'Time-to-amphotericin B' in cryptococcal meningitis in a European low-prevalence setting: analysis of diagnostic delays

QJM. 2014 Oct;107(10):799-803. doi: 10.1093/qjmed/hcu077. Epub 2014 Apr 10.


Background: Cryptococcal meningitis is a rare disease in Europe, resulting in delayed recognition and slower initiation of specific treatment.

Aim: To analyse the time-to-treatment and the factors that delay the diagnosis and treatment in the low-prevalence setting of a European centre.

Design: Retrospective review

Methods: We reviewed full medical records of all adult patients with cryptococcal meningitis referred to an HIV centre in Berlin, Germany in 10-year period between 1st of October 2003 and 31st of September 2013. Multivariant statistics with bootstrap-resampling were performed.

Results: We identified 19 patients with a diagnosis of HIV-related cryptococcal meningitis (0.55% of all consecutive HIV-infected patients). In almost half of our patients the diagnosis was not considered initially on admission to the secondary care centre and the first diagnostic clue being an accidental positive blood, cerebrospinal fluid or bronchoalveolar lavage culture growing Cryptococcus neoformans. The median time-to-treatment was 5 days (range: 1-16). Known positive HIV status accelerated the time-to-diagnosis (p < 0.05) by a median of 1.89 days, whereas the CSF cell count ≤ 10/µl delayed diagnosis by a median time of 1.93 days (p < 0.1).

Conclusions: Diagnostic delays could be avoided by encouraging practising physicians (i) to consider cryptococcal meningitis in immunosuppressed HIV-infected patients irrespective of neurological symptoms; (ii) to test for India ink, cryptococcal antigen and fungal cultures in immunosuppressed HIV-infected patients with normal CSF; (iii) to consider a possibility of underlying HIV infection in patients with unknown HIV status presenting with meningitis; and (iv) to consider early targeted HIV testing in persons at risk according to locally validated criteria.

MeSH terms

  • AIDS-Related Opportunistic Infections / diagnosis*
  • AIDS-Related Opportunistic Infections / drug therapy*
  • AIDS-Related Opportunistic Infections / microbiology
  • Adult
  • Amphotericin B / therapeutic use*
  • Antifungal Agents / therapeutic use*
  • Cryptococcus neoformans
  • Delayed Diagnosis
  • Female
  • Germany / epidemiology
  • Humans
  • Immunocompromised Host
  • Male
  • Meningitis, Cryptococcal / diagnosis*
  • Meningitis, Cryptococcal / drug therapy*
  • Middle Aged
  • Multivariate Analysis
  • Retrospective Studies
  • Time-to-Treatment*
  • Young Adult


  • Antifungal Agents
  • Amphotericin B