Clinical and Molecular Epidemiology of Klebsiella pneumoniae Invasive Disease in Adults: preliminary results from a South African case-control study
Introduction: Klebsiella pneumoniae (Kp) causes two parallel clinical phenomena that confer a significant public health threat: healthcare-associated infections (HAIs) from multidrug resistant (MDR) strains (that account for the greatest burden of Kp infections globally), and community-associated in...
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Elsevier
2025-03-01
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| Series: | International Journal of Infectious Diseases |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S120197122400599X |
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| author | Dr Denasha Reddy Prof Ziyaad Dangor Dr Courtney Olwagen Dr Vicky Baillie Prof Shabir Madhi |
| author_facet | Dr Denasha Reddy Prof Ziyaad Dangor Dr Courtney Olwagen Dr Vicky Baillie Prof Shabir Madhi |
| author_sort | Dr Denasha Reddy |
| collection | DOAJ |
| description | Introduction: Klebsiella pneumoniae (Kp) causes two parallel clinical phenomena that confer a significant public health threat: healthcare-associated infections (HAIs) from multidrug resistant (MDR) strains (that account for the greatest burden of Kp infections globally), and community-associated infections. Antimicrobial resistance (AMR) is a critical issue as it threatens our ability to treat common HAIs caused by MDR bacteria due to limited effective and accessible therapeutic options. There is a paucity of data on the burden of Kp invasive disease (KpID) in South Africa. We conducted a multicentre prospective observational study across three academic hospitals in Johannesburg, South Africa to investigate the clinical and molecular epidemiology of KpID in hospitalised adults. Methods: Between May 2023 and March 2024 we enrolled 441 adult cases with KpID and 543 controls. Two controls were enrolled, matched on age category and duration of admission, for each enrolled alive case. We collected data on comorbidities, infection source, treatment and clinical outcomes. The invasive Kp isolate for each case underwent whole genome sequencing and Kp was subcultured from controls’ rectal swabs to estimate the gastrointestinal colonisation rate. Results: Of the 441 cases enrolled in the 10 month period, 282 (64%) were alive at the time of enrolment, 132 (30%) were deceased and 27 (6%) were already discharged home. The majority of KpID isolates were from blood culture specimens, with 6 from cerebrospinal fluid. Most cases were male (56%) and in the age group 36-50 (32%). The majority of cases were admitted in intensive care units at enrolment (42%), followed by general medical (28%) and general surgical wards (20%). HAIs accounted for 83% of cases, with the most common sources of infection being intra-abdominal, respiratory and urinary tract infections. Almost a third of cases did not receive targeted antibiotic therapy. Of the 282 alive cases enrolled, 112 (40%) died in hospital. 279 controls’ rectal swabs had undergone culture with a 20% Kp colonisation rate. We performed whole genome sequencing on 69 Kp case isolates (randomly selected, including plates of unenrolled cases), which revealed genetically diverse isolates without clusters of epidemiologically and genetically linked cases. 20 different capsule-encoding loci (KL) were identified, the most common being KL64, KL17 and KL1 accounting for 32 (46%), 8 (12%) and 5 (7%) confirmed KpID cases, respectively. 7 lipopolysaccharide-encoding loci (O loci) were identified with a predominance of O1/O2V1 (67%) and O1/O2V2 (19%). Discussion: These observations demonstrate the magnitude of the morbidity and mortality associated with KpID. Conclusion: Rapid identification of patients with invasive antimicrobial-resistant KpID is imperative in order to treat patients appropriately and timeously. The rise of AMR together with a limited antibiotic pipeline has piqued interest in the use of vaccines to prevent KpID in at-risk adults. |
| format | Article |
| id | doaj-art-19e78e5aeeee4363a701460ffc2c4ebe |
| institution | DOAJ |
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| series | International Journal of Infectious Diseases |
