Osteoarticular Infections Research Articles

DAIR in treating chronic PJI after total knee arthroplasty using continuous local antibiotic perfusion therapy: a case series study

BackgroundAntimicrobial agents are administered via intramedullary antibiotic perfusion (iMAP)/intrasoft tissue antibiotic perfusion (iSAP) to infected lesions to control osteoarticular and soft tissue infections. Continuous local antibiotic perfusion (CLAP) has been reported to be useful. This study aimed to investigate the outcomes of DAIR combined with CLAP for chronic PJI after total knee arthroplasty performed at our hospital.Subjects and methodsSix patients (male; one case, female; five cases, mean age 79.5 years (70–94)) underwent CLAP for chronic PJI after TKA at our hospital between July 2020 and June 2022. They were followable for at least one year after surgery. Seven months (17–219), with a mean follow-up of 24.3 months (12–36). In addition to direct debridement and insert exchange, systemic antimicrobial treatment, and CLAP with gentamicin were performed using NPWT. We investigated the organisms causing the inflammation, the duration of iMAP/iSAP implantation, the maximum daily dose of GM, the maximum GM blood concentration, and the presence or absence of GM-induced adverse events.ResultTwo of six patients had a recurrence of infection at five weeks and five months after initial CLAP and required repeat CLAP treatment, but all patients could preserve their components. The organisms responsible for the flare-ups were MSSA in three cases: ESBL-producing E. coli, mixed MSSA and streptococcal infection, Klebsiella pneumonia in one case each, and unknown pathogens in one case. CLAP therapy for all patients was administered eight times in 6 cases: iMAP, mean: 10.0 days (5–16); iSAP, mean: 19.3 days (15–28); GM dose, mean: 162.5 mg/day (80–240); and GM blood concentration, mean: 1.4 µg/mL (0.2-5.0). Adverse events included one case of reversible acute kidney injury during CLAP in a patient with recurrent infection.SummaryDAIR with CLAP for chronic post-TKA infection can be a useful treatment option to preserve components and allow the infection to subside, provided the implant is not markedly loosened.

Concomitant spinal and non-spinal osteoarticular infections

Abstract Background: Treatment of pyogenic spondylodiscitis or septic arthritis can be complicated with a variety of concomitant infectious processes. No study has focused on concomitant osteoarticular infections. Materials and Methods: Between 2015 and 2019, patients over 18 years old, who were diagnosed and treated for spinal infections (SIs) or non-spinal osteoarticular infections, were included. There were six patients with concomitant spinal and non-spinal osteoarticular infections (concomitant infection [CI] group), 30 patients with SI alone (SI group), and 18 patients with articular infection (AI) alone (AI group). The data gained from the patients in the CI group were compared those in the SI group and the AI group. Results: Factors contributing to statistical significance included past or present history of cancer (100% in the CI group, 27% in the SI group, and 33% in the AI group), C-reactive protein (CRP) levels (27.4 mg/dL in the CI group, 13.4 mg/dL in the SI group, and 13.8 mg/dL in the AI Group), albumin levels (2.4 g/dL in the CI group and 2.9 in both the SI group and the AI group), detection of Group B Streptococcus (GBS) (50% in the CI group, 3.3% in the SI group and 5.6% in the AI group), and duration of intravenous antibiotic therapy (131 days in the CI group, 67 days in the SI group and 29 days in the AI group). Conclusions: Patients with concomitant spinal and non-spinal osteoarticular infections were more likely to present with a past and present history of cancer, severe hypoalbuminemia, higher levels of CRP and GBS bacteremia.

State of the art in the diagnostic evaluation of osteomyelitis: exploring the role of advanced MRI sequences-a narrative review.

