG (German Research Foundation) (Grant/Research Support)Entasis (Consultant)F2G (Consultant, Grant/Research Support)German Federal Ministry of Research and Education (Grant/Research Support)Gilead (Consultant, Grant/Research Support)Grupo Biotoscana (Consultant)Immunic (Grant/Research Support)IQVIA (Consultant)Janssen (Grant/Research Support)Matinas (Consultant)Medicines Company (Grant/Research Support)MedPace (Consultant, Grant/Research Support)Melinta Therapeutics (Grant/Research Support)Menarini (Consultant)Merck/MSD (Consultant, Grant/Research Support)Molecular Partners (Consultant)MSG-ERC (Consultant)Mylan (Consultant)Nabriva (Consultant)Noxxon (Consultant)Octapharma (Consultant)Paratek (Consultant)Pfizer (Consultant, Grant/Research Support)PSI (Consultant)Roche Diagnostics (Consultant)Scynexis (Consultant, Grant/Research Support)Seres (Consultant)Shionogi (Consultant)Wiley (Blackwell) (Other Financial or Material Support) Philipp Koehler, MD, Ambu GmbH (Consultant, Speaker’s Bureau)Astellas Pharma (Speaker’s Bureau)Euopean Confederation of Medical Mycology (Speaker’s Bureau)German Federal Ministry of Research and Education (Grant/Research Support)Gilead (Consultant, Speaker’s Bureau)MSD (Speaker’s Bureau)Noxxon N.V. (Consultant)Pfizer (Speaker’s Bureau)State of North Rhine-Westphalia, Germany (Grant/Research Support) Jürgen Prattes, Dr, AbbVie Inc. (Shareholder)Gilead (Speaker’s Bureau)MSD (Grant/Research Support)Novo Nordisk (Shareholder)Pfizer (Advisor or Review Panel member)Stryker (Shareholder) Guenter Weiss, MD, MSD (Speaker’s Bureau)Novartis (Speaker’s Bureau)Pfizer (Speaker’s Bureau)Pharmacosmos (Speaker’s Bureau)Scynexis (Scientific Research Study Investigator)Vifor (Speaker’s Bureau) Nkechi Azie, MD, SCYNEXIS, Inc. (Employee, Shareholder) David A. Angulo, MD, SCYNEXIS, Inc. (Employee, Shareholder)

Bloodstream Infection and Endocarditis Caused by Staphylococcus aureus in Patients with Cancer: A Multicenter Cohort Study.

IntroductionIn a large cohort of patients with Staphylococcus aureus bloodstream infection (SABSI), we aimed to analyze the incidence and risk factors for infective endocarditis (IE) among patients with active cancer (PAC) in comparison with those without cancer (PWC).MethodsMulticenter cohort study of patients with SABSI admitted to two tertiary care hospitals, from 2011 to 2019. PAC were defined as those with an active solid organ cancer or hematological malignancies. SABSI and S. aureus IE were compared between PAC and PWC.ResultsAmong 978 episodes of SABSI, 217 (22.2%) occurred in PAC. PAC were younger, had fewer comorbidities, carried cardiac devices less often, and had less community-acquired SABSI than PWC. Compared to PWC, PAC more frequently had catheter-related SABSI, less IE (2.8% vs 10.9%, p < 0.001) and osteoarticular infection (2.3% vs 14.3%, p < 0.001). Independent risk factors for IE were cardiopathy (aOR 4.392, 95% CI 2.719–7.094) and persistent bacteremia (aOR 3.545, 95% CI 2.159–5.820). Thirty-day mortality was high, and similar between groups (24.2% vs 25.5%, p = 0.282).ConclusionsPAC with SABSI developed IE less frequently than PWC did. This finding seems related to the differences in baseline characteristics and may have significant clinical implications, such as transesophageal echocardiography in PAC without cardiopathy or persistent bacteremia.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00575-8.

Osteoarticular Salmonella infections in healthy children

Abstract Introduction: Osteoarticular infections caused by Salmonella spp. are rare. Salmonella osteomyelitis is more common in children with underlying chronic diseases or immunodeficiency, but is rare in previously healthy children. Patient concerns: Six previously healthy children with Salmonella osteoarticular infections were admitted to our hospital. Identification and characterization of the isolates were also performed and correlated with the clinical findings. Diagnosis: The predominant symptoms were fever, pain, and swelling. Three patients were diagnosed with osteomyelitis (including 2 with left humerus, 1 with left tibia), 1 patient with osteoarthritis (elbow, right), and 2 patients with septic arthritis (knee joint, right). Interventions: Surgical drainage was performed in all children, and the aspirates were subsequently cultured. Intravenous antibiotic therapy combined with surgical drainage of purulent material is necessary to eradicate the infection. Outcomes: A 2-year follow-up showed good healing in all six children after clinical interventions. Conclusion: Osteoarticular infections caused by Salmonella have no distinctive features, clinical manifestations, or radiological characteristics. Intravenous antibiotics combined with surgical debridement/drainage are necessary for eradication of the bacteria.

