Challenges of Antibiotic Formulations and Administration in the Treatment of Bloodstream Infections in Children Under Five Admitted to Kisantu Hospital, Democratic Republic of Congo

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

ABSTRACT.

Severe bacterial infections in children need prompt, appropriate antibiotic treatment. We report challenges observed within a prospective, cohort study on antibiotic efficacy in non-typhi Salmonella bloodstream infection (NCT04850677) in Kisantu district hospital (Democratic Republic of Congo). Children (aged > 28 days to < 5 years) admitted with suspected bloodstream infection (August 1, 2021 through July 31, 2022) were enrolled and followed until day 3 or discharge for non-typhi Salmonella patients. Antibiotics were administered to 98.4% (1,838/1,867) of children, accounting for 2,296 antibiotic regimens (95.7% intravenous, 4.3% oral). Only 78.3% and 61.8% of children were, respectively, prescribed and administered antibiotics on the admission day. At least one dose was not administered in 3.6% of children, mostly because of mismatch of the four times daily cefotaxime schedule with the twice-daily administration rounds. Inappropriate intravenous administration practices included multidose use, air-venting, and direct injection instead of perfusion. There was inaccurate aliquoting in 18.0% (32/178) of intravenous ciprofloxacin regimens, and thus administered doses were > 16% below the intended dose. Dosing accuracy of oral suspensions was impaired by lack of instructions for reconstitution, volume indicators, and/or dosing devices. Adult-dose tablets were split without/beyond scoring lines in 84.4% (27/32) of tablets. Poor availability and affordability of age-appropriate oral formulations contributed to low proportions of intravenous-to-oral switch (33.3% (79/237) of non-typhi Salmonella patients). Other quality issues included poor packaging, nonhomogeneous suspensions, and unsafe water for reconstitution. In conclusion, poor antibiotic products (no age-appropriate formulations, poor quality and access), processes (delayed prescription/administration, missed doses), and practices (inaccurate doses, [bio]safety risks) must be urgently addressed to improve pediatric antibiotic treatment.

Related collections

Most cited references 90

Record: found
Abstract: found
Article: found

Is Open Access

Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis

(2022)

Summary Background Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths, hospital length of stay, and health-care costs for specific pathogen–drug combinations in select locations. To our knowledge, this study presents the most comprehensive estimates of AMR burden to date. Methods We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 23 pathogens and 88 pathogen–drug combinations in 204 countries and territories in 2019. We obtained data from systematic literature reviews, hospital systems, surveillance systems, and other sources, covering 471 million individual records or isolates and 7585 study-location-years. We used predictive statistical modelling to produce estimates of AMR burden for all locations, including for locations with no data. Our approach can be divided into five broad components: number of deaths where infection played a role, proportion of infectious deaths attributable to a given infectious syndrome, proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antibiotic of interest, and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden based on two counterfactuals: deaths attributable to AMR (based on an alternative scenario in which all drug-resistant infections were replaced by drug-susceptible infections), and deaths associated with AMR (based on an alternative scenario in which all drug-resistant infections were replaced by no infection). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. We present final estimates aggregated to the global and regional level. Findings On the basis of our predictive statistical models, there were an estimated 4·95 million (3·62–6·57) deaths associated with bacterial AMR in 2019, including 1·27 million (95% UI 0·911–1·71) deaths attributable to bacterial AMR. At the regional level, we estimated the all-age death rate attributable to resistance to be highest in western sub-Saharan Africa, at 27·3 deaths per 100 000 (20·9–35·3), and lowest in Australasia, at 6·5 deaths (4·3–9·4) per 100 000. Lower respiratory infections accounted for more than 1·5 million deaths associated with resistance in 2019, making it the most burdensome infectious syndrome. The six leading pathogens for deaths associated with resistance (Escherichia coli, followed by Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) were responsible for 929 000 (660 000–1 270 000) deaths attributable to AMR and 3·57 million (2·62–4·78) deaths associated with AMR in 2019. One pathogen–drug combination, meticillin-resistant S aureus, caused more than 100 000 deaths attributable to AMR in 2019, while six more each caused 50 000–100 000 deaths: multidrug-resistant excluding extensively drug-resistant tuberculosis, third-generation cephalosporin-resistant E coli, carbapenem-resistant A baumannii, fluoroquinolone-resistant E coli, carbapenem-resistant K pneumoniae, and third-generation cephalosporin-resistant K pneumoniae. Interpretation To our knowledge, this study provides the first comprehensive assessment of the global burden of AMR, as well as an evaluation of the availability of data. AMR is a leading cause of death around the world, with the highest burdens in low-resource settings. Understanding the burden of AMR and the leading pathogen–drug combinations contributing to it is crucial to making informed and location-specific policy decisions, particularly about infection prevention and control programmes, access to essential antibiotics, and research and development of new vaccines and antibiotics. There are serious data gaps in many low-income settings, emphasising the need to expand microbiology laboratory capacity and data collection systems to improve our understanding of this important human health threat. Funding Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.