Osteomyelitis, a severe bone infection caused mainly by pyogenic organisms, poses diagnostic challenges due to its non-specific magnetic resonance imaging (MRI) manifestations. Conventional MRI, though the imaging modality of choice, often exhibits signal abnormalities with overlapping differential diagnoses, potentially leading to overestimation of infection extent and duration. To address these limitations, advanced MRI sequences, including dynamic contrast-enhanced (DCE) MRI, 1H magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), and Dixon techniques have emerged as promising alternatives. This narrative review explores the potential role of these sequences in aiding the differential diagnosis of osteomyelitis. We used the PubMed database to search for relevant articles using the MeSH keywords: (osteomyelitis) AND (advanced MRI sequences) and we manually selected the most suitable studies to include in our review. Articles outside of original studies were also included. Only records in English or French were considered. In particular, DWI is useful for characterizing fluid collections, distinguishing bone infarcts, and bacterial skull base osteomyelitis from neoplastic lesions. Moreover, DWI assists in differentiating diabetic foot osteomyelitis (DFO) from Charcot neuro-osteoarthropathy, facilitates the diagnosis of pediatric acute osteoarticular infections, and aids in distinguishing osteomyelitis from Modic I degenerative changes. Additionally, DWI proves valuable in monitoring spinal infections and distinguishing pedal osteomyelitis from other conditions, even in patients with renal impairment. DCE-MRI enhances MRI specificity by assessing contrast uptake over time, providing valuable insights into inflammatory microenvironments. It aids in detecting DFO, differentiating it from acute Charcot arthropathy, and distinguishing osteomyelitis from neuropathic arthropathy. Moreover, DCE-MRI shows potential in assessing response to antibiotic therapy in spinal infections. Dixon acquisition improves image quality and facilitates the detection of bone marrow abnormalities, aiding in the differentiation of diabetic foot from osteomyelitis. It also assists in distinguishing osteomyelitis from neuropathic arthropathy and provides valuable information in evaluating the diabetic foot. Proton MR spectroscopy, a well-established modality, offers metabolic information that can differentiate malignant from benign lesions. The role of advanced MRI techniques in evaluating osteomyelitis remains to be fully defined, and further research is required to explore its potential utility in this context. In conclusion, the incorporation of advanced MRI sequences has shown promise in improving the differential diagnosis of osteomyelitis. Future investigations exploring combinations of these techniques and their clinical applications hold significant potential to enhance diagnostic accuracy and patient outcomes.

Adult osteoarticular infections at Kara University Hospital

Adult osteoarticular infections at Kara University Hospital

Therapeutic Drug Monitoring of Dalbavancin in Real Life: A Two-Year Experience.

Dalbavancin is a long-acting lipoglycopeptide that is registered for the treatment of acute bacterial skin and skin structure infections, and it is also increasingly used for infections that require prolonged antibiotic treatment. Here, we present the results from the first 2 years of a service set up in December 2021 for the therapeutic drug monitoring (TDM) of dalbavancin in clinical settings. In particular, we compared the trough concentration (Cmin) to maximum concentration (Cmax) in patients with osteoarticular infections receiving prolonged treatment with dalbavancin. Log-linear regression models were used to estimate the timing of dalbavancin administration with the goal of maintaining Cmin concentrations of >8 mg/L in the two TDM-based strategies. From December 2021 to November 2023, 366 TDMs of dalbavancin from 81 patients were performed. The Cmin and Cmax concentrations of dalbavancin ranged from 4.1 to 70.5 mg/L and from 74.9 to 995.6 mg/L, respectively. With log-linear regression models, we estimated that each injection should be administered every 42-48 days to maintain the Cmin concentrations. Out of the 81 patients, 37 received at least three doses of dalbavancin for the treatment of osteoarticular infections. Despite there being no significant differences in the days of dalbavancin treatment (130 ± 97 versus 106 ± 102 days), the patients in the Cmax-based TDM group received a significantly lower number of dalbavancin injections (5.2 ± 1.8 versus 7.3 ± 2.6 injections, p = 0.005), and they were administered over a longer period of time (40 ± 10 versus 29 ± 14 days, p = 0.013) than in the Cmin-based TDM group. In conclusion, Cmax-based TDM was associated with a significant reduction in the inter-individual variability of dalbavancin concentrations and lower drug dosing frequency than those of Cmin-based TDM. This approach could, therefore, favor a more rational and targeted use of dalbavancin in patients requiring prolonged treatment.