Utility of Methicillin-Resistant Staphylococcus aureus Nares Screening in Hospitalized Children with Acute Infectious Disease Syndromes.

Studies in adults support the use of a negative methicillin-resistant Staphylococcus aureus (MRSA) nares screening (MNS) to help limit empiric anti-MRSA antibiotic therapy. We aimed to evaluate the use of MNS for anti-MRSA antibiotic de-escalation in hospitalized children (<18 years). Records of patients admitted between 1 January 2015 and 31 December 2020 with a presumed infectious diagnosis who were started on anti-MRSA antibiotics, had a PCR-based MNS, and a clinical culture performed were retrospectively reviewed. A total of 95 children were included with a median age (range) of 2 (0–17) years. The top three diagnosis groups were skin and soft tissue infections (n = 38, 40%), toxin-mediated syndromes (n = 17, 17.9%), and osteoarticular infections (n = 14, 14.7%). Nasal MRSA colonization and growth of MRSA in clinical cultures was found in seven patients (7.4%) each. The specificity and the negative predictive value (NPV) of the MNS to predict a clinical MRSA infection were both 95.5%. About half (n = 55, 57.9%) had anti-MRSA antibiotics discontinued in-house. A quarter (n = 14, 25.5%) were de-escalated based on the negative MNS test alone, and another third (n = 21, 38.2%) after negative MNS test and negative culture results became available. A high NPV suggests that MNS may be useful for limiting unnecessary anti-MRSA therapy and thereby a useful antimicrobial stewardship tool for hospitalized children. Prospective studies are needed to further characterize the utility of MNS for specific infectious diagnoses.

Early oral switch to combined cefixime therapy for management of osteoarticular infections in pediatric sickle cell disease patients: A descriptive analysis

BackgroundThe treatment of osteoarticular infections in pediatric patients with sickle cell disease (SCD) is a challenging task for the practitioner. The aim of this study is to evaluate cefixime for the treatment of osteoarticular infections in pediatric SCD patients by retrospective design. MethodsThis study was done in the pediatric hospital of King Saud Medical City, Riyadh, Saudi Arabia. The data was obtained from medical records of patients aged 1–16 years admitted between January 2019 to December 2020, diagnosed with SCD and received cefixime for the treatment of OI. A descriptive study for pediatric patients admitted between January 2019 to December 2020 diagnosed with sickle cell disease and diagnosed with osteoarticular infection. All patients were treated with cefixime. Medians and interquartile ranges (IQRs) were used for the descriptive analysis. ResultsA total of 260 patients were screened, and 51 cases [osteomyelitis (OM), n = 43, and septic arthritis (SA), n = 8] met the inclusion criteria. The median age of OM patients was 7 years, with males making up 67.4% of the cohort. The median length of IV antibiotics and hospital stays were 10 days and 11 days, respectively. The median total duration of antibiotic use was 37 and 25 days for OM and SA, respectively. The treatment success rate was 88% in OM cases and 100% in SA patients. Readmission was noted in 39.5% of the OM patients, while only 25% of the SA patients were recorded for reinfection. ConclusionThe study's findings revealed that Cefixime is a viable oral alternative for treating osteoarticular infection in pediatric SCD patients. Nonetheless, a prospective investigation is required to corroborate the findings of this study.

The Utility of Routine Radiographic Monitoring in Pediatric Osteoarticular Infections.

