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7. Real-World Effectiveness Study of Nirmatrelvir-Ritonavir or Molnupiravir in Hospitalized Unvaccinated Patients with Chronic Respiratory Diseases and Moderate COVID-19 at Presentation

Author

Kwok,Wang Chun, Tam,Terence, Ho,James, Lam,David Chi Leung, Ip,Mary Sau-Man, Ho,Pak Leung, Kwok,Wang Chun, Tam,Terence, Ho,James, Lam,David Chi Leung, Ip,Mary Sau-Man, and Ho,Pak Leung

Abstract

Wang Chun Kwok,1 Terence Chi Chun Tam,1 James Chung Man Ho,1 David Chi Leung Lam,1 Mary Sau-Man Ip,1 Pak Leung Ho2 1Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of China; 2Department of Microbiology and Carol Yu Centre for Infection, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of ChinaCorrespondence: Pak Leung Ho, Department of Microbiology and Carol Yu Centre for Infection, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of China, Tel +852-2255-2584, Fax +852 2855 1241, Email plho@hku.hkIntroduction: Nirmatrelvir-ritonavir (NMV-r) and molnupiravir (MOL) were developed as out-patient anti-viral for mild COVID-19. There was limited data on their role in treating COVID-19 for hospitalized patients, especially among adult patients who are unvaccinated and had chronic respiratory diseases.Methods: A territory-wide retrospective study was conducted in Hong Kong to compare the efficacy of NMV-r and MOL against COVID-19 in unvaccinated adult patients with asthma, chronic obstructive pulmonary disease, bronchiectasis and interstitial lung diseases presenting with moderate COVID-19 from 16th February 2022 to 15th March 2023.Results: A total of 1354 patients were included, 738 received NMV-r and 616 received MOL. NMV-r was more effective in reducing 90-day mortality with adjusted hazard ratios (aHR) of 0.508 (95% confidence interval [CI] = 0.314– 0.822, p = 0.006). Patients who received NMV-r also had significantly shorter length of stay (LOS) than those receiving MOL, with median LOS of 4 (Interquartile range [IQR] = 2– 7) for NMV-r and 6 (IQR = 3– 10) for MOL (p-value < 0.001). There was no statistically significant difference in the development of respiratory failure and severe respiratory failure in

Published
2024

8. Geographical migration and fitness dynamics of Streptococcus pneumoniae.

Author

Belman, Sophie, Lefrancq, Noémie, Nzenze, Susan, Downs, Sarah, du Plessis, Mignon, Lo, Stephanie W., Corso, Alejandra, Gagetti, Paula, Brooks, Abdullah W., Hasanuzzaman, Md, Saha, Samir K., Saha, Senjuti, Davydov, Alexander, Titov, Leonid, Almeida, Samanta Cristine Grassi, Turner, Paul, Zhao, Chunjiang, Wang, Hui, Ip, Margaret, and Ho, Pak Leung

Abstract

Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location1,2. The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95% confidence interval of 1.59–1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient.Mathematical modelling of 15 years of data from South Africa reveals the spread and vaccine-driven changes in fitness and antimicrobial resistance of Streptococcus pneumoniae. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Inoculum Size and False-Positive Detection of NDM- and OXA-48-Type Carbapenemases Using Two Multiplex Lateral Flow Assays.

Author

Lee, Chung-Ho, Cao, Huiluo, Jiang, Shuo, Wong, Tammy Ting-Yan, Tse, Cindy Wing-Sze, and Ho, Pak-Leung

Subjects
WHOLE genome sequencing, AMINO acid sequence, SERRATIA, CARBAPENEMASE, MEDICAL microbiology
Abstract

The NG-Test CARBA 5 and Carbapenem-resistant K.N.I.V.O. Detection K-Set are lateral flow assays (LFAs) that rapidly detect five carbapenemases (KPC, NDM, IMP, VIM and OXA-48-like). We evaluated the effect of inoculum size on the performance of these two assays using 27 Enterobacterales isolates. Whole-genome sequencing (WGS) was used as the reference method. Using the NG-Test CARBA 5, eight Serratia spp. and six M. morganii isolates showed false-positive NDM results with a high inoculum. Using the Carbapenem-resistant K.N.I.V.O. Detection K-Set, eight M. morganii, four Serratia spp. and one K. pneumoniae isolates showed false-positive NDM and/or OXA-48-like bands at large inoculum sizes, while the other two M. morganii isolates demonstrated false-positive NDM and OXA-48-like results at all inoculum sizes. The false-positive bands varied in intensity. WGS confirmed that no carbapenemase gene was present. No protein sequence with a ≥50% identity to NDM or OXA-48-like enzymes was found. This study emphasizes the importance of assessing inoculum size in the diagnostic evaluation of LFAs. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Real-World Study on Effectiveness of Molnupiravir and Nirmatrelvir–Ritonavir in Unvaccinated Patients with Chronic Respiratory Diseases with Confirmed SARS-CoV-2 Infection Managed in Out-Patient Setting

