Nasopharyngeal Carriage of Penicillin-resistant<i>Streptococcus pneumoniae</i>in Children With Sickle Cell Disease

Daw, Najat C.; Wilimas, Judith A.; Wang, W. C.; Presbury, Gerald; Joyner, Royce; Harris, Sylvia; Davis, Yvonne; Chen, G.; Chesney, P. Joan

doi:10.1542/peds.99.4.e7

Cited by 30 publications

(20 citation statements)

References 33 publications

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“…Invasive pneumococcal disease is one of the leading complications of homozygous sickle cell disease (HbSS) [3]. Patients with HbSS are more prone to pneumococcal meningitis [4,5] and to pneumococcal septicemia [6,7].…”

Section: Introductionmentioning

confidence: 99%

Nasopharyngeal carriage rate of Streptococcus pneumoniae in Ugandan children with sickle cell disease

et al. 2012

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BackgroundNasopharyngeal carriage of Streptococcus pneumoniae is a determinant for invasive pneumococcal disease, which often complicates homozygous sickle cell disease. Here, we determined the nasopharyngeal carriage rate of S. pneumoniae in Ugandan children with homozygous sickle cell disease, who attended the outpatient Sickle Cell Clinic at Mulago National Referral hospital in Kampala, Uganda.ResultsS. pneumoniae occurred in 27 of the 81 children with homozygous sickle cell disease (giving a carriage rate of 33%, 27/81). Twenty three children were previously hospitalized of whom S. pneumoniae occurred in only two (9%, 2/23), while among the 58 who were not previously hospitalized it occurred in 25 (43%, 25/58, χ2 = 8.8, p = 0.003), meaning there is an association between high carriage rate and no hospitalization. Two children previously immunized with the pneumococcal conjugate vaccine did not carry the organism. Prior antimicrobial usage was reported in 53 children (65%, 53/81). There was high resistance of pneumococci to penicillin (100%, 27/27) and trimethoprime-sulfamethoxazole (97%, 26/27), but low resistance to other antimicrobials. Of the 70 children without sickle cell disease, S. pneumoniae occurred in 38 (54%, 38/70) of whom 43 were males and 27 females (53% males, 23/43, and 56% females, 15/27).ConclusionNasopharyngeal carriage of penicillin resistant pneumococci in Ugandan children with homozygous sickle cell disease is high. While nasopharyngeal carriage of S. pneumoniae is a determinant for invasive pneumococcal disease, pneumococcal bacteremia is reportedly low in Ugandan children with sickle cell disease. Studies on the contribution of high carriage rates to invasive pneumococcal disease in these children will be helpful. This is the first report on pneumococcal carriage rate in Ugandan children with sickle cell disease.

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Section: Introductionmentioning

confidence: 99%

Nasopharyngeal carriage rate of Streptococcus pneumoniae in Ugandan children with sickle cell disease

et al. 2012

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“…Pneumococcal strains were obtained from three sources: A) 63 NP SCD isolates from 1994-5 (Daw et al, 1997); B) 186 IPD SCD isolates from the CDC ABC bacterial surveillance core, SJCRH patients, and published collections (McCavit et al, 2011); and C) 98 NP SCD isolates from a longitudinal study spanning 2004-2011 in 195 SCD children followed for up to 4 years with serial NP swabs (Table 1). Children with SCD received PPV23 vaccine after 2 years of age, penicillin prophylaxis from birth to at least 5 years of age (Gaston et al, 1986) and frequent empiric antibiotic therapy.…”

Section: Resultsmentioning

confidence: 99%

“…Over 20 years, there has been no change in overall pneumococcal colonization rate in SCD children, and rates of IPD and pneumonia/acute chest syndrome remain markedly higher in SCD than in the general population (Halasa et al, 2007; Payne et al, 2013). Penicillin non-susceptible pneumococcal colonization is much more common in SCD children than in the GP (Daw et al, 1997), but rates have not changed over time despite PCV7 vaccination. Detection of non-typeable pneumococcal isolates in this study, especially those with high-level macrolide resistance, is particularly concerning as non-encapsulated pneumococci offer opportunities for accelerated gene transfer between organisms due to their increased transformability.…”

Section: Discussionmentioning

confidence: 99%

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Genomic Analyses of Pneumococci from Children with Sickle Cell Disease Expose Host-Specific Bacterial Adaptations and Deficits in Current Interventions

