Episode #10 – Lumpy and Grumpy

May 3, 2021

Summary

Dr. Juri Boguniewicz joins us to evaluate a grumpy toddler with chest wall swelling.

Credits

Host: Sara Dong

Guest: Juri Boguniewicz

Writing/Producing/Editing/Cover Art: Sara Dong

Infographics: Sara Dong

Our Guest

Juri Boguniewicz, MD

Dr. Boguniewicz is an Assistant Professor of Pediatrics in the Section of Pediatric Infectious Diseases at the University of Colorado School of Medicine. He attended medical school at the University of Colorado School of Medicine before moving to Houston, TX to complete his pediatric residency and pediatric ID fellowship at Baylor College of Medicine and Texas Children’s Hospital. He is a transplant ID physician at Children’s Hospital Colorado and has a special clinical interest in infections of immunocompromised hosts.

Culture

Juri talked a little about cocktail chemistry and the having fun learning the science behind drinks ! He recommended this book:

Liquid Intelligence: The Art and Science of the Perfect Cocktail by Dave Arnold

Consult Notes

Consult Q

14 month old with chest swelling

One-liner

14 mo old previously healthy girl with Kingella kingae sternal abscess and osteomyelitis

Key Points

Jump to:

Pediatric Osteomyelitis
Differential diagnosis of chest wall swelling or mass
Kingella kingae
Other notes and textbook references

Although a relatively rare presentation, here are some considerations in the differential diagnosis of chest wall swelling or mass:

Infectious disease
- - Local abscess
  - Osteomyelitis
  - Superinfection of cystic lesion
  - Manifestation of empyema necessitans (particularly with Actinomyces or M.tuberculosis)
  - Some organisms to consider:
    - - Typical skin flora and SSTI organisms (such as Staph or Strep)
      - Nocardia (often has more indolent course)
      - Endemic fungal infections (also likely to be indolent course)
      - Actinomyces (perhaps in setting of empyema necessitans as Juri mentioned)
      - Tuberculosis
Benign processes:
- - Soft tissue origin: hemangioma, lymphangioma, fibromatosis, lipoma
  - Skeletal processes: osteochondroma, enchondroma, aneurysmal bone cyst, osteoid osteoma, congenital rib abnormalities
  - Congenital dermoid or epidermoid cysts
Malignant lesions
- - Soft tissue origin: malignant fibrous histiocytosis, rhabdomyosarcoma, lymphoma, metastases
  - Skeletal processes: chondrosarcoma, Ewing’s sarcoma, primitive neuroectodermal tumor, Askin tumor, osteosarcoma, Langerhans cell histiocytosis, metastases (such as neuroblastoma)
Accidental or non-accidental trauma
Foreign body with local inflammation

As mentioned in the beginning of this episode, the new pediatric osteomyelitis guidelines should be coming out soon with an accompanying podcast from PIDS! Links will be updated here once available!

Clinical Practice Guideline on the diagnosis and management of acute hematogenous osteomyelitis in pediatrics from Pediatric Infectious Diseases Society (PIDS) / Infectious Diseases Society of American (IDSA) — Coming soon!
PIDS Osteomyelitis Guidelines Podcast — Coming soon!

A little background on osteomyelitis in pediatrics

Acute osteomyelitis is caused when bacteria reach the bone matrices through:
- - - Hematogenous spread
    - Direct inoculation (e.g. traumatic)
    - Contiguous spread from adjacent soft tissue or synovial fluid
In children, osteomyelitis occurs most commonly in long tubular bones (such as femur, tibia, humerus), and 10-25% of cases may involve short or non-tubular bones (pelvis, vertebra, clavicule, skull, ribs, scapula)
Most cases involve a single bone (95% of cases)
A few pearls on the clinical presentation:
- - - The presentation varies from well-localized infection over single metaphysis to multifocal infection with septic shock
    - Pain with or without warmth/erythema is often present:
      - May just have failure to bear weight or reduced use of extremity in young children aka pseudoparalysis
        When affecting pelvic bones, may have limp, groin pain, inability to bear weight
    - Patient will often present within 1 wk of symptoms but can have indolent cases

Dartnell J, Ramachandran M, Katchburian M. Haematogenous acute and subacute paediatric osteomyelitis: a systematic review of the literature. J Bone Joint Surg Br. 2012;94(5):584-595. doi:10.1302/0301-620X.94B5.28523