Author

Kwok, Wang Chun, primary, Tsoi, Man Fung, additional, Leung, Sze Him Isaac, additional, Tsui, Chung Ki, additional, Tam, Terence Chi Chun, additional, Ho, James Chung Man, additional, Lam, David Chi Leung, additional, Ip, Mary Sau Man, additional, and Ho, Pak Leung, additional

Published
2023
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17. Efficacy of mRNA and Inactivated Whole Virus Vaccines Against COVID-19 in Patients with Chronic Respiratory Diseases

Author

Kwok,Wang Chun, Leung,Sze Him Isaac, Tam,Terence Chi Chun, Ho,James Chung Man, Lam,David Chi-Leung, Ip,Mary Sau Man, Ho,Pak Leung, Kwok,Wang Chun, Leung,Sze Him Isaac, Tam,Terence Chi Chun, Ho,James Chung Man, Lam,David Chi-Leung, Ip,Mary Sau Man, and Ho,Pak Leung

Abstract

Wang Chun Kwok,1,&ast; Sze Him Isaac Leung,2,&ast; Terence Chi Chun Tam,1 James Chung Man Ho,1 David Chi-Leung Lam,1 Mary Sau Man Ip,1 Pak Leung Ho3 1Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, People’s Republic of China; 2Department of Statistics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People’s Republic of China; 3Department of Microbiology and Carol Yu Centre for Infection, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pak Leung Ho, Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Pok Fu Lam, Hong Kong Special Administrative Region, People’s Republic of China, Tel +852 2255 2584, Fax +852 2855 1241, Email plho@hku.hkBackground: While different COVID-19 vaccines have been developed, there has been lack of data on the efficacy comparison between mRNA and inactivated whole virus vaccine among patients with chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and bronchiectasis.Methods: This was a retrospective case control study on the efficacy of BNT162b2 (mRNA vaccine) and CoronaVac (inactivated whole virus vaccine) against COVID-19 in patients with chronic respiratory diseases. A total of 327 patients were included, with 109 patients infected with COVID-19 matched with 218 patients without COVID-19. The co-primary outcomes were vaccine effectiveness against symptomatic COVID-19, COVID-19-related hospitalization and COVID-19-related respiratory failure. Vaccine effectiveness was calculated using the formula (1-adjusted odds ratio) x 100.Results: Patients who received at least 2 doses of CoronaVac had lower risk of being hospitalized for COVID-19 and developing respiratory failure than those who did not have vaccina

Published
2023

22. Evolution and Control of COVID-19 Epidemic in Hong Kong

Author

Wong, Shuk-Ching, primary, Au, Albert Ka-Wing, additional, Lo, Janice Yee-Chi, additional, Ho, Pak-Leung, additional, Hung, Ivan Fan-Ngai, additional, To, Kelvin Kai-Wang, additional, Yuen, Kwok-Yung, additional, and Cheng, Vincent Chi-Chung, additional

Published
2022
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23. Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole-genome sequencing study

