Aetiology and outcomes of sepsis in adults in sub-Saharan Africa: a systematic review and meta-analysis

Lewis, Jessica; Feasey, Nicholas; Rylance, Jamie

doi:10.1186/s13054-019-2501-y

Cited by 62 publications

(69 citation statements)

References 40 publications

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“…Severe HIV‐TB may present with clinical features of bacterial sepsis . In high‐burden settings Mycobacterium tuberculosis bloodstream infection is the most common diagnosis in HIV‐infected patients presenting to hospital with a clinical syndrome of sepsis . Analogous to sepsis, there are many factors in severe HIV‐TB that could reduce drug exposure, such as impaired absorption of orally administered drugs due to delayed gastric emptying and decreased perfusion of the gastrointestinal tract, increased volume of distribution due to fluid shifts, and augmented renal clearance .…”

Section: Introductionmentioning

confidence: 99%

Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus‐associated tuberculosis

Schutz

Chirehwa

Barr

et al. 2020

Brit J Clinical Pharma

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Aims:Patients hospitalized at the time of human immunodeficiency virus-associated tuberculosis (HIV-TB) diagnosis have high early mortality. We hypothesized that compared to outpatients, there would be lower anti-TB drug exposure in hospitalized HIV-TB patients, and amongst hospitalized patients exposure would be lower in patients who die or have high lactate (a sepsis marker). Methods:We performed pharmacokinetic sampling in hospitalized HIV-TB patients and outpatients. Plasma rifampicin, isoniazid and pyrazinamide concentrations were measured in samples collected predose and at 1, 2.5, 4, 6 and 8 hours on the third day of standard anti-TB therapy. Twelve-week mortality was ascertained for inpatients. Noncompartmental pharmacokinetic analysis was performed.Results: Pharmacokinetic data were collected in 59 hospitalized HIV-TB patients and 48 outpatients. Inpatient 12-week mortality was 11/59 (19%). Rifampicin, isoniazid and pyrazinamide exposure was similar between hospitalized and outpatients (maximum concentration [C max ]: 7.4 vs 8.3 μg mL -1 , P = .223; 3.6 vs 3.5 μg mL -1 , P = .569; 50.1 vs 46.8 μg mL -1 , P = .081; area under the concentration-time curve from 0 to 8 hours: 41.0 vs 43.8 mg h L -1 , P = 0.290; 13.5 vs 12.4 mg h L -1 , P = .630; 316.5 vs 292.2 mg h L -1 , P = .164, respectively) and not lower in inpatients who died. Rifampicin and isoniazid C max were below recommended ranges in 61% and 39% of inpatients and 44% and 35% of outpatients. Rifampicin exposure was higher in patients with lactate >2.2 mmol L -1 . Conclusion:Mortality in hospitalized HIV-TB patients was high. Early anti-TB drug exposure was similar to outpatients and not lower in inpatients who died. Rifampicin and isoniazid C max were suboptimal in 61% and 39% of inpatients and rifampicin exposure was higher in patients with high lactate. Treatment strategies need to be optimized to improve survival.The authors confirm that the PI for this paper is Graeme Meintjes and that he had direct clinical responsibility for patients. 966Br J Clin Pharmacol. 2020;86:966-978. wileyonlinelibrary.com/journal/bcp SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section at the end of this article. How to cite this article: Schutz C, Chirehwa M, Barr D, et al. Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus-associated tuberculosis. Br J Clin Pharmacol. 2020;86:966-978. https://doi.

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Section: Introductionmentioning

confidence: 99%

Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus‐associated tuberculosis

Schutz

Chirehwa

Barr

et al. 2020

Brit J Clinical Pharma

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“…The 116 articles had a median Web of Science citations was 5 (IQR: 3-12) on and 5 (IQR: 3-13) median citations when considering additional citation sources (BIOSIS, Chinese Science Citation, Data Citation, Russian Science, and SCIELO). The median usage count (since 2013) was 2 (IQR: 1-4), and the articles had a median of 23 (IQR: [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] references.…”

Section: Resultsmentioning

confidence: 99%

Systematic review and bibliometric analysis of African anesthesia and critical care medicine research Part II: A scientometric analysis of the 116 most cited articles