| spelling | doaj-art-19e78e5aeeee4363a701460ffc2c4ebe2025-08-20T02:55:16ZengElsevierInternational Journal of Infectious Diseases1201-97122025-03-0115210752410.1016/j.ijid.2024.107524Clinical and Molecular Epidemiology of Klebsiella pneumoniae Invasive Disease in Adults: preliminary results from a South African case-control studyDr Denasha Reddy0Prof Ziyaad Dangor1Dr Courtney Olwagen2Dr Vicky Baillie3Prof Shabir Madhi4Vaccines and Infectious Diseases Analytics Research Unit (Wits-VIDA); University of the WitwatersrandVaccines and Infectious Diseases Analytics Research Unit (Wits-VIDA); University of the WitwatersrandVaccines and Infectious Diseases Analytics Research Unit (Wits-VIDA)Vaccines and Infectious Diseases Analytics Research Unit (Wits-VIDA)Vaccines and Infectious Diseases Analytics Research Unit (Wits-VIDA); University of the WitwatersrandIntroduction: Klebsiella pneumoniae (Kp) causes two parallel clinical phenomena that confer a significant public health threat: healthcare-associated infections (HAIs) from multidrug resistant (MDR) strains (that account for the greatest burden of Kp infections globally), and community-associated infections. Antimicrobial resistance (AMR) is a critical issue as it threatens our ability to treat common HAIs caused by MDR bacteria due to limited effective and accessible therapeutic options. There is a paucity of data on the burden of Kp invasive disease (KpID) in South Africa. We conducted a multicentre prospective observational study across three academic hospitals in Johannesburg, South Africa to investigate the clinical and molecular epidemiology of KpID in hospitalised adults. Methods: Between May 2023 and March 2024 we enrolled 441 adult cases with KpID and 543 controls. Two controls were enrolled, matched on age category and duration of admission, for each enrolled alive case. We collected data on comorbidities, infection source, treatment and clinical outcomes. The invasive Kp isolate for each case underwent whole genome sequencing and Kp was subcultured from controls’ rectal swabs to estimate the gastrointestinal colonisation rate. Results: Of the 441 cases enrolled in the 10 month period, 282 (64%) were alive at the time of enrolment, 132 (30%) were deceased and 27 (6%) were already discharged home. The majority of KpID isolates were from blood culture specimens, with 6 from cerebrospinal fluid. Most cases were male (56%) and in the age group 36-50 (32%). The majority of cases were admitted in intensive care units at enrolment (42%), followed by general medical (28%) and general surgical wards (20%). HAIs accounted for 83% of cases, with the most common sources of infection being intra-abdominal, respiratory and urinary tract infections. Almost a third of cases did not receive targeted antibiotic therapy. Of the 282 alive cases enrolled, 112 (40%) died in hospital. 279 controls’ rectal swabs had undergone culture with a 20% Kp colonisation rate. We performed whole genome sequencing on 69 Kp case isolates (randomly selected, including plates of unenrolled cases), which revealed genetically diverse isolates without clusters of epidemiologically and genetically linked cases. 20 different capsule-encoding loci (KL) were identified, the most common being KL64, KL17 and KL1 accounting for 32 (46%), 8 (12%) and 5 (7%) confirmed KpID cases, respectively. 7 lipopolysaccharide-encoding loci (O loci) were identified with a predominance of O1/O2V1 (67%) and O1/O2V2 (19%). Discussion: These observations demonstrate the magnitude of the morbidity and mortality associated with KpID. Conclusion: Rapid identification of patients with invasive antimicrobial-resistant KpID is imperative in order to treat patients appropriately and timeously. The rise of AMR together with a limited antibiotic pipeline has piqued interest in the use of vaccines to prevent KpID in at-risk adults.http://www.sciencedirect.com/science/article/pii/S120197122400599X |
| spellingShingle | Dr Denasha Reddy Prof Ziyaad Dangor Dr Courtney Olwagen Dr Vicky Baillie Prof Shabir Madhi Clinical and Molecular Epidemiology of Klebsiella pneumoniae Invasive Disease in Adults: preliminary results from a South African case-control study International Journal of Infectious Diseases |
| title | Clinical and Molecular Epidemiology of Klebsiella pneumoniae Invasive Disease in Adults: preliminary results from a South African case-control study |
| title_full | Clinical and Molecular Epidemiology of Klebsiella pneumoniae Invasive Disease in Adults: preliminary results from a South African case-control study |
| title_fullStr | Clinical and Molecular Epidemiology of Klebsiella pneumoniae Invasive Disease in Adults: preliminary results from a South African case-control study |
| title_full_unstemmed | Clinical and Molecular Epidemiology of Klebsiella pneumoniae Invasive Disease in Adults: preliminary results from a South African case-control study |
| title_short | Clinical and Molecular Epidemiology of Klebsiella pneumoniae Invasive Disease in Adults: preliminary results from a South African case-control study |
| title_sort | clinical and molecular epidemiology of klebsiella pneumoniae invasive disease in adults preliminary results from a south african case control study |
| url | http://www.sciencedirect.com/science/article/pii/S120197122400599X |
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