Author

Lo, Stephanie W, primary, Mellor, Kate, additional, Cohen, Robert, additional, Alonso, Alba Redin, additional, Belman, Sophie, additional, Kumar, Narender, additional, Hawkins, Paulina A, additional, Gladstone, Rebecca A, additional, von Gottberg, Anne, additional, Veeraraghavan, Balaji, additional, Ravikumar, K L, additional, Kandasamy, Rama, additional, Pollard, Sir Andrew J, additional, Saha, Samir K, additional, Bigogo, Godfrey, additional, Antonio, Martin, additional, Kwambana-Adams, Brenda, additional, Mirza, Shaper, additional, Shakoor, Sadia, additional, Nisar, Imran, additional, Cornick, Jennifer E, additional, Lehmann, Deborah, additional, Ford, Rebecca L, additional, Sigauque, Betuel, additional, Turner, Paul, additional, Moïsi, Jennifer, additional, Obaro, Stephen K, additional, Dagan, Ron, additional, Diawara, Idrissa, additional, Skoczyńska, Anna, additional, Wang, Hui, additional, Carter, Philip E, additional, Klugman, Keith P, additional, Rodgers, Gail, additional, Breiman, Robert F, additional, McGee, Lesley, additional, Bentley, Stephen D, additional, Muñoz-Almagro, Carmen, additional, Varon, Emmanuelle, additional, Brooks, Abdullah, additional, Corso, Alejandra, additional, Davydov, Alexander, additional, Maguire, Alison, additional, Kiran, Anmol, additional, Moiane, Benild, additional, Beall, Bernard, additional, Zhao, Chunjiang, additional, Aanensen, David, additional, Everett, Dean, additional, Faccone, Diego, additional, Foster-Nyarko, Ebenezer, additional, Bojang, Ebrima, additional, Egorova, Ekaterina, additional, Voropaeva, Elena, additional, Sampane-Donkor, Eric, additional, Sadowy, Ewa, additional, Nagaraj, Geetha, additional, Mucavele, Helio, additional, Belabbès, Houria, additional, Elmdaghri, Naima, additional, Verani, Jennifer, additional, Keenan, Jeremy, additional, Lees, John, additional, N Nair Thulasee Bhai, Jyothish, additional, Ndlangisa, Kedibone, additional, Zerouali, Khalid, additional, Bentley, Leon, additional, Titov, Leonid, additional, De Gouveia, Linda, additional, Alaerts, Maaike, additional, Ip, Margaret, additional, de Cunto Brandileone, Maria Cristina, additional, Hasanuzzaman, Md, additional, Paragi, Metka, additional, Nurse-Lucas, Michele, additional, du Plessis, Mignon, additional, Ali, Mushal, additional, Croucher, Nicholas, additional, Wolter, Nicole, additional, Givon-Lavi, Noga, additional, Porat, Nurit, additional, Köseoglu Eser, Özgen, additional, Ho, Pak-Leung, additional, Eberechi Akpaka, Patrick, additional, Gagetti, Paula, additional, Tientcheu, Peggy-Estelle, additional, Law, Pierra, additional, Benisty, Rachel, additional, Mostowy, Rafal, additional, Malaker, Roly, additional, Grassi Almeida, Samanta Cristine, additional, Doiphode, Sanjay, additional, Madhi, Shabir, additional, Devi Sekaran, Shamala, additional, Clarke, Stuart, additional, Srifuengfung, Somporn, additional, Nzenze, Susan, additional, Kastrin, Tamara, additional, Ochoa, Theresa, additional, Hryniewicz, Waleria, additional, and Urban, Yulia, additional

Published
2022
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24. Gastrointestinal Colonization of Carbapenem-Resistant Acinetobacter baumannii: What Is the Implication for Infection Control?

Author

Wong, Shuk-Ching, primary, Chen, Jonathan Hon-Kwan, additional, Chau, Pui-Hing, additional, So, Simon Yung-Chun, additional, AuYeung, Christine Ho-Yan, additional, Yuen, Lithia Lai-Ha, additional, Chan, Veronica Wing-Man, additional, Lam, Germaine Kit-Ming, additional, Chiu, Kelvin Hei-Yeung, additional, Ho, Pak-Leung, additional, Lo, Janice Yee-Chi, additional, Yuen, Kwok-Yung, additional, and Cheng, Vincent Chi-Chung, additional

Published
2022
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25. Subinhibitory Concentrations of Antibiotics Exacerbate Staphylococcal Infection by Inducing Bacterial Virulence

Author

Gao, Peng, primary, Wei, Yuanxin, additional, Wan, Rachel Evelyn, additional, Wong, Ka Wing, additional, Iu, Ho Ting Venice, additional, Tai, Sherlock Shing Chiu, additional, Li, Yongli, additional, Yam, Hin Cheung Bill, additional, Halebeedu Prakash, Pradeep, additional, Chen, Jonathan Hon Kwan, additional, Ho, Pak Leung, additional, Yuen, Kwok Yung, additional, Davies, Julian, additional, and Kao, Richard Yi Tsun, additional

Published
2022
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26. Control of Healthcare-Associated Carbapenem-Resistant Acinetobacter baumannii by Enhancement of Infection Control Measures

Author

Wong, Shuk-Ching, primary, Chau, Pui-Hing, additional, So, Simon Yung-Chun, additional, Lam, Germaine Kit-Ming, additional, Chan, Veronica Wing-Man, additional, Yuen, Lithia Lai-Ha, additional, Au Yeung, Christine Ho-Yan, additional, Chen, Jonathan Hon-Kwan, additional, Ho, Pak-Leung, additional, Yuen, Kwok-Yung, additional, and Cheng, Vincent Chi-Chung, additional

Published
2022
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33. Predictive Factors of Cloxacillin Susceptibility in Primary Bacterial Spinal Infection

