Risk of invasive pneumococcal disease in children with sickle cell disease in the era of conjugate vaccines: a systematic review of the literature.

Pneumococcal conjugate vaccines (PCVs) are highly effective in preventing invasive pneumococcal diseases (IPD) in children, including those with sickle cell disease (SCD). A systematic review of the English literature published between 2000 and 2017 was undertaken to evaluate the serotype distribution, clinical presentation and outcomes of IPD in children with SCD in PCV programmes. We identified 475 potential studies and included 16 publications, involving 9438 children up to 22 years of age with SCD and 182 IPD episodes (prevalence, 1·9%. 95% confidence interval [CI], 1·7-2·2%). Septicaemia was the most prevalent clinical presentation (84/137; 61%) followed by lower respiratory tract infection (39/137; 29%) and meningitis (12/137, 9%). More than half the serotypes associated with IPD (88/148; 59·5%) were not included in the 13-valent PCV; of these, 54% (44/82) were due to serogroup 15. The crude case fatality rate was 11·5% (21/182 cases; 95% CI, 7·3-17·1%). Most cases of IPD in children with SCD were due to serotypes that are not included in any of the licensed PCVs. IPD in children with SCD remains associated with high morbidity and mortality, highlighting the importance of strict adherence to daily penicillin prophylaxis. Until a serotype-independent pneumococcal vaccine becomes available, higher-valent PCVs should include serogroup 15 to protect this highly vulnerable group of children

Twelve Years Of Fluconazole In Clinical Practice: Global-Trends In Species Distribution And Fluconazole Susceptibility Of Bloodstream Isolates Of Candida

We determined the species distribution and in-vitro susceptibility of 6082 bloodstream infection (BSI)isolates ofCandidaspp. collected from 250 medical centres in 32 nations over a 10-year period from 1992through 2001. The species included 3401C. albicans, 984C. glabrata, 796C. parapsilosis, 585C. tropicalis,153C. krusei,67C. lusitaniae,48C. guilliermondii,10C. famata,10C. kefyr, sixC. pelliculosa, fiveC. rugosa,fourC. lipolytica, threeC.dubliniensis, threeC. inconspicua, twoC. sakeand one isolate each ofC. lambica,C. norvegensisandC. zeylanoides. Minimum inhibitory concentration determinations were made usingthe National Committee for Clinical Laboratory Standards reference broth microdilution method.Variation in the rank order and frequency of the different species ofCandidawas observed over time andby geographic area. The proportion of BSI due toC. albicansandC. glabrataincreased andC. parapsilosisdecreased over time in Canada, the USA and Europe.C. glabratawas an infrequent cause of BSI in LatinAmerica and the Asia-Pacific region. Very little variation in fluconazole susceptibility was observedamong isolates ofC. albicans,C. tropicalisandC. parapsilosis. These species accounted for 78%of all BSIand remained highly susceptible (91–100%susceptible) to fluconazole from 1992 to 2001 irrespective ofgeographic origin. The prevalence of fluconazole resistance amongC. glabrataisolates was variable bothover time and among the various countries and regions. Resistance to fluconazole amongC. glabrataisolates was greatest in the USA and varied by US census region (range 0–23%). These observations aregenerally encouraging relative to the sustained usefulness of fluconazole as a systemically activeantifungal agent for the treatment of candida BSI.Scopu