Bacteremia in sickle hemoglobinopathies

Zarkowsky, Harold S.; Gallagher, Dianne; Gill, Frances M.; Wang, Winfred C.; Falletta, John M.; Lande, William M.; Levy, Paul S.; Verter, Joel; Wethers, Doris L.

doi:10.1016/s0022-3476(86)80216-5

Cited by 203 publications

(89 citation statements)

References 12 publications

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“…Based on the high incidence of pneumococcal sepsis (10 events per 100-person years with a high case fatality rate) [13,31,32], some SCD centers were using prophylactic penicillin in children as early as the 1980s. A single center trial [33], followed by a multicenter, randomized clinical trial unequivocally demonstrated the benefit of penicillin prophylaxis for preventing SCD related pneumococcal sepsis.…”

Section: Milestones In Scd Carementioning

confidence: 99%

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

2015

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Over the past 40 years, public health measures such as universal newborn screening, penicillin prophylaxis, vaccinations, and hydroxyurea therapy have led to an impressive decline in sickle cell disease (SCD)-related childhood mortality and SCD-related morbidity in high-income countries. We remain cautiously optimistic that the next 40 years will be focused on meeting current challenges in SCD by addressing chronic complications of SCD to reduce mortality and improve quality of life in a growing population of adults with SCD in high-income countries, while simultaneously decreasing the disparity of medical care between high and low-income countries.

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Section: Milestones In Scd Carementioning

confidence: 99%

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

2015

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“…Children with SCA have a 400-fold greater risk of fulminant, lethal pneumococcal sepsis than their healthy peers or patients with other hemolytic anemias, [8][9][10] a finding recapitulated in the sickle cell mouse model. 11 Despite administration of penicillin prophylaxis, pneumococcal polysaccharide vaccine, and pneumococcal protein-conjugate vaccine, invasive pneumococcal disease continues to be a serious risk for patients with SCA.…”

Section: Introductionmentioning

confidence: 99%

Hydroxyurea therapy of a murine model of sickle cell anemia inhibits the progression of pneumococcal disease by down-modulating E-selectin

Lebensburger¹,

Howard²,

Hu³

et al. 2012

Blood

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Sickle cell anemia is characterized by chronic hemolysis coupled with extensive vascular inflammation. This inflammatory state also mechanistically promotes a high risk of lethal, invasive pneumococcal infection. Current treatments to reduce vaso-occlusive complications include chronic hydroxyurea therapy to induce fetal hemoglobin. Because hydroxyurea also reduces leukocytosis, an understanding of the impact of this treatment on pneumococcal pathogenesis is needed. Using a sickle cell mouse model of pneumococcal pneumonia and sepsis, administration of hydroxyurea was found to significantly improve survival. Hydroxyurea treatment decreased neutrophil extravasation into the infected lung coincident with significantly reduced levels of E-selectin in serum and on pulmonary epithelia. The protective effect of hydroxyurea was abrogated in mice deficient in E-selectin. The decrease in Eselectin levels was also evident in human sickle cell patients receiving hydroxyurea therapy. These data indicate that in addition to induction of fetal hemoglobin, hydroxyurea attenuates leukocyteendothelial interactions in sickle cell anemia, resulting in protection against lethal pneumococcal sepsis. IntroductionSickle cell anemia (SCA) is characterized by chronic hemolytic anemia and vascular inflammation. Hydroxyurea therapy decreases vasoocclusive complications of SCA and reduces mortality, 1,2 but the mechanism of this benefit has been debated. Elevated white blood cell counts have been found to correlate with greater mortality in sickle cell disease (SCD), 3 and early studies suggested hydroxyurea reduced leukocytosis. 4,5 Subsequent studies found no statistical association between reduction of leukocytosis and mortality in SCA patients receiving hydroxyurea, implicating increased levels of hemoglobin F (HbF) as the main predictor of mortality. 6 A recent placebo-controlled clinical trial of hydroxyurea in pediatric SCA patients confirmed a highly significant decrease in total white blood cell and absolute neutrophil counts after hydroxyurea treatment as well as increases in hemoglobin and HbF levels. 7 A significant decrease in acute chest syndrome, which is oftentimes initiated by lung infection, also was observed in this study. 7 Bacteremia was recorded 6 times in the placebo group but only 3 times in the hydroxyurea-treated patients, 7 a trend that was not significant because of the low incidence. Although induction of HbF is generally accepted to be a major benefit of hydroxyurea therapy in SCA, the relative contribution of other factors, including decreased white blood cell counts, to positive outcomes remains a possibility that has yet to be explored.Modulation of leukocytosis by hydroxyurea raises the question of infection risk in SCA. Children with SCA have a 400-fold greater risk of fulminant, lethal pneumococcal sepsis than their healthy peers or patients with other hemolytic anemias, 8-10 a finding recapitulated in the sickle cell mouse model. 11 Despite administration of penicillin prophylaxis, pneumococcal polysac...

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“…[2][3][4] The compliance of parents or caregivers with prophylactic antibiotic therapy prescribed for their children is a challenge and healthcare professionals must better understand the process of compliance considering it as an integral part of treatment plan. [5][6][7] Several deaths, suffering, need for hospitalization and unnecessary medical care expenditures could be avoided if healthcare professionals were better informed and had the means to identify noncompliance with antibiotic prophylaxis as the cause of severe infections in children with SCA.…”

Section: Introductionmentioning

confidence: 99%

Adesão à antibioticoterapia profilática em crianças com anemia falciforme: um estudo prospectivo

Bitarães¹,

Oliveira²,

Viana³

2008

J. Pediatr. (Rio J.)

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Objective: To prospectively assess compliance with antibiotic prophylaxis among children with sickle cell anemia.Methods: A total of 108 children (aged 3 months to 4½ years, 45% male) were recruited from the Hematology Center in Belo Horizonte, Brazil, and followed up for 15 months. Data on compliance were obtained from three interviews with the primary caregivers, from the children's medical records and from assay of antibacterial activity in urine samples of 81 children. Antibiotics were available free of charge.Results: Penicillin was used in 106 cases (majority by oral route); erythromycin in 2 cases. Urine samples tested positive for the antibiotic in 56% of the cases; 48% of the caregivers assured during interviews that all doses had been administered to children; 89% of medical files recorded no compliance failures. Considering a child compliant if none or just one of these methods detected missing doses, the rate of compliance was 67%. The agreement between methods for assigning a child as compliant or not was low. No significant association of compliance rate with gender, nutritional status, per capita income of the family, caregivers' schooling, or number of family members was demonstrated. Conclusions:Compliance rate with prophylactic antibiotic therapy was low when assessed by interviews and urine tests and overestimated by analysis of medical records. Compliance should preferably be assessed by several methods due to the complex character of its measurement. The results of the present study suggest the need for a comprehensive educational program involving healthcare professionals, families and children with sickle cell anemia.J Pediatr (Rio J). 2008;84(4):316-322: Sickle cell anemia, antibiotic prophylaxis, treatment refusal, guideline adherence, penicillin V.

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Bacteremia in sickle hemoglobinopathies

Cited by 203 publications

References 12 publications

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

Hydroxyurea therapy of a murine model of sickle cell anemia inhibits the progression of pneumococcal disease by down-modulating E-selectin

Adesão à antibioticoterapia profilática em crianças com anemia falciforme: um estudo prospectivo

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