0 comments Cited 4178 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: found

Is Open Access

Global, regional, and national causes of under-5 mortality in 2000–15: an updated systematic analysis with implications for the Sustainable Development Goals

Li Liu, Shefali Oza, Dan Hogan … (2016)

Summary Background Despite remarkable progress in the improvement of child survival between 1990 and 2015, the Millennium Development Goal (MDG) 4 target of a two-thirds reduction of under-5 mortality rate (U5MR) was not achieved globally. In this paper, we updated our annual estimates of child mortality by cause to 2000–15 to reflect on progress toward the MDG 4 and consider implications for the Sustainable Development Goals (SDG) target for child survival. Methods We increased the estimation input data for causes of deaths by 43% among neonates and 23% among 1–59-month-olds, respectively. We used adequate vital registration (VR) data where available, and modelled cause-specific mortality fractions applying multinomial logistic regressions using adequate VR for low U5MR countries and verbal autopsy data for high U5MR countries. We updated the estimation to use Plasmodium falciparum parasite rate in place of malaria index in the modelling of malaria deaths; to use adjusted empirical estimates instead of modelled estimates for China; and to consider the effects of pneumococcal conjugate vaccine and rotavirus vaccine in the estimation. Findings In 2015, among the 5·9 million under-5 deaths, 2·7 million occurred in the neonatal period. The leading under-5 causes were preterm birth complications (1·055 million [95% uncertainty range (UR) 0·935–1·179]), pneumonia (0·921 million [0·812 −1·117]), and intrapartum-related events (0·691 million [0·598 −0·778]). In the two MDG regions with the most under-5 deaths, the leading cause was pneumonia in sub-Saharan Africa and preterm birth complications in southern Asia. Reductions in mortality rates for pneumonia, diarrhoea, neonatal intrapartum-related events, malaria, and measles were responsible for 61% of the total reduction of 35 per 1000 livebirths in U5MR in 2000–15. Stratified by U5MR, pneumonia was the leading cause in countries with very high U5MR. Preterm birth complications and pneumonia were both important in high, medium high, and medium child mortality countries; whereas congenital abnormalities was the most important cause in countries with low and very low U5MR. Interpretation In the SDG era, countries are advised to prioritise child survival policy and programmes based on their child cause-of-death composition. Continued and enhanced efforts to scale up proven life-saving interventions are needed to achieve the SDG child survival target. Funding Bill & Melinda Gates Foundation, WHO.

0 comments Cited 1073 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: not found

Access to effective antimicrobials: a worldwide challenge.

Ramanan Laxminarayan, Precious Matsoso, Suraj Pant … (2016)

Recent years have seen substantial improvements in life expectancy and access to antimicrobials, especially in low-income and lower-middle-income countries, but increasing pathogen resistance to antimicrobials threatens to roll back this progress. Resistant organisms in health-care and community settings pose a threat to survival rates from serious infections, including neonatal sepsis and health-care-associated infections, and limit the potential health benefits from surgeries, transplants, and cancer treatment. The challenge of simultaneously expanding appropriate access to antimicrobials, while restricting inappropriate access, particularly to expensive, newer generation antimicrobials, is unique in global health and requires new approaches to financing and delivering health care and a one-health perspective on the connections between pathogen transmission in animals and humans. Here, we describe the importance of effective antimicrobials. We assess the disease burden caused by limited access to antimicrobials, attributable to resistance to antimicrobials, and the potential effect of vaccines in restricting the need for antibiotics.