Septic arthritis of the hip caused by nontyphoidal salmonella: A case report

Salmonella nontyphoidal (NTS) infection can cause bacteremia, enteric fever, and gastroenteritis. However, NTS-induced osteoarticular infections are uncommon. We describe a 65-year-old man who had a right hip infection brought on by NTS. He was successfully treated with staged procedures of debridement and antibiotic mobile spacer insertion followed by an Uncemented hip replacement as the second stage. He was doing well free of recurrence at the 8 year follow up. Septic parameters at this time were normal. This case is given since there have been few cases of hip joint infection caused by NTS. Prompt detection and diagnosis of the organism is crucial.Articular erosion and joint destruction once proved, in delayed presentations, will need radical debridement for eradication of the infection. The use of a prosthesis made of antibiotic-loaded acrylic cement and prolonged antimicrobial therapy is necessary.

Is the emergency MRI protocol for acute pediatric osteoarticular infection a luxury or an absolute priority?

Is the emergency MRI protocol for acute pediatric osteoarticular infection a luxury or an absolute priority?

216. A Comparison of Multidrug-Resistant Gram-negative Bacteremia in Cancer and Non-Cancer Patients

Abstract Background Multidrug-resistant gram-negative bacteremia (MDR-GNB) is a growing threat worldwide as it is associated with increased morbidity and mortality. We sought to describe the clinical features of MDR-GNB and outcomes in cancer and non-cancer Pts. Methods We performed a retrospective study of adult patients with MDR-GNB at the Ochsner LSU Health Shreveport between January 2018 and July 2022. We collected patients' demographics, medical comorbidities, cancer diagnosis, causative bacteria (MDROs), source of bacteremia, antibiotics therapy, and clinical outcomes. Results We identified 112 Pts with MDR-GNB. Pts were divided into 2 groups: cancer group (n=33, 29%) and non-cancer group (n=79, 71%). In the cancer group, the majority of Pts had solid tumors (n=20, 61%) vs liquid tumors (n=13, 39%). Mean age was 69 y in cancer compared to 57 y in the non-cancer group. Enterobacteriaceae were isolated in 28 cancer Pts (85%) including ESBL E. coli in 20 Pts (61%), Klebsiella s.p (CRE/ESBL) in 5 Pts (15%), and ESBL P. mirabilis in 3 Pts (9%). Pseudomonas aeruginosa CRO in 3 Pts (9%) and A. baumannii in 2 Pts (6%). In non-cancer Pts, Enterobacteriaceae were isolated in 65 Pts (82%) including ESBL E. coli in 40 Pts (51%), Klebsiella s.p (CRE/ESBL) in 18 Pts (23%) and ESBL P. mirabilis in 6 Pts (8%). P. aeruginosa CRO found in 6 Pts (8%) and A. baumannii in 8 Pts (10%). The sources of bacteremia in cancer group were UTI in 14 Pts (42.4%), osteoarticular infection (OAI) in 5 Pts (15%), pneumonia in 3 Pts (9%), CLABSI in 2 Pts (6%), endovascular in 1 Pt (3%) and unknown in 8 Pts (24%), whereas in non-cancer group, UTI was reported in 40 Pts (68%), pneumonia in 9 (27%), OAI in 1 (1.3%), endocarditis in 1 Pt (1.3%), and unknown in 20 Pts (25.3%). Mean duration of targeted antibiotics was 9 days in cancer vs 13.3 days in non-cancer group (p-value=0.4). Mean length of hospital stay was comparable, 34 d in cancer vs 31 d in non-cancer(p-value= 0.87). 9 Pts were admitted to ICU in cancer group (27%) vs 39 Pts (49%). Mortality rate was 39% in cancer (8 pts went to hospice) vs 16.4% in non-cancer. Conclusion Our data showed that the common source of MDR-GNB remains urinary tract infection in both groups and the bacterial epidemiology is comparable between the two groups. Further studies are warranted to assess the impact of resistant organisms on cancer Pts. Disclosures All Authors: No reported disclosures

1690. Acute Hematogenous Osteoarticular Infections in Children at Siriraj Hospital, Thailand: A 20-Year Retrospective Review

