Podcast
Questions and Answers
What is the primary method for initial diagnosis of N.meningitidis infection?
What is the primary method for initial diagnosis of N.meningitidis infection?
What percentage of blood cultures may be positive in patients with acute meningococcemia?
What percentage of blood cultures may be positive in patients with acute meningococcemia?
How does the sensitivity of blood cultures change after antibiotic administration?
How does the sensitivity of blood cultures change after antibiotic administration?
What are the typical CSF leukocyte levels in meningococcal meningitis?
What are the typical CSF leukocyte levels in meningococcal meningitis?
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What is the likelihood of isolating N.meningitidis from skin lesions after antibiotic therapy?
What is the likelihood of isolating N.meningitidis from skin lesions after antibiotic therapy?
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Which bodily fluids can be tested for the culture isolation of N.meningitidis?
Which bodily fluids can be tested for the culture isolation of N.meningitidis?
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What is the sensitivity and specificity of PCR testing for N.meningitidis strains?
What is the sensitivity and specificity of PCR testing for N.meningitidis strains?
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Why is PCR not typically employed in the initial diagnostic workup for meningococcal disease?
Why is PCR not typically employed in the initial diagnostic workup for meningococcal disease?
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What is the combined sensitivity of culture and Gram staining for blood and CSF specimens?
What is the combined sensitivity of culture and Gram staining for blood and CSF specimens?
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When should therapy for N.meningitidis infection not be delayed?
When should therapy for N.meningitidis infection not be delayed?
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What advantage does PCR have over traditional cultures in diagnosing chronic meningococcemia?
What advantage does PCR have over traditional cultures in diagnosing chronic meningococcemia?
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In which cases is PCR particularly beneficial for diagnosing meningococcal infections?
In which cases is PCR particularly beneficial for diagnosing meningococcal infections?
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What test is commonly used to detect serogroup B infections of meningococcemia?
What test is commonly used to detect serogroup B infections of meningococcemia?
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What findings can routine pathology of skin biopsy specimens demonstrate in cases of necrotizing vasculitis?
What findings can routine pathology of skin biopsy specimens demonstrate in cases of necrotizing vasculitis?
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What is a limitation of the latex agglutination assay in diagnosing meningococcal infections?
What is a limitation of the latex agglutination assay in diagnosing meningococcal infections?
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Which staining techniques may be useful in the diagnosis of both acute and chronic cases of meningococcal disease?
Which staining techniques may be useful in the diagnosis of both acute and chronic cases of meningococcal disease?
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Which body fluid is most commonly collected for culture isolation in suspected N.meningitidis infections?
Which body fluid is most commonly collected for culture isolation in suspected N.meningitidis infections?
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What is the primary concern regarding delaying therapy for N.meningitidis infection?
What is the primary concern regarding delaying therapy for N.meningitidis infection?
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What typical finding is associated with CSF analysis in meningococcal meningitis?
What typical finding is associated with CSF analysis in meningococcal meningitis?
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What does the sensitivity of cultures from CSF or other sites indicate after antibiotic initiation?
What does the sensitivity of cultures from CSF or other sites indicate after antibiotic initiation?
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Which method showed the highest sensitivity for isolating N.meningitidis from patients?
Which method showed the highest sensitivity for isolating N.meningitidis from patients?
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What is a notable characteristic of the CSF findings in the first hours after antibiotic administration?
What is a notable characteristic of the CSF findings in the first hours after antibiotic administration?
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What percentage of skin biopsy cultures had sensitivity in the study evaluating patients with meningococcemia?
What percentage of skin biopsy cultures had sensitivity in the study evaluating patients with meningococcemia?
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Why may cultures from CSF become sterile shortly after antibiotic therapy begins?
Why may cultures from CSF become sterile shortly after antibiotic therapy begins?
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What significant limitation does PCR testing have compared to traditional cultures in diagnosing N.meningitidis infections?
What significant limitation does PCR testing have compared to traditional cultures in diagnosing N.meningitidis infections?
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In which scenario might PCR be particularly beneficial for diagnosis, according to the information provided?
In which scenario might PCR be particularly beneficial for diagnosis, according to the information provided?
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What is the primary benefit of using the rapid dipstick test in developing countries for meningococcal meningitis?
What is the primary benefit of using the rapid dipstick test in developing countries for meningococcal meningitis?
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What kind of findings may routine pathology of skin biopsy specimens reveal in cases associated with necrotizing vasculitis?
What kind of findings may routine pathology of skin biopsy specimens reveal in cases associated with necrotizing vasculitis?
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What is a notable feature of PCR testing for skin biopsy specimens in diagnosing meningococcal infections?
What is a notable feature of PCR testing for skin biopsy specimens in diagnosing meningococcal infections?
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What limitation is associated with latex agglutination assays in diagnosing meningococcal infections?
What limitation is associated with latex agglutination assays in diagnosing meningococcal infections?
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What is a characteristic of the PCR method compared to cultures that makes it advantageous, especially before antibiotic initiation?
What is a characteristic of the PCR method compared to cultures that makes it advantageous, especially before antibiotic initiation?
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What is an important characteristic that distinguishes PCR's specificity from other diagnostic methods?
What is an important characteristic that distinguishes PCR's specificity from other diagnostic methods?
