Efficacy and safety of colistin plus beta-lactams for bone and joint infection caused by fluoroquinolone-resistant gram-negative bacilli: a prospective multicenter study.

OBJECTIVES: The prognosis of bone and joint infections (BJI) caused by Gram-negative bacilli (GNB) worsens significantly in the face of fluoroquinolone-resistance. In this setting, scarce pre-clinical and clinical reports suggest that intravenous beta-lactams plus colistin may improve outcome. Our aim was to assess the efficacy and safety of this treatment in a well-characterized prospective cohort. METHODS: Observational, prospective, non-comparative, multicenter (14 hospitals) study of adults with BJI caused by fluoroquinolone-resistant GNB treated with surgery and intravenous beta-lactams plus colistin for ≥ 21 days. The primary endpoint was the cure rate. RESULTS: Of the 44 cases included (median age 72 years [IQR 50-81], 22 [50%] women), 32 (73%) had an orthopedic device-related infection, including 17 (39%) prosthetic joints. Enterobacterales were responsible for 27 (61%) episodes, and Pseudomonas spp for 17 (39%), with an overall rate of MDR/XDR GNB infections of 27/44 (61%). Patients were treated with colistin plus intravenous beta-lactam for 28 days (IQR 22-37), followed by intravenous beta-lactam alone for 19 days (IQR 5-35). The cure rate (intention-to-treat analysis; median follow-up = 24 months, IQR 19-30) was 82% (95% CI 68%-90%) and particularly, 80% (95% CI 55%-93%) among patients managed with implant retention. Adverse events (AEs) leading to antimicrobial withdrawal occurred in 10 (23%) cases, all of which were reversible. Colistin AEs were associated with higher plasma drug concentrations (2.8 mg/L vs. 0.9 mg/L, p = 0.0001). CONCLUSIONS: Combination therapy with intravenous beta-lactams plus colistin is an effective regimen for BJI caused by fluoroquinolone-resistant GNB. AEs were reversible and potentially preventable by close therapeutic drug monitoring.

Aspergillus spp. osteoarticular infections: an updated systematic review on the diagnosis, treatment and outcomes of 186 confirmed cases.

Aspergillus spp. osteoarticular infections are destructive opportunistic infections, while there is no clear consensus on their management. The purpose of this review is to investigate the current literature regarding Aspergillus spp. osteoarticular infections. An electronic search of the PubMed and Scopus databases was conducted considering studies that assessed osteoarticular infections from Aspergillus spp. We included only studies with biopsy proven documentation of positive cultures or histological findings for Aspergillus spp., and those with essential information for each case such as the anatomical location of the infection, the type of treatment (conservative, surgical, combination), the antifungal therapy, and the outcome. Overall, 148 studies from 1965 to 2021 including 186 patients were included in the review. One hundred and seven (57.5%) patients underwent surgical debridement in addition to antifungal therapy, while 79 (42.7%) patients were treated only conservatively. Complete infection resolution was reported in 107 (57.5%) patients, while partial resolution in 29 (15.5%) patients. Surgical debridement resulted in higher complete infection resolution rate compared to only antifungal therapy (70.0% vs. 40.5%, P < 0.001), while complete resolution rate was similar for antifungal monotherapy and combination/sequential therapy (58.3% vs. 54.5%; P = 0.76). Last, complete resolution rate was also similar for monotherapy with amphotericin B (58.1%) and voriconazole (58.6%; P = 0.95). The results of this study indicate that antifungal monotherapy has similar efficacy with combination/sequential therapy, while voriconazole has similar efficacy with amphotericin B. Moreover, surgical debridement of the infected focus results in better outcomes in terms of infection eradication compared to conservative treatment. LAY SUMMARY: Antifungal monotherapy has similar efficacy with combination/sequential therapy, and voriconazole has similar efficacy with amphotericin B for the treatment of Aspergillus spp. osteoarticular infections, while surgical debridement of the infected focus improves the infection eradication rate.

Benefits of diffusion-weighted imaging in pediatric acute osteoarticular infections.

