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Background
Synovial fluid and blood cultures often remain negative in acute bone and joint infections of childhood even when characteristic symptoms, signs, and/or radiologic proof are present.
Methods
We analyzed 345 prospectively documented osteoarticular infections in children at age 3 months to 15 years. In 23% of the cases (N = 80), synovial,...
Contexts in source publication
Context 1
... aureus (invariably methicillin-sensitive) was the most common causative organism identified (75%, 199 of 265). The characteristics of the culture-positive and culture-negative cases are summarized in Table 1. Median duration of symptoms on admission was 4 days (interquartile range [IQR], 1-7.5) and 3 days (2-4.5) ...
Context 2
... patients were discharged from hospi- tal 3 days sooner (mean hospital stay 8 ± 0.4 vs 11 ± 0.4 days, P < .0001). Duration of antibiotic therapy or the rate of surgical procedures did not differ from the culture-positive cases (Table 1). C-reactive protein normalized 2 days earlier among the culture-negative patients (P = .06). ...
Citations
... Musculoskeletal infections encompass a wide range of medical and dental conditions, including osteomyelitis, septic arthritis, pyomyositis, myositis, severe periodontitis, and periprosthetic joint infection. In clinical practice, confirming the diagnosis of musculoskeletal infection-including the microbiological cause and mechanism of infection-can be challenging (1,2). Healthcare providers often use a combination of radiological imaging, laboratory testing, patient historical details (including key environmental exposures to potential pathogens), and clinical examination techniques to diagnose the infection and identify a treatment plan (3)(4)(5). ...
Doxycycline is among the most commonly used antibiotics for the treatment and long-term suppression of musculoskeletal infections such as osteomyelitis and periprosthetic joint infection. We systematically reviewed clinical trials and cohort studies that examined outcomes of musculoskeletal infections treated with doxycycline. Eligible studies were published in Medline or Embase in English before March 2, 2021. Eleven reports were included; eight addressed medical/non-dental infections, and three addressed dental infections. Brucella was the most frequently studied organism in the non-dental studies. Random-effects meta-analyses showed no significant difference in Brucella relapse risk after six weeks of treatment with 200 mg doxycycline compared to 400 mg ofloxacin daily (pool risk ratio: 0.94, 95% confidence interval: 0.2 - 4.45, I ² =L0%). Despite a large number of case reports, case series, and cross- sectional studies on this topic, few studies investigated doxycycline treatment outcomes; and evidence was largely limited to rare infections such as Brucella .
... Other bacterial causes include Streptococcus pyogenes, Streptococcus pneumoniae, and Kingella kingae [1,[4][5][6]. Additionally, it is common for cases to yield negative culture results [1,7,8]. Empiric therapy is aimed at treating the most common causes of osteomyelitis, considering a patient's age and risk factors, and antibiotic therapy is later adjusted in concordance with available culture results [1]. ...
Background
Acute hematogenous osteomyelitis (AHO) is a relatively infrequent but significant infection in pediatric patients. As Staphylococcus aureus is the most common cause of AHO, intravenous and oral first-generation cephalosporins are common therapies. Cephalexin is a commonly prescribed oral therapy for pediatric AHO, although it requires frequent dosing that may affect adherence. Cefadroxil is a comparable oral first-generation cephalosporin with a more desirable dosing schedule.
Methods
We reviewed pediatric patients admitted to Mayo Clinic between March 2002 and September 2020 for management of AHO who received treatment with a first-generation cephalosporin. We reviewed timing of oral therapy transition, therapy-associated adverse effects, and recurrence of disease after completion of therapy.
Results
There were 59 patients included in the study. There was similar occurrence of adverse effects in patients receiving cefadroxil and cephalexin, although use of cefadroxil coincided with more gastrointestinal adverse effects and leukopenia and use of cephalexin with more rash and neutropenia. One secondary treatment failure occurred in our study, in a patient receiving cephalexin for treatment of septic arthritis.
Conclusions
Cefadroxil may be a reasonable alternative oral therapy for methicillin-susceptible S aureus or culture-negative AHO in pediatric patients, particularly when a less frequent dosing schedule is desired. Future study with a larger sample size is warranted.
