Kingella kingae: Unmasking the Stealthy Culprit in Osteoarticular Infections

Abstract

Kingella kingae is now increasingly acknowledged to be an important cause of osteoarticular infections, most notably in the youngest age group. In this narrative review, we look into the bacteriological diagnosis of the infection with this fastidious, often elusive pathogen by tracing the problems and advances of diagnosing through culture methods and modern molecular techniques combined with clinical contexts to enable more accurate and timely diagnoses. This review looks to provide an overview of the current diagnostic approaches used today, with a focus on the need for a multi-disciplinary approach to optimize patient management.

Introduction

Osteoarticular infections, encompassing infections of the bones (osteomyelitis) and joints (septic arthritis), represent a significant challenge in pediatric infectious disease. Prompt and accurate diagnosis is crucial for initiating appropriate treatment and preventing long-term sequelae, such as growth disturbances, joint deformities, and chronic pain. Staphylococcus aureus and other common bacterial pathogens are most commonly implicated; however, in children under five years of age, Kingella kingae is now recognized as an important and frequently underdiagnosed cause. This review discusses the bacteriological diagnosis of osteoarticular infections by K. kingae, pointing out the difficulty associated with this diagnosis and highlighting the importance of a comprehensive approach to diagnosis.

Kingella kingae: A Stealthy Pathogen

Kingella kingae is a gram-negative, fastidious bacterium that commonly colonizes the human oropharynx, particularly in young children. While often a commensal, it possesses the capacity to cause a range of invasive infections, including bacteremia, endocarditis, and, notably, osteoarticular infections. Several factors contribute to the diagnostic challenges posed by K. kingae:

• Fastidious Growth: K. kingae requires specific growth conditions, including enriched media and prolonged incubation periods, making it more challenging to culture than many other bacterial pathogens.

• Commensal Colonization: The presence of K. kingae in the oropharynx does not necessarily indicate infection, as it can be a common commensal in young children. Distinguishing between colonization and true infection requires careful interpretation of clinical and laboratory findings.

• Variable Clinical Presentation: K. kingae osteoarticular infections can present with a range of symptoms, sometimes mimicking other conditions, making clinical diagnosis challenging. Fever, pain, swelling, and limited range of motion are common, but these findings are not specific to K. kingae infection.

Traditional Culture Methods: The Gold Standard and its Limitations

Traditional bacterial culture of synovial fluid (from joint aspiration) or bone biopsy remains the gold standard for diagnosing osteoarticular infections, including those caused by K. kingae. However, several limitations exist:

• Sensitivity: K. kingae's fastidious nature can lead to false-negative cultures if appropriate growth conditions are not met or if samples are not processed promptly.

• Time to Result: Bacterial culture requires incubation periods of several days, delaying diagnosis and potentially hindering timely treatment.

• Differentiation from Colonization: As mentioned, K. kingae can be commensal, so a positive culture must be interpreted in conjunction with clinical findings to differentiate colonization from true infection.

Molecular Techniques: Advancing Diagnostic Capabilities

Molecular techniques, such as polymerase chain reaction (PCR), have emerged as valuable tools for diagnosing K. kingae osteoarticular infections, offering several advantages over traditional culture:

• Increased Sensitivity: PCR can detect even small amounts of bacterial DNA, increasing the sensitivity of diagnosis, particularly in cases where bacterial load is low or prior antibiotic therapy has been administered.

• Faster Turnaround Time: PCR results can be obtained within hours, allowing for more rapid diagnosis and initiation of appropriate treatment.

• Species-Specific Identification: PCR can specifically identify K. kingae, even in the presence of other bacteria, aiding in accurate diagnosis.

However, molecular techniques also have limitations:

• Cost: PCR testing can be more expensive than traditional culture methods.

• Availability: Not all laboratories have access to PCR testing.

• Interpretation: Similar to culture, a positive PCR result must be interpreted in the clinical context, as it may not always distinguish colonization from infection.

The Crucial Role of Clinical Context

Bacteriological diagnosis of K. kingae osteoarticular infections cannot rely solely on laboratory findings. Clinical context plays a critical role in interpreting laboratory results and making an accurate diagnosis. Important clinical factors to consider include:

• Patient Age: K. kingae infections are most common in children under five years old.

• Clinical Presentation: The presence of fever, pain, swelling, and limited range of motion in the affected joint or bone suggests infection.

• Laboratory Findings: Elevated inflammatory markers, such as white blood cell count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), can support the diagnosis of infection.

• Imaging Studies: Imaging studies, such as X-ray, ultrasound, or MRI, can help visualize bone or joint involvement and guide aspiration or biopsy procedures.

A Multidisciplinary Approach for Optimal Patient Management

Diagnosing and managing K. kingae osteoarticular infections requires a multidisciplinary approach involving pediatricians, orthopedic surgeons, infectious disease specialists, and microbiologists. Effective communication and collaboration among these specialists are essential for achieving accurate and timely diagnoses, initiating appropriate treatment, and monitoring patient progress.

Current Diagnostic Strategies: A Synthesis

A suggested diagnostic algorithm for suspected K. kingae osteoarticular infection might include:

1. Clinical Suspicion: Consider K. kingae infection in young children presenting with signs and symptoms of osteoarticular infection, particularly in the absence of other obvious causes.

2. Specimen Collection: Obtain synovial fluid (from joint aspiration) or bone biopsy for bacterial culture and PCR testing. Ensure that samples are collected before antibiotic therapy is initiated, if possible, and that they are processed promptly by the laboratory.

3. Laboratory Testing: Perform both bacterial culture and PCR testing on the collected specimens. Use enriched media and prolonged incubation for K. kingae culture.

4. Interpretation of Results: Interpret laboratory results in the context of the patient's clinical presentation, laboratory findings, and imaging studies. Distinguish between colonization and true infection.

5. Multidisciplinary Consultation: Consult with pediatricians, orthopedic surgeons, and infectious disease specialists to develop a comprehensive management plan.

Future Directions: Advancing Diagnostic Capabilities

Several areas of research hold promise for improving the diagnosis of K. kingae osteoarticular infections:

• Improved Molecular Techniques: Developing more rapid and sensitive molecular assays, such as multiplex PCR or next-generation sequencing, could further enhance diagnostic capabilities.

• Point-of-Care Diagnostics: Developing point-of-care diagnostic tests for K. kingae could allow for faster diagnosis and treatment, particularly in resource-limited settings.

• Biomarker Research: Identifying specific biomarkers for K. kingae infection could aid in differentiating colonization from true infection and in monitoring treatment response.

Conclusion

Kingella kingae is an important cause of osteoarticular infections in young children. It is a fastidious organism and a commensal colonizer, which can present some diagnostic challenges. Though culture remains the cornerstone, PCR-based molecular techniques have enhanced detection and diagnosis. The necessary laboratory findings should be well balanced with the clinical presentation of the patient and other diagnostic data. Optimal management requires a multidisciplinary approach in close collaboration with specialists. Research into improved methods of diagnosis remains an exciting and promising area in the continued enhancement of our capacity to rapidly and accurately diagnose K. kingae osteoarticular infections in children, further leading to optimal outcomes for infected children.