The microbiology of hematogenous osteomyelitis in children

Infections are typically monomicrobial.
As Juri mentioned: “Staph, Staph, Staph aureus should be your #1, #2, and #3” — Staph aureus is by far the most common cause. Affects children of all ages. Can be associated with skin and soft tissue infection. Typically has acute presentation and robust inflammatory response
Other gram positive bacteria:
- - Coagulase negative Staph: think neonates or children with indwelling catheter
  - Strep spp seen less commonly but possible:
    - Group A Strep
    - If present, Group B Strep usually in neonates (2-4 wks)
    - Strep pneumoniae: think about in non-immunized or partially immunized children as well as those with underlying conditions such as asplenia
  - Actinomyces: rare. Consider with pelvis, vertebral bodies, facial bones, empyema necessitans
Kingella kingae in children from 6 mo to 3 years old: a clue might be preceding oral ulcers
Other gram negatives can be present in immunocompromised children. Juri also mentioned H.influenzae type b in incompletely immunized children in areas of low immunization rates (unlikely usually)
More atypical bacteria, mycobacteria, or fungi can be culprits in the right setting as well

Russell CD, Ramaesh R, Kalima P, Murray A, Gaston MS. Microbiological characteristics of acute osteoarticular infections in children. J Med Microbiol. 2015;64(Pt 4):446-453. doi:10.1099/jmm.0.000026

Juri spoke about the role of sampling or an invasive procedure to obtain an aspirate or biopsy of bone or fluid collection. These samples should be sent for routine microbiologic studies, and bone and tissue cultures do increase the yield of pathogen identification compared to blood cultures alone.

Confirming a microbiologic diagnosis allows:
- - Optimization of the spectrum of antibiotics → allows you to narrow antibiotic and more easily transition to pathogen-specific oral alternatives. Selection of drug should also take into account the best side effect profile
  - Consideration of duration of therapy (depending on virulence of organism, helps to decide on shorter vs longer course as necessary)
This episode’s case was not a classic osteomyelitis — so sampling for histopath was important for consideration of non-ID etiologies. If culture results are negative or take a long time, staining on histopath may be your only clue to the culprit.
Manz N, Krieg AH, Heininger U, Ritz N. Evaluation of the current use of imaging modalities and pathogen detection in children with acute osteomyelitis and septic arthritis. Eur J Pediatr. 2018;177(7):1071-1080. doi:10.1007/s00431-018-3157-3
McNeil JC, Forbes AR, Vallejo JG, et al. Role of Operative or Interventional Radiology-Guided Cultures for Osteomyelitis. Pediatrics. 2016;137(5):e20154616. doi:10.1542/peds.2015-4616
Section J, Gibbons SD, Barton T, Greenberg DE, Jo CH, Copley LA. Microbiological culture methods for pediatric musculoskeletal infection: a guideline for optimal use. J Bone Joint Surg Am. 2015;97(6):441-449. doi:10.2106/JBJS.N.00477

We also discussed: can antibiotics be withheld until after the anticipated procedure is performed?

It depends on the clinical status of the patient!
If a child is ill-appearing or has rapidly progressive infection (fever, sepsis, unstable vital signs, etc), empiric antimicrobial therapy should be started immediately rather than withholding.
For a well-appearing child who is stable and aspirate or biopsy is planned in the next day or two, it is reasonable to wait up to 48-72h. This decision will be impacted by availability/accessibility of resources or the time required to transport if needed
There are really no data/studies that specifically address the risks/benefits of these delays in antibiotics in setting of osteomyelitis, although there are some that look at sepsis +/ osteomyelitis in children and adults

So if you do start antibiotics, will that reduce the yield of your micro studies significantly?

