{"id":22136,"date":"2022-08-17T04:53:00","date_gmt":"2022-08-16T20:53:00","guid":{"rendered":"http:\/\/csccm.org.cn\/?p=22136"},"modified":"2022-08-17T05:41:06","modified_gmt":"2022-08-16T21:41:06","slug":"lancet-infect-dis%e5%8f%91%e8%a1%a8%e8%ae%ba%e6%96%87%ef%bc%9a%e5%8c%85%e5%90%ab%e6%b0%9f%e8%83%9e%e5%98%a7%e5%95%b6%e7%9a%84%e8%81%94%e5%90%88%e6%8a%97%e7%94%9f%e7%b4%a0%e6%b2%bb%e7%96%97%e5%8d%97","status":"publish","type":"post","link":"https:\/\/csccm.org.cn\/?p=22136","title":{"rendered":"[Lancet Infect Dis\u53d1\u8868\u8bba\u6587]\uff1a\u5305\u542b\u6c1f\u80de\u5627\u5576\u7684\u8054\u5408\u6297\u751f\u7d20\u6cbb\u7597\u5357\u975e\u9690\u7403\u83cc\u8111\u819c\u708e"},"content":{"rendered":"\n

ARTICLES|ONLINE FIRST<\/a><\/p>\n\n\n\n

Outcomes of flucytosine-containing combination treatment for cryptococcal meningitis in a South African national access programme: a cross-sectional observational study<\/h1>\n\n\n\n

Rudzani C Mashau, Susan T Meiring, Vanessa C Quan, et al<\/h3>\n\n\n\n

Lancet Infect Dis Published:June 21, 2022<\/h3>\n\n\n\n

DOI:https:\/\/doi.org\/10.1016\/S1473-3099(22)00234-1<\/a><\/h3>\n\n\n\n

Summary<\/h2>\n\n\n\n

Background<\/h3>\n\n\n\n

Although flucytosine is a key component of WHO-recommended induction treatment for HIV-associated cryptococcal meningitis, this antifungal agent is not widely available in low-income and middle-income countries due to limited production and cost. In 2018, a national flucytosine access programme was initiated in South Africa. We aimed to determine the effectiveness of flucytosine-containing induction regimens in routine care to motivate for the urgent registration of flucytosine and its inclusion in treatment guidelines.<\/p>\n\n\n\n

Methods<\/h3>\n\n\n\n

In this cross-sectional study, we compared outcomes of adults aged 18 years and older with incident laboratory-confirmed cryptococcal meningitis treated with or without flucytosine-containing regimens at 19 sentinel hospitals in South Africa. A case of cryptococcosis was defined as illness in an adult with: (1) positive cerebrospinal fluid (CSF) India ink microscopy; (2) a positive CSF cryptococcal antigen test; or (3) culture of Cryptococcus neoformans<\/em> or Cryptococcus gattii<\/em> from CSF or any other specimen. We excluded patients without a case report form, those with an unknown or negative HIV serology result, those with a recurrent episode, and those who did not receive antifungal treatment in hospital. We assessed cumulative in-hospital mortality at 14 days and 30 days and calculated the overall crude in-hospital case-fatality ratio. We used random-effects logistic regression to examine the association between treatment group and in-hospital mortality.<\/p>\n\n\n\n

Findings<\/h3>\n\n\n\n

From July 1, 2018, to March 31, 2020, 10\u2009668 individuals were diagnosed with laboratory-confirmed cryptococcal meningitis, 7787 cases diagnosed at non-enhanced surveillance sites and 567 cases from eight enhanced surveillance sites with no access to flucytosine were excluded. Of 2314 adults with a first episode of cryptococcosis diagnosed at 19 facilities with access to flucytosine, 1996 had a case report form and of these, 1539 received induction antifungal treatment and were confirmed HIV-seropositive first-episode cases. Of 1539 patients who received antifungal therapy, 596 (38\u00b77%) individuals received a flucytosine-containing regimen and 943 (61\u00b73%) received another regimen. The median age was 36 years (IQR 32\u201343) and 906 (58\u00b79%) participants were male and 633 (41\u00b71%) were female. The crude in-hospital case-fatality ratio was 23\u00b79% (95% CI 20\u00b70\u201327\u00b70; 143 of 596) in those treated with flucytosine-containing regimens and 37\u00b72% (95% CI 34\u00b70\u201340\u00b70; 351 of 943) in those treated with other regimens. Patients admitted to non-academic hospitals (adjusted odds ratio [aOR] 1\u00b795 [95% CI 1\u00b753\u20132\u00b748]; p<0\u00b70001) and those who were antiretroviral treatment-experienced (aOR 1\u00b730 [1\u00b702\u20131\u00b767]; p=0\u00b7033) were more likely to receive flucytosine. After adjusting for relevant confounders, flucytosine treatment was associated with a 53% reduction in mortality (aOR 0\u00b747 [95% CI 0\u00b735\u20130\u00b764]; p<0\u00b70001). Among survivors, the median length of hospital admission in the flucytosine group was 11 days (IQR 8\u201315) versus 17 days (13\u201321) in the comparison group (p=0\u00b70010).<\/p>\n\n\n\n

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Interpretation<\/h3>\n\n\n\n

In-hospital mortality among patients treated with a flucytosine-containing regimen was comparable to reduced mortality reported in patients receiving a flucytosine-containing regimen in a recent multicentre African clinical trial. Flucytosine-based treatment can be delivered in routine care in a middle-income country with a substantial survival benefit.<\/p>\n\n\n\n

Funding<\/h3>\n\n\n\n

National Institute for Communicable Diseases, a Division of the National Health Laboratory Service.<\/p>\n","protected":false},"excerpt":{"rendered":"

ARTICLES|ONLINE FIRST Outcomes of flucytosine-containin […]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[32,23],"tags":[],"_links":{"self":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/22136"}],"collection":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=22136"}],"version-history":[{"count":3,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/22136\/revisions"}],"predecessor-version":[{"id":22163,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/22136\/revisions\/22163"}],"wp:attachment":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=22136"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=22136"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=22136"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}