BACKGROUND: Contrast-enhanced magnetic resonance imaging (MRI) is recommended for the diagnosis of acute osteoarticular infections in children. Diffusion-weighted imaging (DWI) may be an alternative to the injection of gadolinium. OBJECTIVE: To evaluate unenhanced MRI with DWI in comparison to contrast-enhanced MRI for the diagnostic work-up of acute osteoarticular infections in children. MATERIALS AND METHODS: This retrospective study included 36 children (age range: 7 months-12 years) with extra-spinal osteoarticular infections and MRI performed within 24 h of admission. MRI protocol included short tau inversion recovery (STIR), water-only T2 Dixon, T1, DWI, and gadolinium-enhanced T1 sequences. Two readers reviewed three sets of images: 1) unenhanced sequences, 2) unenhanced sequences with DWI and 3) unenhanced followed by contrast-enhanced sequences (reference standard). Sensitivity and specificity of sets 1 and 2 were compared to set 3 and assessed to identify osteoarticular infections: osteomyelitis (long bones, metaphyseal equivalents), septic arthritis and abscess (soft tissues, bone). RESULTS: All 14 cases of osteomyelitis in the metaphyses and diaphyses of long bones and all 27 cases of septic arthritis were identified by unenhanced sequences, but 4/16 abscesses were missed. For the diagnosis of abscess, DWI increased sensitivity to 100%. Among the 18 osteomyelitis in metaphyseal equivalents, 4 femoral head chondroepiphyses were identified by contrast-enhanced sequences only. CONCLUSION: MRI for suspected pediatric acute osteoarticular infections is the best diagnostic modality to guide patient management. An unenhanced protocol with DWI may be an alternative to a contrast-based protocol, even in the presence of an abscess. However, gadolinium remains necessary to assess for chondroepiphyseal involvement of the femoral head.

Osteoarticular infections in infants under 3 months of age.

BACKGROUND: Acute osteoarticular infections (OAI) in infants under 3 months of age (≤3M) are rare and remain a diagnostic challenge. Orthopedic complications and functional sequelae have been less well described in this age group. Our aims were to evaluate trends in aetiology, management, and outcomes of OAI ≤ 3M, and to compare these younger children who have OAI with older children. METHODS: A longitudinal observational study was conducted of OAI cases admitted to tertiary care pediatric hospital from 2008 to 2018. OAI ≤ 3M was compared with children above 3 months. Clinical, microbiological, imaging, and outcome data were analyzed. RESULTS: We identified 24 (9.1%) of the 263 OAI in children under 3 months. Analyzing OAI ≤ 3M there was a twofold increase since 2014; 54% were males with a median age of 28 days (IQR: 13.5-60.0), 10 (41.7%) were premature and nine (37.5%) had healthcare-associated infections. Microbiological causes were identified in 87.5%, mostly Staphylococcus aureus (57.1%) and Group B Streptococcus (23.8%), and 25% were multidrug-resistant (5 methicillin-resistant S. aureus and 1 Enterobacter cloacae). Bacteremia (100% vs 36.8%, P = 0.037), multidrug resistant bacteria (75% vs 16, P = 0.04), and healthcare-associated infections (100% vs 26.3%, P = 0.014) were associated with sequelae. Comparing OAI ≤ 3M with older children, OAI ≤ 3M were treated with longer antibiotic courses, had more complications and sequelae (17.4% vs 3.2%, P = 0.002). CONCLUSIONS: S. aureus is still the most common cause of OAI ≤ 3M, and 25% of causative bacteria were multidrug-resistant bacteria. Complications and sequelae were more frequent in OAI ≤ 3M when compared with older children.

Paediatric Osteomyelitis and Septic Arthritis Pathogen Distribution and Antimicrobial Resistance in a Single Centre: A 15-Year Retrospective Analysis.