Abstract Background Acute hematogenous osteomyelitis (AHO) and septic arthritis (SA) lead to significant morbidity and sequelae. There are limited data in Thai children. Methods This is a single-center retrospective study of patients aged < 18 years who were diagnosed with AHO and SA between 2002- 2021. The acute onset of AHO and SA was defined as the diagnosis of bone and joint infection within 4 weeks after the onset of symptoms or signs in a previously uninfected bone. Data were collected and factors associated with sequelae were determined by using multiple logistic regression analyses. Results Of the 110 patients identified, 19 were AHO, 81 were SA, and 10 were combined AHO and SA. The median (IQR) age was 6.7 (1.4-11.9) years and 66 (60%) were male. Fifteen (13.6%) patients were immunocompromised. The most common sites of AHO were tibia (27.6%) and femur (27.6%), and of SA were hips (41.8%) and knees (31.9%). The pathogens were identified in 68 of 106 (64.1%) patients with specimen submission. The positivity rate of hemoculture, synovial fluid, synovial tissues, bone biopsies and vaginal/urethral culture in patients with suspected disseminated gonococcal infection were 32.1%, 40%, 61.9%, 60% and 50% respectively. The most common organisms were methicillin-sensitive Staphylococcus aureus (30.2%) and non-typhoidal Salmonella (9.4%). We found only one case with community-acquired, methicillin-resistant S.aureus. Non-typhoidal Salmonella was responsible for 22.7% of 22 infants. The one-year sequelae were found in 15.8% of AHO, 18.5% of SA, and 20% of combined. In multivariate models, factors associated with sequelae were being immunocompromised (adjusted OR 14.16, 95%CI 1.96-102.35, P=0.009) and infection of the hips (adjusted OR 6.25, 95%CI 1.45-14.59, P=0.025). Patients' characteristics Pathogens according to age groups Factors associated with sequalae Conclusion Methicillin-sensitive S. aureus was the most common pathogen among Thai children with acute hematogenous osteoarticular infections. However, Salmonella was the predominant causative organism among infants. Appropriate empirical antibiotic therapy should be effective against both pathogens in infants. Long-term follow up is needed particularly in immunocompromised children and infection of the hip. Disclosures All Authors: No reported disclosures

95. What To Do With Prolonged Bacteremia in Staphylococcus aureus Osteoarticular Infection? A Retrospective Analysis at Two Children's Hospitals

Abstract Background Staphylococcus aureus is the most frequent cause of osteoarticular infection (OAI, including hematogenous osteomyelitis and septic arthritis) in children and is commonly associated with bacteremia. Current guidelines suggest that persistent bacteremia may warrant more aggressive treatment, however, data supporting this are limited. We retrospectively evaluated the management and outcomes of children with S. aureus OAI with respect to bacteremia duration. Methods Cases were identified through prospective S. aureus surveillance studies at Texas Children’s and St. Louis Children’s Hospitals. Children < 18 years old with OAI secondary to S. aureus from 2011-2021 were eligible. Prolonged bacteremia was defined a priori as the upper quartile of duration. Orthopedic complications included pathologic fractures, avascular necrosis, angular deformity and chronic osteomyelitis. Results Overall, 532 cases were identified of which 343 (64.5%) had ≥1 positive blood culture; 61 developed orthopedic complications (11.4%, Figure 1). The median duration of bacteremia in the cohort was 1 day (IQR: 1-3 days). Patients with prolonged (≥ 3 days) and non-prolonged bacteremia were similar in terms of demographics. Children with prolonged bacteremia had a longer duration of fever in hospital (median 6 vs. 3 days, p< 0.001), more often had MRSA, pyomyositis and venous thromboses and were less often transitioned to oral therapy (Figure 2). Duration of bacteremia also influenced discharge antibiotic choice (Figure 3). Within the subset of patients with prolonged bacteremia, those who were transitioned to oral therapy had similar outcomes to those treated with prolonged intravenous antibiotics; such patients received a median of 11.5 days (IQR: 6-23) of IV therapy prior to discharge (median 7 days [IQR: 4-20] after last positive blood culture). Conclusion Prolonged bacteremia in the setting of S. aureus OAI greatly impacts management and should prompt evaluation for other foci of infection. However, our data show that a subset of children with S. aureus OAI and prolonged bacteremia can be safely transitioned to oral antibiotics after a period of IV therapy. Additional work is needed to delineate optimal management of OAI with prolonged bacteremia. Disclosures Jonathon C. McNeil, MD, Allergan: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support Kristina G. Hulten, PhD, Pfizer: Grant/Research Support Sheldon L. Kaplan, MD, MeMed: Grant/Research Support|Pfizer: Grant/Research Support|Pfizer: Honoraria