Carter

Wolf

Opijnen

et al. 2014

Cell Host & Microbe

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Summary Sickle cell disease (SCD) patients are at high risk of contracting pneumococcal infection. To address this risk, they receive pneumococcal vaccines, and antibiotic prophylaxis and treatment. To assess the impact of SCD and these interventions on pneumococcal genetic architecture, we examined the genomes of over 300 pneumococcal isolates from SCD patients over 20 years. Modern SCD strains retained invasive capacity but shifted away from the serotypes used in vaccines. These strains had specific genetic changes related to antibiotic resistance, capsule biosynthesis, metabolism and metal transport. A murine SCD model coupled with Tn-seq mutagenesis identified 60 non-capsular pneumococcal genes under differential selective pressure in SCD, which correlated with aspects of SCD pathophysiology. Further, virulence determinants in the SCD context were distinct from the general population and protective capacity of potential antigens was lost over time in SCD. This highlights the importance of understanding bacterial pathogenesis in the context of high-risk individuals.

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“…Testing for susceptibility to Q-D, clindamycin, and erythromycin was performed in triplicate by Etest, according to the manufacturer's instructions, with 68 SCD-associated nasopharyngeal isolates (12) and 80 SCD-associated invasive isolates (1) collected between 1994 and 2002 and, for comparison, with 105 isolates from healthy peers of the infected patients (25,27). Twenty-five (37%) nasopharyngeal SCD-associated isolates and eight (10%) invasive SCD-associated isolates were found to be Q-D nonsusceptible (Etest MIC range, 1.5 to 2 g/ml); no high-level resistance was detected.…”

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confidence: 99%

Quinupristin-Dalfopristin Nonsusceptibility in Pneumococci from Sickle Cell Disease Patients

Obert

Miller

Montgomery

et al. 2007

Antimicrob Agents Chemother

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Sickle cell disease (SCD) is a risk factor for fatal pneumococcal infection. Nonsusceptibilty to quinupristindalfopristin (Q-D) was absent from 105 non-SCD-associated pneumococcal isolates but was present in 33/148 (22%) SCD-associated isolates. One-third of the isolates harbored a known resistance mechanism. Q-D is not optimal for use for the treatment of pneumococcal infection in SCD patients.Sickle cell disease (SCD) is characterized by a 600-fold increased risk of invasive pneumococcal infection (26). Consequently, these patients receive penicillin prophylaxis and empirical antibacterial therapy, measures which in turn promote drug resistance (24). Thus, alternative antimicrobials are an ongoing need in the SCD population. Quinupristin-dalfopristin (Q-D; Synercid) is a semisynthetic, intravenous streptogramin approved for use in 1999, and the components of this compound display synergistic, bactericidal activities (8, 13). Resistance is rare but has emerged in staphylococci and vancomycin-resistant Enterococcus faecium (21). Resistance in pneumococci is uncommon (Յ1.1%) (15,20), but mutations in ribosomal proteins and 23S rRNA have been reported (13,15,20). Equally rare, Q-D nonsusceptibility was previously reported in 97 of 4,626 (2.1%) pneumococcal isolates obtained from the general population by Jones et al. by using Etest for determination of susceptibility (19), although the mechanism of resistance in these strains was not discussed. Here, we report on the Q-D nonsusceptibilities of nasopharyngeal and invasive pneumococci in over 30% of SCD patients.Testing for susceptibility to Q-D, clindamycin, and erythromycin was performed in triplicate by Etest, according to the manufacturer's instructions, with 68 SCD-associated nasopharyngeal isolates (12) and 80 SCD-associated invasive isolates (1) collected between 1994 and 2002 and, for comparison, with 105 isolates from healthy peers of the infected patients (25,27). Twenty-five (37%) nasopharyngeal SCD-associated isolates and eight (10%) invasive SCD-associated isolates were found to be Q-D nonsusceptible (Etest MIC range, 1.5 to 2 g/ml); no high-level resistance was detected. Broth dilution MICs (10) confirmed the nonsusceptibilities of all 33 isolates * Corresponding author. Mailing address:

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Nasopharyngeal Carriage of Penicillin-resistantStreptococcus pneumoniaein Children With Sickle Cell Disease

Cited by 30 publications

References 33 publications

Nasopharyngeal carriage rate of Streptococcus pneumoniae in Ugandan children with sickle cell disease

Nasopharyngeal carriage rate of Streptococcus pneumoniae in Ugandan children with sickle cell disease

Genomic Analyses of Pneumococci from Children with Sickle Cell Disease Expose Host-Specific Bacterial Adaptations and Deficits in Current Interventions

Quinupristin-Dalfopristin Nonsusceptibility in Pneumococci from Sickle Cell Disease Patients

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