Pediatric musculoskeletal (MSK) infections broadly include isolated osteomyelitis (OM), septic arthritis (SA), and combined infections (OM+SA). These diagnoses are often monitored with serum inflammatory markers and serial radiographs to monitor treatment response and development of negative sequelae, despite limited data supporting these practices. The purpose of this study is to evaluate the utility of obtaining serial radiographic follow-up for pediatric osteoarticular infections. An institutional review board-approved retrospective review was completed. Children 18 years and below admitted to a single institution with a culture/biopsy-proven diagnosis of OM, SA, or OM+SA. All postdischarge radiographs were reviewed and retrospectively categorized as either routine (scheduled) or reactive. Routine radiographs were obtained regardless of clinical presentation. Reactive radiographs were obtained in patients presenting with the sign of an altered clinical course. Negative sequelae, defined as growth arrest/disturbance, pathologic fracture, recurrent MSK infection, and underlying neoplastic process, were recorded and tracked. Descriptive statistics were used to summarize demographic and outcome variables. Number needed to screen (NNS) was defined as the inverse of the incidence of negative sequelae detected. A total of 131 patients were included for analysis, with a mean age of 11.9 years (SD: 4.96 y). Ninety (69%) patients were diagnosed and treated for OM, 25 (19%) for SA, and 16 (12%) for combined infections. A total of 329 radiographs were obtained following discharge. Of those obtained, 287 (88%) were routine, resulting in the detection of 2 (0.7%) negative sequelae and a resultant NNS of 143 radiographs (95% confidence interval: 36-573). The remaining 39 were reactive radiographs, resulting in the detection of 2 (5.1%) negative sequelae with an NNS of 20 radiographs (95% confidence interval: 5-78). While radiographs remain a widely utilized tool to screen for the development of negative sequelae in pediatric osteoarticular infections, they rarely alter management in the absence of other concerning clinical signs or symptoms such as recurrent fevers, swelling of the extremity, or limb deformity. Moreover, routine radiographic surveillance should be replaced with a reactive radiographic protocol. Level III-retrospective comparative study.

Multiple-Dose Dalbavancin Regimens as the Predominant Treatment of Deep-Seated or Endovascular Infections: A Scoping Review.

Off-label use of dalbavancin for deep-seated and endovascular infections has been increasing. We performed a scoping review to evaluate the evidence for use of multiple-dose dalbavancin regimens as the predominant therapy for these indications. Predominant therapy was defined as use of dalbavancin without other concurrent antibiotics for more than half of the total treatment duration. Fifteen publications were identified; 2 were small, open-label randomized controlled trials and the remainder were retrospective observational studies or case reports. A total of 144 cases from these publications met eligibility criteria for inclusion in this review. Types of infections included osteoarticular infections, catheter-related or complicated bloodstream infections, and infective endocarditis. Overall, the evidence for use of multiple-dose regimens of dalbavancin for deep-seated and endovascular infections is limited by a paucity of data from controlled trials, heterogeneity of dosing regimens, and a lack of standardized clinical outcomes.

Infections ostéoarticulaires et traitements ciblés des rhumatismes inflammatoires

Patients with chronic inflammatory rheumatic disorders may present an increased risk of osteoarticular infection related to age, comorbidities, previous intra-articular corticosteroid injection, surgical procedures or the use of immunosuppressive drugs including corticosteroids or targeted therapies. Data regarding the risk of osteoarticular infection remain scarce and mainly restricted to TNF-α inhibitors. Although an increased risk of osteoarticular infection in native or prosthetic joints of patients receiving targeted biological therapies has been reported in various national and international registries, it appears to be moderate, lower than respiratory, skin, and urinary infections. The risk of osteoarticular infection also remains stable over time, similar to what was described before the era of biologic therapies. Moreover, this risk must be balanced against that of corticosteroids, which are often necessary to control flare-ups induced by the suspension of the biological agent. Staphylococcus aureus remains the most frequently observed microorganism, but certain species usually barely involved in osteoarticular infections should be assessed in these patients. Osteoarticular infection in patients receiving targeted therapies should not be ruled out in absence of fever and/or elevation of acute phase reactants. Several questions need to be addressed, including the weight of targeted therapies in the increased risk of osteoarticular infection compared to other risk factors, in particular age, the underlying rheumatic disease or corticosteroid therapy.

Usefulness of therapeutic drug monitoring in estimating the duration of dalbavancin optimal target attainment in staphylococcal osteoarticular infections: a proof-of-concept

Dalbavancin is increasingly used for the treatment of staphylococcal osteoarticular infections (OIs). Some population pharmacokinetic studies suggest that a regimen of two 1500 mg doses 1 week apart could ensure effective treatment for several weeks. Here we aim to provide clinicians with a proof-of-concept of the potential role that therapeutic drug monitoring may have in giving real-time feedback of the estimated duration of optimal treatment of staphylococcal OIs with dalbavancin in each single patient.