Based on the data available, cultures obtained within 24-48 hours after initiation of antibiotic therapy likely have similar yield. Can typically recover organisms like Staph aureus
The retrospective studies available do show a higher positivity rate of bone or soft tissue culture if patient did not receive antibiotics — but this may be a bit biased (the sick children who are more likely to get antibiotics prior to sampling may be more likely to have high inoculum of bacteria)
McNeil JC, Forbes AR, Vallejo JG, et al. Role of Operative or Interventional Radiology-Guided Cultures for Osteomyelitis. Pediatrics. 2016;137(5):e20154616. doi:10.1542/peds.2015-4616
Section J, Gibbons SD, Barton T, Greenberg DE, Jo CH, Copley LA. Microbiological culture methods for pediatric musculoskeletal infection: a guideline for optimal use. J Bone Joint Surg Am. 2015;97(6):441-449. doi:10.2106/JBJS.N.00477
van der Merwe M, Rooks K, Crawford H, Frampton CMA, Boyle MJ. The effect of antibiotic timing on culture yield in paediatric osteoarticular infection. J Child Orthop. 2019;13(1):114-119. doi:10.1302/1863-2548.13.180077
Zhorne DJ, Altobelli ME, Cruz AT. Impact of antibiotic pretreatment on bone biopsy yield for children with acute hematogenous osteomyelitis. Hosp Pediatr. 2015;5(6):337-341. doi:10.1542/hpeds.2014-0114

The switch to oral antibiotics and duration of therapy for osteomyelitis in children

The general trend nationally is early transition to oral therapy as opposed to long term outpatient parenteral antibiotic therapy (OPAT). It is overall much safer, well-tolerated, is not associated with worse relapse, and there are less complications (from catheter). The new PIDS guidelines will address this as well
Other considerations to ensure appropriate transition to oral: what oral antibiotic options are available? Can the child can take/tolerate oral therapy?
How long to treat for uncomplicated osteomyelitis? 3-4 weeks is a pretty typical course for pediatric OM. This is a good starting point, and can be adjusted depending on clinical course
Keren R, Shah SS, Srivastava R, et al. Comparative effectiveness of intravenous vs oral antibiotics for postdischarge treatment of acute osteomyelitis in children. JAMA Pediatr. 2015;169(2):120-128. doi:10.1001/jamapediatrics.2014.2822
Zaoutis T, Localio AR, Leckerman K, Saddlemire S, Bertoch D, Keren R. Prolonged intravenous therapy versus early transition to oral antimicrobial therapy for acute osteomyelitis in children. Pediatrics. 2009;123(2):636-642. doi:10.1542/peds.2008-0596
McNeil JC, Kaplan SL, Vallejo JG. The Influence of the Route of Antibiotic Administration, Methicillin Susceptibility, Vancomycin Duration and Serum Trough Concentration on Outcomes of Pediatric Staphylococcus aureus Bacteremic Osteoarticular Infection. Pediatr Infect Dis J. 2017;36(6):572-577. doi:10.1097/INF.0000000000001503

How do we assess treatment response?

This may vary slightly between institutions, but in general, patients prior to discharge should have:
- - Evidence of clinical improvement (e.g. bearing weight, feeling better)
  - Afebrile for 24 hrs
  - Downtrending inflammatory markers. There is not a specific cut-off, but would want to see consistent downtrend in values, suggesting there is improvement in the inflammatory response. Often CRP may normalize within a little under 2 wks:
    - - Pääkkönen M, Kallio MJ, 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):861-866. doi:10.1007/s11999-009-0936-1
After discharge, sequential monitoring of CRP and clinical evaluations should be used. There is no clear utility in end-of-therapy imaging studies unless children have complicated infection or involvement of physis

