Abstract
Background:
Epidemiological data regarding paediatric pyogenic musculoskeletal infections from developing countries of Asia and Africa are sparse and further complicated by the presence of factors like malnutrition, delay in initiating treatment and belief in alternative forms of treatment and under vaccination. The aim of this study is to retrospectively analyse the cases of paediatric pyogenic musculoskeletal infections in a tertiary care centre in India.
Methods:
It is a retrospective study including patients below 18 years of age who had been diagnosed with any pyogenic musculoskeletal infection. Demographic, clinical, laboratory, and radiological details were collected.
Results:
A total of 216 children, with a mean age of 12.8 ± 4.9 years (10 days-18 years), were included in the study. The causative organism could be isolated in 98 cases (45.3%). Escherichia coli and methicillin-sensitive Staphylococcus aureus were the most common pathogens isolated in infants and children, respectively. Imipenem and linezolid were the commonest sensitive antibiotics for children up to 10 years and above 10 years, respectively. Linezolid was the antibiotic of choice in culture-negative cases. The majority (78.3%, n = 169) of children underwent a surgical procedure during the stay at the hospital. A higher relapse rate (61%) was noted in culture-negative patients.
Conclusion:
Improved methods of pathogen detection should be explored to improve the rate of positive cultures. Additional prospective studies with longer patient follow-up and the creation of care protocols are necessary to improve therapeutic decision-making and the prognosis for children with suspected musculoskeletal infection.
Keywords: Paediatric, Pyogenic musculoskeletal infection, Epidemiology, Osteomyelitis, Septic arthritis
INTRODUCTION
Paediatric pyogenic musculoskeletal infections like osteomyelitis and septic arthritis are severe infections with propensity for local and systemic complications like pathological fractures, deformity of the limb and sepsis. These may be initially asymptomatic causing delay in treatment institution which may lead to permanent sequelae. The incidence of osteomyelitis is 2.9-75 per 100,000 children and primarily involves the metaphyseal area of the bone [1]. The incidence of septic arthritis is 5.5-12 per 100,000 children and males are three times commonly involved [2]. The spectrum of disease involvement depends on the age of the patient and the part of bone involved. Fever, pain and limitation of joint movements are usually the common presentations. Culture of the exudate or pus or granulation tissue usually leads to diagnosis in 30%-80% of the cases [3].
Epidemiological studies are important because they point to clinical and demographic differences between patients and help in establishing guidelines for initiating or continuing treatment for the corresponding cases. Such data from developing countries of Asia and Africa are sparse and further complicated by the presence of factors like malnutrition, delay in initiating treatment and belief in alternative form of treatment and under vaccination [4]. Diagnostic facilities of microbiology are limited and resistance to multiple antibiotics are common [5]. The aim of this study is to retrospectively analyse the cases of paediatric pyogenic musculoskeletal infections in terms of its presentation, etiological agent and other epidemiological factors in a tertiary care centre in India and develop an inference regarding the common presentations and course of the disease.
MATERIALS AND METHODS
Study details
This was a retrospective analytical study conducted at a tertiary level medical teaching institution from January 2016 to December 2019. Ethical approval was obtained from the Institutional Ethical Committee and consent was obtained from the parents of children included in the study (AIIMS/IEC/19/715). Patients below 18 years of age who had been diagnosed with any pyogenic musculoskeletal infection and identified from hospital and laboratory records were included in the study. Infections of the craniofacial area, ribs and spine and patients with incomplete data and non-pyogenic infections like tuberculosis were excluded.
Management protocol
The patients were initially evaluated clinically and the symptoms and signs were recorded. Relevant radiographs were obtained to identify soft tissue shadows, if present, and to rule out chronic pathologies. Routine laboratory investigations obtained were complete haemogram, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and liver function tests. Ultrasonography was performed to identify pockets of pus collection, either in the muscle planes or in the joint and to guide its aspiration. All the patients were started empirically on ceftriaxone and amikacin after samples for blood culture and exudate/pus were obtained. Emergent surgical exploration and evacuation were carried out in the following cases: a) suspected septic arthritis of hip joint; b) exudate/pus could not be obtained by percutaneous ultrasonography-guided aspiration; and c) toxic patient with high acute inflammatory markers. Sensitive antibiotics were started on the basis of sensitivity report. Opinions from microbiologists were sought in case of culture-negative reports. Paediatric medicine opinion was obtained to advice regarding nutrition and for prevention of sepsis.