Osteoarticular infections and septic bursitis: about 32 patients seen in the rheumatology department of Dreux hospital

Osteoarticular infections and septic bursitis: about 32 patients seen in the rheumatology department of Dreux hospital

Tedizolid: new data and experiences for clinical practice.

The most relevant information on the clinical uses of tedizolid from studies published in the last 18 months is presented in this brief review. The most important data indicate better tolerance and safety profile of long-term therapeutic regimes in off-label indications, such as osteoarticular infections and those caused by mycobacteria. Its lower risk of hazardous interactions compared to linezolid should be emphasized. Furthermore, tedizolid in its combination with rifampicin shows a more favourable way of acting as demonstrated in vitro and in vivo studies. A recent trial also opens the door for its potential use in nosocomial pneumonia caused by Gram-positive bacteria.

Long-Term Pharmacokinetics of Dalbavancin in ABSSSI and Osteoarticular Settings: A Real-Life Outpatient Context.

Dalbavancin is a lipoglycopeptide approved for treatment of Gram-positive infections of skin and skin-associated structures (ABSSSI). Currently, off-label use at high dosages for osteoarticular infections deserves attention. This work aimed to study the long-term plasma pharmacokinetics of dalbavancin in outpatients with ABSSSI or osteoarticular infections, treated either with one or two 1500 mg doses of dalbavancin. A liquid chromatography-tandem mass spectrometry method was used to measure total dalbavancin concentrations in plasma samples. The results were analyzed through a non-compartmental analysis (NCA). Breakpoint minimum inhibitory concentration (MIC) was used to calculate AUC/MIC and T > MIC parameters, adjusted by 93% protein binding. A total of 14 patients were enrolled, 11 with osteoarticular infection and 3 with ABSSSI. Long-term pharmacokinetics showed median T > MIC (0.125 mg/L) of 11.9 and 13.7 weeks for single and dual dose, respectively. Similarly, median AUC0-2w/MIC ratios of 20,590 and 31,366 were observed for single and dual dose regimens, respectively. No adverse events were observed, and treatment success was achieved in 12/14 patients. Failure was associated with the worst clinical conditions, bone infections, and single dose. The results of this study show that dalbavancin exposure exceeds previously suggested pharmacodynamic targets. Optimization of these targets is needed for the osteoarticular setting.

Differences Between Methicillin-susceptible Versus Methicillin-resistant Staphylococcus aureus Infections in Pediatrics: Multicenter Cohort Study Conducted in Bogotá, Colombia, 2014-2018.

Background:The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) has changed in recent years. The present article is intended to establish differences between clinical, laboratory and imaging findings and outcomes of MSSA and MRSA infections, as well as among subgroups of infection such as skin and soft tissue infection, osteoarticular, bacteremia or pneumonia in a pediatric population from Bogota, Colombia.Methods:Retrospective cohort study using clinical records of patients under 18 years of age treated at the participating centers in Bogota, Colombia, between 2014 and 2018. The first positive S. aureus culture was studied. MSSA and MRSA were compared. The χ2 test, Fisher exact test, and Kruskal-Wallis test were calculated, and the statistical significance was presented using the difference and its 95% CI.Results:Five hundred fifty-one patients were included; 211 (38%) corresponded to MRSA and 340 (62%) to MSSA for a total of 703 cultures. A significantly higher probability of having an MSSA infection than MRSA was found in patients with previous heart disease (3.3% vs. 0.5%), neurologic disease (5.9% vs. 2.5%), recent major surgeries (11% vs. 5%) or who has an implanted device (11% vs. 4%). In contrast, in severe MRSA infections (bacteremia, osteoarticular infections and pneumonia), a higher rate of complications was seen (admission to the pediatric intensive care unit, mechanical ventilation and vasoactive support), and in osteoarticular MRSA, more than 1 surgery per case was seen (89% vs. 61%). Laboratory results and mortality were similar.Conclusions:MRSA was associated with a more severe course in bacteremia, osteoarticular infections and pneumonia. Some classical risk factors associated with MRSA infections were found to be related to MSSA. In general, with the exception of skin and soft tissue infection, there was an increased risk of pediatric intensive care unit admission and mechanical and inotropic support with MRSA in a pediatric population.