... Los pacientes con osteomielitis aguda tuvieron una presentación clínica acorde a la bibliografía con fiebre tumefacción e impotencia funcional (10)(11) , no se han registrado óbitos en nuestra serie a diferencia de los reportado en la serie anterior (11) . ...
... Los pacientes con osteomielitis aguda tuvieron una presentación clínica acorde a la bibliografía con fiebre tumefacción e impotencia funcional (10)(11) , no se han registrado óbitos en nuestra serie a diferencia de los reportado en la serie anterior (11) . ...
... Nuestros resultados sugieren que el tratamiento empírico inicial debe incluir medicamentos que incluyan cobertura contra MRSA (7,(10)(11)13) en estos casos las cefalosporinas de tercera generación ofrecen una cobertura en ese sentido sumado a otros antibióticos para ofrecer una amplia cobertura. ...
Introducción: La osteomielitis aguda es una infección del hueso que afecta principalmente a los niños y tiene generalmente diseminación hematógena, a veces asociada a un trauma. En la etiología influyen factores, como la edad, el estado inmunológico y las enfermedades concomitantes. En la mayoría de los casos, el principal agente etiológico es Staphylococcus aureus. Es importante el diagnóstico oportuno para evitar secuelas a mediano o largo plazo. Objetivo: Describir las características epidemiológicas de un grupo de pacientes con osteomielitis aguda. Métodos: Se realizó la revisión retrospectiva de los expedientes clínicos de pacientes egresados del servicio de pediatría del Instituto de Medicina Tropical, entre enero de 2016 y diciembre de 2020, con diagnóstico de osteomielitis aguda. Resultados: Los varones con osteomielitis corresponden al 67,8% del total de 59 casos registrados, en cuanto a los signos y síntomas, el dolor, la tumefacción y la impotencia funcional fueron predominantes, la fiebre se documentó en 49 (83,1%) pacientes, se registró antecedentes de cirugía en 37 (62,7%) de los pacientes y complicaciones en 42 (71,2%) de los pacientes, la complicación más frecuente fue osteomielitis crónica El sitio anatómico más frecuente fueron los miembros inferiores. El tratamiento empírico fue realizado con cefalosporinas de 3G en 72,9% de los pacientes, ya sea solo o combinado con clindamicina o vancomicina, un paciente con aislamiento de M. tuberculosis recibió tratamiento HRZE. Se aisló algún germen 44 pacientes (74,5%), el microorganismo predominante fue Staphylococcus aureus en 81,8 %, la mitad (52,3%) correspondieron a SAMR Se encontró una alta resistencia a oxacilina del 55,8% y un solo paciente resistente a clindamicina (2,2%). Conclusión Los hallazgos fueron similares a los reportados en la literatura en cuanto a etiología, sitio anatómico afectado y cobertura antibiótica.
... These limitations can significantly impact patient care, particularly in critically ill patients (10, 11). Culture-negative cases often lead to a longer course of empiric antibiotics which are reported to be inadequate in up to 20% of cases with added side effects (4, 6, 12, 13,14,15). In a study published by Spyridakis et al. (13), 89 of 129 (69%) cases of septic arthritis were culture-negative and failed initial empiric antibiotic treatment 9% of the time. ...
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.
... This approach was chosen, because one in three patients had prior antibiotic treatment and routine PCR for pathogen identification had not been implemented. Additionally, no differences in outcomes were detected in patients with and without positive cultures and both were suggested to be treated similarly [21]. Finally, synovial fluid WBS counts were not obtained routinely. ...
Purpose
In recent years an earlier step down to oral antibiotic therapy has been advocated for numerous infections. Trained infectious disease specialists regularly consulting their colleagues may speed up the implementation of such recommendations into clinical practice and thus may improve treatment.
Methods
We retrospectively analyzed bone and joint infections in children admitted to the University Hospital of Cologne between 2010 and 2021. We assessed clinical, imaging, and microbiological findings and treatment modalities. Additionally, we assessed both the impact of a newly implemented pediatric infectious diseases consultation service and publications on revised treatment recommendations by comparing antibiotic therapy in two periods (2010–2016 versus 2017 to 2021).