BACKGROUND: The epidemiological characteristics of the common pathogens underlying acute haematogenous osteoarticular infection (AHOI) and their resistance to drugs have temporal and regional differences. AIMS: To determine the antimicrobial treatment most effective for culture-negative AHOI patients and those without bacterial cultures. METHODS: Retrospective analysis of clinical data of children with AHOI who were culture positive from January 2007 to December 2021. And the distribution of the main pathogens and the drug resistance Staphylococcus aureus were analysed in different time periods, age groups and infection types. RESULTS: A total of 188 cases met the inclusion criteria, including 97 cases of acute haematogenous osteomyelitis (AHO), 75 cases of septic arthritis (SA) and 16 cases of AHO concomitant with SA. The commonest causative pathogen in local children was S. aureus of Gram-positive cocci, followed by Streptococcus, and occasionally Gram-negative bacilli. The distribution of S. aureus had no significant correlation with age or infection type. Staphylococcus aureus accounted for 81.82%, 90.91% and 96.15% of all pathogens, and methicillin-resistant S. aureus (MRSA) accounted for 24.22%, 53.33% and 76.00% of S. aureus in 2007-11, 2012-16 and 2017-21, respectively. The frequency of MRSA infection showed an increasing trend over time. CONCLUSION: Staphylococcus aureus is still the main pathogen of AHOI in local children. The proportion of MRSA in S. aureus has also increased over time to 76% in the last 5 years, and the increased proportion of MRSA can affect the choice of initial empirical medication.

[A pedicled deep inferior epigastric flap to cover a hip arthroplasty infection]. / Couverture d'une prothèse de hanche infectée par un lambeau perforant épigastique inférieur profond pédiculé.

The deep inferior epigastric perforator (DIEP) flap is a reliable flap mostly used in skin resurfacing after signifiant resection for sarcoma or correction contour deformities. This case is about a pedicled DIEP flap covering the trochanteric region after a total hip arthroplasty infection. A 62years old woman with a BMI at 42kg/m2 presents an infected total hip arthroplasty with a cutaneous defect. The hip prosthesis is changed and covered with a pedicled DIEP flap. This original case reports the used of pedicled DIEP flap in hip coverage. This local fasciocutaneous flap covered the hip osteoarticular infection. The limb is salved and the patient can walked again. The success of this surgery is the collaboration between infectious disease specialist, orthopedic surgeon and plastic surgeon.

Prosthetic joint infection due to Mycobacterium xenopi: a review of the literature with a new case report.

PURPOSE: Extrapulmonary infections due to M. xenopi, particularly osteoarticular localizations, are rare. The purpose of this paper is to describe a case of prosthetic hip infection and to review the published literature on cases of M. xenopi osteoarticular infections. METHODS: Literature search was performed in the following databases: MEDLINE (PubMed), Embase, Central (the Cochrane Library 2019, Issue 1), LILACS (BIREME) (Latin American and Caribbean Health Science Information database) and Clinical Trials databases (14th August 2018). We included all case reports and case series on adult patients diagnosed with bone or joint infection by M. xenopi for whom the treatment and outcome were specified. RESULTS: We retrieved 30 cases published between 1982 and 2012, among which 25 (83.3%) were reported from Europe. The two most common infection sites were spine (12/30, 40%) and knee (9/30, 30%). Risk factors for infection were previous invasive procedures (11/30, 36.7%), autoimmune disease (8/30, 26.7%), AIDS (4/30, 13.3%) and other comorbidities (2/30, 6.7%); five patients had no past medical history. All patients were treated with antibiotic combinations, but composition and duration of regimens hugely varied. Surgical intervention was performed in 16 patients (53.3%). Only 11 patients obtained full recovery of articular mobility after treatment. CONCLUSION: This work highlights the difficulties in diagnosing and treating M. xenopi osteoarticular infections. Globally, evidence supporting the best practice for diagnosis and treatment of this infection is scanty.

Yersinia enterocolitica biotype 1B case report: an unusual pathogen in an osteoarticular infection on device.

BACKGROUND: Yersinia enterocolitica is an aero-anaerobic Gram-negative coccobacilli of the Enterobacteriaceae family, rarely reported in osteoarticular infection. CASE PRESENTATION: This report case described a rare septic osteoarticular infection on device due to Yersinia enterocolitica biotype 1B. A purulent fistula appeared after osteosynthesis with plate performed abroad 27 days prior to the presentation for a distal femoral fracture. The treatment consisted of surgical irrigation and washing of the femoral plate and a bitherapy by levoflaxacine and ceftriaxone during 3 months. CONCLUSION: Y. enterocolitica biotype 1B is extremely rare in France. Moreover, the strain implicated in this european case is extremely close from the USA reference strain (with only 2 SNP difference) described in a septicemia in Ohio. The extreme proximity of the strains underlines the need for a sustained surveillance of the spread of this pathogen in France.

