Effect of antibiotic streamlining on patient outcome in pneumococcal bacteraemia

Cremers, Amelieke J. H.; Sprong, Tom; Schouten, Jeroen; Walraven, Grietje; Hermans, Peter W. M.; Meis, Jacques F.; Ferwerda, Gerben

doi:10.1093/jac/dku109

Cited by 24 publications

(16 citation statements)

References 20 publications

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“…In a meta-analysis in adults, the ICT had a high specificity, 94%, but its sensitivity was only 74% (24). Pneumococcal diagnosis is clinically important, as it allows antibiotic de-escalation (25,26). In addition, serotype-specific surveillance after PCV introduction is needed to assess success of vaccine programs and detection of serotype replacement.…”

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confidence: 99%

Multiplex Urinary Antigen Detection for 13 Streptococcus pneumoniae Serotypes Improves Diagnosis of Pneumococcal Pneumonia in South African HIV-Infected Adults

et al. 2017

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A serotype-specific urinary antigen detection (UAD) assay for 13 serotypes included in the pneumococcal conjugate vaccine (PCV13) was recently reported as a useful diagnostic tool for pneumococcal pneumonia. We aimed to assess the diagnostic accuracy of the UAD in HIV-infected South African adults. Urine specimens from a well-defined cohort of HIV-infected South African adults with pneumonia were evaluated retrospectively in the UAD assay. Pneumonia was considered pneumococcal if either sputum Gram stain, sputum culture, blood culture, or the immunochromatographic (ICT) BinaxNow S. pneumoniae test (composite diagnostic) was positive. Among 235 enrolled pneumonia patients, the UAD assay was more frequently positive (104 [44.3%]) than the composite diagnostic (71 [30.2%]; P Ͻ 0.001) and increased the pneumococcal etiology from 30.2% by an additional 22.6% to 52.8%. The UAD assay detected more pneumococcal etiologies (45.0%) than the serotype-independent ICT (23.4%, P Ͻ 0.001). UAD identified 6/7 patients with PCV13 serotype bacteremia without misclassification of bacteremia episodes due to non-PCV13 serotypes. UAD was positive for 5.1% of asymptomatic HIV-infected persons, with higher rates among those with nasopharyngeal carriage. Concordance between serotypes identified by UAD and by Quellung reaction and PCR serotyping was 70/86 (81.4%). UAD identified the dominant serotype in multiple serotype carriage. This study confirms the utility of the UAD assay for HIV-infected adults comparing favorably with other diagnostic tests. A highly valent UAD may become a new standard for detection of pneumococcal pneumonia in adults. Prior to PCV introduction, at least 53% of pneumonia cases were due to pneumococci in HIVinfected South African adults.

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confidence: 99%

Multiplex Urinary Antigen Detection for 13 Streptococcus pneumoniae Serotypes Improves Diagnosis of Pneumococcal Pneumonia in South African HIV-Infected Adults

et al. 2017

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“…In one other case, myocardial infarction was the most probable cause of death. In 16% of the cases, the cause of death was described as being due to respiratory failure or septic shock as a consequence of the primary diagnosis, and in the remaining cases, no cause of death was reported (32). …”

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confidence: 99%

Phage-Derived Protein Induces Increased Platelet Activation and Is Associated with Mortality in Patients with Invasive Pneumococcal Disease

Tunjungputri

Mobegi

Cremers

et al. 2017

mBio

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To improve our understanding about the severity of invasive pneumococcal disease (IPD), we investigated the association between the genotype of Streptococcus pneumoniae and disease outcomes for 349 bacteremic patients. A pneumococcal genome-wide association study (GWAS) demonstrated a strong correlation between 30-day mortality and the presence of the phage-derived gene pblB, encoding a platelet-binding protein whose effects on platelet activation were previously unknown. Platelets are increasingly recognized as key players of the innate immune system, and in sepsis, excessive platelet activation contributes to microvascular obstruction, tissue hypoperfusion, and finally multiorgan failure, leading to mortality. Our in vitro studies revealed that pblB expression was induced by fluoroquinolones but not by the beta-lactam antibiotic penicillin G. Subsequently, we determined pblB induction and platelet activation by incubating whole blood with the wild type or a pblB knockout mutant in the presence or absence of antibiotics commonly administered to our patient cohort. pblB-dependent enhancement of platelet activation, as measured by increased expression of the α-granule protein P-selectin, the binding of fibrinogen to the activated αIIbβ3 receptor, and the formation of platelet-monocyte complex occurred irrespective of antibiotic exposure. In conclusion, the presence of pblB on the pneumococcal chromosome potentially leads to increased mortality in patients with an invasive S. pneumoniae infection, which may be explained by enhanced platelet activation. This study highlights the clinical utility of a bacterial GWAS, followed by functional characterization, to identify bacterial factors involved in disease severity.

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“…For example, in patients being initially treated with a macrolide as part of combination therapy, the macrolide can be discontinued if there is a clinical response and the absence of atypical pathogens is demonstrated. If pneumococci are clearly revealed by blood culture and/or a urinary antigen test, and clinical improvement takes place under empirical treatment, it is recommended that the antibiotic treatment should be narrowed to penicillin (31). Once the criteria for clinical stability have been met, the treatment can be switched to the oral administration of a preparation with good oral bioavailability (e.g., amoxicillin/clavulanic acid) and it should be determined whether the patient is now fit for discharge from the hospital.…”

Section: Narrowing or De-escalation Of Antibiotic Treatmentmentioning

confidence: 99%

Community-Acquired Pneumonia in Adults

Kolditz¹,

Ewig²

2017

Deutsches Ärzteblatt International

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Effect of antibiotic streamlining on patient outcome in pneumococcal bacteraemia

Abstract: Our results suggest that streamlining in eligible pneumococcal bacteraemia cases is safe, irrespective of patient characteristics, severity of disease or empirical treatment regimen.

Cited by 24 publications

References 20 publications

Multiplex Urinary Antigen Detection for 13 Streptococcus pneumoniae Serotypes Improves Diagnosis of Pneumococcal Pneumonia in South African HIV-Infected Adults

Multiplex Urinary Antigen Detection for 13 Streptococcus pneumoniae Serotypes Improves Diagnosis of Pneumococcal Pneumonia in South African HIV-Infected Adults

Phage-Derived Protein Induces Increased Platelet Activation and Is Associated with Mortality in Patients with Invasive Pneumococcal Disease

Community-Acquired Pneumonia in Adults

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