1305. Current Management of Osteoarticular Infections by Infectious Diseases Physicians: Results of an Emerging Infections Network (EIN) Survey

Abstract Background Osteoarticular infections (OAI) have been commonly treated with prolonged intravenous (IV) antimicrobials. The Oral versus Intravenous Antibiotics for Bone and Joint Infection (OVIVA) trial demonstrated that oral (PO) antibiotic therapy was noninferior to IV antibiotics in the treatment of OAIs. We surveyed Infectious disease (ID) physicians to see how often they used PO antibiotics in the treatment of OAIs and the barriers to using PO antibiotics. Methods An EIN survey was sent to 1475 ID physicians. The survey had 9 questions pertaining to antibiotic prescribing patterns in the treatment of OAIs. The questions were mostly multiple choice, Yes/No questions with an area provided for free text. Definitive oral antibiotic therapy was defined as switching to PO antibiotics within 2 weeks of starting antibiotics. Results There were 413 respondents who treated OAIs and responded to the survey. A plurality of respondents 150/413 (36%) switched from IV to PO antibiotics after 4 weeks of IV therapy. 129/413 (31%) switched to oral antibiotics as definitive treatment (Fig 1). PO antibiotics were used as definitive therapy most often for diabetic foot osteomyelitis and native joint septic arthritis (Fig 2). Trimethoprim-sulfamethoxazole was most often used as definitive therapy for Staphylococcus aureus infections followed by doxycycline/minocycline. Amoxicillin/ cefadroxil/ cephalexin was used for treatment of streptococcal infections and fluoroquinolones were used as definitive treatment for infections caused by Gram-negative organisms. The most common reasons for not transitioning to PO antibiotics included non-susceptible pathogen, comorbidities preventing therapeutic drug levels and concern about adherence For the following infections, how often do you use oral antibiotics as definitive therapy? Conclusion A sizeable portion of ID physicians utilize PO antibiotics for the management of OAIs, although significant practice variation exists regarding the timing of IV to PO switch. Disclosures Philip M. Polgreen, MD, Eli Lilly: Case adjudication for a clinical trial Keenan L. Ryan, PharmD, PhC, PharmCon: Honoraria

Chimeric vaccine design against the conserved TonB-dependent receptor-like β-barrel domain from the outer membrane tbpA and hpuB proteins of Kingella kingae ATCC 23330.

Kingella kingae is a Gram-negative bacterium that primarily causes pediatric infections such as septicemia, endocarditis, and osteoarticular infections. Its virulence is attributed to the outer membrane proteins having implications in bacterial adhesion, invasion, nutrition, and host tissue damage. TonB-dependent receptors (TBDRs) play an important role in nutrition and were previously implicated as vaccine targets in other bacteria. Therefore, we targeted the conserved β-barrel TBDR domain of these proteins for designing a vaccine construct that could elicit humoral and cellular immune responses. We used bioinformatic tools to mine TBDR-containing proteins from K. kingae ATCC 23330 and then predict B- and T-cell epitopes from their conserved β-barrel TDR domain. A chimeric vaccine construct was designed using three antigenic epitopes, covering >98% of the world population and capable of inciting humoral and adaptive immune responses. The final construct elicited a robust immune response. Docking and dynamics simulation showed good binding affinity of the vaccine construct to various receptors of the immune system. Additionally, the vaccine was predicted to be safe and non-allergenic, making it a promising candidate for further development. In conclusion, our study demonstrates the potential of immunoinformatics approaches in designing chimeric vaccines against K. kingae infections. The chimeric vaccine we designed can serve as a blueprint for future experimental studies to develop an effective vaccine against this pathogen, which can serve as a potential strategy to prevent K. kingae infections.