The Contemporary Bacteriologic Epidemiology of Osteoarticular Infections in Children in Switzerland.

OBJECTIVES: To assess the contemporary bacteriologic epidemiology of pediatric osteoarticular infection with particular regard to children's ages, because Kingella kingae has gained increasing recognition as the predominant pathogen for osteoarticular infection in young children. STUDY DESIGN: Retrospective file review of enrolled children from 0 to 15 years of age, admitted to our institution from 2007 to 2015 for suspected osteoarticular infection (217 cases). Information on age, sex, the bone or joint infected, imaging studies, and laboratory data (including bacterial investigations) were collected for analysis. RESULTS: Microorganism identification was possible for 138 infected children (63.6%), through blood (cultures or polymerase chain reaction [PCR]) and/or operative samples (cultures or PCR). Thirty-one patients (14.3%) were found to both have positive blood cultures and operative samples. The results of positive bacteriology specimens identified the most common causative pathogen for osteoarticular infection as K kingae (47.8% of microbiologically confirmed osteoarticular infections of all ages, and 87.7% in children between the ages of 6 and 48 months), significantly more common than Staphylococcus aureus (35.5% of microbiologically confirmed osteoarticular infections of all ages, and 78.2% in children >4 years of age). CONCLUSIONS: Use of the appropriate PCR assays demonstrated that K kingae currently is the major bacterial cause of pediatric osteoarticular infection, especially in children <4 years of age in whom K kingae is more common than S aureus. PCR assays should be used in routine microbiologic laboratory evaluation to improve diagnostic performance. However, despite the use of molecular methods, there are many osteoarticular infections in which no microorganism is detected, which suggests that these infections may be caused by other as yet unrecognized fastidious microorganisms.

Temporal trends of ß-haemolytic streptococcal osteoarticular infections in western Norway.

BACKGROUND: Beta-haemolytic streptococci are important contributors to the global burden of osteoarticular infections (OAI). Knowledge on the disease traits specific for streptococcal OAI, however, remains scarce. We wished to explore temporal trends of OAI caused by Group A Streptococci (GAS), Group B Streptococci (GBS) and Group C and G Streptococci (GCGS), and furthermore, to describe the associated host and pathogen characteristics. METHODS: All cases of microbiologically verified ß-haemolytic streptococcal OAI in Health Region Bergen, Norway, in the period 1999-2013 were retrospectively identified. Clinical data were extracted from medical records. Microbial isolates were submitted to antibiotic susceptibility testing and molecular typing. RESULTS: A total of 24 GAS, 45 GBS and 42 GCGS acute OAI were identified. The cumulative incidence of GCGS OAI, but not GAS or GBS OAI, increased significantly from the first to the last 5-year period (IRR 5.7, p = 0.0003), with the annual incidence peaking at 1.9/100 000 in 2013. GAS OAI generally produced the most acute and severe clinical presentation, whereas GBS and GCGS predominantly affected the elderly, and were significantly associated with the presence of host risk factors of systemic and focal origin, respectively. CONCLUSIONS: We found a significantly increasing incidence of GCGS OAI, likely related to the presence of host susceptibility factors, including prosthetic material and pre-existing joint disease. With an increasing application of therapeutic and diagnostic bone and joint procedures, the rising trend of OAI caused by GCGS is likely to continue. Sustained epidemiological attentiveness to GCGS seems warranted.

Update on the Management of Pediatric Acute Osteomyelitis and Septic Arthritis.

Acute osteomyelitis and septic arthritis are two infections whose frequencies are increasing in pediatric patients. Acute osteomyelitis and septic arthritis need to be carefully assessed, diagnosed, and treated to avoid devastating sequelae. Traditionally, the treatment of acute osteoarticular infection in pediatrics was based on prolonged intravenous anti-infective therapy. However, results from clinical trials have suggested that in uncomplicated cases, a short course of a few days of parenteral antibiotics followed by oral therapy is safe and effective. The aim of this review is to provide clinicians an update on recent controversies and advances regarding the management of acute osteomyelitis and septic arthritis in children. In recent years, the emergence of bacterial species resistant to commonly used antibiotics that are particularly aggressive highlights the necessity for further research to optimize treatment approaches and to develop new molecules able to fight the war against acute osteoarticular infection in pediatric patients.