Results
In total, 29 children presented with osteomyelitis, 16 with bacterial arthritis and 7 with discitis. In period 2 (2017–2021) we observed shorter duration of intravenous treatment ( p = 0.009) and a higher percentage of oral antibiotic treatment in relation to the total duration of antibiotics (25% versus 59%, p = 0.007) compared to period 1 (2010–2016).
Yet, no differences were identified for the total length of antibiotic treatment. Additionally, biopsies or synovial fluid samples were retrieved and cultured in more children in period 2 ( p = 0.077). The main pathogen identified in osteomyelitis and bacterial arthritis was Staphylococcus aureus (MSSA), diagnosis was confirmed predominantly with MRI.
Conclusion
Recent guidelines addressing the safety of an earlier step-down (to oral) antibiotic therapy have influenced clinical practice in the treatment of bone and joint infections in our hospital. A newly implemented pediatric infectious diseases consultation service might have accelerated this progress resulting in a faster step down to oral treatment.
... However, no pathogen is isolated here in routine cultures of blood and wound aspirates. This fact is also observed in up to one-half of cases, which are usually presumed to be caused by S. aureus and treated accordingly [9]. Furthermore, patients may present following clearance of bacteremia, so blood cultures are not always positive. ...
... these infections even with negative cultures to avoid complications related to untreated infection. Cultures may not yield the causative organism, or the pathogen may only be isolated from the affected bone or joint [1,[5][6][7]. Rates of culture-negative pediatric musculoskeletal infection range from 16 to 42% [2,8]. ...
... Rates of culture positivity in this study were in keeping with prior studies [6,8,12,14,15]. Antimicrobial data are described separately [18]. There was no association between culture positivity and pretreatment with antibiotics in any of our culture samples. ...
Background
In the management of pediatric osteomyelitis or septic arthritis, delay in treatment may affect outcome, while receipt of antibiotics prior to culture may affect culture results. We aimed to determine if pathogen identification decreased in cultures that were pretreated with antibiotics.
Methods
We conducted a retrospective cohort study of 584 hospitalized children between 30 days and 18 years of age admitted to two tertiary children’s hospitals. Logistic regression assessed the effect of antibiotic duration on blood, bone, joint aspirate, and “other” culture positivity.
Results
Overall, 42% of blood cultures, 70% of bone cultures, 39% of joint cultures, and 70% of “other” cultures were positive. Compared with children who did not receive antibiotics prior to culture, there were no significant differences in odds of a positive culture in children whose cultures were pretreated with antibiotics for any of the culture types [OR (95% CI) 0.90 (0.56–1.44) for blood cultures, 0.77 (0.25–2.34) for bone cultures, 0.71 (0.39–1.28) for joint cultures, 1.18 (0.58–2.41) “for other” cultures; all p > 0.05]. Furthermore, the duration (hours) of antibiotics in the pretreated cultures was also not a significant predictor of culture positivity (OR ranged from 0.99–1.00 for all cultures, p > 0.05).
Conclusions
Culture positivity was not associated with antibiotic pretreatment in any of the samples, even for longer duration of antibiotics prior to culture, though the small sample size of subgroups is an important limitation. In pediatric patients hospitalized with osteomyelitis and/or septic arthritis, early initiation of antibiotics may not affect culture positivity.
... However, these investigators did not specifically assess failure in culture-positive vs culturenegative children. A prospective study of 345 children showed no difference in outcomes between the 265 children who had an identified pathogen and the remaining 80 who did not, though this study was conducted in a population with a very low incidence of MRSA and may not be generalizable to the current epidemiology in the North America [129]. ...
... Often, clinicians must treat AHO without positive cultures. This scenario occurred in 40 (47%) of the 85 children [208] in a 2003 report, in 46 (35%) of the 131 children [129] in Finland, and in 877 (42.6%) of the 2060 children in 36 hospitals in the United States [128]. Initial empiric therapy is selected on the basis of the local epidemiology and resistance patterns of AHO pathogens. ...
