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Haemophilus haemolyticus
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Haemophilus haemolyticus

Haemophilus haemolyticus is a Gram-negative, facultative anaerobic bacterium commonly found in the human upper respiratory tract. It is typically a commensal organism but may act as an opportunistic pathogen. 

Closely related to Haemophilus influenzae, H. haemolyticus is distinguished by its hemolytic activity, though its role in human infections remains under investigation.

What is Haemophilus haemolyticus?

Haemophilus haemolyticus is a Gram-negative bacterium belonging to the Pasteurellaceae family. It is a facultative anaerobe, meaning it can survive in both oxygen-rich and oxygen-poor environments.

This bacterial species is primarily found in the human upper respiratory tract, where it is generally considered a commensal organism but can act as an opportunistic pathogen under certain conditions. 

It is genetically similar to Haemophilus influenzae, although it lacks key genes associated with H. influenzae virulence.

Normal Flora and Opportunistic Pathogen

H. haemolyticus is often part of the normal microbial community in the upper respiratory tract that plays a protective role against infections caused by Haemophilus influenzae, particularly non-typeable H. influenzae (NTHi). 

However, it may have the potential to cause infections in immunocompromised individuals or those with underlying health conditions. 

Hemolytic Activity

The species name "haemolyticus" is derived from its ability to lyse red blood cells, a feature that can be observed on blood agar plates in a laboratory setting.

H. haemolyticus is traditionally differentiated from H. influenzae by its beta-hemolysis on blood agar, but hemolysis can be lost on subculture, and many strains are nonhemolytic, leading to potential misidentification and underestimation of its role in invasive infections.

Haemophilus haemolyticus Association with Infections

While H. haemolyticus is usually harmless, it has been implicated in certain infections, particularly invasive infections (less common), including bacteremia (bacteria in the bloodstream) and endocarditis (infection of the heart valves), although endocarditis due to H. haemophilus is rare

While its pathogenicity remains underexplored, recent studies suggest it may contribute to infections. The emergence of high-level quinolone-resistant strains, such as one isolated from a pediatric patient in Japan, highlights the need for antimicrobial susceptibility testing. 

Who Should Get Tested for Haemophilus haemolyticus?

Testing for H. haemolyticus may be recommended in cases of suspected bacterial infection. It is not a general screening test but is utilized in specific diagnostic scenarios, such as when it needs to be differentiated from H. influenzae.

Individuals with Suspected Respiratory Tract Infections

Patients presenting with symptoms of respiratory tract infection, where the infectious agent must be conclusively determined; symptoms may include: 

  • Sore throat
  • Fever
  • Difficulty swallowing
  • Other signs of upper respiratory tract infections

Individuals with Signs of Invasive Infections

Though rare, blood cultures may be performed in cases of suspected bacteremia or endocarditis to identify H. haemolyticus as a potential causative agent.

What Does a Positive Haemophilus haemolyticus Test Mean?

A positive test result indicates the presence of H. haemolyticus and suggests it may be contributing to the patient's symptoms. However, proper clinical correlation is necessary.

Clinical Significance of a Positive Result

A positive test in a throat swab or blood culture suggests active colonization or infection.

The presence of H. haemolyticus should be interpreted in conjunction with the patient’s symptoms, clinical presentation, and additional lab findings.

Antimicrobial Susceptibility Testing

If H. haemolyticus is isolated from a clinical sample, antimicrobial susceptibility testing is recommended.

This helps determine which antibiotics are effective against the specific strain, aiding in targeted treatment.

What Does a Negative Haemophilus haemolyticus Test Mean?

A negative test does not necessarily exclude bacterial infection but suggests that H. haemolyticus is either absent or present at levels below the detection threshold.

Accurate identification of H. haemolyticus is important, as conventional methods may misidentify it as H. influenzae. Molecular testing like multilocus sequence analysis molecular testing is necessary to ensure proper diagnosis and treatment.