[Osteoarticular pneumococcal infections observed in a tertiary hospital over a period of 11 years]. / Infección osteoarticular neumocócica en un hospital terciario durante un período de 11 años.

INTRODUCTION: Osteoarticular pneumococcal infection is an infrequent complication of pneumococcal bacteremia, due to the advances in antibiotic therapy and in the pattern of immunization. METHODS: A retrospective study was conducted on patients diagnosed with osteoarticular pneumococcal infection between January 2003 and December 2013 in the University Hospital Marqués de Valdecilla in Santander. RESULTS: Five out of 321 patients diagnosed with pneumococcal bacteremia had osteoarticular infection. All of them had at least one chronic underlying disease and had been immunized according to the standard vaccination schedule. Hip and vertebra were the most common joints involved. Outcome was favorable in all cases. CONCLUSIONS: The clinical findings of pneumococcal osteoarticular infection should be borne in mind. Its optimal prevention in high-risk patients should include the 13V conjugate vaccine.

Leptospirosis and melioidosis coinfection presenting as acute respiratory distress syndrome and osteomyelitis: Case report and systematic review.

INTRODUCTION: Leptospirosis and melioidosis are common in tropical and temperate climates and can be acquired by exposure to contaminated water and soil. However, concomitant leptospirosis and melioidosis infection is rarely described in the literature. We report a case of leptospirosis-melioidosis coinfection and systematically review the literature. CASE PRESENTATION: A 42-year-old male presented with fever associated with chills and rigor, dull aching pain in the right thigh, myalgia, progressive breathlessness, and dry cough for 10 days. At presentation, he was tachypneic and had tachycardia, and oxygen saturation was 46% in room air. Chest radiography and computed tomography scan showed interstitial involvement. Magnetic resonance imaging for thigh pain revealed right femur osteomyelitis. Leptospira serology was positive, and blood culture grew Burkholderia pseudomallei, confirming the diagnosis of melioidosis. Thus, a diagnosis of presumptive leptospirosis based on modified Faine's criteria and systemic melioidosis was made. He received doxycycline and intravenous meropenem and improved. RESULTS: We performed a systematic review to understand the spectrum of leptospirosis-melioidosis coinfection. We identified only nine cases of coinfection described in literature. Only one patient had septic arthritis, and our case is the only one presenting with osteomyelitis. Serology diagnosed leptospirosis, whereas melioidosis was confirmed by blood culture in most patients. The majority of coinfected patients developed some complications, and six died. CONCLUSIONS: Leptospirosis-melioidosis coinfection is rarely reported in the literature. Physicians should maintain a high index suspicion of leptospirosis-melioidosis coinfection in patients presenting with acute febrile illness following exposure to soil or freshwater, particularly in tropical and endemic regions.

Diagnosis, Treatment, and Outcome of Coccidioidal Osseous Infections: A Systematic Review.

Extrapulmonary infections by Coccidioides spp., though rare, can occur via dissemination, affecting singular or multiple sites, including the skin and musculoskeletal system. Skeletal involvement often manifests as osteomyelitis, particularly in the axial skeleton. The present systematic review evaluates all documented cases of skeletal coccidioidomycosis to assess the diagnostic and treatment strategies alongside the outcomes, drawing insights from an analysis of 163 verified cases. A systematic review following PRISMA guidelines identified all studies reporting skeletal infections by Coccidioides spp. up to 2023 from the PubMed and Scopus databases. Eligible studies evaluated osteoarticular infections from Coccidioides spp. Data extraction included demographics, microbiological data, diagnostic methods, and treatment outcomes. Of the 501 initially identified records, a total of 163 patients from 69 studies met the inclusion criteria. Most cases were from the USA, predominantly males, while the median age of the population was 36 years. Diabetes mellitus was the common comorbidity (14.7%). C. immitis was the most prevalent pathogen. The spine and hand were common sites of infection (17.5% and 15.1%, respectively). Osteomyelitis by Coccidioides spp. was diagnosed, in most cases, by positive cultures (n = 68; 41.7%), while, in 49 (30.9%), both the histological examination and cultures yielded the fungus. Surgical debridement was performed in 80.9% of cases. A total of 118 (72.3%) patients were treated with monotherapy, while combination therapy with two or more antifungal agents was reported in 45 (17.7%). Amphotericin B (either liposomal or deoxycholate) was the most commonly given agent as monotherapy in 51 (31.2%) patients, while 30 (18.4%) patients received itraconazole as monotherapy. The rate of infection's resolution was higher in patients undergoing surgical debridement (79.5%), compared to those treated only with antifungal agents (51.6%, p = 0.003). Treatment outcomes showed complete resolution in 74.2% of patients, with a mortality rate of 9.2%. Coccidioidal osseous infections present diagnostic and therapeutic challenges. Surgical intervention is often necessary, complementing antifungal therapy. Vigilance for Coccidioides spp. infections, especially in regions with endemicity, is crucial, particularly when bacterial cultures yield negative results.