Data collection and definitions
Data collected were age, gender, initial presentation details, course of hospital stay, and laboratory and radiological investigations. Laboratory investigations included haemoglobin, white blood cell count (WBC), ESR, CRP and results of microbiological tests, including Gram stain, culture and sensitivity results.
Acute osteomyelitis and septic arthritis were defined if one or more of the following were present: 1) fever >37°C; 2) ESR > 20 mm/hour; 3) WBC > 13,000 cells/cu mm; and 4) positive blood culture, along with the presence of one or more of the following: swelling or redness or bony tenderness or positive culture from any sample from the affected bone or joint [6]. Multisite infections were defined as non-adjacent infections of musculoskeletal system and/or other systems.
Statistical analysis
The statistical analysis was calculated using the mean and standard deviation of the quantitative variables (95% confidence interval), as well as frequency analysis (percentage) for the categorical variables (95% confidence interval).
RESULTS
A total of 216 children, with mean age of 12.8 (4.9) years (10 days-18 years), were included in the study. This also included five neonates and eight infants (Table 1). The majority of patients were in the age group of 11-18 years (76.8%, n = 166). Most of the children (n = 166, 76.8%) had obtained some form of inappropriate antibiotic therapy before being referred to the tertiary centre. Males formed the bulk of the cases (67.1%, n = 145). Twelve (5.5%) had a history of prior non-musculoskeletal infection within 2 weeks, the most common being pneumonia and otorhinolaryngological infections. Pain and reduced motion at the adjacent joint were the commonest presenting symptoms (Table 2).
Table 1.
Distribution of patients according to age stratification and the commonest organism and antibiotic according to the culture and sensitivity reports.
| Age group | Number of children | Commonest organism | Commonest antibiotic |
|---|---|---|---|
| 0-1 month | 5 | Escherichia coli, MSSA, Klebsiella | Imipenem, meropenem |
| 1 month-1 year | 8 | Escherichia coli, MSSA, Klebsiella | Imipenem, meropenem, linezolid |
| 1-5 years | 6 | MSSA, MRSA, Escherichia coli | Imipenem, meropenem, linezolid |
| 5-10 years | 31 | MSSA, MRSA, Pseudomonas | Linezolid, meropenem, gentamicin |
| 10-15 years | 83 | MSSA, MRSA, Escherichia coli | Linezolid, gentamicin, meropenem |
| 15-18 years | 83 | MSSA, MRSA, Escherichia coli | Linezolid, cotrimoxazole, gentamicin |
MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive Staphylococcus aureus.
Table 2.
Distribution of the common presenting symptoms.
| Presenting symptoms | Number of patients (%) |
|---|---|
| Pain | 200 (92.5) |
| Reduced range of motion | 158 (73.1) |
| Fever | 105 (48.6) |
| Localised swelling | 25 (11.5) |
Osteomyelitis was the most common pyogenic musculoskeletal infection, followed by concurrent osteomyelitis and septic arthritis (Table 3). Tibia and femur were the commonest bones involved in osteomyelitis, whereas knee and hip joints were commonly involved in septic arthritis. Ilium (n = 5) and clavicle (n = 1) were the uncommon sites involved in osteomyelitis. Thigh and forearm were the common sites of sub-muscular abscess. Among the soft tissue infections, there were two cases of pyomyositis of the thigh in which the muscles of one or more compartments were completely necrosed and liquefied (Table 3). There were 11 (5%) cases of multifocal infections which involved more than 1 non-contiguous area. In these cases, the long bones were commonly involved simultaneously.
Table 3.
Distribution of cases according to the site of involvement.
| Type of infection | Number of patients (%) | Sites (number) |
|---|---|---|
| Osteomyelitis | 142 (65.7) | Tibia (54), femur (38), foot (19), humerus (8), radius (7), ulna (5), ilium (5), fibula (3), hand (2), clavicle (1) |
| Concurrent osteomyelitis and septic arthritis | 25 (11.5) | Knee with distal femur or proximal tibia (17), hip with proximal femur (8) |
| Septic arthritis | 20 (9.2) | Knee (10), hip (9), shoulder (1) |
| Soft tissue infection | 18 (8.3) | Sub-muscular abscess (16), pyomyositis (2) |
| Synovitis | 11 (5.1) | Knee (6), hip (5) |
The causative organism could be isolated in 98 cases (45.3%). Escherichia coli was the commonest organism isolated among neonates and infants, whereas MRSS was the commonest organism isolated across children above 1 year of age (Table 1). Other uncommon bacteria which were isolated were Pseudomonas aeruginosa, Klebsiella, Citrobacter, Proteus mirabilis, Acinetobacter and Morganella. Multi-bacterial infections were seen in Gram-negative infections (n = 7, 3.2%). Imipenem and linezolid were the commonest sensitive antibiotics for children up to 10 years and above 10 years, respectively (Table 1). The mean duration of antibiotic therapy was 7.3 weeks. Patients with negative culture (8.1 weeks) required prolonged therapy as compared to culture-positive patients (4.8 weeks). Linezolid was the antibiotic of choice in patients with negative culture reports.
