International prevalence and risk factors evaluation for drug-resistant Streptococcus pneumoniae pneumonia

doi:10.1016/j.jinf.2019.07.004

Journal of Infection

Volume 79, Issue 4, October 2019, Pages 300-311

https://doi.org/10.1016/j.jinf.2019.07.004 Get rights and content

Highlights

•
Streptococcus pneumoniae was the most frequently identified pathogen in a cohort of patients with community acquired pneumonia (CAP) (268/3193 [8.3%]).
•
The global prevalence of drug resistant S. pneumoniae CAP (DRSP-CAP) was 1.3%.
•
Macrolide resistance was the most frequently identified in subjects with DRSP-CAP (0.6%) followed by penicillin resistance (0.5%).
•
The risk factors associated with specific antibiotic resistance were: asthma (for penicillin and macrolide), liver disease (for tetracycline resistance) and non-cystic fibrosis bronchiectasis (for penicillin resistance).

Summary

Objective

Streptococcus pneumoniae is the most frequent bacterial pathogen isolated in subjects with Community-acquired pneumonia (CAP) worldwide. Limited data are available regarding the current global burden and risk factors associated with drug-resistant Streptococcus pneumoniae (DRSP) in CAP subjects. We assessed the multinational prevalence and risk factors for DRSP-CAP in a multinational point-prevalence study.

Design

The prevalence of DRSP-CAP was assessed by identification of DRSP in blood or respiratory samples among adults hospitalized with CAP in 54 countries. Prevalence and risk factors were compared among subjects that had microbiological testing and antibiotic susceptibility data. Multivariate logistic regressions were used to identify risk factors independently associated with DRSP-CAP.

Results

3,193 subjects were included in the study. The global prevalence of DRSP-CAP was 1.3% and continental prevalence rates were 7.0% in Africa, 1.2% in Asia, and 1.0% in South America, Europe, and North America, respectively. Macrolide resistance was most frequently identified in subjects with DRSP-CAP (0.6%) followed by penicillin resistance (0.5%). Subjects in Africa were more likely to have DRSP-CAP (OR: 7.6; 95%CI: 3.34-15.35, p<0.001) when compared to centres representing other continents.

Conclusions

This multinational point-prevalence study found a low global prevalence of DRSP-CAP that may impact guideline development and antimicrobial policies.

Introduction

Community acquired pneumonia (CAP) is responsible for more than 3 million annual fatalities worldwide.1, 2 The economic burden of CAP is at a steady cost in excess of 17 billion dollars annually for the United States alone.1, 3 Antibiotic resistance associated with CAP is a growing problem for the medical community, and it is estimated that more than 20,000 people die annually in the United States secondary to infections due to resistant bacteria.4, 5 Streptococcus pneumoniae, the most frequently isolated bacterium during CAP, has increasing resistance to the most commonly prescribed antibiotics, including penicillin, macrolides, and fluoroquinolones, and is referred to as drug-resistant Streptococcus pneumoniae (DRSP).6, 7, 8, 9 Antibiotic resistance is an emergent threat in healthcare systems worldwide and can limit antibiotic efficacy against common pathogens responsible for CAP.10, 11

Geographic variations in the prevalence of DRSP have been recognized in different cohorts in antibiotic surveillance studies.12, 13, 14 A higher prevalence of antibiotic resistant strains of S. pneumoniae has been demonstrated in some European countries, such as Spain.¹⁵ Surveillance studies have reported DRSP in up to 35% of S. pneumoniae isolated from different sources (i.e., sputum, blood, cerebrospinal fluid, ear secretions, etc.).16, 17 Risk factors for DRSP infection include older age, recent antibiotic usage, chronic obstructive pulmonary disease (COPD), and nursing home residency; but limited data are available regarding clinically relevant risk factors from larger cohort studies.6, 9, 10, 18 Additionally, the actual prevalence of DRSP-CAP worldwide is unknown, and there is a need to evaluate the global prevalence of DRSP. In this regard, point-prevalence studies are useful to determine the global burden of infectious diseases in a specific time point.¹⁹

Our aim was to determine the prevalence of DRSP-CAP and identify specific DRSP risk factors at global, continental, and multinational levels.