0 comments Cited 343 times – based on 0 reviews      Review now

All references

Author and article information

Journal

Journal ID (nlm-ta): Am J Trop Med Hyg

Journal ID (iso-abbrev): Am J Trop Med Hyg

Journal ID (publisher-id): tpmd

Journal ID (hwp): tropmed

Title: The American Journal of Tropical Medicine and Hygiene

Publisher: The American Society of Tropical Medicine and Hygiene

ISSN (Print): 0002-9637

ISSN (Electronic): 1476-1645

Publication date (Electronic): 30 October 2023

Publication date (Print): December 2023

Publication date PMC-release: 30 October 2023

Volume: 109

Issue: 6

Pages: 1245-1259

Affiliations

[ ¹ ]Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium;

[ ² ]Department of Microbiology, Immunology and Transplantation, KU Leuven, Belgium;

[ ³ ]Department of Pediatrics, KU Leuven University Hospitals Leuven, Belgium;

[ ⁴ ]Saint Luc Hôpital Général de Référence Kisantu, Democratic Republic of Congo;

[ ⁵ ]Médecins Sans Vacances, Mechelen, Belgium;

[ ⁶ ]Department of Development and Regeneration, KU Leuven, Leuven, Belgium;

[ ⁷ ]Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Belgium;

[ ⁸ ]Department of Hospital Pharmacy, Erasmus University Medical Center Rotterdam, the Netherlands;

[ ⁹ ]Department of Microbiology, Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of Congo;

[ ¹⁰ ]Department of Medical Biology, University Teaching Hospital of Kinshasa, Democratic Republic of Congo;

[ ¹¹ ]Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium;

[ ¹² ]School of Public Health, University of the Western Cape, Cape Town, South Africa

Author notes

Disclosures: R. R. is the chair of the institutional review board of the Institute of Tropical Medicine in Antwerp. Her involvement is the study started well after the ethical approval of the TreNTS study protocol.

The datasets generated and/or analyzed during the current study are not publicly available because of the sensitive nature of the study data. Requests to access the data can be made to ITM’s contact point for data access ITMresearchdataaccess@ 123456itg.be . All requests will be reviewed for approval by ITMs Data Access Committee. After approval, data sharing will be managed by the same committee.

Authors’ addresses: Bieke Tack, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium, Department of Microbiology, Immunology and Transplantation, KU Leuven, Belgium, and Department of Pediatrics, KU Leuven University Hospitals Leuven, Belgium, E-mail: btack@ 123456itg.be . Daniel Vita, Emmanuel Ntangu, Japhet Ngina, Pathy Mukoko, and Adèle Lutumba, Saint Luc Hôpital Général de Référence Kisantu, Democratic Republic of Congo, E-mails: dvitamayimona@ 123456gmail.com , emmanuelntangu57@ 123456gmail.com , japhet108@ 123456gmail.com , pathy.mukoko2019@ 123456gmail.com , and adelzomba@ 123456gmail.com . Dina Vangeluwe, Médecins Sans Vacances, Mechelen, Belgium, E-mail: dvangeluwe@ 123456telenet.be . Jaan Toelen, Department of Pediatrics, KU Leuven University Hospitals Leuven, Belgium, and Department of Development and Regeneration, KU Leuven, Belgium, E-mail: jaan.toelen@ 123456kuleuven.be . Karel Allegaert, Department of Development and Regeneration, KU Leuven, Belgium, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Belgium, and Department of Hospital Pharmacy, Erasmus University Medical Center Rotterdam, the Netherlands, E-mail: karel.allegaert@ 123456kuleuven.be . Octavie Lunguya, Department of Microbiology, Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of Congo, and Department of Medical Biology, University Teaching Hospital of Kinshasa, Democratic Republic of Congo, E-mail: octmetila@ 123456yahoo.fr . Raffaella Ravinetto, Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium, and School of Public Health, University of the Western Cape, Cape Town, South Africa, E-mail: rravinetto@ 123456itg.be . Jan Jacobs, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium, and Department of Microbiology, Immunology and Transplantation, KU Leuven, Belgium, E-mail: jjacobs@ 123456itg.be .

[* ]Address correspondence to Bieke Tack, Nationalestraat 155, 2000 Antwerp, Belgium. E-mail: btack@ 123456itg.be

Article

Publisher ID: tpmd230322

DOI: 10.4269/ajtmh.23-0322

PMC ID: 10793067

PubMed ID: 37903440

SO-VID: 1ad3120a-a4cf-436a-b713-760ae0c9f592

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 18 May 2023

Date accepted : 08 September 2023

Page count

Pages: 15

Comments

Comment on this article

Cited by 2

See all cited by

Most referenced authors 4,552

See all reference authors