A total of 169 (78.3%) children underwent a surgical procedure during the stay at the hospital. Surgical evacuation and exploration (n = 149), as well as arthrotomy (n = 20) of the affected joint, were the most common procedures performed. The mean duration of stay of the patients in hospital was 6.6 ± 4 days (2-20 days). The mean ESR and CRP at admission in this study was 68.5 and 78.6, respectively. The laboratory values showed gradual reduction of the values, as the antibiotic therapy was instituted, as well as with improvement of dietary intake and addition of micronutrients (Table 4). There were nine patients who required intensive care because of sepsis which occurred secondary to the pyogenic infection. These patients were comparatively younger (mean 2.6 years) compared to the whole study group and were commonly associated with Gram-negative bacteria. Among these, two children succumbed to septic shock.
Table 4.
Sequential depiction of laboratory values at admission and at discharge.
| Laboratory values | Mean (range) | Standard deviation | 95% confidence level |
|---|---|---|---|
| WBC at admission/cu mm | 15,042 (7,800-27,663) | 4,211 | 1,196 |
| WBC at discharge/cu mm | 9,006 (5,505-13,431) | 1,683 | 478 |
| ESR at admission (mm/hour) | 68.5 (23-121) | 21.4 | 6.1 |
| ESR at discharge (mm/hour) | 37 (21-67) | 11.2 | 3.2 |
| CRP at admission | 78.6 (22-127) | 23.1 | 6.5 |
| CRP at discharge | 18.3 (10-31) | 5.2 | 1.4 |
CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; WBC, white blood cell count.
Relapse of the infective episode was seen in 22.3% of the cases who had shown any growth on the culture of the infected material, whereas this was as high as 61% in patients with no growth on the culture. Joint stiffness (n = 152) was the commonest complication, followed by deformity secondary to physeal damage or pathological fracture (n = 13).
DISCUSSION
This study characterises the epidemiological data of paediatric pyogenic musculoskeletal infections in a tertiary care centre in Northern India with increased preponderance of males, with a mean age of 12.8 years. Majority of the cases were osteomyelitis (75.9%) as compared to septic arthritis (10.6%). This distribution of the infection is different from the other large-scale studies where the proportion of septic arthritis varied between 40% and 50% [7,8]. This can be attributed to the relatively young children in these studies as compared to 12.8 years in the present study. Before the appearance of secondary ossification centres, the cartilaginous physes receive blood supply directly from metaphyseal vessels, hence the spread of infection from bone to joint is common in younger children as compared to adolescents.
The diagnosis of pyogenic episodes of the musculoskeletal system is primarily based on clinical signs and symptoms. Signs of radiographs can take up to 10 days or more to appear and initial laboratory results may not be grossly abnormal [9]. Hence, the primary symptoms of pain, reduced motion at joints and fever should be carefully looked into. The bulk of such patients usually have this triad of symptoms which has been noted in this study. Furthermore, not all cases would lead to a positive culture. The rate of positive cultures lies between 30% and 50% in previous studies, which is consistent with the finding of this study [10]. This can be due to the requirement of specific media for certain bacteria, longer incubation periods or previous antibiotic intake for the same episode. In developing countries of Asia and Africa, the history of previous unsupervised and ill-advised antibiotic intake is relatively common due to poor socio-economic status, as well as scarce healthcare facilities. This may lead to negative cultures necessitating prolonged or multiple antibiotic therapy or both.
The mean ESR and CRP at admission in this study was 68.5 and 78.6, respectively. Sensitivity for diagnosing such cases is 98% when the values of ESR and CRP are considered together [11]. However, CRP alone is more sensitive than ESR due to its rapid normalisation as compared to ESR. These acute inflammatory markers help in gauging the response of patient to antibiotic therapy. It also helps in deciding the conversion of intravenous to oral antibiotic therapy with a persistent reducing trend over a few days.