Section snippets

Study design

We enrolled adult subjects hospitalized with confirmed CAP in 222 hospitals around the world using a point-prevalence study.²⁰ Subjects were recruited on four days randomly selected by each local investigator during the months between March and June 2015. The University of Texas Health at San Antonio (UT Health San Antonio) functioned as the coordinating centre (IRB# HSC20150184E) and waived the need for informed consent due to the nature of the study. All other associated centres were required

Results

A total of 3193 subjects were enrolled from 54 countries. All subjects had pneumonia confirmed by laboratory findings, radiographic imaging, and microbiological testing that were performed within the first 24 h of hospitalization (Fig. 1). Microbiological testing was obtained from blood (2211/3193 [69%]), sputum (1630/3193 [51%]), pneumococcal urinary antigen (1106/3193 [35%]) and bronchoalveolar lavage (311/3193 [10%]). An etiological pathogen was identified in 1173/3193 (37%) of subjects (

Discussion

This multicentre, international, point-prevalence study showed that S. pneumoniae is the most common pathogen isolated in subjects with CAP. The global prevalence rates of DRSP, MDR, and XDR S. pneumoniae infections in subjects with CAP are 1.3%, 0.2%, and 0.03%, respectively. We identified that DRSP-CAP, penicillin-resistant, macrolide-resistant, and tetracycline-resistant prevalence rates are variable among participating centres, revealing important differences between continents and

Conclusion

The multinational prevalence rate of drug-resistant Streptococcus pneumoniae as the causative agent of CAP in this point-prevalence study is lower than previously reported. Differences in DRSP-CAP prevalence rates exist among continents and countries. Therefore, local treatment guidelines and hospital protocols should be based on local prevalence rates. Lastly, global risk factors independently associated with DRSP-CAP may assist medical professionals to appropriately select antibiotic coverage

CRediT authorship contribution statement

Stefano Aliberti: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Visualization, Writing - original draft, Writing - review & editing. Grayden S. Cook: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Writing - original draft, Writing - review & editing. Bettina L. Babu: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation,

Funding

This project was unfunded. However, Nilam Soni's time is partially funded by the Department of Veterans Affairs, Quality Enhancement Research Initiative (QUERI) Partnered Evaluation Initiative Grant (HX002263-01A1). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs, nor the United States Government.

Declarations of interest

None.

Acknowledgments

We would like to thank the European Respiratory Society, the World Federation of Societies of Intensive and Critical Care Medicine, the American College of Chest Physicians, the Asociación Latinoamericana de Tórax (ALAT), and the Sociedad Argentina de Infectología (SAI) for their support of this project.

Appendix A: GLIMP investigators

We would like to thank the following study contributors for their valuable collaboration:

Argentina: Patricia Karina Aruj, Department of Internal Medicine, University Hospital Alfredo Lanari, Buenos Aires, Argentina; Silvia Attorri, Hospital Luis Lago maggiore, Mendoza, Argentina; Enrique Barimboim, Hospital Central de Mendoza, Argentina; Juan Pablo Caeiro and María I. Garzón, Hospital Privado Universitario, Córdoba, Argentina; Victor Hugo Cambursano, V.H. Dr Cazaux A. Servicio de Neumologia,

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¹: See Appendix A for GLIMP investigators.

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Published by Elsevier Ltd on behalf of The British Infection Association.

International prevalence and risk factors evaluation for drug-resistant Streptococcus pneumoniae pneumonia

Highlights

Summary

Objective

Design

Results

Conclusions

Introduction

Section snippets

Study design

Results

Discussion

Conclusion

CRediT authorship contribution statement

Funding

Declarations of interest

Acknowledgments

Appendix A: GLIMP investigators

Lancet

Vaccine

Chest

Lancet Infect Dis

J Microbiol Immunol Infect

J Biomed Inform

Mayo Clin Proc

Lancet

J Infect

Infect Dis Clin North Am

Clin Microbiol Infect

J Infect Public Health

Community-acquired pneumonia requiring hospitalization among U.S. adults

N Engl J Med

Clinical practice. Community-acquired pneumonia

N Engl J Med

A new antibiotic and the evolution of resistance

N Engl J Med

How to choose the duration of antibiotic therapy in patients with pneumonia

Curr Opin Infect Dis

Bacteraemia and antibiotic-resistant pathogens in community acquired pneumonia: risk and prognosis

Eur Respir J