Plasma Microbial Cell-free DNA Next-generation Sequencing Can Be a Useful Diagnostic Tool in Patients With Osteoarticular Infections.

Background: Recent advances in shotgun metagenomic sequencing (sMGS) for detecting microbial cell-free DNA (mcfDNA) in peripheral blood have shown promise across various patient populations. This study evaluates the application of sMGS for diagnosing osteoarticular infections (OAIs), a condition with significant diagnostic challenges. Methods: We conducted a retrospective analysis on 73 patients suspected of OAIs at the Mayo Clinic from 2019 to 2023, incorporating mcfDNA sMGS (Karius test [KT]) into their diagnostic evaluation. We categorized the clinical impact of KT on OAI diagnoses and management into 4 distinct outcomes. (1) KT was able to confirm an established diagnosis, (2) KT supported noninfectious diseases diagnosis, (3) KT established an unsuspected diagnosis, (4) KT did not add relevant information. Results: In our cohort, KT was performed in 73 patients. Among the infected individuals, KT yielded positive results in 22 of 43 (51.2%) cases. Of these 22 cases, 11 (50%) showed agreement with conventional diagnostic workup, whereas in 5 (22.7%) cases, the KT established an unsuspected diagnosis. Native vertebral osteomyelitis diagnosis (P < .001) or OAIs with concomitant presence of endocarditis or endovascular infection (P = .005) were statistically associated with a definite, probable, or possible diagnostic certainty of KT result. Conclusions: In complex OAIs, KT enhanced diagnostic accuracy by 11.6%, proving especially beneficial in diagnosing native vertebral osteomyelitis and infections with concurrent endocarditis or endovascular complications. Our findings underscore the utility of KT in the diagnostic workflow for challenging OAI cases, potentially altering clinical management for a significant subset of patients.

The Kocher-Caird Criteria for Pediatric Septic Arthritis of the Hip: Time for a Change in the Kingella Era?

Pediatric septic arthritis of the hip (SAH) in children is a severe pathology, requiring prompt diagnosis and treatment to avoid destructive sequelae of the joint. Its diagnosis can be challenging, however, due to its spectrum of manifestations and differential diagnosis. Last century, multiple research teams studied the curves of systemic inflammation markers to aid the differential diagnosis. Kocher showed that a history of fever >38.5 °C, non-weight bearing, an erythrocyte sedimentation rate >40 mm/h, and serum white blood cells >12,000/mm3 were highly suggestive of SAH, with a predicted probability of 99.6% when all these predictors manifested in pediatric patients. Caird validated these criteria, also adding a C-reactive protein >20 mg/L, reaching a 98% probability of SAH when these five criteria were present. The Kocher and the Caird criteria were then applied in multiple settings, but were never clearly validated. Moreover, they were studied and validated in the years when Kingella kingae was just emerging, and this was probably responsible for false-negative cases in multiple centers. For this reason, the Kocher and the Caird criteria are still at the center of a debate on the diagnostic tools for pediatric SAH. We provide a historical overview of the development of clinical and laboratory test algorithms for pediatric SAH. Further, new perspectives for future research on the prediction rules of pediatric SAH are here proposed.

Biological Predictors of Osteoarticular Infection Due to K. kingae-A Retrospective Cohort Study of 247 Cases.