Outcomes of Children with Osteoarticular Infections Treated with Trimethoprim-Sulfamethoxazole versus Clindamycin

Abstract Background Early transition to oral antibiotic therapy for the treatment of children with osteoarticular infections (OAI; osteomyelitis [OM], septic arthritis [SA]) has become increasingly common, yet the choice of optimal regimen remains a challenge. With increasing resistance, poor palatability and reported allergies to commonly used oral antibiotics, the treatment options for children with OAI are limited. Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly used antibiotic, with activity against frequently encountered pathogens causing OAI, yet data regarding outcomes of children with OAI treated with TMP-SMX is limited. We sought to describe the characteristics and outcomes of children with OAI treated with TMP-SMX compared to clindamycin. Methods Records of children <18 years old, admitted to Riley Hospital for Children (Indianapolis, IN) between January 2010 to June 2021 for acute OAI were reviewed. Patients were identified by ICD-9/10 codes and an order for TMP-SMX or clindamycin. Patients were excluded if they did not receive TMP-SMX or clindamycin as their primary oral treatment of OAI, had symptoms >30 days, had a hardware associated infection, were immunocompromised or had an alternative diagnosis. Demographic, clinical, and outpatient/follow up data were recorded. Treatment was considered successful if the patient completed treatment with the discharge oral antibiotic (either TMP-SMX or clindamycin), and there was no evidence of infection at the end therapy. Treatment failure was defined as inability to tolerate the medication, development of an infection related complication, recurrent or chronic osteomyelitis. Additionally, significant adverse drug events (ADEs) were recorded. Results A total of 148 children met eligibility criteria (30 TMP-SMX and 118 clindamycin). Demographic and clinical characteristics are highlighted in Table 1. Children receiving TMP/SMX were younger (1.75 years) compared to those receiving clindamycin (7 years). Osteomyelitis was the most common infection type in both groups (47% in the TMP/SMX group vs. 48% in the clindamycin group). Staphylococcus aureus was the causative pathogen in 37% and 49%, while no organism was recovered in 57% and 43% in the TMP/SMX and clindamycin groups, respectively. Complications during hospitalization occurred in 13% in the TMP/SMX group, compared to 16% in the clindamycin group. The median dose of TMP-SMX was 13.4 mg/kg/day (IQR 11.3-14.9) and 38.7 mg/kg/day (IQR 33.4-40.2) for clindamycin. There was no difference in adverse drug events between the two groups with 2 patients (7%) in the TMP/SMX group developing an ADE compared to 13 patients (11%) in the clindamycin group (p=0.74, OR 0.58 [95% CI: 0.12-2.51]). Five (17%) of patients in the TMP/SMX group and 12 (10%) in the clindamycin group were lost to follow up. Of the patients that completed follow-up, there was no difference in treatment success with 84% (21 of 25) in the TMP/SMX and 92% (97 of 106) in the clindamycin group (p=0.27, OR 0.49 [95% CI: 0.15-1.54]) being successfully treated. Conclusions TMP-SMX was well tolerated and not associated with higher odds of treatment failure compared to clindamycin. A larger, prospective, randomized, comparative effectiveness study to control for potential confounding variables, and detect smaller, yet potentially clinically relevant outcome differences is warranted.

STAPHYLOCOCCAL OSTEOARTICULAR INFECTIONS ASSOCIATED WITH BLOOD STREAM INFECTIONS IN CHILDREN: IS PROLONGED IV ANTIBIOTIC THERAPY ALWAYS INDICATED?

Staphylococcus aureus osteo-articular infections (OAI) are frequently accompanied by blood stream infections (BSI) diagnosed by positive blood culture (BC). Microbiological protocols in adults advise prolonged intravenous antibiotics and repeat BC 48-hourly in the presence of a BSI, however evidence to support the systematic employment of these guidelines in paediatric patients is lacking. We aimed to determine whether there was an increased incidence of orthopaedic and systemic complications in patients with s aureus BSI, and whether a shorter duration of intravenous antibiotics was associated with the development of complications.Following ethical approval, the departmental surgical database was searched for patients that underwent surgery for acute OAI over a 5-year period. Patients with no sample taken for BC were excluded, as were those with other or no organisms identified from any site. Demographic and clinical data were captured, including duration of IV antibiotics and development of complications. Statistical significance was set at p<0.05.Following exclusions, 44 patients with a median age of 85 months remained to be analysed. Thirty patients (68%) had a positive BC. A positive BC was associated with a higher rate of systemic complications (p=0.026) but not orthopaedic complications (p=0.159). Patients who had developed any complication had a significantly longer duration of IV antibiotic treatment compared to those without complications (p<0.001). The presenting CRP levels were significantly higher in patients that developed complications (p=0.004).Patients with staphylococcal BSI in association with an OAI are at increased risk of developing systemic complications. In our cohort, a shorter duration of antibiotic use was not associated with the development of complications, which does not support the systematic use of long courses of IV antibiotics in s aureus BSI. Further research will be required to determine the ideal protocol for these patients.