A computerized indicator for surgical site infection (SSI) assessment after total hip or total knee replacement: The French ISO-ORTHO indicator

The French National Authority for Health (HAS), with a multidisciplinary working group, developed an indicator 'ISO-ORTHO' to assess surgical site infections (SSIs) after total hip arthroplasty or total knee arthroplasty (THA/TKA) based on the hospital discharge database. We present the ISO-ORTHO indicator designed for SSI automated detection and its relevance for quality improvement and hospital benchmarks. The algorithm is based on a combination of International Statistical Classification of Diseases, Tenth Revision (ICD-10) and procedure codes of the hospital stay. The target population was selected among adult patients who had a THA or TKA between January 1, 2017, and September 30, 2017. Patients at very high risk of SSI and/or with SSI not related to hospital care were excluded. We searched databases for SSIs up to 3 months after THA/TKA. The standardized infection ratio (SIR) of observed versus expected SSIs was calculated (logistic regression) and displayed as funnel plot with 2 and 3 standard deviations (SD) after adjustment for 13 factors known to increase SSI risk. In total, 790 hospitals and 139,926 THA/TKA stays were assessed; 1,253 SSI were detected in the 473 included hospitals (incidence, 0.9%: 1.0% for THA, 0.80% for TKA). The SSI rate was significantly higher in males (1.2%), in patients with previous osteo-articular infection (4.4%), and those with cancer (2.3%), obesity, or diabetes. Most hospitals (89.9%) were within 2 SD; however, 12 hospitals were classified as outliers at more than +3 SD (1.6% of facilities), and 59 hospitals (7.9%) were outliers between +2 SD and +3 SD. ISO-ORTHO is a relevant indicator for automated surveillance; it can provide hospitals a metric for SSI assessment that may contribute to improving patient outcomes.

Cost of off-label antibiotic therapy for bone and joint infections: a 6-year prospective monocentric observational cohort study in a referral centre for management of complex osteo-articular infections.

Introduction: Costs related to bone and joint infection (BJI) management are increasing worldwide, particularly due to the growing use of off-label antibiotics that are expensive treatments (ETs), in conjunction with increasing incidence of multi-drug-resistant pathogens. The aim of this study was to evaluate the whole costs related to these treatments during the patient route, including those attributed to the rehabilitation centre (RC) stay in one regional referral centre in France. The total annual cost of ETs for managing complex BJIs in France was then estimated.Material and methods: A prospective monocentric observational study was conducted from 2014 to 2019 in a referral centre for BJI management (CRIOAc – Centre de Référence des Infections OstéoArticulaires complexes). Costs related to expensive treatments (“old” ETs, i.e. ceftaroline, ertapenem, daptomycin, colistin, tigecycline, and linezolid and “new” ETs, defined as those used since 2017, including ceftobiprole, ceftazidime-avibactam, ceftolozane-tazobactam, tedizolid, and dalbavancin) were prospectively recorded. In all cases, the use of these ETs was validated during multidisciplinary meetings.Results: Of the 3219 patients treated, 1682 (52.3 %) received at least one ET, and 21.5 % of patients who received ET were managed in RCs. The overall cost of ETs remained high but stable (EUR 1 033 610 in 2014; EUR 1 129 862 in 2019), despite the increase of patients treated by ETs (from 182 in 2014 to 512 in 2019) and in the cumulative days of treatment (9739 to 16 191 d).Daptomycin was the most prescribed molecule (46.2 % of patients in 2014 and 56.8 % in 2019, with 53.8 % overall), but its cost has decreased since this molecule was genericized in 2018; the same trend was observed for linezolid. Thus, costs for old ETs decreased overall, from EUR 1 033 610 in 2014 to EUR 604 997 in 2019, but global costs remained stable due to new ET utilization accounting for 46.5 % of overall costs in 2019. Tedizolid, used as suppressive antimicrobial therapy, represented 77.5 % of total new ET costs. In our centre, dalbavancin was never used.The cost paid by RCs for ETs and the duration of ET remained stable overall between 2016 and 2019.Conclusions: A high consumption of off-label ET is required to treat patients with BJIs in a CRIOAc, and the consequence is a high cost of antimicrobial therapy for these patients, estimated to be almost EUR 10 million in France annually. Costs associated with ET utilization remained stable over the years. On the one hand, the introduction of the generic drugs of daptomycin and linezolid has significantly decreased the share of old ETs, but, on the other hand, the need for new ETs to treat infections associated with more resistant pathogens has not led to decrease in the overall costs. A drastic price reduction of generic drugs is essential to limit the costs associated with more complex BJIs.

Characteristics of Musculoskeletal Involvement in Pediatric Patients with Disseminated Sepsis in a Tertiary Care Center.