Pediatric osteoarticular infections (OAIs) are serious conditions that can lead to severe septic complications, prolonged morbidity with long-term impaired function, and perturbed subsequent bone development. Kingella kingae (K. kingae) is currently accepted as the predominant pathogen in pediatric OAIs, especially among 6-48 month olds. The present study aimed to identify clinical and biological markers that would refine the detection of patients with an OAI due to K. kingae. We retrospectively studied every consecutive case of pediatric OAI admitted to our institution over 17 years. Medical records were examined for patient characteristics such as temperature at admission, affected segment, and biological parameters such as white blood cell (WBC) count, left shift, platelet count (PLT), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The 247 patients included 52.2% males and 47.8% females and mean age was 18.5 ± 10 months old. Four patients were older than 48 months; none were younger than 6 months old. Mean temperature at admission was 37.4 ± 0.9 °C. Regarding biological parameters, mean WBC count was 12,700 ± 4180/mm3, left shift was only present in one patient, mean PLT was 419,000 ± 123,000/mm3, mean CRP was 26.6 ± 27.8 mg/L, and mean ESR was 35.0 ± 18.9 mm/h. Compared to the modified predictors of OAI defined by Kocher and Caird, 17.2% of our cases were above their cut-off values for temperature, 52.3% were above the WBC cut-off, 33.5% were above the ESR cut-off, and 46.4% were above the CRP cut-off. OAIs due to K. kingae frequently remain undetected using the classic biological parameters for investigating bacterial infections. As an addition to the predictors normally used (°C, WBC, CRP, and ESR), this study found that elevated platelet count was frequently present during OAIs caused by K. kingae. Although this biological characteristic was inconstant, its presence was highly significant and very suggestive of an invasive infection due to K. kingae.

Trimethoprim-Sulfamethoxazole for Pediatric Osteoarticular Infections.

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) is active against most Staphylococcus aureus isolates but is not widely used for the treatment of pediatric osteoarticular infections. METHODS: This was a comparative effectiveness study of hospitalized patients ≤18 years treated with TMP-SMX vs. other antibiotic regimens for acute osteoarticular infections between 2016 and 2021 at 3 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 1 dose of TMP-SMX were the exposed group for the AE analysis. RESULTS: One-hundred and sixteen 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 .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 = .012). CONCLUSIONS: 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.

Metagenomic next-generation sequencing in osteoarticular infections with a focus on pediatrics: current concepts and clinical applications.

Osteoarticular infections (OAI) are a significant cause of morbidity and mortality. Cultures and serology are some of the gold standards for identifying infection but are often unable to provide a timely diagnosis or a diagnosis at all. Genetic testing offers capabilities that other modalities lack. Polymerase chain reaction has multiple versions with various costs and turnaround times. This technology has become implemented in multiple pediatric center OAI diagnostic protocols. There is sufficient literature documenting effectiveness in certain clinical situations, especially with fastidious organism diagnosis, but significant limitation still exists. Metagenomic next-generation sequencing is an unbiased or hypothesis-free modality with the capability to detect the genetic material of bacteria, viruses, parasites, fungi, and humans from a single sample. Potential benefits include pathogen identification unaffected by antimicrobial administration, detection of fastidious organisms more quickly, delineation of pathogens in polymicrobial infections, antimicrobial susceptibility, and avoidance of invasive procedures. It is a resource-intensive modality with little standardization of the complex processes. Appropriate use and definitive clinical impact have yet to be determined.

Development and performance of a multiplex PCR assay for the detection of bacteria in sterile body fluids.

Aim: To assess the performance characteristics of a lab-developed multiplex PCR assay for the detection of common bacterial pathogens associated with infections in pediatric patients from normally sterile sites, such as cerebrospinal fluid, synovial and pleural fluids. Materials & methods: A total of 272 specimens were tested by PCR and traditional culture methods to assess the presence of Neisseria meningitidis, Streptococcus pneumoniae, Streptococcus pyogenes, methicillin-sensitive and methicillin-resistant Staphylococcus aureus and Kingella kingae. Results: Compared with culture, the overall positive and negative percentage agreement of the PCR were 95.9% and 74.1%, respectively. Conclusion: This sterile body fluid PCR affords a rapid and sensitive alternative for bacterial detection, allowing for more timely pathogen-directed antimicrobial therapy.