How to Test for Haemophilus haemolyticus

Accurate identification of H. haemolyticus requires proper sample collection and microbiological analysis, such as PCR testing

Sample Types

  • Throat Swabs: Collected from the oropharynx in cases of suspected respiratory tract infections.
  • Blood Cultures: used when invasive infections such as bacteremia or endocarditis are suspected.
  • Sputum Samples: In cases of lower respiratory tract involvement.
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See References

Anderson, R., Wang, X., Briere, E. C., Katz, L. S., Cohn, A. C., Clark, T. A., Messonnier, N. E. M., & Mayer, L. W. (2012). Haemophilus haemolyticus isolates causing clinical disease. Journal of Clinical Microbiology, 50(7), 2462–2465. https://doi.org/10.1128/JCM.06575-11 

Fazal, M.-A., Alexander, S., Grayson, N. E., Deheer-Graham, A., Oliver, K., Holroyd, N., Parkhill, J., & Russell, J. E. (2019). Complete Whole-Genome Sequence of Haemophilus haemolyticus NCTC 10839. Microbiology Resource Announcements, 8(25). https://doi.org/10.1128/mra.00232-19

Hu, F., Rishishwar, L., Sivadas, A., Mitchell, G. J., Jordan, I. K., Murphy, T. F., Gilsdorf, J. R., Mayer, L. W., & Wang, X. (2016). Comparative genomic analysis of Haemophilus haemolyticus and nontypeable Haemophilus influenzae and a new testing scheme for their discrimination. Journal of Clinical Microbiology, 54(12), 3010–3017. https://doi.org/10.1128/JCM.01511-16 

McCrea, K. W., Xie, J., LaCross, N., Patel, M., Mukundan, D., Murphy, T. F., Marrs, C. F., & Gilsdorf, J. R. (2008). Relationships of nontypeable Haemophilus influenzae strains to hemolytic and nonhemolytic Haemophilus haemolyticus strains. Journal of Clinical Microbiology, 46(2), 406–416. https://doi.org/10.1128/JCM.01832-07  

Morton, D. J., Hempel, R. J., Whitby, P. W., Seale, T. W., & Stull, T. L. (2012). An invasive Haemophilus haemolyticus isolate. Journal of Clinical Microbiology, 50(4), 1502–1503. https://doi.org/10.1128/JCM.06688-11

Murphy, T. F., Brauer, A. L., Sethi, S., Kilian, M., Cai, X., & Lesse, A. J. (2007). Haemophilus haemolyticus: a human respiratory tract commensal to be distinguished from Haemophilus influenzae. Journal of Infectious Diseases, 195(1), 81–89. https://doi.org/10.1086/509824  

Pickering, J., Richmond, P. C., & Kirkham, L.-A. S. (2014). Molecular tools for differentiation of non-typeable Haemophilus influenzae from Haemophilus haemolyticus. Frontiers in Microbiology, 5, 664. https://doi.org/10.3389/fmicb.2014.00664 

Tanaka, E., Hirai, Y., Wajima, T., Ishida, Y., Kawamura, Y., & Nakaminami, H. (2022). High-Level Quinolone-Resistant Haemophilus haemolyticus in Pediatric Patient with No History of Quinolone Exposure. Emerging Infectious Diseases, 28(1), 104–110. https://doi.org/10.3201/eid2801.210248

Theodore, M. J., Anderson, R. D., Wang, X., Katz, L. S., Vuong, J. T., Bell, M. E., Juni, B. A., Lowther, S. A., Lynfield, R., MacNeil, J. R., & Mayer, L. W. (2012). Evaluation of new biomarker genes for differentiating Haemophilus influenzae from Haemophilus haemolyticus. Journal of Clinical Microbiology, 50(4), 1422–1424. https://doi.org/10.1128/JCM.06702-11

Zhu, B., Xiao, D., Zhang, H., Zhang, Y., Gao, Y., Xu, L., Lv, J., Wang, Y., Zhang, J., & Shao, Z. (2013). MALDI-TOF MS distinctly differentiates nontypable Haemophilus influenzae from Haemophilus haemolyticus. PLoS ONE, 8(2), e56139. https://doi.org/10.1371/journal.pone.0056139

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