BackgroundPediatric bone and joint infections account for one of the major causes of childhood morbidity. Disseminated sepsis being a systemic disorder with multisystem involvement, overshadows the timely recognition of bone and joint infections. Hence, we did this cross sectional study to evaluate the prevalence of septic arthritis and osteomyelitis in disseminated sepsis in children, the organisms implicated, and their antibiotic sensitivities.MethodsWe prospectively collected data from 1st July 2016 to 31st September 2017 of children aged less than 12 years with disseminated sepsis, i.e., patients with fever and two or more sites of focal infection of anatomically non-contiguous tissues.ResultsFifty-four patients of disseminated disease were included, of which 25 patients (46.3%) had osteoarticular infections. Septic arthritis was seen in 17 patients, and osteomyelitis was seen in 12 patients. The most common joint was hip (41.6%), and the most common bone involved was femur (53.8%). Blood culture showed MRSA in 28% and MSSA in 20%. Joint and bone aspirates showed S. aureus in 56% with 28% of MRSA and MSSA each. All Staphylococcus aureus organisms were found sensitive to vancomycin and teicoplanin. The mean values of CRP, duration of stay and duration of intravenous antibiotic was higher in MRSA infected patients compared to MSSA patients.ConclusionsStaphylococcus aureus is the most prevalent organism in musculoskeletal infection in disseminated sepsis children, with vancomycin sensitivity of 100% and methicillin sensitivity of 46.2% only. Cases of osteoarticular involvement with MRSA were higher compared to MSSA among the cases of disseminated disease. The prevalence of osteoarticular involvement is high in disseminated sepsis in children and increased clinical suspicion for such must be maintained.

Diagnostic test accuracy of serum procalcitonin compared with C-reactive protein for bone and joint infection in children and adolescents: a systematic review and meta-analysis.

The objective of this review was to synthesize the best available evidence for the diagnostic test accuracy of serum procalcitonin compared with serum C-reactive protein for suspected osteomyelitis and septic arthritis in hospitalized children and adolescents. Measurement of serum C-reactive protein remains a routine investigation for the diagnosis of osteoarticular infection in children and adolescents. Measurement of serum procalcitonin has been shown to outperform C-reactive protein in adults with osteomyelitis and septic arthritis. Before procalcitonin can be considered as a potential replacement or add-on test in children and adolescents, a systematic review and meta-analysis targeting this population should be conducted. Original studies reporting the diagnostic accuracy of procalcitonin and/or C-reactive protein in children and adolescents between one month and 18 years of age admitted to hospital with suspected osteoarticular infection were included. Studies must have compared the index test to at least one reference test. Reference test was defined as positive culture or polymerase chain reaction confirmation of a pathogen from blood, bone biopsy, or joint fluid aspirate in combination with at least two of the following: i) purulent material from sterile site, ii) positive radiological findings consistent with osteoarticular infection, and ii) symptoms and signs consistent with osteomyelitis and/or septic arthritis. The JBI methodology for systematic reviews of diagnostic test accuracy was followed. Information was sourced from four databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) and four gray literature sources (MedNar, OpenGrey, Google Scholar, and ProQuest Dissertations and Theses). Only studies published in English were considered. The methodological quality of selected studies was formally evaluated, sensitivity and specificity data were extracted, and 95% confidence intervals determined. Meta-analysis was performed to estimate summary points using a bivariate model and to generate a hierarchical summary receiver operating characteristic (HSROC) curve with global measures of test accuracy performance, such as likelihood ratio and diagnostic odds ratio. A narrative was provided where meta-analysis was not appropriate. Eight studies were included in the review. Four of these studies used a common C-reactive protein test threshold of 20 mg/L. At this threshold, the estimated pooled sensitivity of C-reactive protein was 0.86 (0.68-0.96) and the pooled specificity was 0.9 (0.83-0.94). Using a hierarchical summary receiver operating characteristic model from six studies, the diagnostic odds ratio for C-reactive protein was estimated to be 39.4 (14.8-104.9) with a positive likelihood ratio 5.3 (2.3-11.9) and a negative likelihood ratio 0.1 (0.07-0.2). There were insufficient studies from this review to statistically evaluate the diagnostic accuracy of procalcitonin. Clinicians should continue to measure serum C-reactive protein as the preferred inflammatory marker in hospitalized children and adolescents with suspected osteomyelitis or septic arthritis. More evidence is needed before incorporating procalcitonin routinely into clinicians' diagnostic test strategy. Improvements with the design, quality, and reporting of procalcitonin diagnostic test assays in children and adolescents with osteoarticular infection is needed. PROSPERO CRD42019140276.