This clinical practice guideline for the diagnosis and treatment of acute hematogenous osteomyelitis (AHO) in children was developed by a multidisciplinary panel representing Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA). This guideline is intended for use by healthcare professionals who care for children with AHO, including specialists in pediatric infectious diseases, orthopedics, emergency care physicians, hospitalists, and any clinicians and healthcare providers caring for these patients. The panel’s recommendations for the diagnosis and treatment of AHO are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the diagnosis and treatment of AHO in children. The panel followed a systematic process used in the development of other IDSA and PIDS clinical practice guidelines, which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.
... Furthermore, cultures are often unable to identify a pathogen. Both blood cultures and cultures obtained operatively may be negative in up to 50% of cases [2,4,5,[20][21][22][23]. Pathogen-specific PCR testing may be useful as an adjunct, but commercial clinical PCR assays for the evaluation of osteomyelitis are not widely available (PCR assays for Kingella kingae and for Borrelia burgdorferi for joint aspirate specifically are commercially available) [24,25]. ...
Background
Osteoarticular infections (OAI) are frequently encountered in children. Treatment may be guided by isolation of a pathogen; however, operative cultures are often negative. Metagenomic next-generation sequencing (mNGS) allows for broad and sensitive pathogen detection that is culture-independent. We sought to evaluate the diagnostic utility of mNGS in comparison to culture and usual care testing to detect pathogens in acute osteomyelitis and/or septic arthritis in children.
Methods
This was a single-site study to evaluate the use of mNGS in comparison to culture to detect pathogens in acute pediatric osteomyelitis and/or septic arthritis. Subjects admitted to a tertiary children’s hospital with suspected OAI were eligible for enrollment. We excluded subjects with bone or joint surgery within 30 days of admission or with chronic osteomyelitis. Operative samples were obtained at the surgeon’s discretion per standard care (fluid or tissue) and based on imagining and operative findings. We compared mNGS to culture and usual care testing (culture and PCR) from the same site.
Results
We recruited 42 subjects over the enrollment period. mNGS of the operative samples identified a pathogen in 26 subjects compared to 19 subjects in whom culture identified a pathogen. In four subjects, mNGS identified a pathogen where combined usual care testing (culture and PCR) was negative. Positive predictive agreement and negative predictive agreement both were 93.0% for mNGS.
Conclusion
In this single site prospective study of pediatric OAI, we demonstrated the diagnostic utility of mNGS testing in comparison to culture and usual care (culture and PCR) from operative specimens.
... 4,5 Paediatric patients with culture-negative disease consistently showed a trend towards younger age, lower body temperature, white blood cell (WBC) counts and C-reactive protein (CRP) values on admission, a milder clinical course, a shorter hospital stay and a better prognosis. [6][7][8][9][10] Naturally, the negative cultures could have resulted from the incorrect diagnosis of non-infectious conditions such as rheumatic disorders or transient synovitis, as well as viral arthritides and reactive arthritis. However, the possibility that septic arthritis could be caused by fastidious pathogens of low virulence that require special cultivation conditions and, thus, cannot be recovered by traditional bacteriological methods could also be considered. ...
The management of septic arthritis in children requires the prompt administration of antibiotic therapy and the identification of the causative pathogen. In the past, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae and Haemophilus influenzae type b were considered the main causative agents of the disease, but a substantial fraction of presumptive joint infections remained unconfirmed by conventional bacteriologic cultures. In the last two decades, our knowledge of the aetiology of paediatric infectious arthritis has substantially changed as the result of the implementation of vaccination programmes against H. influenzae type b and pneumococci, and by the use of improved detection methods. In 1988, the inoculation of synovial fluid aspirates into blood culture vials revealed that Kingella kingae, a commensal member of the oropharyngeal microbiota, was the prime aetiology of skeletal system infections in children aged 6–48 months. The clinical presentation of K. kingae arthritis is subtle, and the disease is frequently missed by classic clinical and laboratory diagnostic criteria. Many children are afebrile, the acute phase reactants levels and the white blood cell counts in the blood and synovial fluid specimens are frequently normal, requiring a high clinical acumen. Increasing use of sensitive molecular methods in recent years, and particularly nucleic acid amplification tests that target K. kingae-specific genes, has further improved the detection of this elusive pathogen, demonstrated that it is responsible for 30–93% of all cases of septic arthritis below 4 years of age and reduced the fraction of culture-negative infections.