The inoculation of bacteria in paediatric musculoskeletal infection is haematogenous in nature, primarily from the respiratory tract and very rarely due to direct insemination secondary to trauma or internal fixation [12]. Staphylococcus aureus was the most common pathogen isolated in this study in children above 1 year of age. This correlates with previous studies citing S. aureus as the most common causative agent [7,9]. Escherichia coli and Klebsiella were the common pathogens isolated in infants, where the incidence of Gram-negative infections is more common [10].
The guide to treatment of these cases usually includes appropriate antibiotic therapy and surgery, if indicated. Initial empirical antibiotics are started in accordance with the age of child and the local prevalence of infectious agents, followed by targeted antibiotic therapy as per the sensitivity reports. Ceftriaxone and amikacin were the empirical antibiotics used in this study since both Gram-positive and Gram-negative organisms are covered by them. Although oxacillin with vancomycin has been suggested as the empirical antibiotic of choice in such cases, studies have proven a third-generation cephalosporin, like ceftriaxone, is better suited as compared to oxacillin and vancomycin due to its reduced toxicity and cost [13,14].
The duration and route of antibiotic therapy depend on the virulence of the organism along with the clinical and laboratory response to it and the switch from intravenous to oral therapy is essential to complete the course as well as to prevent relapse [13]. The average duration of therapy in this study was 7.3 weeks and patients were advised oral therapy after discharge. The mean duration of stay of the patients in this study was 6.6 days, which is comparable to previous studies [7]. This study also included nine patients who required intensive care because of sepsis which occurred secondary to the pyogenic infection. These patients were comparatively younger (mean 2.6 years) compared to the whole study group and were commonly associated with Gram-negative bacteria. Among these, two children succumbed to septic shock.
Surgical interventions in paediatric pyogenic musculoskeletal infection are required in up to 75% of the cases [9]. This is comparable to this study where 78.3% of the children underwent surgical intervention. The indications for surgical exploration and evacuation are as follows: a) suspected septic arthritis of hip joint; b) exudate/pus could not be obtained by percutaneous ultrasonography-guided aspiration; and c) toxic patient with high acute inflammatory markers.
The main limitations of this study are its retrospective nature and its lack of long-term follow-up. The small sample size also made it unfeasible to model risk factors predicting relapse. This study is, however, one of the largest in terms of sample size from the developing countries of Asia and Africa. The findings of the study can guide physicians and orthopaedic surgeons in initiating the empirical treatment, as well as predict the common pathogen. The need for prospective multicentric studies covering a large geographical region with long-term follow-up is evident. Improved patient care can be obtained by standardisation of diagnosis and treatment from such prospective studies.
CONCLUSION
Adolescent males with osteomyelitis are the most common presenters with paediatric pyogenic musculoskeletal infections. Staphylococcus aureus is the most common pathogen in children above 1 year of age, whereas in infants, E. coli is more common. Imipenem and linezolid are the commonest sensitive antibiotics for children up to 10 years and above 10 years, respectively. Since 54.7% of the cultures were negative in this study, improved methods of pathogen detection should be explored. Additional prospective studies with longer patient follow-up and the creation of care protocols are necessary to improve therapeutic decision-making and the prognosis for children with suspected musculoskeletal infection.
CONFLICT OF INTEREST
The authors have no conflict of interest to declare.
FUNDING
None.
ETHICAL APPROVAL
Ethical approval was obtained from the Institutional Ethics Committee of the All India Institute of Medical Sciences, Rishikesh, India (AIIMS/IEC/19/715), and consent was obtained from the parents of children included in the study. Dated 26/12.2019.