Kanmounye

Tochie

Mbonda

et al. 2020

Preprint

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BackgroundScientometrics is used to assess the impact of research in several health fields, including Anesthesia and Critical Care Medicine. The purpose of this study was to define the landscape and key players of Anesthesia and Critical Care Medicine research in Africa.MethodsThe authors searched Web of Science from inception to May 4, 2020, for articles on and about Anesthesia and Critical Care Medicine in Africa with ≥ 2 citations. Quantitative (H-index) and qualitative (descriptive analysis of yearly publications and interpretation of document, co-authorship, author country, and keyword) bibliometric analyses were done.ResultsThe search strategy returned 116 articles that had a median of 5 (IQR: 3-12) citations on Web of Science. The most frequent journals were Anesthesia and Analgesia (18, 15.5%), World Journal of Surgery (13, 11.2%), and South African Medical Journal (8, 6.9%). Most (74, 63.8%) articles were published on or after 2013, and seven authors had more than 1 article in the top 116 articles: Epiu I (3, 2.6%), Elobu AE (2, 1.7%), Fenton PM (2, 1.7%), Kibwana S (2, 1.7%), Rukewe A (2, 1.7%), Sama HD (2, 1.7%), and Zoumenou E (2, 1.7%). The bibliometric coupling analysis of documents highlighted 10 clusters with the most significant nodes being Biccard BM, 2018; Baker T, 2013; Llewellyn RL, 2009; Nigussie S, 2014; and Aziato L, 2015. Dubowitz G (5) and Ozgediz D (4) had the highest H-indices among the authors referenced by the most-cited African Anesthesia and Critical Care Medicine articles. The U.S.A. had the largest global node, while South Africa and Uganda had the largest African nodes. The most prominent keywords were anesthesia, mortality, and surgery. ConclusionThis study highlighted a decline in the number of top-cited African articles and the roles of the U.S.A, Southern African, and East African countries in scholarly output. Future studies should focus on understanding the time trends of the publications.

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“…It is possible, although untested, that in LIC other patient characteristics might provide ways of refining treatment pathways where facilities are limited. Evidence from treatment of mycobacteraemic sepsis, which is common in sub-Saharan Africa [4] suggests a relative intolerance to fluids. Similarly, HIV is associated with high rates of diastolic heart failure (43% of those on established antiretroviral therapy [27]) and in areas in of high seroprevalence this may become relevant in the majority of admitted patients.…”

Section: Discussionmentioning

confidence: 99%

Recommendations for fluid management of adults with sepsis in sub-Saharan Africa: A systematic review of guidelines

Silberberg

Aston

Boztepe

et al. 2020

Preprint

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Background Sepsis guidelines are widely used in High Income Countries and intravenous fluids are an important supportive treatment modality. However, fluids have been harmful in intervention trials in Low-Income Countries, most notably in sub-Saharan Africa. We assessed the relevance, quality and applicability of available guidelines for the fluid management of adult patients with sepsis in this region. Methods We identified sepsis guidelines by systematic review with broad search terms, duplicate screening and data extraction. We included peer-reviewed publications with explicit relevance to sepsis and fluid therapy. We excluded those designed for specific medical conditions, for limited geographic locations, or for non-adult populations. We used the AGREE II tool to assess the quality of guideline development, performed a narrative synthesis and using theoretical case scenarios to assess practical applicability to everyday clinical practice in resource-constrained settings. Results Published sepsis guidelines are heterogeneous in sepsis definition and in quality: 8/10 guidelines had significant deficits in applicability, particularly with reference to resource considerations in low-income settings. Indications for intravenous fluid were: hypotension (8/10); clinical markers of hypoperfusion (6/10); lactataemia (3/10). Crystalloids were overwhelmingly recommended (9/10). Suggested volumes varied; 5/10 explicitly recommended “fluid challenges” with reassessment, totalling between 1L and 4L during initial resuscitation. Fluid balance, including later de-escalation of therapy was not specifically described in any. Norepinephrine was the preferred initial vasopressor (5/10), specifically targeted to MAP >65mmHg (3/10), with higher values suggested in pre-existing hypertension (1/10). Recommendations for guidelines were almost universally derived from evidence in High Income Countries. None of the guidelines suggested any refinement for patients with malnutrition. Conclusions Widely used international guidelines contain disparate recommendations on intravenous fluid use, lack specificity and are largely unattainable in Low-Income Countries given available resources. A relative lack of high-quality evidence from sub-Saharan Africa increases reliance on recommendations which may not be relevant or implementable.

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Aetiology and outcomes of sepsis in adults in sub-Saharan Africa: a systematic review and meta-analysis

Cited by 62 publications

References 40 publications

Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus‐associated tuberculosis

Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus‐associated tuberculosis

Systematic review and bibliometric analysis of African anesthesia and critical care medicine research Part II: A scientometric analysis of the 116 most cited articles

Recommendations for fluid management of adults with sepsis in sub-Saharan Africa: A systematic review of guidelines

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