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Study Notes
Initial Diagnosis
- Initial diagnosis of N.meningitidis infection is typically clinical
- Blood cultures should be collected swiftly and empiric antimicrobial therapy administered immediately
- Lumbar puncture is also warranted, in addition to fluid collection from other bodily sites of suspected dissemination
- These tests should never delay therapy
Laboratory Testing
- The gold standard for diagnosis is culture of N.meningitidis from blood, CSF, synovial fluid, pleural fluid, pericardial fluid, or skin biopsy tissues
- Culture enables etiologic confirmation as well as determination of antibiotic susceptibility
- In acute meningococcemia, blood cultures may be positive in 40%-80% of patients and sensitivity declines quickly following initiation of antibiotics
- Cultures from CSF and other organ sites may also have a low sensitivity, especially once antibiotics are started
- In the setting of meningococcal meningitis, CSF leukocytes typically exceed 100 × 106/L with elevated protein and decreased glucose, however, 1 or more of these classic findings may be absent.
- The skin may provide another site for bacterial isolation, either via needle aspiration of cutaneous lesions or punch biopsy
- In contrast to blood and CSF, meningococci have been cultured from skin lesions up to 13 hours following antibiotic administration
- PCR can quickly type N.meningitidis strains and is highly sensitive (96%) and specific (100%).
- PCR is not typically employed in initial diagnostic workup
- PCR is being investigated in skin biopsy specimens which may offer even higher sensitivity compared to PCR of blood or CSF samples
- Silver staining and immunohistochemical staining of skin lesions may be useful in both acute and chronic cases of meningococcal disease
- Additional tests include a latex agglutination assay and rapid dipstick test
- The latex agglutination test is not routinely performed due to the high proportion of serogroup B infections in the US and Europe
- The rapid dipstick test is particularly useful in developing countries
Pathology
- Pathology of skin biopsy specimens may reveal findings consistent with necrotizing vasculitis, including perivascular infiltrates of neutrophils and monocytes with microvascular thrombosis and perivascular hemorrhage
- Gram stain may reveal Gram-negative cocci
- In the setting of chronic meningococcemia, perivascular infiltrates are comprised of lymphocytes and neutrophils and leukocytoclastic vasculitis may be appreciated in petechial lesions
Diagnosis
- Initial diagnosis is typically clinical, as systemic infection constitutes a medical emergency
- Treatment should not be delayed waiting for test results.
- Blood cultures should be swiftly collected and empiric antimicrobial therapy administered immediately.
- Lumbar puncture and fluid collection from other bodily sites are warranted but should not delay therapy.
Laboratory Testing
- The gold standard for diagnosis is culture isolation of N. meningitidis from blood, CSF, synovial fluid, pleural fluid, pericardial fluid, or skin biopsy tissues.
- Culture allows for etiologic confirmation and determination of antibiotic susceptibility.
- Blood cultures may be positive in 40% to 80% of patients with acute meningococcemia, and sensitivity declines quickly following the initiation of antibiotics.
- Cultures from CSF and other organ sites may also have a low sensitivity, especially once antibiotics are started.
- CSF sterilization in pneumococcal or group B streptococcal infection typically takes several hours, but meningococcal infection can sterilize within 2 hours.
- In meningococcal meningitis, CSF leukocytes typically exceed 100 × 106/L with elevated protein and decreased glucose; however, 1 or more of these classic findings may be absent.
- N. meningitidis can be isolated from the skin via needle aspiration of cutaneous lesions or punch biopsy.
- Meningococci have been cultured from skin lesions up to 13 hours following antibiotic administration.
- In a prospective study of 31 patients and 12 controls, the sensitivities of blood, CSF, and skin biopsy cultures were 56%, 50%, and 36%, respectively. When culture and Gram staining were combined, the sensitivities were 56% (blood), 64% (CSF), and 56% (skin biopsy).
- PCR is highly sensitive (96%) and specific (100%) for N. meningitidis, and because live bacteria are not required, sensitivity is not diminished by initiation of antibiotics. PCR takes less than 4 hours, and in-house test results are typically available the same day as collection.
- PCR is indicated when cultures are uninformative and is not typically employed in initial diagnostic workup.
- PCR is being investigated in skin biopsy specimens, which may offer even higher sensitivity compared to PCR of blood or CSF samples. This testing modality may be especially useful in chronic meningococcemia as skin lesions are nonspecific, and positive cultures may be more difficult to come by because of waxing and waning bacterial levels.
- Silver staining and immunohistochemical staining of skin lesions also may be useful in both acute and chronic cases of meningococcal disease.
- Latex agglutination assays detect capsular antigens of serogroups A, C, W135, and Y, with significantly lower sensitivity for serogroup B. Latex agglutination tests are not routinely performed due to low sensitivity for serogroup B, which is prevalent in the United States and Europe.
- A rapid dipstick test for detection of serogroups A, C, W135, and Y in CSF has been found to detect 90% of meningitis cases caused by A and W135 in Niger when compared to PCR.
Pathology
- Routine pathology of skin biopsy specimens may reveal findings consistent with necrotizing vasculitis, including perivascular infiltrates comprised of neutrophils and monocytes with microvascular thrombosis and perivascular hemorrhage.
- Gram stain may reveal Gram-negative cocci. In the setting of chronic meningococcemia, perivascular infiltrates are comprised of lymphocytes and neutrophils, and leukocytoclastic vasculitis may be appreciated in petechial lesions.
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Description
This quiz covers the initial diagnosis and laboratory testing for N. meningitidis infections. It highlights clinical considerations, the importance of timely blood cultures, and the significance of various diagnostic tests. Test your understanding of the gold standards in diagnosing this serious infection.