REFERENCES
- 1.Blyth MJ, Kincaid R, Craigen MA, Bennet GC. The changing epidemiology of acute and subacute haematogenous osteomyelitis in children. J Bone Joint Surg Br. 2001;83(1):99–102. doi: 10.1302/0301-620x.83b1.10699. https://doi.org/10.1302/0301-620X.83B1.0830099. [DOI] [PubMed] [Google Scholar]
- 2.Jaña Neto FC, Ortega CS, Goiano E. Epidemiological study of osteoarticular infections in children. Acta Ortop Bras. 2018;26(3):201–5. doi: 10.1590/1413-785220182603145650. https://doi.org/10.1590/1413-785220182603145650. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Mitha A, Boulyana M, Hue V, Pruvost I, Martinot A, European French-speaking expert group, et al. Consensus in diagnostic definitions for bone or joint infections in children by a Delphi method with European French-speaking experts. Acta Paediatr. 2012;101(8):e350–6. doi: 10.1111/j.1651-2227.2012.02716.x. https://doi.org/10.1111/j.1651-2227.2012.02716.x. [DOI] [PubMed] [Google Scholar]
- 4.Stoesser N, Pocock J, Moore CE, Soeng S, Hor P, Sar P, et al. The epidemiology of pediatric bone and joint infections in Cambodia, 2007-11. J Trop Pediatr. 2013;59(1):36–42. doi: 10.1093/tropej/fms044. https://doi.org/10.1093/tropej/fms044. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Jean SS, Hsueh PR. High burden of antimicrobial resistance in Asia. Int J Antimicrob Agents. 2011;37(4):291–5. doi: 10.1016/j.ijantimicag.2011.01.009. https://doi.org/10.1016/j.ijantimicag.2011.01.009. [DOI] [PubMed] [Google Scholar]
- 6.Goergens ED, McEvoy A, Watson M, Barrett IR. Acute osteomyelitis and septic arthritis in children. J Paediatr Child Health. 2005;41(1-2):59–62. doi: 10.1111/j.1440-1754.2005.00538.x. https://doi.org/10.1111/j.1440-1754.2005.00538.x. [DOI] [PubMed] [Google Scholar]
- 7.Grammatico-Guillon L, Maakaroun Vermesse Z, Baron S, Gettner S, Rusch E, Bernard L. Paediatric bone and joint infections are more common in boys and toddlers: a national epidemiology study. Acta Paediatr. 2013;102(3):e120–5. doi: 10.1111/apa.12115. https://doi.org/10.1111/apa.12115. [DOI] [PubMed] [Google Scholar]
- 8.Mitha A, Boutry N, Nectoux E, Petyt C, Lagrée M, Happiette L, et al. Community-acquired bone and joint infections in children: a 1-year prospective epidemiological study. Arch Dis Child. 2015;100(2):126–9. doi: 10.1136/archdischild-2013-305860. https://doi.org/10.1136/archdischild-2013-305860. [DOI] [PubMed] [Google Scholar]
- 9.Chen WL, Chang WN, Chen YS, Hsieh KS, Chen CKH, Peng NJ, et al. Acute community-acquired osteoarticular infections in children: high incidence of concomitant bone and joint involvement. J Microbiol Immunol Infect. 2010;43(4):332–8. doi: 10.1016/S1684-1182(10)60051-5. https://doi.org/10.1016/S1684-1182(10)60051-5. [DOI] [PubMed] [Google Scholar]
- 10.Dodwell ER. Osteomyelitis and septic arthritis in children: current concepts. Curr Opin Pediatr. 2013;25(1):58–63. doi: 10.1097/MOP.0b013e32835c2b42. https://doi.org/10.1097/MOP.0b013e32835c2b42. [DOI] [PubMed] [Google Scholar]
- 11.Pääkkönen M, Kallio MJT, Kallio PE, Peltola H. Sensitivity of erythrocyte sedimentation rate and C-reactive protein in childhood bone and joint infections. Clin Orthop Relat Res. 2010;468(3):861–6. doi: 10.1007/s11999-009-0936-1. https://doi.org/10.1007/s11999-009-0936-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Ceroni D, Kampouroglou G, Valaikaite R, Anderson Della Llana R, Salvo D. Osteoarticular infections in young children: what has changed over the last years? [2020 Apr 9];Swiss Med Wkly. 2014 144(2324) doi: 10.4414/smw.2014.13971. Available from: https://smw.ch/article/doi/smw.2014.13971 https://doi.org/10.4414/smw.2014.13971 . [DOI] [PubMed] [Google Scholar]
- 13.Kaplan SL. Recent lessons for the management of bone and joint infections. J Infect. 2014;68:S51–6. doi: 10.1016/j.jinf.2013.09.014. https://doi.org/10.1016/j.jinf.2013.09.014. [DOI] [PubMed] [Google Scholar]
- 14.Wieland BW, Marcantoni JR, Bommarito KM, Warren DK, Marschall J. A retrospective comparison of ceftriaxone versus oxacillin for osteoarticular infections due to methicillin-susceptible Staphylococcus aureus. Clin Infect Dis. 2012;54(5):585–90. doi: 10.1093/cid/cir857. https://doi.org/10.1093/cid/cir857. [DOI] [PMC free article] [PubMed] [Google Scholar]