Kingella kingae

Juri did a quick shout-out for a cool female pioneer in microbiology for International Women’s Day, the namesake of this bacteria: Elizabeth O. King
- - - An American microbiologist who discovered and described several important bacteria while working at the predecessor of the current CDC (the US Communicable Disease Center)
    - Kingella kingae and Elizabethkingia genus (important causes of neonatal meningitis) are named after her!
    - Kingella kingae was originally called Moraxella kingii before is was renamed
Microbiology/Virulence/Pathogenesis notes:
- - - Facultative anaerobic, b-hemolytic gram negative coccobacilli. Often short chains of “plump” bacilli with tapered ends
    - Organism can resist decolorization and may be misidentified as gram positive!
    - Believed that children have breach in mucosal lining that facilitates bloodstream invasion (such as viral URI, herpetic gingivostomatitis, hand-foot-mouth disease, herpangina). As Juri mentioned, it may coincide with Coxsackie or respiratory viral infection → so often a clue to diagnosis is preceding oral ulcers or respiratory symptoms in a patient who presents with bone and joint infection
    - Produces a potent toxin that belongs to the RTX family: capable of lysing synovial cells, leukocytes and macrophages
    - There have been studies looking at different strains of K.kingae, which have variable invasive capabilities (some with asymptomatic carriage; some with more invasive disease)
Epidemiology:
- - - Has a unique niche in the posterior pharynx flora (such as the tonsillar crypts) and is interestingly almost never isolated from nasopharyngeal cultures
    - Most colonizes in children 6-36 months old — so toddler age is a big clue! The colonization rate declines beyond that age
    - Majority of publications related to Kingella are from France, Switzerland, Israel, and the US → unclear whether this represents geographic variation or perhaps lack of reports where expensive automated blood culture systems are unavailable
    - Geographic clustering of isolates have been found in households and neighborhoods, indicating Kingella can disseminate in close interpersonal contact (such as child to child like siblings and playmates). There are also well described outbreaks in daycare settings, and childcare attendance increases risk of colonization and transmission
Clinical presentations:
- - - K.kingae infections are limited mostly to young children in the age range described above (6 months to ~36-48 months)
    - Increasingly recognized etiology for pediatric osteoarticular infections
      - Pyogenic arthritis is the most common presentation, but may also see osteomyelitis or spondylodiscitis
        Skeletal system infection generally involves large joints (knee, hip, ankle, shoulder), but some studies describe other locations such as small joints
        There are very few cases in English literature of Kingella involvement of lower sternum and manubrium-xyphoid junction, similar to this episode’s case
    - Occult bacteremia
    - Soft tissue infection
    - The most severe manifestation is a complicated endocarditis, although this is relatively rare. Typically native valve. Kingella is a member of the “HACEK” group
    - There are also case reports with pneumonia, CNS infection/meningitis, ocular infection, peritonitis
Kingella seems to have a more indolent course with less inflammatory host response in many cases
- - - Often patients are afebrile with few constitutional symptoms
    - CRP and ESR are generally mildly elevated but may be normal
    - The main exception to this seems to be children with endocardial involvement
Diagnosis can be tricky
- - - Kingella kingae is fastidious and doesn’t readily grow in blood cultures. Isolation from blood or synovial fluid is challenging with a detection rate of ~40%
    - Yield can be improved with inoculation of synovial fluid or bone aspirate into an aerobic blood culture bottle from some automated blood culture systems (e.g. BACTEC)
    - Molecular methods can also help with diagnosis. PCR can be sent in select population with the right epi risk factors if available. There is broad-range 16s rRNA PCR as well as some newer real-time PCRs with highly specific K.kingae probes
Treatment
- - - Highly susceptible to penicillins and cephalosporins, which are drugs of choice
    - Also susceptible to: aminoglycosides, macrolides, TMP-SMX, tetracycline, chloramphenicol, fluoroquinolones
    - Generally expect resistance to vancomycin, clindamycin, oxacillin, nafcillin
    - Some isolates can have beta-lactamase, in which case amox-clav may be appropriate
    - Juri mentioned that Cephalexin is a nice option. In particular, if you do not have a confirmed Kingella diagnosis and are not sure MSSA is off the table either, Cephalexin is a good choice that covers both bases
References:
Similar cases to this episode:

Other miscellaneous mentions and notes:

Like textbook references?
- AAP Red Book >> Section 3: Summaries of Infectious Diseases >> Kingella kingae infections p 497-98
- Long, Principles and Practice of Pediatric ID, 5th Ed.:
  - Chapter 176: Kingella Species
  - Chapter 76: Osteomyelitis
- Mandell, Principles and Practice of ID, 8th Ed., 9th Ed.:
  - Chapter 215: Moraxella catarrhalis, Kingella, and other gram-negative cocci
- Comprehensive Review of Infectious Diseases

Episode Art & Infographics

Goal

Listeners will be able to identify Kingella kingae as a cause of pediatric osteomyelitis

Learning Objectives

After listening to this episode, listeners will be able to:

Create a differential diagnosis for chest swelling in a pediatric patient
List the typical microbiology of acute hematogenous osteomyelitis
Discuss the role of sampling or invasive procedures in the diagnosis of osteomyelitis
Describe the common clinical presentations and management of K.kingae infections

Disclosures

Our guest (Juri Boguniewicz) as well as Febrile podcast and hosts report no relevant financial disclosures

Citation

Boguniewicz, J., Dong, S. “#10: Lumpy and Grumpy”. Febrile: A Cultured Podcast. https://player.captivate.fm/episode/f98ae274-364b-4abc-964d-33280c7dc0cb

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