Author

Tang, Chris Yuk Kwan and Ho, Pak Leung

Abstract

Study Design Prognostic study.Objectives The objective of this study is to identify predictive factors for cloxacillin susceptibility in spinal infections.Methods A retrospective analysis was conducted using data from January 1, 1997, to December 31, 2021. The study included patients presenting with back pain and either a positive bacterial culture from the spine or radiological evidence of spinal infection (spondylodiscitis and/or epidural abscess) along with positive bacterial blood culture.Results Among 171 patients (127 males, 44 females), 53.2% had Staphylococcusisolates, with 40.4% showing cloxacillin resistance. Lower globulin levels (<33.5 g/L), recent hospitalization within 90 days, and residence in an old age home predicted gram-positive bacteria with cloxacillin resistance and gram-negative bacteria as causative organisms (P<.05). The 30-day and 1-year all-cause mortality rates were 0% and 8.2%, respectively. Higher red cell distribution width (RDW >16.1%) and Charlson comorbidity index (CCI) scores predicted 1-year all-cause mortality (P<.05). Intensive care unit admission was required for 9.9% of patients.Conclusions This study identified predictive factors for spinal infection by gram-positive bacteria with cloxacillin resistance and gram-negative bacteria. Patients with lower globulin levels (<33.5 g/L), recent hospitalization within 90 days, or residency in an old age home upon admission should avoid standalone cloxacillin therapy and consider antibiotics with gram-negative coverage. Higher RDW (>16.1%) and CCI scores were associated with increased 1-year all-cause mortality. These findings contribute to treatment decision-making and improving patient outcomes in spinal infections.

Published
2024
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34. A Streptococcus pneumoniae lineage usually associated with pneumococcal conjugate vaccine (PCV) serotypes is the most common cause of serotype 35B invasive disease in South Africa, following routine use of PCV.

Author

Ndlangisa KM, du Plessis M, Lo S, de Gouveia L, Chaguza C, Antonio M, Kwambana-Adams B, Cornick J, Everett DB, Dagan R, Hawkins PA, Beall B, Corso A, Grassi Almeida SC, Ochoa TJ, Obaro S, Shakoor S, Donkor ES, Gladstone RA, Ho PL, Paragi M, Doiphode S, Srifuengfung S, Ford R, Moïsi J, Saha SK, Bigogo G, Sigauque B, Eser ÖK, Elmdaghri N, Titov L, Turner P, Kumar KLR, Kandasamy R, Egorova E, Ip M, Breiman RF, Klugman KP, McGee L, Bentley SD, von Gottberg A, and The Global Pneumococcal Sequencing Consortium

Subjects
Humans, Pneumococcal Vaccines, Serogroup, South Africa epidemiology, Vaccines, Conjugate, Pneumococcal Infections epidemiology, Pneumococcal Infections prevention & control, Streptococcus pneumoniae genetics
Abstract

Pneumococcal serotype 35B is an important non-conjugate vaccine (non-PCV) serotype. Its continued emergence, post-PCV7 in the USA, was associated with expansion of a pre-existing 35B clone (clonal complex [CC] 558) along with post-PCV13 emergence of a non-35B clone previously associated with PCV serotypes (CC156). This study describes lineages circulating among 35B isolates in South Africa before and after PCV introduction. We also compared 35B isolates belonging to a predominant 35B lineage in South Africa (GPSC5), with isolates belonging to the same lineage in other parts of the world. Serotype 35B isolates that caused invasive pneumococcal disease in South Africa in 2005-2014 were characterized by whole-genome sequencing (WGS). Multi-locus sequence types and global pneumococcal sequence clusters (GPSCs) were derived from WGS data of 63 35B isolates obtained in 2005-2014. A total of 262 isolates that belong to GPSC5 (115 isolates from South Africa and 147 from other countries) that were sequenced as part of the global pneumococcal sequencing (GPS) project were included for comparison. Serotype 35B isolates from South Africa were differentiated into seven GPSCs and GPSC5 was most common (49 %, 31/63). While 35B was the most common serotype among GPSC5/CC172 isolates in South Africa during the PCV13 period (66 %, 29/44), 23F was the most common serotype during both the pre-PCV (80 %, 37/46) and PCV7 period (32 %, 8/25). Serotype 35B represented 15 % (40/262) of GPSC5 isolates within the global GPS database and 75 % (31/40) were from South Africa. The predominance of the GPSC5 lineage within non-vaccine serotype 35B, is possibly unique to South Africa and warrants further molecular surveillance of pneumococci.

Published
2022
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