Multicenter evaluation of BioFire JI panel related to improved microbiological diagnostics on acute osteoarticular infections

Microbiological diagnosis of osteoarticular infections (OI) is crucial for a successful treatment. A prospective multicenter study including 262 synovial fluids with suspicion of acute OI was performed between July 2021 and October of 2022. BioFire Joint Infection Panel multiplex-PCR test was performed and results were compared with conventional cultures of synovial fluid specimens. In total, 136 microorganisms were detected, and fourteen samples were positive for more than one microorganism. In monomicrobial infections (n = 87) agreement with culture was 69%. In 26 samples, the multiplex PCR yield an additional positive result when culture result was negative. It helped in the detection of fastidious microorganisms as K. kingae and N. gonorrhoeae. This multiplex PCR has proven to be a useful technique that can be used for patients with high suspicion of acute OI in a rapid and automated manner.

Improved Management of Pediatric Osteoarticular Infections

Improved Management of Pediatric Osteoarticular Infections

Invasive Bacterial Infections in Children With Sickle Cell Disease: 2014-2019.

Children with sickle cell disease (SCD) are at a high risk of invasive bacterial infections (IBI). Universal penicillin prophylaxis and vaccination, especially against Streptococcus pneumoniae, have deeply changed its epidemiology. Analysis of IBI in children with SCD in a post-13-valent pneumococcal vaccine era is limited. Twenty-eight pediatric hospitals from 5 European countries retrospectively collected IBI episodes in SCD children aged 1 month to 18 years between 2014 and 2019. IBI was defined as a positive bacterial culture or polymerase chain reaction from a normally sterile fluid: blood, cerebrospinal, joint, or pleural fluid and deep surgical specimen. We recorded 169 IBI episodes. Salmonella spp. was the main isolated bacteria (n = 44, 26%), followed by Streptococcus pneumonia (Sp; n = 31, 18%) and Staphylococcus aureus (n = 20, 12%). Salmonella prevailed in osteoarticular infections and in primary bacteremia (45% and 23% of episodes, respectively) and Sp in meningitis and acute chest syndrome (88% and 50%, respectively). All Sp IBI occurred in children ≤10 years old, including 35% in children 5 to 10 years old. Twenty-seven (17%) children had complications of infection and 3 died: 2 because of Sp, and 1 because of Salmonella. The main risk factors for a severe IBI were a previous IBI and pneumococcal infection (17 Sp/51 cases). In a post-13-valent pneumococcal vaccine era, Salmonella was the leading cause of bacteremia in IBI in children with SCD in Europe. Sp came second, was isolated in children ≤10 years old, and was more likely to cause severe and fatal cases.

Trimethoprim-Sulfamethoxazole for Pediatric Osteoarticular Infections.

Trimethoprim-sulfamethoxazole (TMP-SMX) is active against most Staphylococcus aureus isolates but is not widely used for treatment of pediatric osteoarticular infections. This was a comparative effectiveness study of hospitalized patients ≤18 years treated with TMP-SMX versus other antibiotic regimens for acute osteoarticular infections between 2016 and 2021 at three hospitals using inverse probability of treatment weighted propensity score analysis. The primary outcome was treatment failure, a composite of unanticipated emergency department (ED) or outpatient visits, hospital readmissions, extension or change of antibiotic therapy due to inadequate clinical response, or death, all within 6 months after completing antibiotics. The secondary outcome was antibiotic-associated adverse events (AEs) within 6 months. The exposed group for the treatment failure analysis included children who received ≥7 days of TMP-SMX and did not experience treatment failure while on another antibiotic. Children receiving at least one dose of TMP-SMX were the exposed group for the AE analysis. 116 patients met eligibility criteria; 26 (22.4%) patients were classified into the TMP-SMX cohort and 90 (77.6%) into the other antibiotics cohort (most commonly clindamycin, vancomycin, and cefazolin). There was no significant difference in treatment failure between TMP-SMX and other antibiotics (43% vs 19%; 95% CI 0.9-10.4). More patients in the TMP-SMX cohort experienced an unplanned ED or outpatient visit (OR 4.8, 95% CI 1.3-17.8). There was no difference in hospital readmission, antibiotic change, or duration extension. Exposure to TMP-SMX was associated with more AEs (41% vs 19%, p=0.012). Treatment with TMP-SMX was not associated with greater clinical failure but was associated with more AEs compared to alternative agents for the treatment of pediatric acute osteoarticular infections.

Switching from intravenous vancomycin to oral antibiotics reduces adverse events in a retrospective cohort of outpatients with orthopedic infections.

Vancomycin is frequently used for prolonged courses in treating osteoarticular infections despite a high rate of adverse drug events (ADE). The objective of this study was to evaluate the safety and effectiveness of transitioning to oral therapy compared to continuing parenteral vancomycin in patients with orthopedic infections. We conducted a single-center, retrospective cohort study of patients with orthopedic infections discharged on parenteral vancomycin with a planned duration of at least four weeks. We compared rates of ADE while on vancomycin to rates of ADE after switching to an oral regimen. As a secondary analysis, we compared unplanned hospital readmission within 60 days and treatment failure at one year between patients who were transitioned to oral antibiotics within four weeks of vancomycin initiation and those that were not. Two hundred twenty-eight patients met inclusion criteria. Vancomycin was associated with significantly greater toxicity compared to oral regimens. Fifty-one patients had an adverse event while on vancomycin (5.87 ADE per 1000 patient-days) while 9 patients had an adverse event on oral therapy (1.49 ADE per 1000 patient-days) (Rate difference 4.39 per 1000 patient days, 95% CI: 2.52 to 6.26 events per 1000 patient-days). In proportional hazards analysis, transition to an oral antibiotic regimen was independently associated with a lower rate of ADE (aHR 0.12, 95% CI: 0.02-0.86). Forty-one patients (18%) were transitioned to oral therapy within four weeks; these patients did not have an increased rate of unplanned readmission (12.2% vs 17.1%) or treatment failure (17.1% vs 21.9%). Patients transitioned to oral therapy within 4 weeks of discharge had significantly fewer adverse events and similar incidences of one-year treatment failure compared to patients maintained on parenteral vancomycin. Substituting oral antibiotics for parenteral vancomycin is a potential strategy to minimize vancomycin toxicity during the treatment of orthopedic infections.

A Systematic Review on the Clinical Pharmacokinetics of Cephalexin in Healthy and Diseased Populations.

Cephalexin is a first-generation β-lactam antibiotic used in adults and pediatrics to treat various streptococcal and staphylococcal infections. This review aims to summarize and evaluate all the pharmacokinetic (PK) data on cephalexin by screening out all pertinent studies in human beings following the per oral (PO) route. By employing different online search engines such as Google Scholar, PubMed, Cochrane Central, and Science Direct, 23 studies were retrieved, among which nine were in healthy subjects, five in diseased ones, and the remaining were drug-drug, drug-food, and bioequivalence-related. These studies were included only based on the presence of plasma concentration-time profiles or PK parameters, i.e., maximum plasma concentration (Cmax), half-life (t1/2) area under the curve from time 0-infinity (AUC0-∞), and clearance (CL/F). A dose-proportional increase in AUC0-∞ and Cmax can be portrayed in different studies conducted in the healthy population. In comparison to cefaclor, Cmax was recorded to be 0.5 folds higher for cephalexin in the case of renal impairment. An increase in AUC0-∞ was seen in cephalexin on administration with probenecid, i.e., 117 µg.h/mL vs. 68.1 µg.h/mL. Moreover, drug-drug interactions with omeprazole, ranitidine, zinc sulfate, and drug-food interactions for cephalexin and other cephalosporins have also been depicted in different studies with significant changes in all PK parameters. This current review has reported all accessible studies containing PK variables in healthy and diseased populations (renal, dental, and osteoarticular infections, continuous ambulatory peritoneal dialysis) that may be favorable for health practitioners in optimizing doses among the latter.